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清水太郎

徳島大学

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2023年3月22日更新

職名: 特任助教
電話: 研究者総覧に該当データはありませんでした。
電子メール: shimizu.tarou@tokushima-u.ac.jp
学歴: 2003/4: 徳島大学薬学部製薬化学科 ( - 2007. 3.)
2007/4: 徳島大学大学院薬科学教育部博士前期課程 ( - 2009. 3.)
2011/10: 徳島大学大学院薬科学教育部博士後期課程 ( - 2014. 9.)
学位: 博士(薬学)
職歴・経歴: 2014/10: 徳島大学特任助教, 大学院ヘルスバイオサイエンス研究部 (-2015.3.)
2015/4: 徳島大学特任助教, 大学院医歯薬学研究部

専門分野・研究分野: ライフサイエンス (Life sciences) [医療薬学 (Clinical pharmacy)]

研究者総覧で最新データを確認する

2023年3月22日更新

専門分野・研究分野: ライフサイエンス (Life sciences) [医療薬学 (Clinical pharmacy)]
担当経験のある授業科目: コアDDS講義 (学部)
薬剤学実習 (学部)
製剤学実習 (学部)
指導経験: 研究者総覧に該当データはありませんでした。

研究者総覧で最新データを確認する

2023年3月22日更新

専門分野・研究分野: ライフサイエンス (Life sciences) [医療薬学 (Clinical pharmacy)]

研究テーマ: 研究者総覧に該当データはありませんでした。

著書

清水太郎, 石田竜弘 :
中分子医薬品やDDSに対する免疫応答,
株式会社シーエムシー出版, 2022年3月. 清水太郎, 石田竜弘 :
タンパクやナノ粒子に対するPEG修飾の有用性と免疫系に与える影響,
株式会社技術情報協会, 2021年8月. Lila Selim Ahmed Ali Abu Amr, Taro Shimizu and Tatsuhiro Ishida :
PEGylation and anti-PEG antibodies.,
Pan Stanford Publishing, Jan. 2018.

論文

Taro Shimizu, Takaaki Matsuzaki, Shoishiro Fukuda, Chihiro Yoshioka, Yuna Shimazaki, Shunsuke Takese, Katsuhiro Yamanaka, Takashi Nakae, Masaki Ishibashi, Hidetoshi Hamamoto, Hidenori ANDO, Yu Ishima and Tatsuhiro Ishida :
Ionic liquid-based transcutaneous peptide antitumor vaccine; therapeutic effect in a mouse tumor model,
The AAPS J, Vol.25, No.2, 27, 2023.

(出版サイトへのリンク): ● Publication site (DOI): 10.1208/s12248-023-00790-w
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1208/s12248-023-00790-w

(DOI: 10.1208/s12248-023-00790-w) Mohamed Ibrahim, Taro Shimizu, Hidenori ANDO, Yu Ishima, Helmy Omar Elgarhy, A Hatem Sarhan, K Amal Hussein and Tatsuhiro Ishida :
Investigation of anti-PEG antibody response to PEG-containing cosmetic products in mice,
Journal of Controlled Release, Vol.354, 260-267, 2023.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jconrel.2023.01.012
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.jconrel.2023.01.012

(DOI: 10.1016/j.jconrel.2023.01.012) Naoto Okada, Taro Shimizu, Hidenori ANDO, Shingen Nakamura, Mitsuhiro Goda, Masahiro Abe, Takashi Kitahara, Tatsuhiro Ishida and Keisuke Ishizawa :
Clinical impact of anti-polyethylene glycol (PEG) antibody in haematological patients administered PEGylated-granulocyte colony-stimulating factor,
Clinical Pharmacology in Drug Development, 2023.

(要約): Polyethylene glycol (PEG) is a polymer covalently attached to proteins to improve their half-life and efficacy. We previously reported that the PEGylated granulocyte colony-stimulating factor (PEG-G-CSF) is immunogenic, which could adversely impact drug efficacy and safety in animal models. Here, we analyzed the relationship between anti-PEG antibody titers and the clinical impact of PEG-G-CSF in 19 hematological patients. A gradual decrease of anti-PEG antibody titers from baseline was observed after PEG-G-CSF administration. Of the 19 participants, 10 were assessed for noninfectious fever after the first administration of PEG-G-CSF and three experienced this reaction. The receiver operating characteristic curve revealed that the cut-off values of pretreated anti-PEG IgM and IgG titers for noninfectious fever were set at 5.0 and 96.6 U/mL, respectively. All patients who experienced noninfectious fever had anti-PEG antibody titers above this cut-off value (P = .033). An enzyme-linked immunosorbent assay revealed that some anti-PEG antibodies in patients with anti-PEG antibody titers above the cut-off value reacted with the PEGylated liposome. These results indicate the reactivity of the anti-PEG antibodies to PEGylated therapeutics observed in hematologic patients and the possibility of the relationship between high titers of anti-PEG antibodies and the development of adverse events after PEG-G-CSF administration.
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/cpdd.1225
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36708147; ● Search Scopus @ Elsevier (PMID): 36708147; ● Search Scopus @ Elsevier (DOI): 10.1002/cpdd.1225

(DOI: 10.1002/cpdd.1225, PubMed: 36708147) Kohki Tachibana, Kohshi Kusumoto, Mai Ogawa, Hidenori ANDO, Taro Shimizu, Yu Ishima, Tatsuhiro Ishida and Keiichiro Okuhira :
FTY720 reduces lipid accumulation by upregulating ABCA1 through liver X receptor and sphingosine kinase 2 signaling in macrophages,
International Journal of Molecular Sciences, Vol.23, 14617, 2022.

(出版サイトへのリンク): ● Publication site (DOI): 10.3390/ijms232314617
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.3390/ijms232314617

(DOI: 10.3390/ijms232314617) Hiroshi Azuma, Toraji Amano, Naoya Kamiyama, Naofumi Takehara, Maki Jingu, Harumi Takagi, Osamu Sugita, Naoko Kobayashi, Tomoko Kure, Taro Shimizu, Tatsuhiro Ishida, Masanori Matsumoto and Hiromi Sakai :
First-in-human Phase 1 trial of artificial red blood cells, hemoglobin vesicles, developed as a transfusion alternative,
Blood Advances, Vol.6, No.21, 5711-5715, 2022.

(徳島大学機関リポジトリ): ● Metadata: 117961
(出版サイトへのリンク): ● Publication site (DOI): 10.1182/bloodadvances.2022007977
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35939788; ● Search Scopus @ Elsevier (PMID): 35939788; ● Search Scopus @ Elsevier (DOI): 10.1182/bloodadvances.2022007977

(徳島大学機関リポジトリ: 117961, DOI: 10.1182/bloodadvances.2022007977, PubMed: 35939788) Yu Ishima, Nio Yamazaki, V Chuang, Taro Shimizu, Hidenori ANDO and Tatsuhiro Ishida :
A maleimide-terminally modified PEGylated liposome induced the accelerated blood clearance independent of the production of anti-PEG IgM antibodies,
Biological & Pharmaceutical Bulletin, Vol.45, No.10, 1518-1524, 2022.

(キーワード): liposome / polyethylene glycol / accelerated blood clearance / maleimide / complement activation
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b22-00389
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390856583390911232; ● Search Scopus @ Elsevier (DOI): 10.1248/bpb.b22-00389

(DOI: 10.1248/bpb.b22-00389, CiNii: 1390856583390911232) Hidenori ANDO, Ai Ikeda, Maho Tagami, Nana Matsuo, Taro Shimizu, Yu Ishima, K Eshima and Tatsuhiro Ishida :
Oral administration of sodium bicarbonate can enhance the therapeutic outcome of Doxil® via neutralizing the acidic tumor microenvironment,
Journal of Controlled Release, Vol.350, 414-420, 2022.

(要約): The pH of the tumor microenvironment in solid tumors is reported to be more acidic than that of normal tissues. The pH is controlled by over-expression of several transporters that are associated with the progression, angiogenesis, and metastasis of solid tumors. Antitumor effects of weak-base anticancer agents, such as doxorubicin (DXR), could be reduced in an acidic environment because of increases in the ionized form of the drug under these conditions, reducing its membrane penetrability. In our previous studies, we demonstrated that oral administration of sodium bicarbonate (NaHCO) can neutralize the acidic tumor microenvironment and enhance the effects of small molecule anticancer drugs. However, it is not known whether or not increasing the tumor pH by oral administration of NaHCO leads to enhanced antitumor effects of lipidic nanoparticle formulations of weak-base anticancer drugs, such as Doxil®. In this study, we investigated the antitumor efficacy of Doxil® in combination with oral administration of NaHCO in a Colon26 tumor-bearing mouse model. NaHCO clearly enhanced the tumor-growth inhibitory effect of Doxil® without exacerbating any systemic side effects. In vitro studies indicated that high levels of DXR were internalized into cells at neutral pH. These studies demonstrate that the neutralization of acidic tumor microenvironment by an oral administration of NaHCO could be a promising approach to enhance the therapeutic outcomes of Doxil®.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jconrel.2022.08.031
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35988781; ● Search Scopus @ Elsevier (PMID): 35988781; ● Search Scopus @ Elsevier (DOI): 10.1016/j.jconrel.2022.08.031

(DOI: 10.1016/j.jconrel.2022.08.031, PubMed: 35988781) Yoshino Kawaguchi, Taro Shimizu, Hidenori ANDO, Yu Ishima and Tatsuhiro Ishida :
Development of a nanocarrier-based splenic B cell-targeting system for loading antigens in vitro,
Biological & Pharmaceutical Bulletin, Vol.45, No.7, 926-933, 2022.

(徳島大学機関リポジトリ): ● Metadata: 117224
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b22-00222
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1248/bpb.b22-00222

(徳島大学機関リポジトリ: 117224, DOI: 10.1248/bpb.b22-00222) Taro Shimizu, Yoshino Kawaguchi, Hidenori ANDO, Yu Ishima and Tatsuhiro Ishida :
Development of an antigen delivery system for a B cell-targeted vaccine as an alternative to dendritic cell-targeted vaccines,
Chemical & Pharmaceutical Bulletin, Vol.70, No.5, 341-350, 2022.

(出版サイトへのリンク): ● Publication site (DOI): 10.1248/cpb.c22-00047
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1248/cpb.c22-00047

(DOI: 10.1248/cpb.c22-00047) Marwa Sayed El, Taro Shimizu, Lila Selim Ahmed Ali Abu Amr, Elhewan Emam Elsadek Emam Ali Nehal, Emam Emam Abdallah Sherif, Eman Alaaeldin, Amal Kamal, Hatem Sarhan, Hidenori ANDO, Yu Ishima and Tatsuhiro Ishida :
A mouse model for studying the effect of blood anti-PEG IgMs levels on the in vivo fate of PEGylated liposomes,
International Journal of Pharmaceutics, Vol.615, 121539, 2022.

(要約): The presence of anti-polyethylene glycol (PEG) antibodies in the systemic circulation might have potential implications for the therapeutic activity of PEGylated products in vivo in the clinic. In order to study the effect of pre-existing anti-PEG antibodies on the in vivo fate and the therapeutic efficiency of PEGylated therapeutics, we developed a BALB/c mouse model by virtue of the intraperitoneal (i.p.) inoculation of hybridoma cells (HIK-M09 and HIK-M11), secreting monoclonal anti-PEG IgM, mimicking the presence of pre-existing anti-PEG antibodies in the blood. In the model, the titers of anti-PEG IgM in the blood increased as a function of hybridoma cells numbers and time after i.p. inoculation. The in vivo levels of anti-PEG IgM decreased in a dose-dependent manner, following i.v. administration of empty PEGylated liposomes. C26 tumor-bearing mice with measurable levels of anti-PEG IgM, receiving i.v. injection of DiR-labeled empty PEGylated liposomes, showed lower levels of liposomal tumor accumulation and higher levels of liver and spleen accumulation, compared to C26 tumor-bearing mice without measurable anti-PEG IgM. This specifies that the presence of anti-PEG IgM in the murine circulation induced accelerated blood clearance of PEGylated liposomes and reduced their tumor accumulation. The biodistribution and antitumor efficacy of commercially available doxorubicin (DXR)-containing PEGylated liposomes, Doxil®, were scrutinized in the anti-PEG IgM mouse model. In C26 tumor-bearing mice having circulating anti-PEG IgM, at 24 h after injection almost no DXR was observed in blood and tumor, and increased DXR accumulation was observed in spleen and liver, compared to tumor-bearing mice with no circulating anti-PEG IgM. The antitumor efficacy of Doxil® was significantly compromised in the C26 tumor-bearing mice in the presence of anti-PEG IgM. These results demonstrate that the anti-PEG IgM mouse model could be a useful prognostic indicator for the therapeutic effectiveness of different formulations of PEGylated therapeutics in pre-clinical studies.
(キーワード): Animals / Immunoglobulin M / Liposomes / Mice / Mice, Inbred BALB C / Polyethylene Glycols / Tissue Distribution
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2022.121539
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35124114; ● Search Scopus @ Elsevier (PMID): 35124114; ● Search Scopus @ Elsevier (DOI): 10.1016/j.ijpharm.2022.121539

(DOI: 10.1016/j.ijpharm.2022.121539, PubMed: 35124114) M Mostafa Mahmoud, Elhewan Emam Elsadek Emam Ali Nehal, Emam Emam Abdallah Sherif, Hidenori ANDO, Taro Shimizu, H Abdelkader, Yu Ishima, U Aly Farghaly, A H Sarhan and Tatsuhiro Ishida :
Using Bio-Layer Interferometry to evaluate anti-PEG antibody-mediated complement activation,
Biological & Pharmaceutical Bulletin, Vol.45, No.1, 129-135, 2022.

(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b21-00772
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1248/bpb.b21-00772

(DOI: 10.1248/bpb.b21-00772) Rie Ando-Matsuoka, Hidenori ANDO, Lila Selim Ahmed Ali Abu Amr, Noriyuki Maeda, Taro Shimizu, Yu Ishima and Tatsuhiro Ishida :
I.p.-injected cationic liposomes are retained and accumulate in peritoneally disseminated tumors,
Journal of Controlled Release, Vol.341, 524-532, 2022.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jconrel.2021.12.004
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.jconrel.2021.12.004

(DOI: 10.1016/j.jconrel.2021.12.004) Keisuke Mogi, Ikumi Kamiya, Aimi Makino, Ayaka Hirao, Reina Abe, Yusuke Doi, Taro Shimizu, Hidenori ANDO, Katsuya Morito, Kentaro Takayama, Tatsuhiro Ishida and Kazuki Nagasawa :
Liposomalization of oxaliplatin exacerbates the non-liposomal formulation-induced decrease of sweet taste sensitivity in rats,
Journal of Pharmaceutical Sciences, Vol.110, No.12, 3937-3945, 2021.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.xphs.2021.07.004
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.xphs.2021.07.004

(DOI: 10.1016/j.xphs.2021.07.004) Kazuyuki Saito, Taro Shimizu, Katsue Suzuki-Inoue, Tatsuhiro Ishida and Yoshiaki Wada :
Aseptic meningitis after vaccination of the BNT162b2 mRNA COVID19 vaccine,
Neurological Sciences, 2021.

(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s10072-021-05543-1
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1007/s10072-021-05543-1

(DOI: 10.1007/s10072-021-05543-1) Ryo Kinoshita, Yu Ishima, Victor T.G. Chuang, Hiroshi Watanabe, Taro Shimizu, Hidenori ANDO, Keiichiro Okuhira, Masaki Otagiri, Tatsuhiro Ishida and Toru Maruyama :
The therapeutic effect of HSA dimer-doxorubicin complex against human pancreatic tumour,
Pharmaceutics, Vol.13, No.8, 1209, 2021.

(徳島大学機関リポジトリ): ● Metadata: 116618
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/pharmaceutics13081209
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.3390/pharmaceutics13081209

(徳島大学機関リポジトリ: 116618, DOI: 10.3390/pharmaceutics13081209) Hidenori ANDO, Takashi Mochizuki, Amr Abu Ali Ahmed Selim Lila, Shunsuke Akagi, Kenji Tajima, Kenji Fujita, Taro Shimizu, Yu Ishima, Tokuo Matsushima, Takatomo Kusano and Tatsuhiro Ishida :
Doxorubicin embedded into nanofibrillated bacterial cellulose (NFBC) produces a promising therapeutic outcome for peritoneally metastatic gastric cancer in mice models via intraperitoneal direct injection,
Nanomaterials, Vol.11, 1697, 2021.

(徳島大学機関リポジトリ): ● Metadata: 116603
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/nano11071697
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.3390/nano11071697

(徳島大学機関リポジトリ: 116603, DOI: 10.3390/nano11071697) Emam Emam Abdallah Sherif, Elhewan Emam Elsadek Emam Ali Nehal, Lila Selim Ahmed Ali Abu Amr, Haruka Takata, Yoshino Kawaguchi, Taro Shimizu, Hidenori ANDO, Yu Ishima and Tatsuhiro Ishida :
Anti-PEG IgM production and accelerated blood clearance phenomenon after the administration of PEGylated exosomes in mice,
Journal of Controlled Release, Vol.334, 327-334, 2021.

(要約): Recently, there is an increasing interest in exosomes or extracellular vesicles as potential candidates for delivering RNAs, proteins, genes, and anticancer agents. Engineering of exosome properties is rapidly evolving as a means of expanding exosome applications. PEGylation of exosomes is a technique used to improve their in vivo stability, circulation half-lives, and sometimes to allow the binding targeting ligands to the exosome exterior. According to FDA guidelines for the development of PEGylated proteins, immunological responses to PEGylated molecules and particles should be examined. In this study, we prepared PEGylated exosomes and investigated the production of anti-PEG IgM antibodies after single i.v. injections in mice. In addition, we monitored blood concentrations and tumor accumulation of a second dose of PEGylated exosomes administered after the initial dose. Single injections of PEGylated exosomes in mice induced anti-PEG IgM production in a T cell-dependent manner. The anti-PEG IgM production decreased when the injection dose of PEGylated exosomes was further increased. Anti-PEG IgM induced by injection of PEGylated exosomes decreased blood concentrations of a second dose of PEGylated exosomes and suppressed their tumor accumulation in a C26 murine colorectal cancer model. Initial injection doses of either PEGylated liposomes or PEGylated ovalbumin (PEG-OVA), both of them induced anti-PEG IgM production, also decreased the blood concentration of PEGylated exosomes. Interestingly, anti-PEG IgM induced by injection of PEGylated exosomes did not affect the blood concentration of PEG-OVA. These results imply the importance of monitoring anti-PEG IgM when repeat PEGylated exosome doses are required and/or when PEGylated exosomes are used together with other PEGylated therapeutics.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jconrel.2021.05.001
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33957196; ● Summary page in Scopus @ Elsevier: 2-s2.0-85105280797

(DOI: 10.1016/j.jconrel.2021.05.001, PubMed: 33957196, Elsevier: Scopus) Milad Reda Qelliny, Taro Shimizu, Nehal Ali Emam Elsadek Emam Elhewan, Sherif Abdallah Emam Emam, Haruka Takata, Zeinab M. A. Fathalla, Amal K. Hussein, Khaled A. Khaled, Hidenori ANDO, Yu Ishima and Tatsuhiro Ishida :
Incorporating gangliosides into PEGylated cationic liposomes that complexed DNA attenuates anti-PEG antibody production, but not anti-DNA antibody production in mice,
Molecular Pharmaceutics, Vol.18, No.6, 2406-2415, 2021.

(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acs.molpharmaceut.1c00255
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1021/acs.molpharmaceut.1c00255

(DOI: 10.1021/acs.molpharmaceut.1c00255) Hidenori ANDO, Sherif Abdallah Emam Emam, Yoshino Kawaguchi, Taro Shimizu, Yu Ishima, Kiyoshi Eshima and Tatsuhiro Ishida :
Increasing tumor extracellular pH by an oral alkalinizing agent improves antitumor responses of anti-PD-1 antibody: Implication of relationships between serum bicarbonate concentrations, urinary pH, and therapeutic outcomes,
Biological & Pharmaceutical Bulletin, Vol.44, No.6, 844-852, 2021.

(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b21-00076
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1248/bpb.b21-00076

(DOI: 10.1248/bpb.b21-00076) Naoki Hirakawa, Yu Ishima, Ryo Kinoshita, Ryuto Nakano, Chuang Tuan Giam Victor, Hidenori ANDO, Taro Shimizu, Keiichiro Okuhira, Toru Maruyama, Masaki Otagiri and Tatsuhiro Ishida :
Reduction-responsive and Multi-drug Deliverable Albumin Nanoparticles: an antitumor drug to Abraxane® against Human Pancreatic Tumor-Bearing Mice,
ACS Applied Bio Materials, Vol.4, No.5, 4302-4309, 2021.

(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acsabm.1c00110
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1021/acsabm.1c00110

(DOI: 10.1021/acsabm.1c00110) Haruka Takata, Taro Shimizu, Yoshino Kawaguchi, Hiro Ueda, Nehal Ali Emam Elsadek Emam Elhewan, Hidenori ANDO, Yu Ishima and Tatsuhiro Ishida :
Nucleic acids delivered by PEGylated cationic liposomes in systemic lupus erythematosus-prone mice: a possible exacerbation of lupus nephritis in the presence of pre-existing anti-nucleic acid antibodies,
International Journal of Pharmaceutics, Vol.601, 120529, 2021.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2021.120529
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.ijpharm.2021.120529

(DOI: 10.1016/j.ijpharm.2021.120529) Maichi Hama, Yu Ishima, Chuang V, Hidenori ANDO, Taro Shimizu and Tatsuhiro Ishida :
Evidence for delivery of Abraxane® via a denatured-albumin transport system,
ACS Applied Materials & Interfaces, Vol.13, No.17, 19736-19744, 2021.

(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acsami.1c03065
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1021/acsami.1c03065

(DOI: 10.1021/acsami.1c03065) Shunsuke Akagi, Hidenori ANDO, Kenji Fujita, Taro Shimizu, Yu Ishima, Kenji Tajima, Tokuo Matsushima, Takatomo Kusano and Tatsuhiro Ishida :
Therapeutic efficacy of a paclitaxel-loaded nanofibrillated bacterial cellulose (PTX/NFBC) formulation in a peritoneally disseminated gastric cancer xenograft model,
International Journal of Biological Macromolecules, Vol.174, 494-501, 2021.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijbiomac.2021.01.201
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.ijbiomac.2021.01.201

(DOI: 10.1016/j.ijbiomac.2021.01.201) Taro Shimizu, Yuki Watanabe, Hidenori ANDO, Yu Ishima and Tatsuhiro Ishida :
Lymphoid follicle antigen (Ag) delivery and enhanced rodent humoral immune responses mediated by Ag-containing PEGylated liposomes,
Vaccine, Vol.39, No.7, 1131-1139, 2021.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.vaccine.2021.01.008
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.vaccine.2021.01.008

(DOI: 10.1016/j.vaccine.2021.01.008) Taro Shimizu, Mizuki Awata, Lila Selim Ahmed Ali Abu Amr, Chihiro Yoshioka, Yoshino Kawaguchi, Hidenori ANDO, Yu Ishima and Tatsuhiro Ishida :
Complement activation induced by PEG enhances humoral immune responses against antigens encapsulated in PEG-modified liposomes,
Journal of Controlled Release, Vol.329, 1046-1053, 2021.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jconrel.2020.10.033
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.jconrel.2020.10.033

(DOI: 10.1016/j.jconrel.2020.10.033) Takuma Takayama, Taro Shimizu, Lila Selim Ahmed Ali Abu Amr, Yuki Kanazawa, Hidenori ANDO, Yu Ishima and Tatsuhiro Ishida :
Adjuvant antitumor immunity contributes to the overall antitumor effect of PEGylated liposomal doxorubicin (Doxil®) in C26 tumor-bearing immunocompetent mice,
Pharmaceutics, Vol.12, No.10, 990, 2020.

(徳島大学機関リポジトリ): ● Metadata: 116247
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/pharmaceutics12100990
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.3390/pharmaceutics12100990

(徳島大学機関リポジトリ: 116247, DOI: 10.3390/pharmaceutics12100990) Elhewan Emam Elsadek Emam Ali Nehal, Emam Emam Abdallah Sherif, Lila Selim Ahmed Ali Abu Amr, Taro Shimizu, Hidenori ANDO, Yu Ishima and Tatsuhiro Ishida :
Pegfilgrastim (PEG-G-CSF) induces anti-polyethylene glycol (PEG) IgM via a T cell-dependent mechanism,
Biological & Pharmaceutical Bulletin, Vol.43, No.9, 1393-1397, 2020.

(要約): Protein-based therapeutics are beginning to be widely used in various clinical settings. Conjugation of polyethylene glycol (PEGylation) to protein therapeutics improves their circulation half-lives in the body. However, we and other groups observed that the initial dose of some PEGylated protein-based therapeutics may induce anti-PEG antibodies (primarily immunoglobulin M (IgM)), resulting in the accelerated clearance of a second dose. The mechanism behind the induction of anti-PEG IgM by PEGylated protein-based therapeutics is still unclear. In this study, we found that Pegfilgrastim (PEG-G-CSF, the PEGylated form of the recombinant human granulocyte colony-stimulating factor) induced anti-PEG IgM in mice when administered via either intravenous or subcutaneous administration. However, the anti-PEG IgM induction is diminished both in athymic nude mice lacking T cells and in splenectomized mice. In addition, anti-PEG IgM production was significantly diminished in the cyclophosphamide-treated mice depleted of B-cells. These results indicate that anti-PEG IgM production by Pegfilgrastim occurs in spleen in a T cell-dependent manner, which differs from anti-PEG IgM induced by PEGylated liposomes. However, B cells, both marginal zone and follicular, are essential for anti-PEG IgM production in both PEGylated preparations.
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b20-00345
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32879214; ● Search Scopus @ Elsevier (PMID): 32879214; ● Search Scopus @ Elsevier (DOI): 10.1248/bpb.b20-00345

(DOI: 10.1248/bpb.b20-00345, PubMed: 32879214) Takaaki Ryujin, Taro Shimizu, Ryo Miyahara, Daisuke Asai, Rena Shimazui, Takuma Yoshikawa, Akihiro Kishimura, Takeshi Mori, Tatsuhiro Ishida and Yoshiki Katayama :
Blood retention and antigenicity of polycarboxybetaine-modified liposomes,
International Journal of Pharmaceutics, Vol.586, 119521, 2020.

(要約): Zwitterionic polycarboxybetaines (PCBs) have gained attention as alternative stealth polymers whose liposomal formulation and protein conjugates were reported not to elicit anti-polymer antibodies. Here, we studied the blood retention and antigenicity of liposomes modified with PCBs focusing on their chemical structures and doses. We compared PCBs with either 1 or 3 (PCB1 or PCB3) spacer carbons between the carboxylate and ammonium groups. PCB3-modified liposomes had a short blood retention, whereas PCB1-modified liposomes demonstrated extended blood retention that was somewhat superior to PEGylated liposome. This confirmed the excellent non-fouling nature of PCB1 reported previously. Interestingly, PCB1-liposome as well as PCB3-liposome elicited specific IgMs toward each PCB. The dose-dependent production of specific IgMs to PCB-liposomes was similar to that of PEGylated liposome, i.e., high doses of PCB-liposomes reduced the production of specific IgMs, termed immunological tolerance. These results indicate the importance of investigating the effect of dose to clarify the existence of antigenicity of stealth polymers.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2020.119521
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32561308; ● Summary page in Scopus @ Elsevier: 2-s2.0-85086721197

(DOI: 10.1016/j.ijpharm.2020.119521, PubMed: 32561308, Elsevier: Scopus) Elhewan Emam Elsadek Emam Ali Nehal, Eri Hondoh, Taro Shimizu, Haruka Takata, Lila Selim Ahmed Ali Abu Amr, Emam Emam Abdallah Sherif, Hidenori ANDO, Yu Ishima and Tatsuhiro Ishida :
Impact of pre-existing or induced anti-PEG IgM on the pharmacokinetics of peginterferon alfa-2a (Pegasys®) in mice,
Molecular Pharmaceutics, Vol.17, No.8, 2964-2970, 2020.

(要約): PEGylation had been used successfully to improve the circulation half-lives and some physicochemical properties of protein therapeutics. However, anti-polyethylene glycol (anti-PEG) antibodies, either pre-existing or treatment-induced, can negatively affect the pharmacokinetics and pharmacological efficacy of PEGylated proteins. We have examined anti-PEG immune responses in mice for peginterferon alfa-2a (Pegasys), a clinically approved PEGylated protein therapeutic, at both the recommended dose (equivalent to 3 μg/kg in mice) and at higher doses (150 μg/kg) for single or repeated subcutaneous (s.c.) administrations. The effect of treatment-induced anti-PEG IgM on serum concentrations of Pegasys, following repeated administrations, was evaluated. In addition, the effect of pre-existing anti-PEG IgM elicited by a different PEGylated protein, PEG-OVA, on the systemic clearance of Pegasys, was investigated. At a s.c. dose of 3 μg/kg, single injections of Pegasys barely elicited anti-PEG immune responses. Four repeated doses of 150 μg/kg Pegasys elicited anti-PEG IgM production, depending on dose frequency, and triggered the rapid clearance of subsequent doses. In addition, anti-PEG-IgM produced in response to prior administration of PEG-OVA caused a rapid blood clearance of Pegasys. Our results, therefore, underscore the importance of screening for both pre-existing and treatment-induced anti-PEG antibodies in patients prior to and during treatment with PEGylated protein drugs.
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acs.molpharmaceut.0c00366
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32519877; ● Search Scopus @ Elsevier (PMID): 32519877; ● Search Scopus @ Elsevier (DOI): 10.1021/acs.molpharmaceut.0c00366

(DOI: 10.1021/acs.molpharmaceut.0c00366, PubMed: 32519877) M Sayed M El, Haruka Takata, Taro Shimizu, Yoshino Kawaguchi, Lila Selim Ahmed Ali Abu Amr, Elhewan Emam Elsadek Emam Ali Nehal, E Alaaeldin, Yu Ishima, Hidenori ANDO, A Kamal, A H Sarhan and Tatsuhiro Ishida :
Hepatosplenic phagocytic cells indirectly contribute to anti-PEG IgM production in the accelerated blood clearance (ABC) phenomenon against PEGylated liposomes: Appearance of an unexplained mechanism in the ABC phenomenon,
Journal of Controlled Release, Vol.323, 102-109, 2020.

(要約): The accelerated blood clearance (ABC) phenomenon, caused in large degree via in vivo anti-PEG IgM production, is one of obstacles for development of PEGylated liposome and protein formulations, due to decreased efficiency and/or side effects such as anaphylaxis upon repeat administrations. We have shown in murine ABC models that splenectomy suppressed the level of anti-PEG IgM production induced by PEGylated liposomes, indicating that murine splenic B cells play an important role in its production. However, splenectomy did not completely inhibit production of anti-PEG IgM, suggesting that other cells may contribute to its production in the ABC phenomenon. In this study, we examined the contribution of hepatosplenic phagocytic cells to anti-PEG IgM production and clearance of PEGylated liposomes during the ABC phenomenon. Depletion of hepatosplenic phagocytic cells by pretreatment of mice with clodronate-containing non-PEGylated liposomes suppressed anti-PEG IgM production to a considerable degree, without a change in the number of splenic B cells, and attenuated the enhanced clearance of second dose of PEGylated liposomes. These results suggest that hepatosplenic phagocytic cells, in addition to splenic B cells, contribute to the production of anti-PEG IgM and the ABC phenomenon against PEGylated liposomes. The mechanism whereby splenic B cells interact with hepatosplenic phagocytic cells to produce anti-PEG IgM, upon administration of an initial dose of PEGylated liposomes remains to be elucidated.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jconrel.2020.04.011
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32278827; ● Summary page in Scopus @ Elsevier: 2-s2.0-85083399688

(DOI: 10.1016/j.jconrel.2020.04.011, PubMed: 32278827, Elsevier: Scopus) Nehal Ali Emam Elsadek Emam Elhewan, Amr Abu Ali Ahmed Selim Lila, Sherif Abdallah Emam Emam, Taro Shimizu, Haruka Takata, Hidenori ANDO, Yu Ishima and Tatsuhiro Ishida :
Pegfilgrastim (PEG-G-CSF) induces anti-PEG IgM in a dose dependent manner and causes the accelerated blood clearance (ABC) phenomenon upon repeated administration in mice,
European Journal of Pharmaceutics and Biopharmaceutics, Vol.152, 56-62, 2020.

(要約): Pegfilgrastimis a recombinant PEGylated human granulocyte colony-stimulating factor (G-CSF) analog filgrastim (trade names Neulasta® or G-Lasta®) that stimulates the production of white blood cells (neutrophils). It is employed as an alternative to filgrastim (G-CSF) for chemotherapy-induced neutropenia in patients due to its longer half-life. In clinical settings, PEG-G-CSF is administered to cancer patients via both the s.c. and i.v. routes. In a murine study, we showed that, regardless of administration route, initial doses of PEG-G-CSF above 0.06 mg/kg elicited anti-PEG immune response in a dose-dependent manner. I.v. administration elicited higher levels of anti-PEG IgM than the s.c. route. Initial doses of PEG-G-CSF (6 mg/kg) that were high enough to trigger production of anti-PEG IgM, did not trigger the accelerated clearance of a lower subsequent dose (0.06 mg/kg) that was similar to i.v. clinical doses of PEG-G-CSF, but when the subsequent dose of PEG-G-CSF was raised to (6 mg/kg), the initial dose triggered the accelerated clearance of the second dose via an anti-PEG IgM-mediated complement activation. Similar observations were noted when an increased PEG-OVA dose was given as the second dose, indicating that pre-existing and/or treatment-induced anti-PEG antibodies might compromise the therapeutic activity and/or reduce tolerance of other PEGylated formulations. To the best of our knowledge, this is the first report to suggest the induction of the ABC phenomenon upon repeated injections of pegfilgrastim. In the clinic, cancer patients, receiving multiple cycles of chemotherapy, receive multiple cycles of pegfilgrastim to avoid infections and substantial morbidity. The ABC phenomenon to pegfilgrastim appears to be the cause of loss of clinical benefit of sequential treatments with pegfilgrastim in patients.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ejpb.2020.04.026
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32376372; ● Search Scopus @ Elsevier (PMID): 32376372; ● Search Scopus @ Elsevier (DOI): 10.1016/j.ejpb.2020.04.026

(DOI: 10.1016/j.ejpb.2020.04.026, PubMed: 32376372) Yukiko Oh, Hitomi Niijima, Yuta Kawahara, Tomomi Hayase, Taro Shimizu, Tatsuhiro Ishida and Akira Morimoto :
An immediate hypersensitivity reaction induced by PEGylated recombinant factor VIII,
Haemophilia, 2020.

(出版サイトへのリンク): ● Publication site (DOI): 10.1111/hae.14048
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1111/hae.14048

(DOI: 10.1111/hae.14048) Hidenori ANDO, Noriko Saito-Tarashima, Lila Selim Ahmed Ali Abu Amr, Nozomi Kinjoh, Taro Shimizu, Yu Ishima, Noriaki Minakawa and Tatsuhiro Ishida :
A unique gene-silencing approach, using an intelligent RNA expression device (iRed), results in minimal immune stimulation when given by local intrapleural injection in malignant pleural mesothelioma,
Molecules, Vol.25, No.7, 1725, 2020.

(要約): We have recently introduced an intelligent RNA expression device (iRed), comprising the minimum essential components needed to transcribe short hairpin RNA (shRNA) in cells. Use of iRed efficiently produced shRNA molecules after transfection into cells and alleviated the innate immune stimulation following intravenous injection. To study the usefulness of iRed for local injection, the engineered iRed encoding luciferase shRNA (Luc iRed), complexed with cationic liposomes (Luc iRed/liposome-complexes), was intrapleurally injected into an orthotopic mesothelioma mouse model. Luc iRed/liposome-complexes markedly suppressed the expression of a luciferase marker gene in pleurally disseminated mesothelioma cells. The suppressive efficiency was correlated with the expression level of shRNA within the mesothelioma cells. In addition, intrapleural injection of iRed/liposome-complexes did not induce IL-6 production in the pleural space and consequently in the blood compartment, although plasmid DNA (pDNA) or dsDNA (the natural construct for iRed) in the formulation did. Local delivery of iRed could augment the in vivo gene silencing effect without eliciting pronounced innate immune stimulation. Our results might hold promise for widespread utilization of iRed as an RNAi-based therapeutic for intracelial malignant cancers.
(徳島大学機関リポジトリ): ● Metadata: 115605
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/molecules25071725
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32283709; ● Summary page in Scopus @ Elsevier: 2-s2.0-85083281974

(徳島大学機関リポジトリ: 115605, DOI: 10.3390/molecules25071725, PubMed: 32283709, Elsevier: Scopus) Emam Emam Abdallah Sherif, Lila Selim Ahmed Ali Abu Amr, Elhewan Emam Elsadek Emam Ali Nehal, Hidenori ANDO, Taro Shimizu, Keiichiro Okuhira, Yu Ishima, M Mahdy, E Ghazy and Tatsuhiro Ishida :
Cancer cell-type tropism is one of crucial determinants for the efficient systemic delivery of cancer cell-derived exosomes to tumor tissues,
European Journal of Pharmaceutics and Biopharmaceutics, Vol.145, 27-34, 2019.

(要約): Exosomes are gaining increasing attention as drug delivery vehicles due to their low toxicity and ability to functionally transfer biological cargos between cells. However, the therapeutic applicability of exosomes is partially hampered by a lack of cell-type specificity. In this study, therefore, we investigated the impact of cell-type tropism on the in vivo systemic delivery of exosomes to tumor tissues. Exosomes derived from murine colorectal cancer cells (C26) (C26-Exos) and murine melanoma cells (B16BL6) (B16BL6-Exos) were collected. In vitro cellular uptake of either autologous (C26) or allogeneic (B16BL6) exosomes by C26 tumor cells was determined. In vivo tumor accumulation of each type of exosomes in mice bearing C26 tumors was monitored with an in vivo imaging system (IVIS). In in vitro studies, autologous C26-Exos were more efficiently taken up by C26 cancer cells, compared to allogeneic B16BL6-Exos. For in vivo studies, exosomes were modified with surface polyethylene glycol (PEG) to improve their circulation lifetimes. Although both types of PEGylated exosomes accumulated in C26-tumor tissue, autologous exosomes were preferentially accumulated within C26-tumor tissue compared to allogeneic exosomes. The increased tumor accumulation of autologous PEGylated exosomes was accompanied by the preferential uptake of exosomes by not only C26-tumor cells but also tumor-associated immune cells. This study implies that cancer cell-type tropism is an important factor in the achievement of tumor cell targeting with cancer cell-derived exosomes.
(キーワード): Animals / Cell Line, Tumor / Colorectal Neoplasms / Drug Delivery Systems / Exosomes / Male / Melanoma / Mice / Mice, Inbred BALB C / Polyethylene Glycols / Tropism
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ejpb.2019.10.005
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31629787; ● Summary page in Scopus @ Elsevier: 2-s2.0-85073758566

(DOI: 10.1016/j.ejpb.2019.10.005, PubMed: 31629787, Elsevier: Scopus) Hidenori ANDO, M Fukushima, K Eshima, Taichi Hasui, Taro Shimizu, Yu Ishima, C Huang, H Wada and Tatsuhiro Ishida :
A novel intraperitoneal therapy for gastric cancer with DFP-10825, a unique RNAi therapeutic targeting thymidylate synthase, in peritoneally disseminated xenograft model,
Cancer Medicine, Vol.8, No.17, 7313-7321, 2019.

(要約): In advanced gastric cancer, peritoneal dissemination is a life-threatening mode of metastasis. Since the treatment options with conventional chemotherapy remain limited, any novel therapeutic strategy that could control such metastasis would improve the outcome of treatment. We recently developed a unique RNA interference therapeutic regimen (DFP-10825) consisting of short hairpin RNA against thymidylate synthase (TS shRNA) and cationic liposomes. The treatment with DFP-10825 has shown remarkable antitumor activity in peritoneally disseminated human ovarian cancer-bearing mice via intraperitoneal administration. In this study, we expanded DFP-10825 to the treatment of peritoneally disseminated gastric cancer. DFP-10825 was administered intraperitoneally into mice with intraperitoneally implanted human gastric cancer cells (MKN45 or NCI-N87). Antitumor activity and host survival benefits were monitored. Intraperitoneal distribution of fluorescence-labeled DFP-10825 was monitored in this MKN45 peritoneally disseminated mouse model. Intraperitoneal injection of DFP-10825 suppressed tumor growth in two peritoneally disseminated cancer models (MKN45 and NCI-N87) and increased the survival time of the MKN45 model without severe side effects. Throughout the treatment regimen, no significant body weight loss was associated with the administration of DFP-10825. Interestingly, after intraperitoneal injection, fluorescence-labeled DFP-10825 retained for more than 72 hours in the peritoneal cavity and selectively accumulated in disseminated tumors. Intraperitoneal injection of DFP-10825 demonstrated effective antitumor activity without systemic severe adverse effects via the selective delivery of RNAi molecules into disseminated tumors in the peritoneal cavity. Our current study indicates that DFP-10825 could become an alternative option to improve the outcomes of patients with peritoneally disseminated gastric cancer.
(徳島大学機関リポジトリ): ● Metadata: 115036
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/cam4.2598
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31609087; ● Search Scopus @ Elsevier (PMID): 31609087; ● Search Scopus @ Elsevier (DOI): 10.1002/cam4.2598

(徳島大学機関リポジトリ: 115036, DOI: 10.1002/cam4.2598, PubMed: 31609087) 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
PEG修飾リポソームに対する免疫応答,
人工血液, Vol.27, 37-43, 2019年. S Ichimizu, H Watanabe, H Maeda, K Hamasaki, K Ikegami, V Chuang, Ryo Kinoshita, K Nishida, Taro Shimizu, Yu Ishima, Tatsuhiro Ishida, T Seki, H Katsuki, S Futaki, M Otagiri and T Maruyama :
Cell-penetrating mechanism of intracellular targeting albumin: Contribution of macropinocytosis induction and endosomal escape,
Journal of Controlled Release, Vol.304, 156-163, 2019.

(要約): We recently developed a cell-penetrating drug carrier composed of albumin (HSA) combined with palmitoyl-cyclic-(D-Arg). While it is possible that the palmitoyl-cyclic-(D-Arg)/HSA enters the cell mainly via macropinocytosis, the mechanism responsible for the induction of macropinocytosis and endosomal escape remain unknown. We report herein that palmitoyl-cyclic-(D-Arg)/HSA might interact with heparan sulfate proteoglycan and the chemokine receptor CXCR4 followed by multiple activations of the PKC/PI3K/JNK/mTOR signaling pathways to induce macropinocytosis. This result was further confirmed by a co-treatment with 70 kDa dextran, a macropinocytosis marker. Using liposomes that mimic endosomes, the leakage of 5,6-carboxyfluorescein from liposome was observed in the presence of palmitoyl-cyclic-(D-Arg)/HSA only in the case of the anionic late endosome-like liposomes but not the neutral early endosome-like liposomes. Heparin largely inhibited this leakage, suggesting the importance of electrostatic interactions between palmitoyl-cyclic-(D-Arg)/HSA and the late-endosomal membrane. Immunofluorescence staining and Western blotting data indicated that the intact HSA could be transferred from endosomes to the cytosol. These collective data suggest that the palmitoyl-cyclic-(D-Arg)/HSA is internalized via macropinocytosis and intact HSA is released from the late endosomes to the cytoplasm before the endosomes fuse with lysosomes. Palmitoyl-cyclic-(D-Arg)/HSA not only functions as an intracellular drug delivery carrier but also as an inducer of macropinocytosis.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jconrel.2019.05.015
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31082432; ● Summary page in Scopus @ Elsevier: 2-s2.0-85065581511

(DOI: 10.1016/j.jconrel.2019.05.015, PubMed: 31082432, Elsevier: Scopus) Hidenori ANDO, Lila Selim Ahmed Ali Abu Amr, M Fukushima, Rie Matsuoka, Taro Shimizu, Keiichiro Okuhira, Yu Ishima, C Huang, H Wada and Tatsuhiro Ishida :
A simplified method for manufacturing RNAi therapeutics for local administration,
International Journal of Pharmaceutics, Vol.564, 256-262, 2019.

(要約): RNA interference (RNAi) is one of the most promising strategies for cancer therapeutics. The successful translation of RNAi therapeutics to a clinic setting requires a delivery system that is efficient and simple to upscale. In this study, we devised a simple industrial method to manufacture lipoplex, which includes short hairpin RNA against the expression of thymidylate synthase (TS shRNA) - a key molecule for DNA biosynthesis. An aqueous solution of TS shRNA was gently mixed with either a precursor of cationic liposome (Presome DF-1) or a cationic lipid mixture in an o/w emulsion. This solution was subsequently lyophilized under optimal conditions to obtain either FD-lipoplex-1 or FD-lipoplex-2, respectively. With this method, a lipoplex in activated form was obtained via a simple "one-step" hydration with saline. Both forms of FD-lipoplex showed physicochemical properties comparable to those of conventional lipoplex. FD-lipoplexes stably retained TS shRNA within their formulations in the presence of tumor ascites fluid. Intraperitoneal treatment with either FD-lipoplex-1 or FD-lipoplex-2 provided a therapeutic level of efficacy comparable to that of conventional lipoplex in the treatment of a peritoneal disseminated gastric cancer mouse model. Collectively, established freeze-drying-based methods for RNAi-therapeutic preparation could realistically be used in a clinical setting for the treatment of patients with peritoneal disseminated cancer.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2019.04.054
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31015002; ● Summary page in Scopus @ Elsevier: 2-s2.0-85064496754

(DOI: 10.1016/j.ijpharm.2019.04.054, PubMed: 31015002, Elsevier: Scopus) Yusuke Doi, Taro Shimizu, Yu Ishima and Tatsuhiro Ishida :
Long-term storage of PEGylated liposomal oxaliplatin with improved stability and long circulation times in vivo,
International Journal of Pharmaceutics, Vol.564, 237-243, 2019.

(要約): Liposomal anticancer drugs have been developed with improved clinical effects and reduced side effects. We have developed a PEGylated liposomal formulation of oxaliplatin that has anticancer effects in animal models of colorectal cancer with a favorable toxicity profile. To move this formulation into clinical development, a formulation that is stable during long term storage is needed, which has similar pharmacokinetics and therapeutic activity against solid tumors to the original formulation. In this study, we found that PEGylated liposomal oxaliplatin showed no changes in particle size after long term storage (12 months at 2-8 °C), but phospholipid degradation had occurred. Hence, the stored formulation had compromised membrane integrity, resulting in decreased in vivo circulation times of the liposomes. To improve the stability during long-term storage, a screening study to obtain an appropriate stabilizer was carried out. The buffer 2-morpholinoethansulfonic acid (MES) attenuated not only phospholipid degradation but also oxaliplatin degradation, unlike most other excipients. After 12 months storage at 2-8 °C in the presence of MES only slight degradation of phospholipids in PEGylated liposomal oxaliplatin occurred, resulting in similar in vivo pharmacokinetic profiles of the encapsulated oxaliplatin to the original formulation. Long term stability of PEGylated liposomal oxaliplatin was achieved by addition of MES, resulting in long circulation half-lives in vivo, a property which would be expected to lead to increased suppression of tumor growth and reduced side effects. Our formulation may now be suitable for clinical development.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2019.04.042
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31002935; ● Summary page in Scopus @ Elsevier: 2-s2.0-85064481198

(DOI: 10.1016/j.ijpharm.2019.04.042, PubMed: 31002935, Elsevier: Scopus) Mayumi Ikeda, Yu Ishima, VTG Chuang, Maki Sakai, Hiroki Osafune, Hidenori ANDO, Taro Shimizu, Keiichiro Okuhira, H Watanabe, T Maruyama, M Otagiri, T Akaike and Tatsuhiro Ishida :
Distribution of Polysulfide in Human Biological Fluids and Their. Association with Amylase and Sperm Activities,
Molecules, Vol.24, No.9, 1689, 2019.

(要約): Intracellular polysulfide could regulate the redox balance via its anti-oxidant activity. However, the existence of polysulfide in biological fluids still remains unknown. Recently, we developed a quantitative analytical method for polysulfide and discovered that polysulfide exists in plasma and responds to oxidative stress. In this study, we confirmed the presence of polysulfide in other biological fluids, such as semen and nasal discharge. The levels of polysulfide in these biological fluids from healthy volunteers ( = 9) with identical characteristics were compared. Additionally, the circadian rhythm of plasma polysulfide was also investigated. The polysulfide levels detected from nasal discharge and seminal fluid were approximately 400 and 600 μM, respectively. No correlation could be found between plasma polysulfide and the polysulfide levels of tear, saliva, and nasal discharge. On the other hand, seminal polysulfide was positively correlated with plasma polysulfide, and almost all polysulfide contained in semen was found in seminal fluid. Intriguingly, saliva and seminal polysulfide strongly correlated with salivary amylase and sperm activities, respectively. These results provide a foundation for scientific breakthroughs in various research areas like infertility and the digestive system process.
(徳島大学機関リポジトリ): ● Metadata: 115606
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/molecules24091689
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31052207; ● Summary page in Scopus @ Elsevier: 2-s2.0-85065659717

(徳島大学機関リポジトリ: 115606, DOI: 10.3390/molecules24091689, PubMed: 31052207, Elsevier: Scopus) Taro Shimizu, Lila Selim Ahmed Ali Abu Amr, Mizuki Awata, Yukiyo Kubo, Yu Mima, Yosuke Hashimoto, Hidenori ANDO, Keiichiro Okuhira, Yu Ishima and Tatsuhiro Ishida :
A cell assay for detecting anti-PEG immune response against PEG-modified therapeutics,
Pharmaceutical Research, Vol.35, No.11, 223, 2018.

(要約): Immunogenicity of PEGylated proteins and nanomedicines represents a potential impediment against their development and use in clinical settings. The purpose of this study is to develop a method for detecting anti-PEG immunity of PEGylated proteins and/or nanomedicines using flow cytometry. The binding of fluorescence-labeled mPEG-modified liposomes to HIK-G11 cells, PEG-specific hybridoma cells, or spleen cells was evaluated by flow cytometry for detecting immunogenicity of PEGylated therapeutics. The fluorescence-labeled methoxy PEG (mPEG)-modified liposomes were efficiently bound to HIK-G11 cells. Such staining with fluorescence-labeled mPEG-modified liposomes was significantly inhibited in the presence of either non-labeled mPEG-modified liposomes or mPEG-modified ovalbumin (OVA) but not polyglycerol-modified liposomes. In addition, we found that mPEG-modified liposomes, highly immunogenic, caused proliferation of PEG-specific cells, while hydroxyl PEG-modified liposomes, less immunogenic, scarcely caused. Furthermore, after intravenous injection of mPEG-modified liposomes, the percentage of PEG-specific cells in the splenocytes, as determined by flow cytometry, corresponded well with the production level of anti-PEG antibodies, as determined by ELISA. PEG-specific B cell assay we introduced may become a useful method to detect an anti-PEG immune response against PEGylated therapeutics and clarify the mechanism for anti-PEG immune responses.
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s11095-018-2505-3
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30280273; ● Summary page in Scopus @ Elsevier: 2-s2.0-85054175366

(DOI: 10.1007/s11095-018-2505-3, PubMed: 30280273, Elsevier: Scopus) Taro Shimizu, Lila Selim Ahmed Ali Abu Amr, Yoshino Kawaguchi, Yuna Shimazaki, Yu Mima, Yosuke Hashimoto, Keiichiro Okuhira, G Storm, Yu Ishima and Tatsuhiro Ishida :
A novel platform for cancer vaccines: Antigen-selective delivery to splenic marginal zone B cells via repeated injections of PEGylated liposomes,
The Journal of Immunology, Vol.201, No.10, 2969-2976, 2018.

(要約): Treating cancer with vaccines has been a challenge. In this study, we introduce a novel Ag delivery platform for cancer vaccines that delivers an encapsulated Ag to splenic marginal zone B (MZ-B) cells via the aid of a PEGylated liposome (PL) system. Splenic MZ-B cells have recently attracted interest as alternative APCs. In mice, preimmunization with empty (no Ag encapsulation) PLs triggered the efficient delivery of a subsequent dose of Ag-containing PLs, injected 3 d later, to the spleen compared with a single dose of Ag-containing PLs. In addition, immunization with empty PLs allowed three subsequent sequential injections of OVA-PLs to efficiently induce a CTL response against OVA-expressing murine thymoma (EG7-OVA) cells and resulted in in vivo growth inhibition of subsequently inoculated EG7-OVA cells. However, these sequential treatments require repeated immunizations to achieve their antitumor effect. Therefore, to improve the antitumor effect of our novel vaccine system, an adjuvant, -galactosylceramide (GC), was incorporated into the OVA-PLs (GC/OVA-PLs). As expected, the incorporation of GC reduced the required number of immunizations with OVA-PLs to the point that a single immunization treatment with empty PLs and an injection of GC/OVA-PL efficiently triggered a potent CTL induction, resulting in a rejection of the development and a suppression of the growth of tumors that had already developed s.c. Results of this study indicate that a novel Ag delivery platform that grants efficient Ag delivery to splenic MZ-B cells shows promise as a therapeutic modality for conquering tumor growth and/or progression.
(出版サイトへのリンク): ● Publication site (DOI): 10.4049/jimmunol.1701351
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30333124; ● Search Scopus @ Elsevier (PMID): 30333124; ● Search Scopus @ Elsevier (DOI): 10.4049/jimmunol.1701351

(DOI: 10.4049/jimmunol.1701351, PubMed: 30333124) T Mészáros, G Kozma, Taro Shimizu, Kohga Miyahara, K Turjeman, Tatsuhiro Ishida, Y Barenholz, R Urbanics and J Szebeni :
Involvement of complement activation in the pulmonary vasoactivity of polystyrene nanoparticles in pigs: Unique surface properties underlying alternative pathway activation and instant opsonization,
International Journal of Nanomedicine, Vol.13, 6345-6357, 2018.

(要約): It has been proposed that many hypersensitivity reactions to nanopharmaceuticals represent complement (C)-activation-related pseudoallergy (CARPA), and that pigs provide a sensitive animal model to study the phenomenon. However, a recent study suggested that pulmonary hypertension, the pivotal symptom of porcine CARPA, is not mediated by C in cases of polystyrene nanoparticle (PS-NP)-induced reactions. To characterize PS-NPs and reexamine the contribution of CARPA to their pulmonary reactivity in pigs. C activation by 200, 500, and 750 nm (diameter) PS-NPs and their opsonization were measured in human and pig sera, respectively, and correlated with hemodynamic effects of the same NPs in pigs in vivo. Physicochemical characterization of PS-NPs included size, ζ-potential, cryo-transmission electron microscopy, and hydrophobicity analyses. C activation in human serum was measured by ELISA and opsonization of PS-NPs in pig serum by Western blot and flow cytometry. Pulmonary vasoactivity of PS-NPs was quantified in the porcine CARPA model. PS-NPs are monodisperse, highly hydrophobic spheres with strong negative surface charge. In human serum, they caused size-dependent, significant rises in C3a, Bb, and sC5b-9, but not C4d. Exposure to pig serum led within minutes to deposition of C5b-9 and opsonic iC3b on the NPs, and opsonic iC3b fragments (C3dg, C3d) also appeared in serum. PS-NPs caused major hemodynamic changes in pigs, primarily pulmonary hypertension, on the same time scale (minutes) as iC3b fragmentation and opsonization proceeded. There was significant correlation between C activation by different PS-NPs in human serum and pulmonary hypertension in pigs. PS-NPs have extreme surface properties with no relevance to clinically used nanomedicines. They can activate C via the alternative pathway, entailing instantaneous opsonization of NPs in pig serum. Therefore, rather than being solely C-independent reactivity, the mechanism of PS-NP-induced hypersensitivity in pigs may involve C activation. These data are consistent with the "double-hit" concept of nanoparticle-induced hypersensitivity reactions involving both CARPA and C-independent pseudoallergy.
(キーワード): Animals / Complement Activation / Complement C3b / Drug Hypersensitivity / Humans / Immunologic Factors / Liposomes / Male / Nanoparticles / Polystyrenes / Pulmonary Circulation / Surface Properties / Swine
(徳島大学機関リポジトリ): ● Metadata: 115154
(出版サイトへのリンク): ● Publication site (DOI): 10.2147/IJN.S161369
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30349254; ● Search Scopus @ Elsevier (PMID): 30349254; ● Search Scopus @ Elsevier (DOI): 10.2147/IJN.S161369

(徳島大学機関リポジトリ: 115154, DOI: 10.2147/IJN.S161369, PubMed: 30349254) Emam Emam Abdallah Sherif, Hidenori ANDO, Lila Selim Ahmed Ali Abu Amr, Taro Shimizu, Keiichiro Okuhira, Yu Ishima, M Mahdy, F Ghazy, I Sagawa and Tatsuhiro Ishida :
Liposome co-incubation with cancer cells secreted exosomes (extracellular vesicles) with different proteins expressions and different uptake pathways,
Scientific Reports, Vol.8, No.1, 14493, 2018.

(要約): We recently showed that in vitro incubation of cells with liposomes of varying compositions can increase exosome secretion and increase the yield of harvested exosomes (extracellular vesicles, EVs). This might foster their potential therapeutic implementations. In the current study, we investigated the surface proteins and the uptake of the harvested exosomes (EVs) to see if the incubation of cells with liposomes would change the biological properties of these exosomes (EVs). Interestingly, exosomes (EVs) induced by solid cationic liposomes lacked some major exosome marker proteins such as CD9, flotillin-1, annexin-A2 and EGF, and subsequently had lower levels of cellular uptake upon re-incubation with donor cancer cells. However, exosomes (EVs) induced under normal condition and by fluid cationic liposomes, displayed the entire spectrum of proteins, and exhibited higher uptake by the donor cancer cells. Although endocytosis was the major uptake pathway of exosomes (EVs) by tumor cells, endocytosis could occur via more than one mechanism. Higher exosome uptake was observed in donor B16BL6 cells than in allogeneic C26 cells, indicating that donor cells might interact specifically with their exosomes (EVs) and avidly internalize them. Taken together, these results suggest a technique for controlling the characteristics of secreted exosomes (EVs) by incubating donor cancer cells with liposomes of varying physiochemical properties.
(徳島大学機関リポジトリ): ● Metadata: 114955
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/s41598-018-32861-w
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30262875; ● Summary page in Scopus @ Elsevier: 2-s2.0-85054056121

(徳島大学機関リポジトリ: 114955, DOI: 10.1038/s41598-018-32861-w, PubMed: 30262875, Elsevier: Scopus) Emam Emam Abdallah Sherif, Hidenori ANDO, Lila Selim Ahmed Ali Abu Amr, Shinya Kobayashi, Taro Shimizu, Keiichiro Okuhira, Yu Ishima and Tatsuhiro Ishida :
Doxorubicin expands in vivo secretion of circulating exosome in mice,
Biological & Pharmaceutical Bulletin, Vol.41, No.7, 1078-1083, 2018.

(要約): Modulation of tumor immunity is a known factor in the antitumor activity of many chemotherapeutic agents. Exosomes are extracellular nanometric vesicles that are released by almost all types of cells, which includes cancer cells. These vesicles play a crucial role in tumor immunity. Many in vitro studies have reproduced the aggressive secretion of exosomes following treatment with conventional anticancer drugs. Nevertheless, how chemotherapeutic agents including nanomedicines such as Doxil affect the in vivo secretion of exosomes is yet to be elucidated. In this study, the effect of intravenous injection of either free doxorubicin (DXR) or liposomal DXR formulation (Doxil) on exosome secretion was evaluated in BALB/c mice. Exosomes were isolated from serum by using an ExoQuick™ kit. Free DXR treatment markedly increased serum exosome levels in a post-injection time-dependent manner, while Doxil treatment did not. Exosomal size distribution and marker protein expressions (CD9, CD63, and TSG101) were studied. The physical/biological characteristics of treatment-induced exosomes were comparable to those of control mice. Interestingly, splenectomy significantly suppressed the copious exosomal secretions induced by free DXR. Collectively, our results indicate that conventional anticancer agents induce the secretion of circulating exosomes, presumably via stimulating immune cells of the spleen. As far as we know, this study represents the first report indicating that conventional chemotherapeutics may induce exosome secretion which might, in turn, contribute partly to the antitumor effect of chemotherapeutic agents.
(キーワード): Animals / Antibiotics, Antineoplastic / Doxorubicin / Exocytosis / Exosomes / Injections, Intravenous / Male / Mice / Mice, Inbred BALB C / Models, Animal / Polyethylene Glycols / Spleen
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b18-00202
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29962402; ● Summary page in Scopus @ Elsevier: 2-s2.0-85049360539

(DOI: 10.1248/bpb.b18-00202, PubMed: 29962402, Elsevier: Scopus) Taro Shimizu, Lila Selim Ahmed Ali Abu Amr, Risako Fujita, Mizuki Awata, Munehira Kawanishi, Yosuke Hashimoto, Keiichiro Okuhira, Yu Ishima and Tatsuhiro Ishida :
A hydroxyl PEG version of PEGylated liposomes and its impact on anti-PEG IgM induction and on the accelerated clearance of PEGylated liposomes,
European Journal of Pharmaceutics and Biopharmaceutics, Vol.127, 142-149, 2018.

(要約): Surface decoration of liposomes with polyethylene glycol (PEG), PEGylation, is recognized as a method to bestow liposomes with a prolonged circulation time following intravenous administration. However, many reports have emphasized that a first dose of PEGylated liposomes (PL) elicits an anti-PEG IgM antibody response that can trigger a rapid systemic clearance of a second dose of PL via a phenomenon that is referred to as "accelerated blood clearance (ABC)." Such a phenomenon is usually observed with PL that has been modified with methoxy-PEG. In the current study, we introduced various functional groups, methoxy (OCH), amino (NH), carboxyl (COOH), and hydroxyl (OH), at the chain ends of PEG to investigate the effect on anti-PEG IgM induction. Among different PEG-modified liposomes, hydroxyl PEG-modified liposomes (PL-OH) efficiently attenuated the anti-PEG IgM response in vitro. In addition, PL-OH was less recognizable by anti-PEG IgM compared with other PLs. These findings raised the possibility that PL-OH could attenuate/abrogate elicitation of the ABC phenomenon. Nonetheless, upon repeated intravenous injection, PL-OH triggered the enhanced clearance of a subsequently injected second dose. Furthermore, in vitro studies have demonstrated that, as a complement activator, PL-OH is stronger than PL-OCH and induces further complement activation in the presence of anti-PEG IgM, which was the predominant contributor to the rapid clearance of a second dose of PL-OH. Our results suggest that the screening of complement activation by polymer-modified products in tandem with anti-polymer antibody production should be a prerequisite in the development of polymers that might enhance the therapeutic efficacy of nanocarriers.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ejpb.2018.02.019
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29462689; ● Summary page in Scopus @ Elsevier: 2-s2.0-85042257067

(DOI: 10.1016/j.ejpb.2018.02.019, PubMed: 29462689, Elsevier: Scopus) Emam Emam Abdallah Sherif, Hidenori ANDO, Lila Selim Ahmed Ali Abu Amr, Taro Shimizu, Masami Ukawa, Keiichiro Okuhira, Yu Ishima, A M Mahdy, S F Ghazy and Tatsuhiro Ishida :
A novel strategy to increase the yield of exosomes (extracellular vesicles) for an expansion of basic research,
Biological & Pharmaceutical Bulletin, Vol.41, No.5, 733-742, 2018.

(要約): Exosomes are tiny extracellular vesicles that are usually harvested in small quantities. Such small yield has been an obstacle for the expansion of the basic research regarding exosome analysis and applications in drug delivery. To increase exosome yield, we attempted to stimulate tumor cells via the addition of liposomes in vitro. Neutral, cationic-bare or PEGylated liposomes were incubated with four different tumor cell lines. The stimulatory effect of liposomal formulations on exosome secretion and cellular uptake propensity of the collected exosome by mother cells or different cells was evaluated. Both neutral and cationic-bare liposomes enhanced exosome secretion in a dose-dependent manner. Fluid cationic liposomes provided the strongest stimulation. Surprisingly, the PEGylation of bare liposomes diminished exosome secretion. Exosomes harvested in the presence of fluid cationic liposomes showed increased cellular uptake, but solid cationic liposomes did not. Our findings indicate that the physicochemical properties of liposomes determine whether they will act as a stimulant or as a depressant on exosome secretion from tumor cells. Liposomal stimulation may be a useful strategy to increase exosome yield, although further preparation to increase the purity of exosomes may be needed. In addition, fine-tuning of the biological properties of induced exosomes could be achieved via controlling the physicochemical properties of the stimulant liposomes.
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b17-00919
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29709910; ● Summary page in Scopus @ Elsevier: 2-s2.0-85046668949

(DOI: 10.1248/bpb.b17-00919, PubMed: 29709910, Elsevier: Scopus) M Ikeda, Yu Ishima, R Kinoshita, V Chuang, N Tasaka, N Matsuo, H Watanabe, Taro Shimizu, Tatsuhiro Ishida, M Otagiri and T Maruyama :
A Novel S-Sulfhydrated Human Serum Albumin Preparation Suppresses Melanin Synthesis,
Redox Biology, Vol.14, 354-360, 2018.

(徳島大学機関リポジトリ): ● Metadata: 115707
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.redox.2017.10.007
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29040960; ● Summary page in Scopus @ Elsevier: 2-s2.0-85042682163

(徳島大学機関リポジトリ: 115707, DOI: 10.1016/j.redox.2017.10.007, PubMed: 29040960, Elsevier: Scopus) Hidenori ANDO, Lila Selim Ahmed Ali Abu Amr, Masao Tanaka, Yusuke Doi, Yasuko Terada, Naoto Yagi, Taro Shimizu, Keiichiro Okuhira, Yu Ishima and Tatsuhiro Ishida :
Intratumoral visualization of oxaliplatin within a liposomal formulation using X-ray fluorescence spectrometry,
Molecular Pharmaceutics, Vol.15, No.2, 403-409, 2018.

(要約): Microsynchrotron radiation X-ray fluorescence spectrometry (-SR-XRF) is an X-ray procedure that utilizes synchrotron radiation as an excitation source. -SR-XRF is a rapid, nondestructive technique that allows mapping and quantification of metals and biologically important elements in cell or tissue samples. Generally, the intratumor distribution of nanocarrier-based therapeutics is assessed by tracing the distribution of a labeled nanocarrier within tumor tissue, rather than by tracing the encapsulated drug. Instead of targeting the delivery vehicle, we employed -SR-XRF to visualize the intratumoral microdistribution of oxaliplatin (l-OHP) encapsulated within PEGylated liposomes. Tumor-bearing mice were intravenously injected with either l-OHP-containing PEGylated liposomes (l-OHP liposomes) or free l-OHP. The intratumor distribution of l-OHP within tumor sections was determined by detecting the fluorescence of platinum atoms, which are the main elemental components of l-OHP. The l-OHP in the liposomal formulation was localized near the tumor vessels and accumulated in tumors at concentrations greater than those seen with the free form, which is consistent with the results of our previous study that focused on fluorescent labeling of PEGylated liposomes. In addition, repeated administration of l-OHP liposomes substantially enhanced the tumor accumulation and/or intratumor distribution of a subsequent dose of l-OHP liposomes, presumably via improvements in tumor vascular permeability, which is also consistent with our previous results. In conclusion, -SR-XRF imaging efficiently and directly traced the intratumor distribution of the active pharmaceutical ingredient l-OHP encapsulated in liposomes within tumor tissue. -SR-XRF imaging could be a powerful means for estimating tissue distribution and even predicting the pharmacological effect of nanocarrier-based anticancer metal compounds.
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acs.molpharmaceut.7b00762
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29287147; ● Summary page in Scopus @ Elsevier: 2-s2.0-85041697937

(DOI: 10.1021/acs.molpharmaceut.7b00762, PubMed: 29287147, Elsevier: Scopus) Hidenori ANDO, Lila Selim Ahmed Ali Abu Amr, Munehira Kawanishi, Taro Shimizu, Keiichiro Okuhira, Yu Ishima and Tatsuhiro Ishida :
Reactivity of IgM antibodies elicited by PEGylated liposomes or PEGylated lipoplexes against auto and foreign antigens,
Journal of Controlled Release, Vol.270, 114-119, 2018.

(要約): Polyethylene glycol (PEG) is an attractive tool for the development of nanoparticle-based cancer therapy since it endows nanoparticles with extended-circulation properties. Nevertheless, recent reports have revealed that intravenous injection of either PEGylated liposomes (SLs) or PEGylated lipoplex (PLpx) could elicit an anti-PEG immunoglobulin (IgM) response in a T cell-independent (TI) manner that would substantially compromise the in vivo fate of PEGylated products upon repeated administration. In the same context, viral or bacterial infections trigger the production of polyreactive IgM that binds both self and foreign antigens. The polyreactivity of IgM elicited by SLs or PLpx, to bacteria and other polymers, however, is yet to be elucidated. In this study, the polyreactivity of IgM elicited by SLs or PLpx was challenged against different bacteria (TI antigens) and against synthetic polymer composed of repetitive structures (PVP-360 or FITC-dextran). Results demonstrated that anti-PEG IgM elicited by either SLs or PLpx showed no reactivity to various bacteria examined, while the IgM showed remarkable reactivity to both PVP-360 and FITC-dextran. In addition, interestingly, anti-PEG IgM elicited by either SLs or PLpx showed no antinuclear antibody-like immune reactivity, and, therefore, treatment with either SLs or PLpx was not expected to exacerbate autoimmune diseases such as systemic lupus erythematosus. Collectively, our findings could provide information supporting the safety of PEGylated nanoparticle-based pharmaceutics, particularly in patients with autoimmune diseases.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jconrel.2017.12.002
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29217175; ● Summary page in Scopus @ Elsevier: 2-s2.0-85037534004

(DOI: 10.1016/j.jconrel.2017.12.002, PubMed: 29217175, Elsevier: Scopus) Sheuli Afroz, Ayano Yagi, Kouki Fujikawa, M. Motiur Rahman, Katsuya Morito, Tatsuya Fukuta, Shiro Watanabe, Kazunori Toida, Emi Kiyokage, Taro Shimizu, Tatsuhiro Ishida, Kentaro Kogure, Akira Tokumura and Tamotsu Tanaka :
Lysophosphatidic acid in medicinal herbs enhances prostaglandin E2 and protects against indomethacin-induced gastric cell damage in vivo and in vitro,
Prostaglandins & Other Lipid Mediators, Vol.135, 36-44, 2018.

(要約): Lysophosphatidic acid (LPA) is a bioactive phospholipid that induces diverse biological responses. Recently, we found that LPA ameliorates NSAIDs-induced gastric ulcer in mice. Here, we quantified LPA in 21 medicinal herbs used for treatment of gastrointestinal (GI) disorders. We found that half of them contained LPA at relatively high levels (40-240 μg/g) compared to soybean seed powder (4.6 μg/g), which we previously identified as an LPA-rich food. The LPA in peony (Paeonia lactiflora) root powder is highly concentrated in the lipid fraction that ameliorates indomethacin-induced gastric ulcer in mice. Synthetic 18:1 LPA, peony root LPA and peony root lipid enhanced prostaglandin E production in a gastric cancer cell line, MKN74 cells that express LPA abundantly. These materials also prevented indomethacin-induced cell death and stimulated the proliferation of MKN74 cells. We found that LPA was present in stomach fluids at 2.4 μM, which is an effective LPA concentration for inducing a cellular response in vitro. These results indicated that LPA is one of the active components of medicinal herbs for the treatment of GI disorder and that orally administered LPA-rich herbs may augment the protective actions of endogenous LPA on gastric mucosa.
(徳島大学機関リポジトリ): ● Metadata: 112025
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.prostaglandins.2018.01.003
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29462674; ● Summary page in Scopus @ Elsevier: 2-s2.0-85042401633

(徳島大学機関リポジトリ: 112025, DOI: 10.1016/j.prostaglandins.2018.01.003, PubMed: 29462674, Elsevier: Scopus) Ryo Kinoshita, Yu Ishima, Victor T.G. Chuang, Hideaki Nakamura, Jun Fang, Hiroshi Watanabe, Taro Shimizu, Keiichiro Okuhira, Tatsuhiro Ishida, Hiroshi Maeda, Masaki Otagiri and Toru Maruyama :
Improved anticancer effects of albumin-bound paclitaxel nanoparticle via augmentation of EPR effect and albumin-protein interactions using S-Nitrosated Human Serum Albumin Dimer,
Biomaterials, Vol.140, 162-169, 2017.

(要約): In the latest trend of anticancer chemotherapy research, there were many macromolecular anticancer drugs developed based on enhanced permeability and retention (EPR) effect, such as albumin bound paclitaxel nanoparticle (nab- PTX, also called Abraxane). However, cancers with low vascular permeability posed a challenge for these EPR based therapeutic systems. Augmenting the intrinsic EPR effect with an intrinsic vascular modulator such as nitric oxide (NO) could be a promising strategy. S-nitrosated human serum albumin dimer (SNO-HSA Dimer) shown promising activity previously was evaluated for the synergistic effect when used as a pretreatment agent in nab-PTX therapy against various tumor models. In the high vascular permeability C26 murine colon cancer subcutaneous inoculation model, SNO-HSA Dimer enhanced tumor selectivity of nab-PTX, and attenuated myelosuppression. SNO-HSA Dimer also augmented the tumor growth inhibition of nab-PTX in low vascular permeability B16 murine melanoma subcutaneous inoculation model. Furthermore, nab-PTX therapy combined with SNO-HSA Dimer showed higher antitumor activity and improved survival rate of SUIT2 human pancreatic cancer orthotopic model. In conclusion, SNO-HSA Dimer could enhance the therapeutic effect of nab-PTX even in low vascular permeability or intractable pancreatic cancers. The possible underlying mechanisms of action of SNO-HSA Dimer were discussed.
(キーワード): Albumin-Bound Paclitaxel / Albumins / Animals / Antineoplastic Agents / Capillary Permeability / Cell Line, Tumor / Drug Synergism / Female / Humans / Male / Melanoma, Experimental / Mice / Mice, Inbred BALB C / Mice, Inbred C57BL / Neoplasms / Nitric Oxide / Nitroso Compounds / Paclitaxel / Pancreatic Neoplasms / Protein Multimerization / Serum Albumin, Human
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.biomaterials.2017.06.021
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28651144; ● Summary page in Scopus @ Elsevier: 2-s2.0-85021192830

(DOI: 10.1016/j.biomaterials.2017.06.021, PubMed: 28651144, Elsevier: Scopus) Taro Shimizu, Lila Selim Ahmed Ali Abu Amr, Miho Nishio, Yusuke Doi, Hidenori ANDO, Masami Ukawa, Yu Ishima and Tatsuhiro Ishida :
Modulation of antitumor immunity contributes to the enhanced therapeutic efficacy of liposomal oxaliplatin in mouse model,
Cancer Science, Vol.108, No.9, 1864-1869, 2017.

(要約): Immune modulation of the tumor microenvironment has been reported to participate in the therapeutic efficacy of many chemotherapeutic agents. Recently, we reported that liposomal encapsulation of oxaliplatin (l-OHP) within PEGylated liposomes conferred a superior antitumor efficacy to free l-OHP in murine colorectal carcinoma-bearing mice through permitting preferential accumulation of the encapsulated drug within tumor tissue. However, the contribution of the immune-modulatory properties of liposomal l-OHP and/or free l-OHP to the overall antitumor efficacy was not elucidated. In the present study, therefore, we investigated the effect of liposomal encapsulation of l-OHP within PEGylated liposomes on the antitumor immunity in both immunocompetent and immunodeficient mice. Liposomal l-OHP significantly suppressed the growth of tumors implanted in immunocompetent mice, but not in immunodeficient mice. In immunocompetent mice, liposomal l-OHP increased the tumor MHC-1 level and preserved antitumor immunity through decreasing the number of immune suppressor cells, including regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages, which collectively suppress CD8(+) T cell-mediated tumor cells killing. In contrast, free l-OHP ruined antitumor immunity. These results suggest that the antitumor efficacy of liposomal l-OHP is attributed, on the one hand, to its immunomodulatory effect on tumor immune microenvironment that is superior to that of free l-OHP, and on the other hand, to its direct cytotoxic effect on tumor cells.
(徳島大学機関リポジトリ): ● Metadata: 112372
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/cas.13305
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28643902; ● Search Scopus @ Elsevier (PMID): 28643902; ● Search Scopus @ Elsevier (DOI): 10.1111/cas.13305

(徳島大学機関リポジトリ: 112372, DOI: 10.1111/cas.13305, PubMed: 28643902) Mayumi Ikeda, Yu Ishima, Akitomo Shibata, Victor T.G. Chuang, Tomohiro Sawa, Hideshi Ihara, Hiroshi Watanabe, Ming Xian, Yuya Ouchi, Taro Shimizu, Hidenori ANDO, Masami Ukawa, Tatsuhiro Ishida, T Akaike, M Otagiri and T Maruyama :
Quantitative determination of polysulfide in albumins, plasma proteins and biological fluid samples using a novel combined assays approach,
Analytica Chimica Acta, Vol.969, 18-25, 2017.

(要約): Hydrogen sulfide (H2S) signaling involves polysulfide (RSSnSR') formation on various proteins. However, the current lack of sensitive polysulfide detection assays poses methodological challenges for understanding sulfane sulfur homeostasis and signaling. We developed a novel combined assay by modifying Sulfide Antioxidant Buffer (SAOB) to produce an "Elimination Method of Sulfide from Polysulfide" (EMSP) treatment solution that liberates sulfide, followed with methylene blue (MB) sulfide detection assay. The combined EMSP-MB sulfide detection assay performed on low molecular weight sulfur species showed that sulfide was produced from trisulfide compounds such as glutathione trisulfide and diallyl trisulfide, but not from the thiol compounds such as cysteine, cystine and glutathione. In the case of plasma proteins, this novel combined detection assay revealed that approximately 14.7, 1.7, 3.9, 3.7 sulfide mol/mol released from human serum albumin, 1-anti-trypsin, 1-acid glycoprotein and ovalbumin, respectively, suggesting that serum albumin is a major pool of polysulfide in human blood circulation. Taken together with the results of albumins of different species, the liberated sulfide has a good correlation with cysteine instead of methionine, indicating the site of incorporation of polysulfide is cysteine. With this novel sulfide detention assay, approximately 8,000, 120 and 1100 M of polysulfide concentrations was quantitated in human healthy plasma, saliva and tear, respectively. Our promising polysulfide specific detection assay can be a very important tool because quantitative determination of polysulfide sheds light on the functional consequence of protein-bound cysteine polysulfide and expands the research area of reactive oxygen to reactive polysulfide species.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.aca.2017.03.027
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28411626; ● Summary page in Scopus @ Elsevier: 2-s2.0-85017155399

(DOI: 10.1016/j.aca.2017.03.027, PubMed: 28411626, Elsevier: Scopus) Yu Mima, Lila Selim Ahmed Ali Abu Amr, Taro Shimizu, Masami Ukawa, Hidenori ANDO, Yasuko Kurata and Tatsuhiro Ishida :
Ganglioside inserted into PEGylated liposome attenuates anti-PEG immunity,
Journal of Controlled Release, Vol.250, 20-26, 2017.

(要約): Despite the clinical introduction of a vast number of polyethylene glycol (PEG)-conjugated therapeutics, conjugated PEG is also known for an unfortunate inclination toward immunogenicity. Immunogenicity of PEG, manifested by the robust production of anti-PEG IgM, is known to compromise the therapeutic efficacy and/or reduce the tolerance of PEGylated therapeutics. In the present study, we inserted ganglioside into the membrane of PEGylated liposome (PL) to prepare ganglioside-modified PEGylated liposomes (G-PL), and investigated its efficacy in attenuating the anti-PEG IgM response against PL. A single intravenous injection of G-PL significantly attenuated the anti-PEG IgM production, compared with that of naïve PL. In addition, pretreatment with G-PL substantially alleviated the anti-PEG IgM response elicited by a subsequent dose of PL, presumably via inducing B cell tolerance, and as a consequence, this modification abrogated/attenuated the incidence of the rapid clearance of subsequently administrated PL. These results indicate that incorporating gangliosides in PEGylated liposome membrane not only prevents the immunogenicity of PEG but also induces the tolerance of B cells to subsequent doses of the immunogenic PL. Consequently, liposomal membrane modification with ganglioside might represent a promising approach to attenuating the immunogenicity of PEGylated liposomes while preserving their therapeutic efficacy, particularly upon repeated administration.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jconrel.2017.01.040
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28179196; ● Summary page in Scopus @ Elsevier: 2-s2.0-85011965687

(DOI: 10.1016/j.jconrel.2017.01.040, PubMed: 28179196, Elsevier: Scopus) Yusuke Doi, Lila Selim Ahmed Ali Abu Amr, Haruna Matsumoto, Tomoko Okada, Taro Shimizu and Tatsuhiro Ishida :
Improvement of intratumor microdistribution of PEGylated liposome via tumor priming by metronomic S-1 dosing,
International Journal of Nanomedicine, Vol.11, 5573-5582, 2016.

(要約): The efficient delivery of nanocarrier-based cancer therapeutics into tumor tissue is problematic. Structural abnormalities, tumor vasculature heterogeneity, and elevated intratumor pressure impose barriers against the preferential accumulation of nanocarrier-based cancer therapeutics within tumor tissues and, consequently, compromise their therapeutic efficacy. Recently, we have reported that metronomic S-1, orally available tegafur formulation, dosing synergistically augmented the therapeutic efficacy of oxaliplatin (l-OHP)-containing PEGylated liposome without increasing the toxicity in animal model. However, the exact mechanism behind such synergistic effect was not fully elucidated. In this study, therefore, we tried to shed the light on the contributions of metronomic S-1 dosing to the enhanced accumulation and/or spatial distribution of PEGylated liposome within tumor tissue. Tumor priming with metronomic S-1 treatment induced a potent apoptotic response against both angiogenic endothelial cells and tumor cells adjacent to tumor blood vessels, resulting in enhanced tumor blood flow via transient normalization of tumor vasculature, along with alleviation of intratumor pressure. Such a change in the tumor microenvironment imparted by S-1 treatment allows efficient delivery of PEGylated liposome to tumor tissue and permits their deep penetration/distribution into the tumor mass. Such a priming effect of S-1 dosing can be exploited as a promising strategy to enhance the therapeutic efficacy of nanocarrier-based cancer therapeutics suffering from inadequate/heterogeneous delivery to tumor tissues.
(キーワード): Animals / Apoptosis / Cell Line, Tumor / Chemistry, Pharmaceutical / Drug Carriers / Drug Combinations / Drug Delivery Systems / Electron Spin Resonance Spectroscopy / Humans / Liposomes / Male / Mice / Mice, Inbred BALB C / Nanomedicine / Organoplatinum Compounds / Oxonic Acid / Perfusion / Polyethylene Glycols / Pressure / Tegafur / Tissue Distribution / Tumor Microenvironment
(徳島大学機関リポジトリ): ● Metadata: 115155
(出版サイトへのリンク): ● Publication site (DOI): 10.2147/IJN.S119069
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27822036; ● Search Scopus @ Elsevier (PMID): 27822036; ● Search Scopus @ Elsevier (DOI): 10.2147/IJN.S119069

(徳島大学機関リポジトリ: 115155, DOI: 10.2147/IJN.S119069, PubMed: 27822036) Takuma Takayama, Masami Ukawa, Yuki Kanazawa, Hidenori ANDO, Taro Shimizu and Tatsuhiro Ishida :
Hydrodynamic tail vein injection as a simple tool for yielding extended transgene expression in solid tumors.,
Biological & Pharmaceutical Bulletin, Vol.39, No.9, 1555-1558, 2016.

(要約): Hydrodynamic tail vein injection was considered an in vivo transfection method that yields a higher level of gene expression mainly in the liver. This method has been applied to cancer gene therapy targeting both hepatic and non-hepatic cancers. However, intratumor transgene expression in non-hepatic tumors has not been well studied. In this study, we showed an extended transgene expression of -galactosidase (LacZ), a nonsecretory protein, in a subcutaneously implanted murine solid tumor following the hydrodynamic injection of plasmid DNA (LacZ pDNA). Our result may indicate that the hydrodynamic injection method is a powerful tool that can be used to gain transgene expression not only in the liver but also in solid tumors.
(キーワード): Animals / Cell Line, Tumor / DNA / Gene Expression / Gene Transfer Techniques / Genetic Therapy / Injections, Intravenous / Liver / Male / Mice / Mice, Inbred BALB C / Neoplasms / Plasmids / Tail / Transgenes / beta-Galactosidase
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b16-00283
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27582335; ● Summary page in Scopus @ Elsevier: 2-s2.0-84984698994

(DOI: 10.1248/bpb.b16-00283, PubMed: 27582335, Elsevier: Scopus) Masami Ukawa, Yukako Fujiwara, Hidenori ANDO, Taro Shimizu and Tatsuhiro Ishida :
Hepatic tumor metastases cause enhanced PEGylated liposome uptake by Kupffer cells,
Biological & Pharmaceutical Bulletin, Vol.39, No.2, 215-220, 2016.

(要約): Kupffer cells in livers bearing tumor metastases were found to have promoted tumor invasion and exacerbated the metastasis. This implies that the function of Kupffer cells might differ between animals bearing hepatic metastases and those that are healthy. Kupffer cells are considered responsible for the accumulation of liposomes in the liver. In this study, we hypothesized that the alteration in the function of Kupffer cells by hepatic metastasis would also affect the biodistribution of liposomes following intravenous administration. The hepatic accumulation and the blood concentration of PEGylated liposomes were compared between healthy mice and tumor-bearing mice. We noted that hepatic accumulation and elimination from the blood were significantly accelerated in tumor-bearing mice, indicating that our hypothesis was correct. In the tumor-bearing mice, the proportion of Kupffer cells taking up liposomes was significantly increased. Intravenous injection of oxaliplatin (l-OHP) containing PEGylated liposomes decreased the fraction of Kupffer cells, but this administration caused no injury to the hepatocytes. These results suggest that PEGylated liposomes containing l-OHP may have the potential to treat metastatic hepatic cancer-not only via the direct killing of the cancer cells but also via a reduction in tumor-supportive Kupffer cells.
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b15-00611
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26830481; ● Summary page in Scopus @ Elsevier: 2-s2.0-84958964867

(DOI: 10.1248/bpb.b15-00611, PubMed: 26830481, Elsevier: Scopus) Hidenori ANDO, Sakiko Kobayashi, Lila Selim Ahmed Ali Abu Amr, N Eldin Essam, Chihiro Katoh, Taro Shimizu, Masami Ukawa, Kazuyoshi Kawazoe and Tatsuhiro Ishida :
Advanced therapeutic approach for the treatment of malignant pleural mesothelioma via the intrapleural administration of liposomal pemetrexed,
Journal of Controlled Release, Vol.220, 29-36, 2015.

(要約): Malignant pleural mesothelioma (MPM) is an aggressive cancer that proliferates in the pleural cavity. Pemetrexed (PMX) in combination with cisplatin is currently the approved standard care for MPM, but a dismal response rate persists. Recently, we prepared various liposomal PMX formulations using different lipid compositions and evaluated their in vitro cytotoxicity against human mesothelioma cells (MSTO-211H). In the present study, we investigated the in vivo therapeutic effect of our liposomal PMX formulations using an orthotopic MPM tumor mouse model. PMX encapsulated within either cholesterol-containing (PMX/Chol CL) or cholesterol-free (PMX/Non-Chol CL) cationic liposome was intrapleurally injected into tumor-bearing mice. PMX encapsulated in cholesterol-free liposomes (PMX/Non-Chol CL) drastically inhibited the tumor growth in the pleural cavity, while free PMX and PMX encapsulated in cholesterol-containing liposomes (PMX/Chol CL) barely inhibited the tumor growth. The enhanced in vivo anti-tumor efficacy of PMX/Non-Chol CL was credited, on the one hand, for prolonging the retention of cationic liposomes in the pleural cavity via their electrostatic interaction with the negatively charged membranes of tumor cells, but on the other hand, it was charged with contributing to a higher drug release from the "fluid" liposomal membrane following intrapleural administration. This therapeutic strategy of direct intrapleural administration of liposomal PMX, along with the great advances in CL-guided therapeutics, might be a promising therapeutic approach to conquering the poor prognosis for MPM.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jconrel.2015.10.019
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26476173; ● Summary page in Scopus @ Elsevier: 2-s2.0-84944717805

(DOI: 10.1016/j.jconrel.2015.10.019, PubMed: 26476173, Elsevier: Scopus) Taro Shimizu, Yu Mima, Yosuke Hashimoto, Masami Ukawa, Hidenori ANDO, Hiroshi Kiwada and Tatsuhiro Ishida :
Anti-PEG IgM and complement system are required for the association of second doses of PEGylated liposomes with splenic marginal zone B cells,
Immunobiology, Vol.220, No.10, 1151-1160, 2015.

(要約): The accelerated blood clearance (ABC) phenomenon makes it crucial to use PEGylated liposomes and micelles to deliver drugs. The ABC phenomenon is an immune response against an initial dose of PEGylated liposome, which causes subsequent doses to be rapidly cleared by macrophages in the liver. We recently found that in the early phase of the ABC phenomenon, subsequent doses of PEGylated liposomes were associated with splenic marginal zone (MZ)-B cells and were transported from the MZ to the follicle (FO). In this study, we investigated the underlying mechanisms behind the association of subsequent doses of PEGylated liposomes with MZ-B cells in the spleen. Serum factors, anti-PEG IgM and complement system, were crucial to the association of PEGylated liposomes with MZ-B cells, while the sensitization of MZ-B cells by the first dose of PEGylated liposomes was not significant. It was the complement receptors (CRs) on the MZ-B cells, rather than either the PEG-specific B-cell receptors or the IgM Fc receptors, that were the main contributors to the association between PEGylated liposomes and MZ-B cells. It appeared that anti-PEG IgM would bind to PEGylated liposomes and causes subsequent complement activation, resulting in the formation of immune complexes of PEGylated liposome-anti-PEG IgM-complement. The MZ-B cells then recognized these immune complexes via their CRs. Such an association via CRs might have triggered the transport of the immune complex by MZ-B cells to the FO in the spleen. The information obtained in this study might be useful in the development of an efficient antigen delivery system to usher PEGylated nanoparticles into FO dendritic cells.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.imbio.2015.06.005
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26095176; ● Summary page in Scopus @ Elsevier: 2-s2.0-84937974851

(DOI: 10.1016/j.imbio.2015.06.005, PubMed: 26095176, Elsevier: Scopus) Munehira Kawanishi, Yosuke Hashimoto, Taro Shimizu, Ikuko Sagawa, Tatsuhiro Ishida and Hiroshi Kiwada :
Comprehensive analysis of PEGylated liposome-asscociated proteins relating to the accelerated blood clearance phenomenon by combination with shotgun analysis and conventional methods,
Biotechnology and Applied Biochemistry, Vol.62, No.4, 547-555, 2015.

(要約): PEGylated liposome, sterically stabilized by polyethylene glycol (PEG), results in reduced recognition of the liposome by the mononuclear phagocyte system. Recently, we reported regarding the accelerated blood clearance (ABC) phenomenon that PEGylated liposome is cleared very rapidly from blood circulation upon repeated injection. Anti-PEG IgM production and subsequent complement activation were crucial in causing the ABC phenomenon. However, there still remains the possibility that unknown plasma factors might affect the fate of PEGylated liposome that is subjected to the ABC phenomenon. A label-free approach to shotgun analysis is a great tool for characterizing proteins in a biological system. In this study, therefore, a shotgun analysis was employed to identify plasma protein bound on PEGylated liposome after the ABC phenomenon was induced in the mouse model. The analysis revealed that immunoglobulin and complement components (C1 and C3) are the major proteins. Subsequent analysis with enzyme-linked immunosorbent assay and Western blotting showed that the immunoglobulin was IgM and that the complement system was mainly activated via an anti-PEG IgM-mediated classical pathway. These results support our earlier assumptions-anti-PEG IgM and complement activation were the major causes of the ABC phenomenon. Our proposed analytical strategy would be expected to provide useful information for the development and design of the nanocarrier drug delivery system.
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/bab.1291
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25196743; ● Summary page in Scopus @ Elsevier: 2-s2.0-84939520973

(DOI: 10.1002/bab.1291, PubMed: 25196743, Elsevier: Scopus) Yu Mima, Yosuke Hashimoto, Taro Shimizu, Hiroshi Kiwada and Tatsuhiro Ishida :
Anti-PEG IgM is a major contributor to the accelerated blood clearance of polyethylene glycol-conjugated protein,
Molecular Pharmaceutics, Vol.12, No.7, 2429-2435, 2015.

(要約): Limited therapeutic efficacy of polyethylene glycol-conjugated (PEGylated) protein drugs has been recently reported in animals and human following repeat injections. Since there are reports that an accelerated blood clearance (ABC) phenomenon is caused by repeated injection of PEGylated liposome, there is an assumption that PEGylated proteins lose their long circulating property when they are injected repeatedly due to the induction of anti-PEG antibody. Although induction of anti-PEG antibody by PEGylated protein has been reported, there is little evidence of accelerated blood clearance of PEGylated protein upon repeated injection. Herein, we investigated the blood concentration of PEGylated ovalbumin (PEG-OVA), a model PEGylated protein, upon its repeated injection. A single intravenous administration of PEG-OVA elicited an anti-PEG IgM response but not anti-PEG IgG response, while the administration did not elicit antibody against OVA. At 24 h postinjection of test PEG-OVA, although control mice showed 41.6% dose of PEG-OVA in blood, the mice pretreated with PEG-OVA showed rapid clearance of test PEG-OVA from blood and undetectable level of PEG-OVA. Interestingly, the anti-PEG IgM induced by PEGylated liposome did not affect the blood concentration of subsequent dose of PEG-OVA. Our result suggests that anti-PEG IgM is a major contributor to the accelerated blood clearance of PEG-conjugated protein, but the presence of anti-PEG IgM in blood circulation does not necessarily affect circulating property of entire PEGylated materials.
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acs.molpharmaceut.5b00144
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26070445; ● Summary page in Scopus @ Elsevier: 2-s2.0-84936758421

(DOI: 10.1021/acs.molpharmaceut.5b00144, PubMed: 26070445, Elsevier: Scopus) Yosuke Hashimoto, Taro Shimizu, Lila Selim Ahmed Ali Abu Amr, Tatsuhiro Ishida and Hiroshi Kiwada :
Relationship between the concentration of anti-polyethylene glycol (PEG) in immunoglobulin M (IgM) and the intensity of the accelerated blood clearance (ABC) phenomenon against PEGylated liposomes in mice,
Biological & Pharmaceutical Bulletin, Vol.38, No.3, 417-424, 2015.

(要約): PEGylation, which is the surface modification of nanocarriers with polyethylene glycol (PEG), has increased the circulation time and reduced the immunogenic responses to nanocarriers. However, many reports have demonstrated that the intravenous injection of sterically stabilized PEGylated liposome (SL) causes an accelerated blood clearance (ABC) of subsequent doses via anti-PEG immunoglobulin M (IgM)-mediated complement activation. In the present study, the relationships between serum anti-PEG IgM concentration, the intensity of complement activation and the hepatic clearance of SL were quantitatively investigated for their role in the ABC phenomenon. Interestingly, with increasing serum anti-PEG IgM concentrations, the intensity of complement activation increased linearly, while the intensity of the hepatic clearance of SL was increased and then saturated. In addition, only 15-17% of anti-PEG IgM in blood circulation induced by SL at different doses was associated with a second dose SL. The present results indicate that it is the hepatic uptake of SL that is the limiting step in the ABC phenomenon, rather than the association of anti-PEG IgM to the SL and a subsequent complement activation.
(キーワード): anti-polyethylene glycol (PEG) / immunoglobulin M (IgM) / PEGylated liposome (SL) / accelerated blood clearance (ABC) phenomenon / complement activation
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b14-00653
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25757923; ● CiNii @ 国立情報学研究所 (CRID): 1390282679608052736; ● Summary page in Scopus @ Elsevier: 2-s2.0-84937217183

(DOI: 10.1248/bpb.b14-00653, PubMed: 25757923, CiNii: 1390282679608052736, Elsevier: Scopus) Yosuke Hashimoto, Lila Selim Ahmed Ali Abu Amr, Taro Shimizu, Tatsuhiro Ishida and Hiroshi Kiwada :
B cell-intrinsic toll-like receptor 7 is responsible for the enhanced anti-PEG IgM production following injection of siRNA-containing PEGylated lipoplex in mice,
Journal of Controlled Release, Vol.184, 1-8, 2014.

(要約): Recently, we reported that immunostimulatory siRNA-containing PEGylated lipoplex (PEGylated siRNA-lipoplex) activates the immune system, resulting in the enhanced production of anti-PEG IgM. However, the enhancing mechanism upon anti-PEG IgM production has not been fully elucidated. In this study, we employed toll-like receptor 7 knock out (TLR7 KO) mice, and showed how PEGylated siRNA-lipoplex activates the innate immune system through TLR7 and consequently enhances anti-PEG IgM production. In addition, we showed that SCID mice reconstituted with TLR7-deficient B cells failed to enhance anti-PEG IgM production following the injection of PEGylated siRNA-lipoplex, but that SCID mice reconstituted with wild type B cells did enhance anti-PEG IgM production. These results suggest that immune activation via B cell-intrinsic TLR7, but not other TLR7-expressing cells, contributes predominantly to an enhanced anti-PEG IgM production in response to the intravenous injection of PEGylated siRNA-lipoplexes. A strategy to evade B cell-intrinsic TLR7 activation by siRNA, such as chemical modification, may overcome immunological barriers to PEGylated liposome-based siRNA therapeutics.
(キーワード): Adoptive Transfer / Animals / B-Lymphocytes / Cytokines / Immunoglobulin M / Liposomes / Male / Membrane Glycoproteins / Mice, Inbred BALB C / Mice, Knockout / Mice, SCID / Polyethylene Glycols / RNA, Small Interfering / Spleen / Toll-Like Receptor 7
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jconrel.2014.04.003
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24727075; ● Summary page in Scopus @ Elsevier: 2-s2.0-84899502162

(DOI: 10.1016/j.jconrel.2014.04.003, PubMed: 24727075, Elsevier: Scopus) Yosuke Hashimoto, Taro Shimizu, Yu Mima, Lila Selim Ahmed Ali Abu Amr, Tatsuhiro Ishida and Hiroshi Kiwada :
Generation, characterization and in vivo biological activity of two distinct monoclonal anti-PEG IgMs,
Toxicology and Applied Pharmacology, Vol.277, No.1, 30-38, 2014.

(要約): PEGylation, the attachment of polyethylene glycol (PEG) to nanocarriers and proteins, is a widely accepted approach to improving the in vivo efficacy of the non-PEGylated products. However, both PEGylated liposomes and PEGylated proteins reportedly trigger the production of specific antibodies, mainly IgM, against the PEG moiety, which possibly leads to a reduction in safety and therapeutic efficacy of the PEGylated products. In the present study, two monoclonal anti-PEG IgMs--HIK-M09 via immunization with an intravenous injection of PEGylated liposomes (SLs) and HIK-M11 via immunization with a subcutaneous administration of PEGylated ovalbumin (PEG-OVA) were successfully generated. The generated IgMs showed efficient reactivity to mPEG2000 conjugated to 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine (DSPE), PEGylated liposome (SL) and PEG-OVA. It appears that HIK-M09 recognizes ethoxy (OCH2CH2) repeat units along with a terminal motif of PEG, while HIK-M11 recognizes only ethoxy repeat units of PEG. Such unique properties allow HIK-M09 to bind with dense PEG. In addition, their impact on the in vivo clearance of the PEGylated products was investigated. It was found that the generated ant-PEG IgMs induced a clearance of SL as they were intravenously administered with SL. Interestingly, the HIK-M11, generated by PEG-OVA, induced the clearance of both SL and PEG-OVA, while the HIK-M09, generated by SL, induced the clearance of SL only. We here revealed that the presence of serum anti-PEG IgM and the subsequent binding of anti-PEG IgM to the PEGylated products are not necessarily related to the enhanced clearance of the products. It appears that subsequent complement activation following anti-PEG IgM binding is the most important step in dictating the in vivo fate of PEGylated products. This study may have implications for the design, development and clinical application of PEGylated products and therapeutics.
(キーワード): Animals / Antibodies, Anti-Idiotypic / Antibodies, Monoclonal / Cell Line, Tumor / Complement Activation / Hybridomas / Liposomes / Male / Mice / Mice, Inbred BALB C / Ovalbumin / Phosphatidylethanolamines / Polyethylene Glycols / Rats, Wistar / Spleen
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.taap.2014.03.002
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24632081; ● Summary page in Scopus @ Elsevier: 2-s2.0-84897940686

(DOI: 10.1016/j.taap.2014.03.002, PubMed: 24632081, Elsevier: Scopus) Lila Selim Ahmed Ali Abu Amr, Masako Ichihara, Taro Shimizu, Tatsuhiro Ishida and Hiroshi Kiwada :
Ex-Vivo/In-Vitro Anti-Polyethylene Glycol (PEG) IgM Production From Murine Splenic B Cells Stimulated by PEGylated Liposome,
Biological & Pharmaceutical Bulletin, Vol.36, No.11, 1842-1848, 2013.

(要約): We have reported that PEGylated liposomes lose their long-circulating properties when injected twice into the same animal within a certain interval (the accelerated blood clearance (ABC) phenomenon). We assumed that this phenomenon was triggered via the abundant secretion of anti-polyethylene glycol (PEG) immunoglobulin M (IgM) in response to the first dose of PEGylated liposomes and that the spleen played an important role in the production of anti-PEG IgM. However, no direct evidence has yet confirmed this suspicion. In the current study, we verified, both in vitro and ex vivo, that spleen cells are indeed responsible for the production of anti-PEG IgM in response to PEGylated liposomes. In this study, spleen cells obtained from either naïve mice or mice pre-treated with PEGylated liposomes induced the production of anti-PEG IgM in a dose- and time-dependent manner, upon incubation with PEGylated liposomes. In addition, we confirmed that among the different fractions of splenic B cells, IgM-positive B cells, rather than CD45R-positive or CD19-positive splenic B cells, which are presumed to be the marginal zone B (MZB) cells, are the major cells producing anti-PEG IgM in the response to stimulation by PEGylated liposomes. These results may provide new insights into the mechanisms underlying the anti-PEG IgM production in response to the stimulation by PEGylated liposomes.
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b13-00562
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24189428; ● Search Scopus @ Elsevier (PMID): 24189428; ● Search Scopus @ Elsevier (DOI): 10.1248/bpb.b13-00562

(DOI: 10.1248/bpb.b13-00562, PubMed: 24189428) Lila Selim Ahmed Ali Abu Amr, Kousuke Nawata, Taro Shimizu, Tatsuhiro Ishida and Hiroshi Kiwada :
Use of polyglycerol (PG), instead of polyethylene glycol (PEG), prevents induction of the accelerated blood clearance phenomenon against long-circulating liposomes upon repeated administration,
International Journal of Pharmaceutics, Vol.456, No.1, 235-242, 2013.

(要約): The accelerated blood clearance (ABC) phenomenon accounts for the rapid systemic clearance of PEGylated nanocarriers upon repeated administrations. IgM production against the polyethylene glycol (PEG) coating in PEGylated liposomes is now known to be responsible for such unexpected pharmacokinetical alterations. The ABC phenomenon poses a remarkable clinical challenge by reducing the therapeutic efficacy of encapsulated drugs and causing harmful effects due to the altered tissue distribution pattern of the drugs. In this study, we investigated the in vivo performance of liposomes modified with polyglycerol (PG) upon repeated injection, and the in vivo therapeutic efficacy of such liposomes when they encapsulated a cytotoxic agent, doxorubicin (DXR). Repeated injection of PEG-coated liposomes in rats induced the ABC phenomenon, while repeated injection of PG-coated liposomes did not. In addition, DXR-containing PG-coated liposomes showed antitumor activity that was superior to that of free DXR and similar to that of DXR-containing PEG-coated liposomes upon repeated administration. These results indicate that polyglycerol (PG) might represent a promising alternative to PEG via enhancing the in vivo performance of liposomes by not eliciting the ABC phenomenon upon repeated administration.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2013.07.059
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23928149; ● Search Scopus @ Elsevier (PMID): 23928149; ● Search Scopus @ Elsevier (DOI): 10.1016/j.ijpharm.2013.07.059

(DOI: 10.1016/j.ijpharm.2013.07.059, PubMed: 23928149) Taro Shimizu, Tatsuhiro Ishida and Hiroshi Kiwada :
Transport of PEGylated liposomes from the splenic marginal zone to the follicle in the induction phase of the accelerated blood clearance phenomenon.,
Immunobiology, Vol.218, No.5, 725-732, 2013.

(要約): The accelerated blood clearance (ABC) phenomenon has been reported to enhance the clearance of PEGylated liposomes from the blood circulation when the liposomes are injected into the same animal repeatedly. We have shown that anti-PEG IgM production from splenic B cells is crucial in the ABC phenomenon. In this study, we describe the crucial role of marginal zone (MZ) B cells in the anti-PEG IgM production and recognition of PEGylated liposomes in the induction phase of ABC phenomenon. Suppression of the anti-PEG IgM production was correlated with the disappearance of IgM(high) cells in the MZ, particularly MZ-B cells, following cyclophosphamide (CPA)-treatment, confirming that splenic MZ-B cells are responsible for anti-PEG IgM production. The MZ-B cells stimulated by a first dose of PEGylated liposomes internalized the second dose of PEGylated liposomes in a PEG modification-dependent manner and transported the liposomes into the follicle (FO) region. To the best of our knowledge, this is the first report showing that PEGylated liposome is recognized by MZ-B cells and transported to the FO region like blood-borne antigens or immune complexes. It is likely that PEGylated liposomes are recognized as a TI-2 antigen by the first line of defense against life-threatening infections by blood-borne organisms. Our study may have implications for immunogenicity of synthesized polymer-grafted therapeutics including nanocarriers, nucleic acids and proteins.
(キーワード): Animals / Antigens, T-Independent / B-Lymphocytes / Biological Transport / Cyclophosphamide / Immunoglobulin M / Injections, Intravenous / Liposomes / Male / Metabolic Clearance Rate / Molecular Mimicry / Polyethylene Glycols / Rats / Rats, Wistar / Spleen
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.imbio.2012.08.274
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22995937; ● Search Scopus @ Elsevier (PMID): 22995937; ● Search Scopus @ Elsevier (DOI): 10.1016/j.imbio.2012.08.274

(DOI: 10.1016/j.imbio.2012.08.274, PubMed: 22995937) Taro Shimizu, Masako Ichihara, Yasuo Yoshioka, Tatsuhiro Ishida, Shinsaku Nakagawa and Hiroshi Kiwada :
Intravenous administration of polyethylene glycol-coated (PEGylated) proteins and PEGylated adenovirus elicits an anti-PEG immunoglobulin M response.,
Biological & Pharmaceutical Bulletin, Vol.35, No.8, 1336-1342, 2012.

(要約): A single intravenous administration of polyethylene glycol-coated (PEGylated) bovine serum albumin (BSA) and ovalbumin (OVA) elicited an anti-PEG immunoglobulin M (IgM) response, similar to that from PEGylated liposomes, although the administration did not elicit specific neutralizing antibodies to BSA and OVA. A cross-reactivity was observed between anti-PEG IgMs elicited by PEG-BSA and PEGylated liposomes. The anti-PEG IgM level induced by PEGylated proteins (BSA and OVA) reached the maximum at day 5 following intravenous injection. This production pattern was consistent with that induced by PEGylated liposomes. Splenectomy suppressed the anti-PEG IgM response against PEG-BSA and PEGylated liposomes. These observations relating PEG-BSA and PEGylated liposomes indicate that PEGylated proteins might promote the immune responses against PEG with a mechanism similar to that of PEGylated liposomes. In addition, a single intravenous administration of PEGylated adenovirus (PEG-Ad) also elicited an anti-PEG IgM response in a PEG-modification ratio dependent manner. To the best of our knowledge, this is the first report showing that an intravenous administration can elicit an anti-PEG IgM response against PEGylated substances. It appears that anti-PEG IgMs can be produced by the systemic administration of a PEGylated substance and may limit the efficacy of PEGylated substances such as proteins, Ad vector and nanoparticles, due to a cross-reactivity seen in some patients. The immunogenicity of PEGylated substances is usually tested against those very substances, rather than against covalently attached PEG. Our study suggests that the PEG immunogenicity of PEGylated therapeutic agents and particles merits further investigation.
(キーワード): Adenoviridae / Animals / Cattle / Immunoglobulin M / Injections, Intravenous / リポソーム (liposomes) / Male / Ovalbumin / Polyethylene Glycols / Rats / Rats, Wistar / Serum Albumin / Splenectomy
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b12-00276
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22863934; ● CiNii @ 国立情報学研究所 (CRID): 1390001204632293632; ● Search Scopus @ Elsevier (PMID): 22863934; ● Search Scopus @ Elsevier (DOI): 10.1248/bpb.b12-00276

(DOI: 10.1248/bpb.b12-00276, PubMed: 22863934, CiNii: 1390001204632293632) Masako Ichihara, Taro Shimizu, Ami Imoto, Yuki Hashiguchi, Yumi Uehara, Tatsuhiro Ishida and Hiroshi Kiwada :
Anti-PEG IgM response against PEGylated liposomes in mice and rats.,
Pharmaceutics, Vol.3, No.1, 1-11, 2011.

(出版サイトへのリンク): ● Publication site (DOI): 10.3390/pharmaceutics3010001
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.3390/pharmaceutics3010001

(DOI: 10.3390/pharmaceutics3010001) Tatsuaki Tagami, Kazuya Nakamura, Taro Shimizu, Naoshi Yamazaki, Tatsuhiro Ishida and Hiroshi Kiwada :
CpG motifs in pDNA-sequences increase anti-PEG IgM production induced by PEG-coated pDNA-lipoplexes.,
Journal of Controlled Release, Vol.142, No.2, 160-166, 2010.

(要約): Gene therapy is largely dependent on the development of efficient delivery vehicles. To prolong their circulating time, PEGylation of the surface of a delivery vehicle is frequently applied. However, we have reported previously that anti-PEG IgM produced by intravenous injection of PEG-coated liposome is responsible for enhanced clearance of second dose PEG-coated liposomes, which is known as the "accelerated blood clearance (ABC) phenomenon." A similar phenomenon has been observed with PEG-coated pDNA-lipoplexes (PDCLs) upon their repeated injection. But the effect of the sequence of pDNA in PDCLs on inducing the ABC phenomenon has not been thoroughly investigated. Here, we focus on CpG motifs in pDNA, which are known to have a potent immune-stimulatory activity. PDCLs with non-CpG pDNA (PNDCL) diminished the anti-PEG IgM response, resulting in significant accumulation of a second dose in tumor tissue, comparable to that of a single injection, but not in enhanced accumulation in liver. In addition, PDCL induced proliferation of IgM(+) splenic cells including B cells. These results suggest that the CpG motif is a major cause of the induction of the ABC phenomenon when PDCLs are repeatedly injected. Immunogenicity is a relevant point of concern for non-viral delivery systems. Our results indicate that the use of non-CpG pDNA may allow meaningful repeated dosing of pDNA formulations without the induction of a strong immune reaction and thus may have important implications for therapeutic use of liposomal formulations of nucleic acids.
(キーワード): Animals / B-Lymphocytes / Cell Proliferation / CpG Islands / DNA / Immunoglobulin M / Liposomes / Male / Mice / Mice, Inbred BALB C / Mice, Nude / Polyethylene Glycols
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jconrel.2009.10.017
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19850094; ● Search Scopus @ Elsevier (PMID): 19850094; ● Search Scopus @ Elsevier (DOI): 10.1016/j.jconrel.2009.10.017

(DOI: 10.1016/j.jconrel.2009.10.017, PubMed: 19850094) Tatsuaki Tagami, Kazuya Nakamura, Taro Shimizu, Tatsuhiro Ishida and Hiroshi Kiwada :
Effect of siRNA in PEG-coated siRNA-lipoplex on the anti-PEG IgM production.,
Journal of Controlled Release, Vol.137, No.3, 234-240, 2009.

(要約): For efficient delivery of small interfering RNA (siRNA) in vivo, it is important to control the blood circulation of the delivery vehicle. Surface modification of the siRNA/cationic liposome complex (siRNA-lipoplex) with polyethylene glycol (PEG) is expected to enhance circulation time in blood. However, we have recently reported that anti-PEG IgM production after the first injection of PEG-coated liposome is responsible for a reduction in the blood circulation of the second dose of the liposome, which is known as the accelerated blood clearance (ABC) phenomenon. It is unknown whether a PEG-coated siRNA-lipoplex (PSCL) can cause the ABC phenomenon and anti-PEG IgM production. In this study, an anti-PEG IgM response to PSCL was detected and was inversely related to the PSCL dose. Interestingly, the anti-PEG IgM response was significantly lower for PSCL than it was for PEG-coated naked cationic liposomes (PCL). The studies with splenectomized mice and nude mice indicated that anti-PEG IgM production was closely related to an interaction of PSCL and PCL with the spleen, which is associated with a T cell-independent mechanism. In addition, PSCL induced apoptosis on IgM-expressing splenic cells more strongly than PCL did, which suggests that accumulation in the spleen and the apoptotic effect of PEG-coated substances on splenic B cells could affect the potency of anti-PEG IgM production.
(キーワード): Animals / Apoptosis / B-Lymphocytes / Dose-Response Relationship, Immunologic / Immunoglobulin G / Immunoglobulin M / Liposomes / Male / Mice / Mice, Inbred BALB C / Mice, Nude / Polyethylene Glycols / RNA, Small Interfering / Spleen / Splenectomy
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jconrel.2009.04.006
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19361546; ● Search Scopus @ Elsevier (PMID): 19361546; ● Search Scopus @ Elsevier (DOI): 10.1016/j.jconrel.2009.04.006

(DOI: 10.1016/j.jconrel.2009.04.006, PubMed: 19361546) Tatsuhiro Ishida, Wang Xinyu, Taro Shimizu, Kousuke Nawata and Hiroshi Kiwada :
PEGylated liposomes elicit an anti-PEG IgM response in a T-cells independent manner.,
Journal of Controlled Release, Vol.122, No.3, 349-355, 2007.

(要約): We recently reported that intravenous injections of "empty" PEGylated liposomes without encapsulated or surface coupled proteins elicit a PEG-specific IgM response in rats. In the present study, simultaneous weak anti-PEG IgG and strong anti-PEG IgM responses were detected following intravenous injections of "empty" PEGylated liposomes. The pattern of immune response appears to differ from the classic primary response against T cell-dependent (TD) antigens. The anti-PEG IgM response was detected in T-cell deficient nude BALB/c mice following intravenous injection of "empty" PEGylated liposomes, suggesting that "empty" PEGylated liposomes initiate the immune response against PEG in a T cell-independent manner. In vitro splenic lymphocytes-proliferation assay indicated that TNP-LPS, a typical type 1 T cell-independent (TI) antigen (TI-1 antigen), significantly primed the proliferation, while TNP-Ficoll, a typical type 2 TI antigen (TI-2 antigen), and "empty" PEGylated liposomes did not prime any proliferation under these experimental conditions. In addition, in splenic marginal zone (MZ) B-cell-depleted rats, the anti-PEG IgM response was diminished, while the immune reactions against TNP-BSA (a TD antigen) and TNP-LPS (TI-1 antigen) were not diminished. These results demonstrate that "empty" PEGylated liposomes may promote the immune response against PEG as a result of priming the activation of MZ B cells, as TI-2 antigen promotes a specific IgM response. In conclusion, although the mechanistic details behind the immune reaction against "empty" PEGylated liposomes are not yet clear, the liposomes elicit an anti-PEG IgM response in a T cell-independent manner and appear to be a TI-2 antigen, and splenic MZ B cells may be essential for the immune response against "empty" PEGylated liposomes.
(キーワード): Animals / Antigens, T-Independent / Cell Proliferation / Cyclophosphamide / Immunoglobulin G / Immunoglobulin M / Injections, Intravenous / リポソーム (liposomes) / Male / Mice / Mice, Inbred BALB C / Mice, Nude / Polyethylene Glycols / Rats / Rats, Wistar / Spleen / Tリンパ球 (T lymphocytes)
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jconrel.2007.05.015
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17610982; ● Search Scopus @ Elsevier (PMID): 17610982; ● Search Scopus @ Elsevier (DOI): 10.1016/j.jconrel.2007.05.015

(DOI: 10.1016/j.jconrel.2007.05.015, PubMed: 17610982)

MISC

研究者総覧に該当データはありませんでした。

総説・解説

Ibrahim Mohamed, Eslam Mostafa Ramadan Abdelhameed, Nehal Ali Emam Elsadek Emam Elhewan, Sherif Abdallah Emam Emam, Taro Shimizu, Hidenori ANDO, Yu Ishima, Elgarhy Helmy Omar, Sarhan A Hatem, Hussein K Amal and Tatsuhiro Ishida :
Polyethylene glycol (PEG): The nature, immunogenicity, and role in the hypersensitivity of PEGylated products,
Journal of Controlled Release, Vol.351, 215-230, Nov. 2022.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jconrel.2022.09.031
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.jconrel.2022.09.031

(DOI: 10.1016/j.jconrel.2022.09.031) Nana Matsuo, Hidenori ANDO, Yusuke Doi, Taro Shimizu, Yu Ishima and Tatsuhiro Ishida :
The challenge to deliver oxaliplatin (l-OHP) to solid tumors: development of liposomal l-OHP formulations,
Chemical & Pharmaceutical Bulletin, Vol.70, No.5, 351-358, May 2022.

(出版サイトへのリンク): ● Publication site (DOI): 10.1248/cpb.c22-00099
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1248/cpb.c22-00099

(DOI: 10.1248/cpb.c22-00099) G Kozma, Taro Shimizu, Tatsuhiro Ishida and J Szebeni :
Anti-PEG antibodies: Properties, formation and role in adverse immune reactions to PEGylated nano-biopharmaceuticals,
Advanced Drug Delivery Reviews, Vol.154-155, 163-175, Aug. 2020.

(徳島大学機関リポジトリ): ● Metadata: 116267
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.addr.2020.07.024
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.addr.2020.07.024

(徳島大学機関リポジトリ: 116267, DOI: 10.1016/j.addr.2020.07.024) 清水太郎, 異島優, 石田竜弘 :
タンパクのPEG修飾によるPEG免疫応答の誘導,
薬学雑誌, Vol.140, No.2, 163-169, 2020年2月.

(出版サイトへのリンク): ● Publication site (DOI): 10.1248/yakushi.19-00187-5
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1248/yakushi.19-00187-5

(DOI: 10.1248/yakushi.19-00187-5) 安藤英紀, 清水太郎, 石田竜弘 :
リポソームDDS 製剤開発における免疫系の制御と動態解析の重要性,
オレオサイエンス, Vol.20, No.2, 71-76, 2020年2月.

(出版サイトへのリンク): ● Publication site (DOI): 10.5650/oleoscience.20.71
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390283659849385728; ● Search Scopus @ Elsevier (DOI): 10.5650/oleoscience.20.71

(DOI: 10.5650/oleoscience.20.71, CiNii: 1390283659849385728) M Mohamed, Lila Selim Ahmed Ali Abu Amr, Taro Shimizu, E Alaaeldin, A Hussein, H Sarhan, J Szebeni and Tatsuhiro Ishida :
PEGylated liposomes: immunological responses,
Science and Technology of Advanced Materials, Vol.20, No.1, 710-724, Jun. 2019.

(要約): A commonly held view is that nanocarriers conjugated to polyethylene glycol (PEG) are non-immunogenic. However, many studies have reported that unexpected immune responses have occurred against PEG-conjugated nanocarriers. One unanticipated response is the rapid clearance of PEGylated nanocarriers upon repeat administration, called the accelerated blood clearance (ABC) phenomenon. ABC involves the production of antibodies toward nanocarrier components, including PEG, which reduces the safety and effectiveness of encapsulated therapeutic agents. Another immune response is the hypersensitivity or infusion reaction referred to as complement (C) activation-related pseudoallergy (CARPA). Such immunogenicity and adverse reactivities of PEGylated nanocarriers may be of potential concern for the clinical use of PEGylated therapeutics. Accordingly, screening of the immunogenicity and CARPA reactogenicity of nanocarrier-based therapeutics should be a prerequisite before they can proceed into clinical studies. This review presents PEGylated liposomes, immunogenicity of PEG, the ABC phenomenon, C activation and lipid-induced CARPA from a toxicological point of view, and also addresses the factors that influence these adverse interactions with the immune system.
(徳島大学機関リポジトリ): ● Metadata: 115719
(出版サイトへのリンク): ● Publication site (DOI): 10.1080/14686996.2019.1627174
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31275462; ● Summary page in Scopus @ Elsevier: 2-s2.0-85068089055

(徳島大学機関リポジトリ: 115719, DOI: 10.1080/14686996.2019.1627174, PubMed: 31275462, Elsevier: Scopus) 清水太郎, 異島優, 石田竜弘 :
Accelerated blood clearance (ABC) 現象における動物種差,
Drug Delivery System, Vol.32, No.5, 396-401, 2017年11月.

(出版サイトへのリンク): ● Publication site (DOI): 10.2745/dds.32.396
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390001204641700864; ● Search Scopus @ Elsevier (DOI): 10.2745/dds.32.396

(DOI: 10.2745/dds.32.396, CiNii: 1390001204641700864) 清水太郎, 異島優, 石田竜弘 :
ナノ粒子に対する補体活性化の功罪,
Drug Delivery System, Vol.32, No.3, 199-207, 2017年8月.

(出版サイトへのリンク): ● Publication site (DOI): 10.2745/dds.32.199
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390282679617948032; ● Search Scopus @ Elsevier (DOI): 10.2745/dds.32.199

(DOI: 10.2745/dds.32.199, CiNii: 1390282679617948032) 清水太郎, 石田竜弘 :
Poly(ethylene glycol)に対する抗体の特性，評価，抑制,
Drug Delivery System, Vol.31, No.4, 300-307, 2016年6月.

(要約): PEG(poly(ethylene glycol))修飾は，バイオ医薬品の生体内安定性を向上させる最も標準的な方法である．しかし，PEG修飾体投与後にPEGに特異的な抗体(抗PEG抗体)が誘導され，繰り返し投与時のPEG修飾体の血中滞留性を著しく低下させることが明らかになっている．これまでに，実験動物だけでなく，ヒトにおいても抗PEG抗体の誘導が確認されている．また，さまざまなPEG修飾体投与によって，さまざまな特性を持った抗PEG抗体が誘導されることも明らかになっている．PEG修飾技術による治療効果の向上を損なわないためにも，抗PEG免疫応答の正しい理解と抑制法の開発は非常に重要である．本稿では，抗PEG抗体の特性・評価・抑制法について概説する．
(キーワード): PEGylated drug / Anti-PEG antibody / Accelerated blood clearance
(出版サイトへのリンク): ● Publication site (DOI): 10.2745/dds.31.300
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390001204640457984; ● Search Scopus @ Elsevier (DOI): 10.2745/dds.31.300

(DOI: 10.2745/dds.31.300, CiNii: 1390001204640457984) Masami Ukawa, Hidenori ANDO, Taro Shimizu and Tatsuhiro Ishida :
Pharmaceutics of Nanoparticles,
Nanomaterials in Pharmacology, 219-238, Nov. 2015.

(出版サイトへのリンク): ● Publication site (DOI): 10.1007/978-1-4939-3121-7_11
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1007/978-1-4939-3121-7_11

(DOI: 10.1007/978-1-4939-3121-7_11)

講演・発表

Haruka Yamamoto, Hidenori ANDO, Omoto Yasukazu, Taro Shimizu, Yu Ishima and Tatsuhiro Ishida :
Induction of neutralizing antibodies by immunization with inactivated human TNF-alpha in mice,
15th International Symposium on Nanomedicine, Tokushima, Dec. 2022. Shunto Yamamoto, Hidenori ANDO, Taro Shimizu, Yu Ishima and Tatsuhiro Ishida :
Development of a novel technique for antibody induction against membrane proteins by spleen immunization with membrane protein-loaded PEG-modified liposomes,
15th International Symposium on Nanomedicine, Tokushima, Dec. 2022. Takaaki Matsuzaki, Taro Shimizu, Hidenori ANDO, Yu Ishima, K Yamanaka, H Hamamoto and Tatsuhiro Ishida :
An ionic liquids-based topical antitumor vaccine: a mechanism for induction of antitumor immunity via topical application of cancer-antigen peptides,
15th International Symposium on Nanomedicine, Tokushima, Dec. 2022. Aiko Hashimoto, Yu Ishima, Hidenori ANDO, Taro Shimizu and Tatsuhiro Ishida :
Differential organ-specific distribution of human serum albumin denatured by various modifications,
15th International Symposium on Nanomedicine, Tokushima, Dec. 2022. Riku Uehara, Hidenori ANDO, Taro Shimizu, Yu Ishima and Tatsuhiro Ishida :
Neutralization of acidic tumor microenvironment by dosing of sodium potassium citrate (K/Na citrate) enhances antitumor effects of Abraxane®,
15th International Symposium on Nanomedicine, Tokushima, Dec. 2022. Shoichiro Fukuda, Hidenori ANDO, Atsuya Maruyama, Takashi Nakae, Noboru Tatsumi, Hidetoshi Hamamoto, Taro Shimizu, Yu Ishima and Tatsuhiro Ishida :
The mechanism investigation of intestinal absorption enhancement of drugs using ionic liquids,
15th International Symposium on Nanomedicine, Tokushima, Dec. 2022. Eslam Mostafa Ramadan Abdelhameed, Hidenori ANDO, Haruka Yamamoto, Mako Fukumoto, Taro Shimizu, Yu Ishima and Tatsuhiro Ishida :
Preparation, optimization, and evaluation of anionic DPPG-based LNPs for delivery of peptide antigens,
15th International Symposium on Nanomedicine, Tokushima, Dec. 2022. Nana Matsuo, Hidenori ANDO, Taro Shimizu, Yu Ishima and Tatsuhiro Ishida :
Oral sodium bicarbonate enhances accumulation and antitumor effects of PEGylated liposomal doxorubicin (Doxil®),
15th International Symposium on Nanomedicine, Tokushima, Dec. 2022. Yoshino Kawaguchi, Taro Shimizu, Hidenori ANDO, Yu Ishima and Tatsuhiro Ishida :
Transfusion of mouse B cells, embedded antigens with hydroxyl PEG-modified liposomes in vitro, induces cellular immune responses in mice,
15th International Symposium on Nanomedicine, Tokushima, Dec. 2022. A S Gaballa, Taro Shimizu, Hidenori ANDO, Yu Ishima, Sherif Abdallah Emam Emam, M Ibrahim, M F Mady, W Y Naguib, A K Khaled and Tatsuhiro Ishida :
Accelerated blood clearance of PEGylated liposomal antitumor agents after topical application of PEG derivatives containing cosmetics in a mouse model,
15th International Symposium on Nanomedicine, Tokushima, Dec. 2022. Taro Shimizu, H Hamamoto and Tatsuhiro Ishida :
Application of ionic liquids for transcutaneous delivery of hydrophilic macromolecules,
15th International Symposium on Nanomedicine, Tokushima, Dec. 2022. Takeru Hirai, Nanami Tasaka, Hidenori ANDO, Taro Shimizu, Tatsuhiro Ishida and Yu Ishima :
Biological roles of supersulfide in human hair,
Redox Week in Sendai 2022, Sendai, Oct. 2022. Yamade Rina, Taro Shimizu, Hirakawa Naoki, Hidenori ANDO, Yu Ishima and Tatsuhiro Ishida :
Human serum albumin (HSA)-based nanocarriers efficiently deliver antigens to the spleen and induce antigen-specific humoral immunity,
14th International Symposium on Nanomedicine, Nov. 2021. Takata Haruka, Taro Shimizu, Ueda Hiro, Hidenori ANDO, Yu Ishima and Tatsuhiro Ishida :
The induction level of anti-PEG IgM by PEGylated liposomes depends on the route of administration and the presence of nucleic acids,
14th International Symposium on Nanomedicine, Nov. 2021. Taro Shimizu, Haruka Takata, Milad Reda Qelliny and Tatsuhiro Ishida :
Evaluation of immunogenicity and adverse effects of nucleic acid-loaded nanoparticles,
14th International Symposium on Nanomedicine, Online, Nov. 2021. Tatsuhiro Ishida and Taro Shimizu :
A novel antigen delivery system: Antigen-selective delivery to splenic marginal zone B cells via repeated injections of PEGylated liposomes,
13th Anniversary International Symposium on Nanomedicine, Kobe, Dec. 2019. Taro Shimizu and Tatsuhiro Ishida :
Liposomal anticancer drugs enhanced antitumor effect of cancer immunotherapy by modulating immune systrem,
13th Anniversary International Symposium on Nanomedicine, Kobe, Dec. 2019. Taro Shimizu, Kohga Miyahara, G Kozma, Hidenori ANDO, Yu Ishima, J Szebeni and Tatsuhiro Ishida :
Pre-treatment with Doxebo suppresses anti-PEG IgM immune responses through PEG-specific immune tolerance,
17th International Symposium on Blood Substitutes & Oxygen Therapeutics, Nara, Nov. 2019. Tatsuhiro Ishida and Taro Shimizu :
A novel antigen delivery system: Antigen-selective delivery to splenic marginal zone B cells via repeated injections of PEGylated liposomes,
Liposome Research Days 2019, Sapporo, Sep. 2019. Nehal Ali Emam Elsadek Emam Elhewan, Taro Shimizu and Tatsuhiro Ishida :
PEG-G-CSF immunogenicity in mice: Anti-PEG IgM induction,
Liposome Research Days 2019, Sapporo, Sep. 2019. Sherif Abdallah Emam Emam, Hidenori ANDO, Taro Shimizu and Tatsuhiro Ishida :
The impact of cell-type tropism on the intratumor accumulation of exosomes derived from cancer cells,
Liposome Research Days 2019, Sapporo, Sep. 2019. M Mohamed, Taro Shimizu and Tatsuhiro Ishida :
Macrophages contribute to anti-PEG IgM production and the subsequent accelerated blood clearance of PEGylated liposomes,
Liposome Research Days 2019, Sapporo, Sep. 2019. Taro Shimizu, Shunsuke Takese, Yu Ishima and Tatsuhiro Ishida :
Combination of cancer vaccines with liposomal oxaliplatin increased anti-cancer therapeutic efficacy by stimulating antitumor immunity,
Liposome Research Days 2019, Sapporo, Sep. 2019. Haruka Takata, Taro Shimizu and Tatsuhiro Ishida :
Gene therapy with lipoplexes may worsen inflammation via formation of immune complexes with pre-existing anti-DNA antibodies in SLE-prone mice,
Liposome Research Days 2019, Sapporo, Sep. 2019. Yuna Shimazaki, Hidenori ANDO, Taro Shimizu, Yu Ishima and Tatsuhiro Ishida :
Immunization method to obtain antigen-specific antibodies by antigen delivery to splenic marginal zone B cells using PEGylated liposomes,
Liposome Research Days 2019, Sapporo, Sep. 2019. Taro Shimizu :
Immunomodulation of cancer microenvironment using liposomal oxaliplatin,
7TH CHINA-JAPAN SYMPOSIUM ON NANOMEDICINE, Xi'an, May 2019. Tatsuhiro Ishida and Taro Shimizu :
Immunological responses against PEGylated liposomes: the application of ABC phenomenon into cancer vaccine,
12th International Symposium on Nanomedicine, Ube, Dec. 2018. Mayumi Ikeda, Taro Shimizu, Yu Ishima and Tatsuhiro Ishida :
A Novel S-Sulfhydrated Serum Albumin Preparation Suppresses Melanin Synthesis,
AAPS PharmSci 360, Washington, D.C., Nov. 2018. Nanami Tasaka, Mayumi Ikeda, Taro Shimizu, Yu Ishima and Tatsuhiro Ishida :
Reactive Sulfur Species in Human Hair Keratin Respond To Oxidative Stress,
5th World Congress on Hydrogen Sulfide in Biology&Medicine, Toronto, Jun. 2018. Mayumi Ikeda, Nanami Tasaka, Taro Shimizu, Yu Ishima and Tatsuhiro Ishida :
A Novel S-Sulfhydrated Human Serum Albumin Preparation Suppresses Melanin Synhtesis,
5th World Congress on Hydrogen Sulfide in Biology&Medicine, Toronto, Jun. 2018. Taro Shimizu :
Development of marginal zone B cell-targeted cancer vaccine,
6TH JAPAN-CHINA SYMPOSIUM ON NANOMEDICINE, Matsue, May 2018. Taro Shimizu :
Cancer immunotherapy using PEGylated liposomes,
Joint meeting on Cancer and Nanotechnology, Los Angeles, Nov. 2016. Taro Shimizu :
Development of a unique vaccine by using immune response against intravenously injected PEGylated liposomes,
Seminars in Nanomedicine, Budapest, Jun. 2016. Takuma Takayama, Taro Shimizu, Masami Ukawa and Tatsuhiro Ishida :
Liposomal doxorubicin (DXR) exerts antitumor effect via securing antitumor immunity against DXR in tumor microenvironment,
Liposome Advances 2015, London, Dec. 2015. Yuka Kitayama, Ryo Abe, Taro Shimizu and Tatsuhiro Ishida :
Anti-PEG IgM production induced by siRNA-containing PEGylated liposome,
Liposome Advances 2015, London, Dec. 2015. Mizuki Awata, Risako Fujita, Yu Mima, Munehira Kawanishi, Taro Shimizu and Tatsuhiro Ishida :
Altering PEGylated liposomes modification from DSPE-PEG-OCH3 to DSPE-PEG-OH suppresses secretion of anti-PEG IgM and proliferation of PEG-specific B cell,
Liposome Advances 2015, London, Dec. 2015. Taro Shimizu, Yuki Watanabe, Yu Mima, Tatsuhiro Ishida and Hiroshi Kiwada :
Antigen delivery with PEGylated liposome and presentation via MZ-B cells enhanced induction of antigen-specific cytotoxic T lymphocyte,
Liposome Research Days 2014, Copenhagen, Aug. 2014. Munehira Kawanishi, Yosuke Hashimoto, Taro Shimizu, I Sagawa, Tatsuhiro Ishida and Hiroshi Kiwada :
Comprehensive analysis of proteins bound on PEGylated liposome relating to the accelerated blood clearance (ABC) phenomenon by shotgun analysis,
Liposome Research Days 2014, Copenhagen, Aug. 2014. Yu Mima, Taro Shimizu, Hiroshi Kiwada and Tatsuhiro Ishida :
Inclusion of ganglioside into PEGylated liposome suppresses the anti-PEG immunity against PEGylated liposome,
Liposome Research Days 2014, Copenhagen, Aug. 2014. Taro Shimizu, Tatsuhiro Ishida and Hiroshi Kiwada :
Potentiation of specific antibody response against antigen encapsulated in PEGylated liposomes via active transport of the liposomes from marginal zone into follicle,
5th Asian Arden Conference, Nagoya, Aug. 2013. Taro Shimizu, Tatsuhiro Ishida and Hiroshi Kiwada :
Transport of PEGylated liposomes to follicle induced by pre-stimulation of empty liposomes: Potentiating specific antibody responses against antigen encapsulated in the liposomes,
40th Annual Meeting & Exposition of the Controlled Release Society, Hawaii, Jul. 2013. Yosuke Hashimoto, Taro Shimizu, Tatsuhiro Ishida and Hiroshi Kiwada :
Serum anti-PEG IgM concentration is a determinant factor on hepatic accumulation of PEGylated liposome in the accelerated blood clearance phenomenon,
40th Annual Meeting & Exposition of the Controlled Release Society, Hawaii, Jul. 2013. Yu Mima, Yosuke Hashimoto, Taro Shimizu, Tatsuhiro Ishida and Hiroshi Kiwada :
Accelerated blood clearance phenomenon upon PEGylated protein,
40th Annual Meeting & Exposition of the Controlled Release Society, Hawaii, Jul. 2013. Risako Fujita, Yosuke Hashimoto, Taro Shimizu, Tatsuhiro Ishida and Hiroshi Kiwada :
Effect of terminal group of PEG on induction of ABC phenomenon to PEGylated liposome,
40th Annual Meeting & Exposition of the Controlled Release Society, Hawaii, Jul. 2013. Taro Shimizu, Tatsuhiro Ishida and Hiroshi Kiwada :
Activation of splenic marginal zone B cell by PEGylated liposome with lower dose: triggering transport of antigen-containing second dose PEGylated liposome from marginal zone to follicle,
39th Annual Meeting & Exposition of the Controlled Release Society, Québec City, Jul. 2012. Taro Shimizu, Tatsuhiro Ishida and Hiroshi Kiwada :
Contribution of spleen marginal zone B cells on anti-PEG IgM responses against PEGylated liposomes and transport of PEGylated liposomes.,
International Liposome Society 2011 meeting, University of London,, London, Dec. 2011. Yuki Hashiguchi, Taro Shimizu, Masako Ichihara, Tatsuhiro Ishida and Hiroshi Kiwada :
PEG on nanocarriers induces anti PEG IgM production as a result of activation of immune system.,
Nano in Cancer: Linking Chemistry, Biology and Clinical Applications in vivo, Miami, Jan. 2011. Yuki Hashiguchi, Taro Shimizu, Tatsuhiro Ishida and Hiroshi Kiwada :
Sequential treatment, pre-dose with empty PEGylated liposome (SL) and second dose antigen-encapsulating SL, promotes activation in a primary immune response.,
International Liposome Research Days & Lipids, Liposomes & Membrane Biophysics, Vancouver, Aug. 2010. Tatsuaki Tagami, Kazuya Nakamura, Taro Shimizu, Tatsuhiro Ishida and Hiroshi Kiwada :
Effect of siRNA on anti-PEG IgM production in the accelerated blood clearance (ABC) phenomenon when formulated with PEGylated cationic liposome.,
11th Liposome Research Days conference, Yokohama, Jul. 2008. Taro Shimizu, Tatsuhiro Ishida and Hiroshi Kiwada :
Interaction of PEGylated liposomes with splenic marginal zone B cells may trigger production of anti-PEG IgM in the ABC phenomenon.,
11th Liposome Research Days conference, Yokohama, Jul. 2008. Taro Shimizu, Tatsuhiro Ishida and Hiroshi Kiwada :
Accelerated blood clearance (ABC) phenomenon on PEGylated nanocarrier: Unexpected immune-reaction against PEGylated liposome.,
International Symposium on ``Nanotoxicology Assessment and Biomedical, Environmental Application of Fine Particles and Nanotubes'' (ISNT2008), Sapporo, Jun. 2008. Rina Yamade, Taro Shimizu, Hidenori ANDO, Yu Ishima and Tatsuhiro Ishida :
Investigation of the usefulness of human serum albumin nanoparticles as antigen delivery carriers to the spleen,
日本薬剤学会第2回英語セミナー, Feb. 2023. 山本遥香, 安藤英紀, 大本安一, 川口桂乃, 清水太郎, 異島優, 石田竜弘 :
不活化ヒト TNFα 誘導体のマウスへの免疫による中和抗体の誘導評価,
第1回日本抗体学会設立記念学術大会, 2022年11月. 松尾アモリムクリスティーナ菜々, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
白金製剤と血漿タンパク質との相互作用:時間依存性に関する検討,
日本薬物動態学会第37回年会, 2022年11月. 水町健太, 清水太郎, 上田大, 高田春風, 清水太郎, 異島優, 石田竜弘 :
全身性エリテマトーデスモデルマウス由来B細胞の取り込み能についての検討,
第61回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2022年11月. 山本遥香, 安藤英紀, 大本安一, 清水太郎, 異島優, 石田竜弘 :
Humira®(adalimumab)投与時の抗薬物抗体(ADA)誘導に関する検討:マウス型抗ヒトTNFαモノクローナル抗体をマウスに投与した際のADA誘導,
第61回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2022年11月. 高田春風, 清水太郎, 阿部舜史, 安藤英紀, 異島優, 石田竜弘 :
デキサメタゾンが及ぼすPEG修飾ナノ粒子による抗PEG抗体誘導への影響,
第16回次世代を担う若手医療薬科学シンポジウム, 2022年10月. 山本舜人, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
膜タンパク質搭載PEG修飾リポソームの脾臓送達による抗膜タンパク質抗体誘導,
第43回生体膜と薬物の相互作用シンポジウム, 2022年10月. 高田春風, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
PEG修飾リポソームの投与経路がおよぼす抗PEG抗体誘導への影響に関する検討,
第43回生体膜と薬物の相互作用シンポジウム, 2022年10月. 岡田直人, 中村信元, 清水太郎, 安藤英紀, 相澤風花, 新村貴博, 八木健太, 合田光寛, 石田竜弘, 石澤啓介 :
免疫不全リスクを有する患者における新型コロナワクチンによる抗体獲得能に関連する因子の検討,
第32回日本医療薬学学会, 2022年9月. 角南尚哉, 安藤英紀, 土井祐輔, 清水太郎, 異島優, 安倍正博, 石田竜弘 :
オキサリプラチン封入PEG修飾リポソームの悪性リンパ腫治療への展開,
第27回創剤フォーラム若手研究会, 2022年9月. 福田翔一郎, 安藤英紀, 丸山敦也, 中江崇, 辰巳昇, 濱本英利, 清水太郎, 異島優, 石田竜弘 :
イオン液体による薬物の腸管吸収促進メカニズムの検討,
第27回創剤フォーラム若手研究会, 2022年9月. 松尾アモリムクリスティーナ菜々, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
重曹の経口投与によるDoxil®の腫瘍集積性向上と抗腫瘍効果増強,
第27回創剤フォーラム若手研究会, 2022年9月. 中野琉人, 平川尚樹, 安藤英紀, 清水太郎, 石田竜弘, 異島優 :
難水溶性薬物に対する溶解補助及び動態改善を企図した新規アルブミンナノ粒子の有用性評価,
日本薬剤学会第3回超分子薬剤学FGシンポジウム, 2022年9月. 川口桂乃, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
B細胞に標的化されたヒドロキシ末端PEG修飾リポソームは補体受容体を介して他の免疫細胞へと受け渡される,
日本薬剤学会第3回超分子薬剤学FGシンポジウム, 2022年9月. 平井傑琉, 清水太郎, 安藤英紀, 石田竜弘, 異島優 :
毛髪中に含まれる超硫黄分子の検出および機能解明,
フォーラム2022:衛生薬学・環境トキシコロジー, 2022年8月. 石橋賢汰, 岸村顕広, 清水太郎, 森健, 石田竜弘, 片山佳樹 :
イオン間距離の異なるベタインポリマー修飾リポソームに対する抗体産生,
遺伝子・デリバリー研究会第20回夏期セミナー, 2022年8月. 阿部舜史, 高田春風, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
血中の抗PEG抗体が筋肉内投与後のmRNA搭載LNPのタンパク質発現に与える影響に関する検討,
遺伝子・デリバリー研究会第20回夏期セミナー, 2022年8月. 高田春風, 清水太郎, 上田大, 安藤英紀, 異島優, 石田竜弘 :
siRNA搭載PEG修飾リポソームの投与経路がおよぼす抗PEG抗体誘導への影響に関する検討,
遺伝子・デリバリー研究会第20回夏期セミナー, 2022年8月. 阿部舜史, 高田春風, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
mRNA搭載LNP構成成分のPEG脂質が示す免疫原性及びアナフィラキシー様反応への影響,
日本核酸医薬学会第7回年会, 2022年8月. 上田大, 清水太郎, 安藤英紀, 異島優, 山吉麻子, 石田竜弘 :
核酸搭載リポソームの物理化学的性質が抗核酸抗体の誘導に与える影響の検討,
日本核酸医薬学会第7回年会, 2022年8月. 川口桂乃, 安藤英紀, 田島健次, 長澤一樹, 清水太郎, 異島優, 石田竜弘 :
ナノフィブリル化バクテリアセルロースの経口摂取による腸内細菌叢の変動と肥満抑制効果の評価,
セルロース学会第29回年次大会, 2022年7月. 高田春風, 安藤英紀, 田島健次, 清水太郎, 異島優, 松島得雄, 草野貴友, 石田竜弘 :
ナノフィブリル化バクテリアセルロースを懸濁剤として用いたシクロスポリンA製剤の調製と乾癬治療効果の評価,
セルロース学会第29回年次大会, 2022年7月. 平井傑琉, 田坂菜々美, 清水太郎, 安藤英紀, 石田竜弘, 異島優 :
毛髪中に含まれる超硫黄分子の検出および機能解明,
第49回日本毒性学会学術年会, 2022年7月. 十鳥有希菜, 平川尚樹, 木下遼, 清水太郎, 安藤英紀, 石田竜弘, 異島優 :
スルホサリチル酸を用いた新規アルブミンナノ粒子化法の開発と敗血症への応用,
第49回日本毒性学会学術年会, 2022年7月. 向井愛菜, 清水太郎, 安藤英紀, 石田竜弘, 異島優 :
致死性エンドトキシンショックに対するヒト血清アルブミンの治療効果の機序,
第49回日本毒性学会学術年会, 2022年7月. 橋本怜奈, 清水太郎, 安藤英紀, 石田竜弘, 異島優 :
皮膚角質層に含まれる超硫黄分子の検出,
第49回日本毒性学会学術年会, 2022年7月. 倉本伶音, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
緑色蛍光タンパク質(EGFP)をモデル抗原として封入したPEG修飾エクソソームの脾臓送達による抗原特異的抗体の誘導,
第38回日本DDS学会学術集会, 2022年6月. 角南尚哉, 安藤英紀, 清水太郎, 異島優, 安倍正博, 石田竜弘 :
オキサリプラチン封入PEG修飾リポソームの悪性リンパ腫に対する治療効果の検討,
第38回日本DDS学会学術集会, 2022年6月. 山出莉奈, 清水太郎, 平川尚樹, 安藤英紀, 異島優, 石田竜弘 :
ヒト血清アルブミンナノ粒子(HSAnp)を利用したDDSの新規開発とがんワクチンへの展開,
第38回日本DDS学会学術集会, 2022年6月. 山本遥香, 安藤英紀, 大本安一, 清水太郎, 異島優, 石田竜弘 :
抗TNFαモノクローナル抗体(Humira)をマウスに投与した際の抗薬物抗体の誘導評価,
第38回日本DDS学会学術集会, 2022年6月. 山本舜人, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
抗原とオボアルブミンを共封入したPEG修飾リポソームの脾臓送達による抗原特異的抗体誘導の増強効果,
第38回日本DDS学会学術集会, 2022年6月. 高田春風, Milad Qelliny, 清水太郎, 上田大, 安藤英紀, 異島優, 石田竜弘 :
ガングリオシドを用いた抗核酸抗体誘導抑制効果の検討,
日本薬剤学会第37年会, 2022年5月. 阿部舜史, 高田春風, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
mRNA封入脂質ナノ粒子構成成分のPEGに対する抗PEG抗体の誘導及びアナフィラキシー様反応への影響,
日本薬剤学会第37年会, 2022年5月. 山本舜人, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
抗原封入PEG修飾リポソームを利用した抗体誘導におけるOVAのアジュバント効果の検証,
日本薬剤学会第37年会, 2022年5月. 山本舜人, 安藤英紀, 冨田康治, 前田典之, 清水太郎, 異島優, 石田竜弘 :
末端構造の異なるPEGで作製した抗原封入リポソームの静脈内投与による抗体誘導に関わる免疫細胞の評価,
日本薬学会第142年会, 2022年3月. 松﨑隆朗, 清水太郎, 安藤英紀, 異島優, 山中勝弘, 三輪泰司, 濱本英利, 石田竜弘 :
イオン液体を用いた経皮吸収ワクチンによる皮膚およびリンパ節における免疫細胞の活性化評価,
日本薬学会第142年会, 2022年3月. 川口桂乃, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
脾臓中B細胞は補体受容体介在性に捕捉した抗原キャリアを他の抗原提示細胞へ輸送する,
日本薬学会第142年会, 2022年3月. 清水太郎, 山口雪洲, 安藤英紀, 異島優, 石田竜弘 :
新型コロナウイルスに対する効率的な抗体誘導を目指した脾臓辺縁帯B細胞標的化ワクチン開発に関する検討,
日本薬学会第142年会, 2022年3月. 山本舜人, 安藤英紀, 前田典之, 清水太郎, 異島優, 石田竜弘 :
抗原封入リポソームの脾臓免疫による抗体誘導に関するPEG末端構造の影響,
第60回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2021年11月. 高田正希, 安藤英紀, 赤木俊介, 田島健次, 松島得雄, 草野貴友, 清水太郎, 異島優, 石田竜弘 :
表面物性の異なるナノフィブリル化バクテリアセルロースを用いたパクリタキセル製剤の開発と腹膜播種治療評価,
第60回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2021年11月. 上原陸, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
重曹経口投与による腫瘍内微小環境中性化にともなう遺伝子発現解析,
第60回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2021年11月. 松尾菜々, 異島優, 安藤英紀, 清水太郎, 石田竜弘 :
Sulfane sulfur付加型HSAを用いた還元ストレス誘導を介するがん治療戦略,
第60回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2021年11月. 清水太郎, Qelliny Milad, 高田春風, 上田大, 安藤英紀, 異島優, 石田竜弘 :
核酸搭載PEG修飾カチオン性リポソームによる抗PEG抗体および抗核酸抗体誘導に及ぼすガングリオシド修飾の影響,
第60回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2021年11月. 橋本愛子, 異島優, 安藤英紀, 清水太郎, 石田竜弘 :
アルブミンを基盤とした臓器特異的移行性を有するDDSキャリアの作製,
第15回次世代を担う若手のための医療薬科学シンポジウム, 2021年10月. 安藤英紀, 赤木俊介, 田島健次, 清水太郎, 異島優, 松島得雄, 草野貴友, 石田竜弘 :
ナノフィブリル化バクテリアセルロース(NFBC)を利用した3次元細胞培養に関する基礎的検討,
セルロース学会第28回年次大会, 2021年9月. 赤木俊介, 安藤英紀, 田島健次, 松島得雄, 草野貴友, 清水太郎, 異島優, 石田竜弘 :
ナノフィブリル化バクテリアセルロース(NFBC)を用いた3次元培養によるヒト肝がんHepG2細胞の機能変動評価,
セルロース学会第28回年次大会, 2021年9月. 山出莉奈, 平川尚樹, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
高い抗体産生誘導能を有する抗原搭載アルブミンナノ粒子の開発,
日本薬剤学会第2回超分子薬剤学FGシンポジウム, 2021年9月. Yoshino Kawaguchi, Taro Shimizu, Hidenori ANDO, Yu Ishima and Tatsuhiro Ishida :
Enhancement of the anti-tumor effect of B cell-based vaccines via increasing the loading amount of antigens by utilizing novel antigen carrier system,
2021 Tokushima Bioscience Retreat, Sep. 2021. 松尾菜々, 異島優, 安藤英紀, 清水太郎, 石田竜弘 :
活性イオウ付加型ヒト血清アルブミンの腫瘍への送達は小疱形成を介した細胞死を誘導する,
第29回DDSカンファランス, 2021年9月. 安藤英紀, 山口雪洲, 清水太郎, 異島優, 石田竜弘 :
新規脾臓免疫で誘導した抗体の多様性および結合性の評価,
第37回日本DDS学会学術集会, 2021年6月. 清水太郎, 島崎優奈, 安藤英紀, 異島優, 石田竜弘 :
脾臓辺縁帯B細胞を標的としたペプチド封入リポソームによる免疫誘導に関する検討,
第37回日本DDS学会学術集会, 2021年6月. 石橋賢汰, 清水太郎, 石田竜弘 :
イオン間距離の異なるベタインポリマー修飾リポソームに対する抗体産生,
第37回日本DDS学会学術集会, 2021年6月. 髙田春風, 清水太郎, 川口桂乃, 安藤英紀, 異島優, 石田竜弘 :
投与経路が及ぼすPEG修飾リポソーム投与時の抗PEG抗体誘導に与える影響に関する検討,
第37回日本DDS学会学術集会, 2021年6月. 坂元智香, 清水太郎, 安藤英紀, 異島優, 小林勝則, 石橋賢樹, 三輪泰司, 濱本英利, 石田竜弘 :
イオン液体を用いたIL-23 特異的siRNAの経皮送達はイミキモド誘発乾癬モデルマウスの皮膚症状を改善する,
日本核酸医薬学会第6回年会, 2021年6月. 髙田春風, Milad Reda Qelliny, 清水太郎, 上田大, 安藤英紀, 異島優, 石田竜弘 :
ガングリオシドによるDNA搭載PEG修飾カチオン性リポソーム投与時のPEG及びDNAに対する抗体の産生への影響の検討,
日本核酸医薬学会第6回年会サテライト若手シンポジウム, 2021年6月. 橋本愛子, 濱眞壱, 異島優, 安藤英紀, 清水太郎, 石田竜弘 :
様々なヒト血清アルブミン受容体を介した薬物キャリアの開発,
日本薬剤学会第36年会, 2021年5月. 向井愛菜, 異島優, 安藤英紀, 清水太郎, 石田竜弘 :
致死性エンドトキシンショックに対するヒト血清アルブミンの治療効果の機序解明,
日本薬剤学会第36年会, 2021年5月. 橋本怜奈, 異島優, 安藤英紀, 清水太郎, 石田竜弘 :
紫外線による皮膚角質中に含まれる活性イオウ分子種の変動,
日本薬剤学会第36年会, 2021年5月. 角南尚哉, 安藤英紀, 中江崇, 三輪泰司, 辰巳昇, 濱本英利, 清水太郎, 異島優, 石田竜弘 :
イオン液体を基剤としたLixisenatide製剤の開発と腸管吸収評価,
日本薬剤学会第36年会, 2021年5月. 丸山敦也, 安藤英紀, 中江崇, 三輪泰司, 濱本英利, 清水太郎, 異島優, 石田竜弘 :
イオン液体を用いた難経口吸収性化合物の腸管吸収促進効果の検討,
日本薬剤学会第36年会, 2021年5月. 上田大, 髙田春風, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
全身性エリテマトーデスモデルマウス由来マイクロパーティクルにおけるプロテオーム解析,
日本薬剤学会第36年会, 2021年5月. 川口桂乃, 粟田瑞月, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
細胞ワクチンへの応用を目指した補体受容体標的化キャリアを用いる新規B細胞抗原刺激法の確立,
日本薬剤学会第36年会, 2021年5月. 川口桂乃, 粟田瑞月, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
効果的な細胞免疫療法の開発に向けたB細胞への新規抗原刺激法の有用性評価,
日本薬剤学会第36年会, 2021年5月. Nehal Emam Elsadek Emam Ali Elhewan, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
Pegfilgrastim (PEG-G-CSF) induces anti-PEG IgM in a dose dependent manner and causes the accelerated blood clearance (ABC) phenomenon upon repeated administer,
日本薬剤学会第36年会, 2021年5月. 山本舜人, 山口雪洲, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
抗原封入リポソームの脾臓免疫による抗原特異的IgGの誘導とサブクラス多様性の評価,
日本薬剤学会第36年会, 2021年5月. 山出莉奈, 平川尚樹, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
効率的な体液性免疫誘導に向けたアルブミンナノキャリアの開発,
日本薬剤学会第36年会, 2021年5月. 松﨑隆朗, 清水太郎, 安藤英紀, 異島優, 三輪泰司, 濱本英利, 石田竜弘 :
経皮吸収型がんペプチドワクチンによるE.G7-OVA担がんマウスにおける腫瘍成長抑制効果,
日本薬剤学会第36年会, 2021年5月. 高田正希, 赤木俊介, 安藤英紀, 清水太郎, 異島優, 松島得雄, 草野貴友, 石田竜弘 :
菌由来セルロースナノファイバーを用いた細胞の三次元培養と機能性評価,
日本薬剤学会第36年会, 2021年5月. 上原陸, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
重曹経口投与による腫瘍酸性環境の中性化とDoxil®の抗腫瘍効果の増強,
日本薬剤学会第36年会, 2021年5月. 山口雪洲, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
新規脾臓免疫法による特異抗体の誘導とその多様性および結合親和性の評価,
日本薬剤学会第36年会, 2021年5月. 松木佑樹, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
マレイミド-チオール結合を介した抗がん剤封入リポソームの脾臓細胞への搭載とそのがん細胞障害性の評価,
日本薬剤学会第36年会, 2021年5月. 倉本伶音, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
エクソソームの脾臓免疫で得た抗血清(ポリクローナル抗体)の結合性評価,
日本薬剤学会第36年会, 2021年5月. 福田悠花, 中島祟樹, 異島優, 安藤英紀, 清水太郎, 長野一也, 柴田寛子, 石田竜弘 :
PEG修飾タンパクの凝集体形成が及ぼす抗PEG抗体産生・血中滞留性への影響,
日本薬剤学会第36年会, 2021年5月. 坂元智香, 清水太郎, 安藤英紀, 異島優, 小林勝則, 石橋賢樹, 三輪泰司, 濱本英利, 石田竜弘 :
経皮送達可能なsiRNA含有イオン液体製剤による新規乾癬治療,
日本薬剤学会第36年会, 2021年5月. 赤木俊介, 安藤英紀, 田島健次, 松島得雄, 草野貴友, 清水太郎, 異島優, 石田竜弘 :
物性の異なるナノフィブリル化バクテリアセルロースを用いた新規PTX製剤の開発と腹膜播種治療評価,
日本薬剤学会第36年会, 2021年5月. 髙田春風, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
核酸搭載PEG修飾リポソームが全身性エリテマトーデスの発症時期，増悪に与える影響,
日本薬剤学会第36年会, 2021年5月. 濵眞壱, 異島優, 安藤英紀, 清水太郎, 石田竜弘 :
アルブミン結合型パクリタキセル製剤AbraxaneⓇの変性アルブミン受容体を介した薬物輸送メカニズム,
日本薬剤学会第36年会, 2021年5月. Sherif Emam Abdallah Emam, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
Cell-type tropism promotes the intratumor accumulation of PEGylated cancer cell-derived exosomes,
日本薬剤学会第36年会, 2021年5月. 清水太郎, 三輪泰司, 濱本英利, 石田竜弘 :
イオン液体を用いた中分子経皮送達法の開発,
日本薬剤学会第36年会, 2021年5月. 中野琉人, 平川尚樹, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
難溶性薬物に対する溶解補助及び動態改善を企図した新規アルブミンナノ粒子の開発,
日本薬学会第141年会, 2021年3月. 倉本伶音, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
エクソソームの脾臓免疫により誘導した抗体のエクソソームタンパク質への結合評価,
日本薬学会第141年会, 2021年3月. 宮原康嘉, 清水太郎, 安藤英紀, 異島優, Szebeni Janos, 石田竜弘 :
高用量PEG修飾リポソーム投与時の抗PEG抗体誘導抑制機序に関する検討,
日本薬学会第141年会, 2021年3月. 川口桂乃, 島崎優奈, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
脾臓B細胞上の補体受容体を介した抗原送達法を利用する新規細胞免疫療法の開発,
日本薬学会第141年会, 2021年3月. 松尾菜々, 異島優, 池田真由美, 安藤英紀, 清水太郎, 石田竜弘 :
活性イオウ付加アルブミンの設計と還元ストレス誘導による抗腫瘍効果の評価,
日本薬学会第141年会, 2021年3月. 山口雪洲, 安藤英紀, 島崎優奈, 清水太郎, 異島優, 石田竜弘 :
抗原封入リポソームの脾臓免疫で誘導された抗体の多様性・親和性評価,
日本薬学会第141年会, 2021年3月. 山出莉奈, 平川尚樹, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
ヒト血清アルブミン(HSA)を利用した脾臓への抗原送達による体液性免疫の誘導,
日本薬学会第141年会, 2021年3月. 角南尚哉, 安藤英紀, 丸山敦也, 三輪泰司, 濱本英利, 清水太郎, 異島優, 石田竜弘 :
イオン液体を用いたGLP-1受容体作動薬の腸管吸収性検討,
日本薬学会第141年会, 2021年3月. 清水太郎 :
イオン液体を用いた経皮薬物送達法の開発,
徳島大学薬学部若手教員講演会, 2021年1月. 山口雪洲, 島崎優奈, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
脾臓標的化リポソーム技術を用いた短期間で抗体を誘導する抗体産生誘導技術の開発,
第59回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2020年12月. 向井愛菜, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
致死性エンドトキシンショックに対するヒト血清アルブミンの治療効果,
第59回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2020年12月. 松木佑樹, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
脾臓細胞搭載抗がん剤封⼊カチオン性リポソームによるがん細胞障害性のin vitro評価,
第59回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2020年12月. 橋本怜奈, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
皮膚角質中に含まれる活性イオウ分子種の検出,
第59回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2020年12月. 清水太郎 :
ナノ粒子に対する免疫応答を利用した抗原送達とコロナワクチンへの応用,
コロナウイルス感染症とナノメディシン, 2020年12月. 酒井真紀, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
ストレプトゾトシン誘発Ⅰ型糖尿病モデルマウスにおける血清活性イオウ分子の変動,
第93回日本生化学会大会, 2020年9月. 長船裕輝, 池田真由美, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
生体液中の活性イオウ分子種含有タンパク質の同定と生理学的意義の解明,
第93回日本生化学会大会, 2020年9月. 清水太郎, 吉岡千尋, 島崎優奈, 竹瀬俊輔, 石橋賢樹, 三輪泰司, 濱本英利, 石田竜弘 :
イオン液体を用いた経皮吸収型がんペプチドワクチン開発に関する検討,
第36回日本DDS学会学術集会, 2020年8月. 島居伶奈, 宮原涼, 龍神尭昌, 岸村顕広, 清水太郎, 石田竜弘, 森健, 片山佳樹 :
ポリカルボキシベタイン修飾リポソームはABC現象を誘導する,
第36回日本DDS学会学術集会, 2020年8月. 松木佑樹, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
抗がん剤搭載脾臓細胞によるがん細胞障害性評価に関する検討,
第36回日本DDS学会学術集会, 2020年8月. 坂元智香, 清水太郎, 安藤英紀, 異島優, 小林勝則, 石橋賢樹, 三輪泰司, 濱本英利, 石田竜弘 :
イオン液体を用いたsiRNAの経皮送達による新規乾癬治療法の開発,
第36回日本DDS学会学術集会, 2020年8月. 川口桂乃, 粟田瑞月, 島崎優奈, 吉岡千尋, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
ヒドロキシ末端PEG修飾リポソームによる抗原刺激を利用した新規B細胞ワクチンの開発,
第36回日本DDS学会学術集会, 2020年8月. 山口雪洲, 島崎優奈, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
脾臓辺縁帯B細胞への抗原送達による抗体産生誘導技術の開発,
日本薬剤学会第35年会, 2020年5月. 丸山敦也, 安藤英紀, 三輪泰司, 濱本英利, 清水太郎, 異島優, 石田竜弘 :
インドシアニングリーンを用いたイオン液体の腸管吸収促進効果の検討,
日本薬剤学会第35年会, 2020年5月. 濵眞壱, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
アルブミン結合型パクリタキセル製剤であるAbraxane®の新たな腫瘍移行機序の発見,
日本薬剤学会第35年会, 2020年5月. 丸山敦也, 安藤英紀, 三輪泰司, 濱本英利, 清水太郎, 異島優, 石田竜弘 :
イオン液体によるインドシアニングリーンの経口吸収性改善の検討,
日本薬学会第140年会, 2020年3月. 川口桂乃, 粟田瑞月, 島崎優奈, 吉岡千尋, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
細胞ワクチン療法への利用に適したB細胞サブセットの同定に関する検討,
日本薬学会第140年会, 2020年3月. 金山忠史, 大川内健人, 清水太郎, 重永章, 大髙章, 石田竜弘, 奥平桂一郎 :
人工HDLの化学的性状と抗腫瘍効果への影響に関する検討,
日本薬学会第140年会, 2020年3月. 濵眞壱, 異島優, 安藤英紀, 清水太郎, 石田竜弘 :
アルブミン結合型パクリタキセル製剤であるAbraxane®の新たな腫瘍移行機序の発見,
日本薬学会第140年会, 2020年3月. 酒井真紀, 池田真由美, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
糖尿病患者血清におけるサルフェン硫黄の変動,
日本薬学会第140年会, 2020年3月. 長船裕輝, 池田真由美, 酒井真紀, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
ヒト唾液α-amylase活性に及ぼすサルフェン硫黄の影響,
日本薬学会第140年会, 2020年3月. 田坂菜々美, 池田真由美, 清水太郎, 安藤英紀, 奥平桂一郎, 異島優, 石田竜弘 :
毛髪キューティクルに存在するポリスルフィドの発見とイオウ供給による毛髪損傷抑制効果の検討,
日本薬学会第140年会, 2020年3月. 翁由紀子, 新島瞳, 川原勇太, 早瀬朋美, 清水太郎, 石田竜弘 :
PEG化第8因子製剤によるアナフィラキシーの経験,
第61回日本小児血液・がん学会学術集会, 2019年11月. 坂元智香, 清水太郎, 安藤英紀, 異島優, 小林勝則, 石橋賢樹, 三輪泰司, 濱本英利, 石田竜弘 :
siRNA含有イオン液体製剤の経皮送達による乾癬治療,
第58回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2019年11月. 上田大, 高田春風, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
全身性エリテマトーデス病態時の脾臓免疫細胞によるマイクロパーティクルの取り込み変化の検討,
第58回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2019年11月. 佐々井雅樹, 清水太郎, 奥平桂一郎, 異島優, 石橋賢樹, 三輪泰司, 濱本英利, 石田竜弘 :
イオン液体を用いた新規インスリン含有経皮吸収製剤は糖尿病治療薬になりうる,
第28回DDSカンファランス, 2019年9月. 一水翔太, 渡邊博志, 前田仁志, 清水太郎, 異島優, 石田竜弘, 二木史朗, 小田切優樹, 丸山徹 :
細胞膜透過型アルブミンの細胞内移行機序の解明∼マクロピノサイトーシス誘導とエンドソーム脱出経路∼,
第35回日本DDS学会学術集会, 2019年7月. 上田大, 高田春風, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
マイクロパーティクルによる抗体産生誘導は全身性エリテマトーデスの症状進行に関与する,
第35回日本DDS学会学術集会, 2019年7月. 島崎優奈, 安藤英紀, 清水太郎, 異島優, 石田竜弘 :
脾臓への抗原デリバリー技術を利用した新規抗体産生技術の開発,
第35回日本DDS学会学術集会, 2019年7月. 田坂菜々美, 池田真由美, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
毛髪ケラチン中に存在するポリスルフィドの酸化ストレス応答,
第72回日本酸化ストレス学会学術集会, 2019年6月. 井上改, 異島優, 池田真由美, 清水太郎, 安藤英紀, 石田竜弘 :
細胞培養系における血清アルブミン結合sulfane sulfurの役割,
第19回日本NO学会学術集会, 2019年6月. 池田真由美, 異島優, 酒井真紀, 清水太郎, 安藤英紀, 渡邊博志, 丸山徹, 小田切優樹, 石田竜弘 :
ヒト血清アルブミンに存在するポリスルフィドによるユニークな酸化ストレス応答,
第19回日本NO学会学術集会, 2019年6月. 金山忠史, 大川内健人, 清水太郎, 重永章, 大髙章, 石田竜弘, 奥平桂一郎 :
腫瘍DDSキャリアとしての人工HDLの調製および動態の評価,
日本薬剤学会第34年会, 2019年5月. 池田真由美, 異島優, 清水太郎, 安藤英紀, 奥平桂一郎, 渡邊博志, 丸山徹, 小田切優樹, 石田竜弘 :
血清アルブミンの酸化ストレス応答を模倣した新規抗酸化剤の設計,
日本薬剤学会第34年会, 2019年5月. 平川尚樹, 異島優, 木下遼, 清水太郎, 丸山徹, 奥平桂一郎, 石田竜弘 :
難治性膵臓がんへの高い移行性を有するアルブミンナノ粒子の開発,
日本薬剤学会第34年会, 2019年5月. 清水太郎, 異島優, 石田竜弘 :
タンパクのPEG修飾による抗PEG免疫応答の誘導,
日本薬学会第139年会, 2019年3月. 清水太郎 :
脾臓辺縁帯B細胞への抗原送達を利用したがんワクチン研究,
第2回徳島大学統合的がん創薬研究クラスター合同ミーティング, 2019年2月. 島崎優奈, 清水太郎, 安藤英紀, 石田竜弘 :
Expansion of the delivering technique of PEGylated liposomes to marginal zone B cells for immunization with peptide antigen,
第47回日本免疫学会学術集会, 2018年12月. 高田春風, 清水太郎, 石田竜弘 :
Oligonucleotide therapeutics with pDNA/lipoplex would not cause systemic lupus erythematosus but exacerbate systemic lupus erythematosus via formation immune complexes (pDNA/lipoplex-anti DNA antibodies),
第47回日本免疫学会学術集会, 2018年12月. 平川尚樹, 異島優, 木下遼, 清水太郎, 丸山徹, 奥平桂一郎, 石田竜弘 :
共有結合型アルブミンナノ粒子を用いたセラノスティックナノDDS抗がん剤の開発,
第57回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2018年11月. 佐々井雅樹, 清水太郎, 異島優, 石橋賢樹, 三輪泰司, 濱本英利, 石田竜弘 :
イオン液体を用いた新規インスリン含有経皮吸収製剤の開発,
第57回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2018年11月. 宮原康嘉, 清水太郎, 異島優, Janos Szebeni, 石田竜弘 :
高投与量Doxebo前処置によるABC現象の抑制に関する検討,
第57回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2018年11月. 酒井真紀, 池田真由美, 今福匡司, 安藤英紀, 清水太郎, 異島優, 丸山徹, 石田竜弘 :
糖尿病患者における血清中サルフェン硫黄と抗酸化能の評価,
第57回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2018年11月. 川口桂乃, 渡辺優希, 清水太郎, 異島優, 石田竜弘 :
辺縁帯B細胞標的化抗原デリバリーシステムによる抗腫瘍免疫応答増強効果,
第57回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2018年11月. 金山忠史, 奥平桂一郎, 大川内健人, 清水太郎, 重永章, 大髙章, 石田竜弘 :
人工HDLの化学的性状と体内動態への影響に関する検討,
第57回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2018年11月. 長船裕輝, 池田真由美, 酒井真紀, 清水太郎, 安藤英紀, 異島優, 石田竜弘 :
生体液に含まれる活性イオウ分子種の検出,
第57回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2018年11月. 中見祥一, 清水太郎, 異島優, 石田竜弘 :
Doxil前処置による養子免疫細胞のがん移行性向上に関する検討,
第57回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2018年11月. 木下遼, 異島優, 渡邊博志, 清水太郎, 石田竜弘, 小田切優樹, 丸山徹 :
新規ナノEPR増強剤であるNO搭載型アルブミンダイマーと高分子抗がん剤の併用による次世代型難治性がん治療法の構築,
第1回超分子薬剤学FGシンポジウム, 2018年9月. 異島優, 木下遼, 池田真由美, 安藤英紀, 清水太郎, 小田切優樹, 丸山徹, 石田竜弘 :
ガス状リガンドと相互作用するヒト血清アルブミンの臨床応用,
第1回超分子薬剤学FGシンポジウム, 2018年9月. 山﨑仁王, 清水太郎, 異島優, 石田竜弘 :
ABC現象回避における末端マレイミドPEG-リン脂質の有用性に関する検討,
第27回DDSカンファランス, 2018年9月. 竹瀬俊輔, 清水太郎, 異島優, 石田竜弘 :
がん化学・免疫併用療法におけるオキサリプラチン封入リポソームの有用性に関する検討,
第27回DDSカンファランス, 2018年9月. 平川尚樹, 木下遼, 異島優, 清水太郎, 丸山徹, 奥平桂一郎, 石田竜弘 :
共有結合型アルブミンナノ粒子をキャリアとしたナノDDS抗がん剤の開発及び有用性評価,
第34回日本DDS学会学術集会, 2018年6月. 川口桂乃, 島崎優奈, 渡辺優希, 清水太郎, 異島優, 石田竜弘 :
脾臓標的化ワクチンによる免疫誘導における辺縁帯B細胞の役割,
第34回日本DDS学会学術集会, 2018年6月. 清水太郎, 吉岡千尋, 粟田瑞月, 川口桂乃, 異島優, 石田竜弘 :
ヒドロキシ末端PEG修飾リポソームを用いた新規脾臓標的化ワクチンの開発に関する検討,
第34回日本DDS学会学術集会, 2018年6月. 木下遼, 異島優, 渡邊博志, 清水太郎, 石田竜弘, 小田切優樹, 丸山徹 :
新規腫瘍DDSキャリアである共有結合型アルブミンナノ粒子の有用性評価,
日本薬剤学会第33年会, 2018年6月. Taro Shimizu :
Development of marginal zone B cell-targeted cancer vaccine,
第6回日中ナノメディシンシンポジウム, May 2018. 長船裕輝, 池田真由美, 酒井真紀, 清水太郎, 異島優, 石田竜弘 :
生物由来健康食品に含まれる活性イオウ分子種の検出,
第71回日本酸化ストレス学会・第18回日本NO学会合同学術集会, 2018年5月. 池田真由美, 清水太郎, 丸山徹, 小田切優樹, 異島優, 石田竜弘 :
ポリスルフィド付加血清アルブミンによるメラニン産生の抑制,
第71回日本酸化ストレス学会・第18回日本NO学会合同学術集会, 2018年5月. 酒井真紀, 池田真由美, 今福匡司, 清水太郎, 丸山徹, 小田切優樹, 異島優, 石田竜弘 :
アルブミン製剤中のサルフェン硫黄含有量の差異と抗酸化能の評価,
第71回日本酸化ストレス学会・第18回日本NO学会合同学術集会, 2018年5月. 田坂菜々美, 池田真由美, 清水太郎, 異島優, 石田竜弘 :
毛髪ケラチンに存在する活性イオウの発見と酸化ストレス応答,
日本薬学会第138年会, 2018年3月. 久保幸代, 清水太郎, 鵜川真実, 藤本麻葉, 松本陽子, 異島優, 石田竜弘 :
自然抗体としてのanti-PEG IgMがDoxilの血中濃度に与える影響,
日本薬学会第138年会, 2018年3月. 清水太郎, 久保幸代, 異島優, 石田竜弘 :
マクロファージによるPEG修飾体のin vitro取り込み量評価によるABC現象の発現予測に関する検討,
日本薬学会第138年会, 2018年3月. 池田真由美, 異島優, 清水太郎, 居原秀, 赤池孝章, 丸山徹, 石田竜弘 :
ポリスルフィド運搬体としてのヒト血清アルブミン,
日本薬学会第138年会, 2018年3月. 竹瀬俊輔, 清水太郎, 石田竜弘 :
The combined effect of liposomal oxaliplatin with cancer vaccine on anticancer therapy,
第46回日本免疫学会学術集会, 2017年12月. 松尾菜々, 池田真由美, 清水太郎, 異島優, 石田竜弘 :
新規抗がん剤としての活性イオウ付加アルブミンの設計,
第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2017年10月. 田坂菜々美, 池田真由美, 清水太郎, 異島優, 石田竜弘 :
毛髪中に存在する活性イオウの発見とその生理的意義,
第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2017年10月. 田神舞帆, 池田愛, 高山拓磨, 異島優, 清水太郎, 石田竜弘 :
抗PD-1抗体の併用はl-OHP liposomeによる抗腫瘍効果の個体差を減少させる,
第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2017年10月. 島崎優奈, 吉岡千尋, 粟田瑞月, 清水太郎, 石田竜弘 :
ペプチド抗原封入リポソーム投与による抗腫瘍免疫の誘導に関する検討,
第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2017年10月. 高田春風, 久保幸代, 松岡里英, 清水太郎, 石田竜弘 :
pDNA搭載PEG修飾カチオニックリポソーム静脈内投与時の抗二本鎖DNA抗体分泌に関する検討,
第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2017年10月. 清水太郎, 久保幸代, 粟田瑞月, 北山由佳, 美馬優, 異島優, 石田竜弘 :
PEG特異的細胞測定法を用いた抗PEG免疫反応の評価,
第26回DDSカンファランス, 2017年9月. 清水太郎, 北山由佳, 異島優, 石田竜弘 :
siRNA搭載PEG修飾リポソームの静脈内投与後に腹腔から分泌されるanti-PEG IgM誘導機構の解明に関する検討,
第33回日本DDS学会学術集会, 2017年7月. 吉岡千尋, 粟田瑞月, 渡辺優希, 清水太郎, 石田竜弘 :
脾臓辺縁帯B細胞標的化能をもつポリマー修飾リポソームを用いた静注型ワクチン開発に関する検討,
第33回日本DDS学会学術集会, 2017年7月. 池田真由美, 異島優, 田坂菜々美, 清水太郎, 渡邊博志, 小田切優樹, 丸山徹, 石田竜弘 :
ヒト血清アルブミンに存在する活性イオウの検出とその機能解明,
第17回日本NO学会学術集会, 2017年5月. 清水太郎, 粟田瑞月, 吉岡千尋, 異島優, 石田竜弘 :
補体活性化能を持つポリマー修飾リポソームによる脾臓辺縁帯B細胞標的化に関する検討,
日本薬剤学会第32年会, 2017年5月. 田坂菜々美, 池田真由美, 清水太郎, 異島優, 石田竜弘 :
毛髪中における活性イオウの検出とその生物活性評価,
日本薬剤学会第32年会, 2017年5月. 異島優, 池田真由美, 清水太郎, 渡邊博志, 小田切優樹, 丸山徹, 石田竜弘 :
活性酸素スカベンジャーとしての血清アルブミンパースルフィド,
日本薬剤学会第32年会, 2017年5月. 池田真由美, 異島優, 田坂菜々美, 清水太郎, 渡邊博志, 小田切優樹, 丸山徹, 石田竜弘 :
活性イオウトラフィックタンパク質としてのヒト血清アルブミンの役割,
日本薬剤学会第32年会, 2017年5月. Elhewan Emam Elsadek Emam Ali Nehal, 清水太郎, 石田竜弘 :
Anti-PEG IgM-mediated accelerated blood clearance against PEG-G-CSF,
日本薬剤学会第32年会, 2017年5月. 山﨑仁王, 異島優, 清水太郎, 石田竜弘 :
PEGリポソームへのアルブミン修飾は，抗PEG抗体の産生を抑制する,
第55回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2016年11月. 中見祥一, 清水太郎, 中村教泰, 石田竜弘 :
PEG修飾有機シリカ粒子に対する免疫応答に関する検討,
第55回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2016年11月. 竹瀬俊輔, 高山拓磨, 西尾美穂, 清水太郎, 石田竜弘 :
抗がん剤封入リポソームとの併用によるがんワクチン効果の増強に関する検討,
第55回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2016年11月. 松本陽子, 藤本麻葉, 清水太郎, 久保幸代, 曾根献文, 森繭代, 足立克之, 長阪一憲, 有本貴英, 織田克利, 川名敬, 石田竜弘, 藤井知行 :
ヒトにおける抗 PEG IgM 抗体の産生と PLD 投与への影響,
第75回日本癌学会学術総会, 2016年10月. 蔵田靖子, 清水太郎, 久保幸代, 石田竜弘, 田端雅弘, 二宮崇, 渡邊洋美, 中西将元, 槇本剛, 秦雄介, 狩野裕久, 西井和也, 木浦勝行, 北村佳久, 千堂年昭 :
血中抗PEG抗体がペグフィルグラスチムの有効性に与える影響に関する探索的検討,
第26回日本医療薬学会年会, 2016年9月. 山﨑仁王, 異島優, 清水太郎, 石田竜弘 :
PEGリポソーム頻回投与時の課題であるABC現象は，アルブミン修飾によって克服可能であるか?,
ナノライフサイエンス・オープンセミナー2016, 2016年9月. 中見祥一, 清水太郎, 中村教泰, 石田竜弘 :
PEG修飾有機シリカ粒子に対するanti-PEG IgM応答に関する検討,
ナノライフサイエンス・オープンセミナー2016, 2016年9月. 竹瀬俊輔, 高山拓磨, 西尾美穂, 清水太郎, 石田竜弘 :
がんワクチンと抗がん剤封入リポソームの併用における投与計画の至適化に関する検討,
ナノライフサイエンス・オープンセミナー2016, 2016年9月. 清水太郎, 渡辺優希, 美馬優, 際田弘志, 石田竜弘 :
脾臓辺縁帯B細胞を標的としたリポソームワクチンの開発,
第25回DDSカンファランス, 2016年9月. 粟田瑞月, 吉岡千尋, 渡辺優希, 清水太郎, 石田竜弘 :
リポソーム修飾剤が脾臓辺縁帯B細胞結合能に与える影響,
第25回DDSカンファランス, 2016年9月. 川添和義, 阿部真治, 清水太郎, 石田竜弘, 大髙章 :
徳島大学発「インタラクティブYAKUGAKUJIN」の育成―新しい視点に立脚した教育の開発と実践―,
第1回日本薬学教育学大会, 2016年8月. 清水太郎, 久保幸代, 藤本麻葉, 松本洋子, 川名敬, 石田竜弘 :
ヒトanti-PEG IgMがDoxilの体内動態に与える影響,
第32回日本DDS学会学術集会, 2016年7月. 粟田瑞月, 吉岡千尋, 渡辺優希, 清水太郎, 石田竜弘 :
脾臓辺縁帯B細胞標的化能をもつポリマー修飾リポソームの探索,
第32回日本DDS学会学術集会, 2016年6月. 北山由佳, 阿部遼, 清水太郎, 石田竜弘 :
siRNA搭載PEG修飾カチオニックリポソーム刺激によるPEG抗体産生に寄与する細胞群の検討,
第32回日本DDS学会学術集会, 2016年6月. 清水太郎, 久保幸代, 石田竜弘 :
ヒトにおける抗PEG抗体保有率の調査,
日本薬剤学会第31年会, 2016年5月. 高山拓磨, 清水太郎, 鵜川真実, 石田竜弘 :
リポソーム化抗がん剤投与が引き起こす腫瘍免疫細胞の影響,
日本薬剤学会第31年会, 2016年5月. 高山拓磨, 清水太郎, 鵜川真美, 石田竜弘 :
Doxil投与による腫瘍内免疫細胞の変動とこの変動による抗腫瘍効果への影響,
日本薬学会第136年会, 2016年3月. 本藤栄里, 美馬優, 清水太郎, 石田竜弘 :
ポリエチレングリコール修飾タンパク製剤Pegasysに対する抗PEG IgM応答,
日本薬学会第136年会, 2016年3月. 吉岡千尋, 粟田瑞月, 渡辺優希, 清水太郎, 石田竜弘 :
PEG修飾リポソームのPEG末端構造ががんワクチン効果に与える影響,
ナノライフサイエンス・オープンセミナー2015, 2016年2月. 久保幸代, 本藤栄里, 阿部遼, 美馬優, 清水太郎, 石田竜弘 :
PEG化製剤に対するanti-PEG IgMの結合性と補体活性化能に関する検討,
ナノライフサイエンス・オープンセミナー2015, 2016年2月. 藤川昂樹, 生駒照, 森戸克弥, 清蔭恵美, 徳田一徳, 清水太郎, 石田竜弘, 德村彰, 田中保 :
ヒト胃由来培養細胞におけるリゾホスファチジン酸誘導性小胞分泌現象の解析,
第88回日本生化学会大会, 2015年12月. 清水太郎, 渡辺優希, 美馬優, 際田弘志, 石田竜弘 :
脾臓辺縁帯B細胞を標的とした新規がんワクチンの開発,
第4回若手研究者シーズ発表会, 2015年11月. 本藤栄里, 美馬優, 清水太郎, 石田竜弘 :
PEG修飾タンパク製剤Pegasysに対する抗PEG免疫反応,
第37回生体膜と薬物の相互作用シンポジウム, 2015年11月. 清水太郎, 高橋孝典, 石田竜弘 :
FTY720併用によるドキシルの細胞内取り込み向上に関する検討,
第37回生体膜と薬物の相互作用シンポジウム, 2015年11月. 吉岡千尋, 粟田瑞月, 渡辺優希, 清水太郎, 石田竜弘 :
ヒドロキシ末端PEG修飾リポソームを用いた静注型ワクチン開発に関する基礎的検討,
第54回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2015年10月. 久保幸代, 本藤栄里, 阿部遼, 美馬優, 清水太郎, 石田竜弘 :
PEG化製剤に対するanti-PEG IgM結合特性に関する検討,
第54回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2015年10月. 渡辺優希, 清水太郎, 石田竜弘 :
PEG修飾リポソーム(PL)繰り返し投与時における脾臓内各種細胞による取り込みに関する検討,
第24回DDSカンファランス, 2015年9月. 本藤栄里, 美馬優, 清水太郎, 石田竜弘 :
ポリエチレングリコール修飾タンパク製剤Pegasys投与によるABC現象発現,
第24回DDSカンファランス, 2015年9月. 田中保, 藤川昂樹, 森戸克弥, 清蔭恵美, 樋田一徳, 清水太郎, 石田竜弘, 德村彰 :
リゾホスファチジン酸が誘導する小胞分泌現象の解析,
第57回日本脂質生化学会, 2015年5月. 渡辺優希, 清水太郎, 石田竜弘 :
静脈内投与PEG修飾リポソームの濾胞への輸送に関与する脾臓細胞の検討,
日本薬剤学会第30年会, 2015年5月. 阿部遼, 清水太郎, 石田竜弘 :
IV 投与PEGリポソームに対するanti-PEG IgM応答への腹腔内免疫細胞の関与,
日本薬剤学会第30年会, 2015年5月. 藤川昂樹, 森戸克弥, 生駒照, 清蔭恵美, 樋田一徳, 清水太郎, 石田竜弘, 德村彰, 田中保 :
ヒト胃由来培養細胞におけるリゾホスファチジン酸誘導性小胞分泌現象の解析,
日本膜学会第37年会, 2015年5月. 高橋孝典, 西尾美穂, 清水太郎, 石田竜弘 :
Doxil®投与によるがんのDoxil®耐性化,
日本薬学会第135年会, 2015年3月. 清水太郎, 西尾美穂, 橋本洋佑, 中瀬博, 際田弘志, 石田竜弘 :
オキサリプラチン封入リポソームの頻回投与が腫瘍免疫系に与える影響,
日本薬学会第135年会, 2015年3月. 清水太郎, 渡辺優希, 美馬優, 石田竜弘, 際田弘志 :
PEG修飾リポソームに対する免疫反応を利用した静脈内投与型がんワクチンの開発に関する研究,
第36回生体膜と薬物の相互作用シンポジウム, 2014年11月. 美馬優, 清水太郎, 際田弘志, 石田竜弘 :
PEG修飾リポソーム膜へのガングリオシド添加による抗PEG免疫応答の抑制効果,
第36回生体膜と薬物の相互作用シンポジウム, 2014年11月. 北山由佳, 美馬優, 川西宗平, 清水太郎, 石田竜弘 :
siRNA搭載PEG修飾カチオニックリポソーム静脈内投与時の抗体産生に寄与する細胞群に関する検討,
第53回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2014年11月. 髙山拓磨, 清水太郎, 西尾美穂, 石田竜弘 :
Doxil®の抗腫瘍効果における免疫細胞の関与に関する検討,
第53回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2014年11月. 粟田瑞月, 美馬優, 川西宗平, 清水太郎, 石田竜弘 :
PEG修飾リポソームのPEG修飾剤末端構造の違いが免疫活性化に与える影響に関する検討,
第53回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2014年11月. 川西宗平, 橋本洋佑, 清水太郎, 際田弘志, 石田竜弘 :
Shotgun分析を用いたPEG修飾リポソーム結合タンパク質の網羅的解析,
第23回DDSカンファランス, 2014年9月. 阿部遼, 清水太郎, 石田竜弘, 際田弘志 :
PEG修飾リポソームの投与経路の違いがanti-PEG IgM分泌に及ぼす影響に関する検討(第2報),
第23回DDSカンファランス, 2014年9月. 髙山拓磨, 清水太郎, 西尾美穂, 石田竜弘 :
Doxil®投与による免疫細胞の変化に関する検討,
ナノライフサイエンス・オープンセミナー2014, 2014年8月. 粟田瑞月, 藤田理紗子, 美馬優, 川西宗平, 清水太郎, 石田竜弘 :
PEG修飾剤末端構造が免疫活性化に与える影響に関する検討,
ナノライフサイエンス・オープンセミナー2014, 2014年8月. 北山由佳, 美馬優, 川西宗平, 清水太郎, 石田竜弘 :
siRNA搭載PEG修飾リポプレックス静脈内投与による抗体産生への脾臓とその他の細胞群の関与に関する検討,
ナノライフサイエンス・オープンセミナー2014, 2014年8月. 清水太郎, 高橋孝典, 石田竜弘, 際田弘志 :
マウス肺癌細胞に対するFTY720とドキシルとの併用効果に関する検討,
第30回日本DDS学会学術集会, 2014年7月. 清水太郎, 渡辺優希, 美馬優, 石田竜弘, 際田弘志 :
脾臓辺縁帯B細胞による抗原封入PEG修飾リポソームの濾胞への輸送現象を利用した抗腫瘍免疫誘導効果,
日本薬剤学会第29年会, 2014年5月. 美馬優, 橋本洋佑, 清水太郎, 石田竜弘, 際田弘志 :
Ganglioside添加がPEG修飾リポソームに対する抗PEG IgM分泌に与える影響,
日本薬学会第134年会, 2014年3月. 清水太郎, 渡辺優希, 美馬優, 橋本洋佑, 石田竜弘, 際田弘志 :
PEG修飾リポソームを用いた脾臓濾胞への抗原送達が抗腫瘍免疫誘導に与える影響,
日本薬学会第134年会, 2014年3月. 渡辺優希, 清水太郎, 石田竜弘, 際田弘志 :
PEG修飾リポソーム前刺激が二回目投与PEG修飾リポソームの脾臓内分布を変化させる,
第52回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2013年10月. 藤田理紗子, 橋本洋佑, 清水太郎, 石田竜弘, 際田弘志 :
PEG修飾剤末端構造が与えるABC現象誘導への影響に関する検討,
第22回DDSカンファランス, 2013年9月. 美馬優, 橋本洋佑, 清水太郎, 石田竜弘, 際田弘志 :
高用量PEG修飾リポソームによる抗PEG IgMの分泌抑制に関する検討,
第22回DDSカンファランス, 2013年9月. 渡辺優希, 清水太郎, 石田竜弘, 際田弘志 :
PEG修飾リポソーム(SL)前刺激により変化する二回目PEG修飾リポソーム(SL)の脾臓内分布の検討,
ナノライフサイエンス・オープンセミナー2013, 2013年9月. 美馬優, 橋本洋佑, 清水太郎, 石田竜弘, 際田弘志 :
高用量PEG修飾リポソームを用いたABC現象の回避,
第29回日本DDS学会学術集会, 2013年7月. 橋本洋佑, 清水太郎, 石田竜弘, 際田弘志 :
siRNA搭載PEG修飾リポプレックス投与時に惹起される抗PEG IgM分泌応答機構の解明,
日本薬剤学会第28年会, 2013年5月. 清水太郎, 渡辺優希, 美馬優, 橋本洋佑, 石田竜弘, 際田弘志 :
脾臓辺縁体B細胞によるPEG修飾リポソームの濾胞への輸送現象を利用した特異的抗体誘導効果,
日本薬剤学会第28年会, 2013年5月. 清水太郎, 石田竜弘, 際田弘志 :
PEG修飾リポソームを用いた濾胞への抗原送達による抗体誘導効果,
第133年会日本薬学会, 2013年3月. 美馬優, 橋本洋佑, 清水太郎, 石田竜弘, 際田弘志 :
PEG修飾タンパクによるABC現象誘導に関する研究,
第133年会日本薬学会, 2013年3月. 井本亜美, 清水太郎, 石田竜弘, 際田弘志 :
ABC現象を引き起こす抗PEG IgM分泌細胞の特定,
第133年会日本薬学会, 2013年3月. 藤田理紗子, 橋本洋佑, 清水太郎, 石田竜弘, 際田弘志 :
ABC現象誘導へのPEG修飾剤末端構造の影響に関する検討,
第133年会日本薬学会, 2013年3月. 盛山裕太, 美馬優, 清水太郎, 石田竜弘, 際田弘志 :
GangliosideのPEG修飾リポソーム膜への挿入がPEGに対する免疫応答に及ぼす影響,
第133年会日本薬学会, 2013年3月. 清水太郎, 橋本洋佑, 石田竜弘, 際田弘志 :
PEG修飾リポソームの濾胞への輸送現象を利用した免疫誘導に関する検討,
創剤フォーラム第18回若手研究会, 2012年11月. 美馬優, 橋本洋佑, 清水太郎, 石田竜弘, 際田弘志 :
血中anti-PEG IgMがPEG修飾タンパクのクリアランスに与える影響,
創剤フォーラム第18回若手研究会, 2012年11月. 井本亜美, 清水太郎, 石田竜弘, 際田弘志 :
抗PEG-IgMを分泌する脾臓B細胞に関する検討,
創剤フォーラム第18回若手研究会, 2012年11月. 藤田理紗子, 清水太郎, 石田竜弘, 際田弘志 :
PEG修飾剤末端構造が与えるanti-PEG IgM分泌誘導への影響に関する検討,
創剤フォーラム第18回若手研究会, 2012年11月. 橋本洋佑, 藤田理紗子, 西尾美穂, 清水太郎, 石田竜弘, 際田弘志 :
血中anti-PEG IgM濃度とABC現象発現強度の定量的関係の評価,
創剤フォーラム第18回若手研究会, 2012年11月. 盛山裕太, 美馬優, 清水太郎, 石田竜弘, 際田弘志 :
GangliosideのPEG修飾リポソーム膜への挿入はABC現象を抑制する,
創剤フォーラム第18回若手研究会, 2012年11月. 盛山裕太, 美馬優, 清水太郎, 石田竜弘, 際田弘志 :
ガングリオシドのPEG 修飾リポソーム膜への挿入はPEG に対する自然免疫活性化を抑制する,
第51回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2012年11月. 美馬優, 橋本洋佑, 清水太郎, 石田竜弘, 際田弘志 :
血中anti-PEG IgM によるPEG 修飾タンパクのクリアランスに関する検討,
第51回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2012年11月. 川西宗平, 清水太郎, 橋本洋佑, 石田竜弘, 際田弘志 :
ショットガン分析によるPEG 修飾リポソームに結合するタンパクの解析,
第51回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2012年11月. 阿部遼, 清水太郎, 石田竜弘, 際田弘志 :
PEG修飾リポソームの投与経路の違いがanti-PEG IgM分泌に及ぼす影響に関する検討,
第51回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2012年11月. 阿部遼, 清水太郎, 美馬優, 石田竜弘, 際田弘志 :
PEG修飾リポソームの投与経路の違いが及ぼすanti-PEG IgM分泌への影響,
ナノライフサイエンス・オープンセミナー2012, 2012年8月. 川西宗平, 清水太郎, 橋本洋佑, 石田竜弘, 際田弘志 :
ショットガン分析を用いたPEG修飾リポソームに結合する血漿タンパクの解析,
ナノライフサイエンス・オープンセミナー2012, 2012年8月. 美馬優, 橋本洋佑, 清水太郎, 市原理子, 石田竜弘, 際田弘志 :
血中anti-PEGIgMがPEG修飾タンパクのクリアランスに与える影響に関する検討,
ナノライフサイエンス・オープンセミナー2012, 2012年8月. 美馬優, 橋本洋佑, 清水太郎, 市原理子, 石田竜弘, 際田弘志 :
遊離型PEG静脈内投与による抗PEGIgM応答に関する研究,
第28回日本DDS学会学術集会, 2012年7月. 井本亜美, 市原理子, 清水太郎, 石田竜弘, 際田弘志 :
養子細胞移入法を用いた抗PEG-IgM分泌細胞に関する検討,
第28回日本DDS学会学術集会, 2012年7月. 清水太郎, 井本亜美, 市原理子, 石田竜弘, 際田弘志 :
脾臓辺縁帯B細胞によるPEG修飾リポソームの輸送機構に関する検討,
第28回日本DDS学会学術集会, 2012年7月. 市原理子, 清水太郎, 井本亜美, 石田竜弘, 際田弘志 :
PEG修飾リポソーム投与により誘導される抗PEG IgM分泌細胞は脾臓辺縁帯B細胞である,
第28回日本DDS学会学術集会, 2012年7月. 市原理子, 清水太郎, 井本亜美, 石田竜弘, 際田弘志 :
脾臓辺縁帯B細胞がABC現象における抗PEG IgM分泌細胞である,
日本薬剤学会第27年会, 2012年5月. 橋本洋佑, 清水太郎, 石田竜弘, 際田弘志 :
PEG修飾リポソームの体内動態変動因子anti-PEG IgMの定量評価系の構築,
日本薬剤学会第27年会, 2012年5月. 清水太郎, 石田竜弘, 際田弘志 :
脾臓辺縁帯B細胞によるPEG修飾リポソーム輸送現象を利用した免疫誘導の試み,
日本薬剤学会第27年会, 2012年5月. 清水太郎, 石田竜弘, 際田弘志 :
PEG修飾リポソームと脾臓辺縁帯B 細胞との相互作用に関する検討,
日本薬学会第132年会, 2012年3月. 橋口優紀, 清水太郎, 市原理子, 石田竜弘, 際田弘志 :
PEG修飾リポソームに対する抗PEG-IgM分泌における脾臓辺縁帯B細胞の関与について,
第26回日本DDS学会, 2010年6月. 橋口優紀, 清水太郎, 石田竜弘, 際田弘志 :
ABC現象における抗PEG-IgM分泌とMZ-B細胞の活性化について,
日本薬学会第130年会, 2010年3月. 橋口優紀, 清水太郎, 石田竜弘, 際田弘志 :
ABC現象の要因とされる抗PEG-IgMの分泌と脾臓辺縁帯B細胞の活性化の関係について,
第48回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2009年11月. 田上辰秋, 中村和也, 清水太郎, 山﨑尚志, 石田竜弘, 際田弘志 :
ポリエチレングリコール(PEG)を利用した核酸送達システムにおいてプラスミドDNA配列内のCpG除去が抗PEG抗体産生に与える影響,
第25回日本DDS学会, 2009年7月. 橋口優紀, 清水太郎, 石田竜弘, 際田弘志 :
PEG修飾リポソームによる抗PEG-IgMの誘導と脾臓辺緑体B細胞の活性化の関係に関する検討,
第25回日本DDS学会, 2009年7月. 清水太郎, 賀登浩章, 石田竜弘, 際田弘志 :
PEG修飾リポソーム投与による脾臓辺縁帯B細胞の活性化,
日本薬学会第129年会, 2009年3月. 田上辰秋, 中村和也, 清水太郎, 山﨑尚志, 石田竜弘, 際田弘志 :
CpG-free pDNAを使用したPEG修飾リポプレックス投与がABC現象に与える影響,
日本薬学会第129年会, 2009年3月. 阿部正義, 清水太郎, 石田竜弘, 際田弘志 :
PEG化リポソーム投与による抗PEG-lgMの発想と精製法の研究,
第47回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2008年11月. 清水太郎, 石田竜弘, 際田弘志 :
ナノキャリアの生体反応性とバイオ応用に関する研究,
日本薬物動態学会第23回年会, 2008年11月. 清水太郎, 石田竜弘, 際田弘志 :
投与量逆依存的なABC現象発現と脾臓B細胞活性化との相関に関する検討,
第17回DDSカンファランス, 2008年9月. 田上辰秋, 中村和也, 清水太郎, 石田竜弘, 際田弘志 :
PEG修飾siRNA-lipoplex投与時におけるanti-PEG IgM分泌に対するsiRNAの影響,
第30回生体膜と薬物の相互作用シンポジウム, 2008年8月. 清水太郎, 名和田幸介, 吉岡靖雄, 石田竜弘, 中川晋作, 際田弘志 :
PEG修飾タンパクおよびPEG修飾アデノウイルス投与による抗PEG IgM誘導に関する検討,
第24回日本DDS学会, 2008年6月. 清水太郎, 名和田幸介, 成毛一恵, 石田竜弘, 際田弘志 :
ポリエチレングリコール修飾タンパク投与による抗PEG IgM誘導に関する研究,
日本薬剤学会第23年会, 2008年5月. 田上辰秋, 中村和也, 清水太郎, 石田竜弘, 際田弘志 :
PEG修飾siRNAリポプレックス投与時におけるanti-PEG IgM分泌に関する検討,
日本薬剤学会第23年会, 2008年5月.

研究会・報告書: 研究者総覧に該当データはありませんでした。

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補助金・競争的資金: 脳腫瘍移行性の高い免疫細胞の探索と免疫細胞への薬物搭載による脳腫瘍治療法の開発 (研究課題/領域番号: 22K19897 )
物質共生のための人工物質とＢ細胞の相互作用解析と免疫応答評価 (研究課題/領域番号: 21H05526 )
高活性抗体の誘導を実現する抗原発現エキソソームの脾臓免疫技術基盤の構築 (研究課題/領域番号: 21H02644 )
動脈硬化治療法の確立に向けたHDLリモデリングの分子基盤の解明とその応用 (研究課題/領域番号: 20H04124 )
PEG修飾タンパクによるアナフィラキシー誘導機構の解明とその制御に関する研究 (研究課題/領域番号: 19KK0279 )
全身性エリテマトーデスにおけるマイクロパーティクルの生理学的意義の解明 (研究課題/領域番号: 19K07194 )
イオン液体を利用した革新的経皮デリバリー技術の開発 (研究課題/領域番号: 18K19925 )
がん移行性免疫細胞を用いた薬物デリバリー法の開発 (研究課題/領域番号: 17K15505 )
TI抗原としてのPEG化ナノキャリアを用いた静注型ネオワクチンアジュバントの開発 (研究課題/領域番号: 16K15108 )
補体活性化ポリマー修飾リポソームを用いた新規がんワクチン開発に関する研究 (研究課題/領域番号: 15K18921 )
核酸医薬デリバリーにおける自然免疫活性化機構の解明とその制御に関する研究 (研究課題/領域番号: 15H04639 )
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2023年3月22日更新

専門分野・研究分野: ライフサイエンス (Life sciences) [医療薬学 (Clinical pharmacy)]
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受賞: 2021年5月, 日本薬剤学会奨励賞 (日本薬剤学会)
2021年12月, 徳島大学若手研究者学長表彰 (徳島大学)
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Jグローバル最終確認日: 2023/3/18 01:27
氏名（漢字）: 清水太郎
氏名（フリガナ）: シミズタロウ
氏名（英字）: Shimizu Taro
所属機関: 徳島大学特任助教

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researchmap最終確認日: 2023/3/19 01:36
氏名（漢字）: 清水太郎
氏名（フリガナ）: シミズタロウ
氏名（英字）: Shimizu Taro
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研究者番号: 30749388

所属（現在）: 2022/4/1 : 徳島大学, 大学院医歯薬学研究部(薬学域), 特任助教

所属（過去の研究課題 情報に基づく）*注記: 2018/4/1 – 2022/4/1 : 徳島大学, 大学院医歯薬学研究部(薬学域), 特任助教
2016/4/1 – 2017/4/1 : 徳島大学, 大学院医歯薬学研究部(薬学系), 特任助教
2015/4/1 : 徳島大学, 大学院医歯薬学研究部, 特任助教

審査区分/研究分野

研究代表者

生物系 / 医歯薬学 / 薬学 / 医療系薬学
小区分47060:医療薬学関連
学術変革領域研究区分(Ⅱ)
中区分90:人間医工学およびその関連分野

研究代表者以外

生物系 / 医歯薬学 / 薬学 / 物理系薬学
中区分90:人間医工学およびその関連分野
小区分59040:栄養学および健康科学関連
小区分47060:医療薬学関連

キーワード

研究代表者

ワクチン / 抗原送達 / 補体 / リポソーム / 辺縁帯B細胞 / 癌 / 免疫学 / がん / 養子移入療法 / 薬物送達 / .細胞送達 / がん免疫療法 / 細胞送達 / 癌免疫療法 / がん化学療法 / 免疫細胞 / 外部刺激 / 全身性エリテマトーデス / 自己免疫疾患 / マイクロパーティクル / 自己抗原 / プロテオーム解析 / 脾臓免疫細胞 / SLE / 自己抗体 / 免疫複合体 / 物質共生 / B細胞 / 人工高分子 / 核酸 / 寛容 / ナノ粒子 / 抗体 / 脳腫瘍 / 遊走

研究代表者以外

核酸 / 免疫 / Anti-PEG IgM / リポソーム / DDS / 核酸デリバリー / 自然免疫活性化 / ワクチン / アジュバント / ナノキャリア / イオン液体 / 経皮吸収 / ペプチド / PEG修飾製剤 / 抗PEG抗体 / infusion reaction / CARPA / 高密度リポ蛋白質 / 動脈硬化 / 高密度リポタンパク質 / アポリポタンパク質 / アポリポタンタンパク質 / 脾臓免疫 / 抗体誘導 / エキソソーム / 膜タンパク / 抗血清

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2022年2月21日

B細胞を標的とした新規ワクチンの開発

清水太郎石田竜弘異島優安藤英紀

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清水 太郎

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