Development of super-selective cancer therapy by utilizing vitamin C-activatable oxidized polymeric micelles

• Project/Area Number: 15K12534
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Kawasaki Institute of Industrial Promotion Innovation Center of NanoMedicine
• Principal Investigator: Mochida Yuki 公益財団法人川崎市産業振興財団(ナノ医療イノベーションセンター), 川崎市産業振興財団, 主任研究員 (60739134)
• Co-Investigator(Kenkyū-buntansha): Cabral Horacio 東京大学, 大学院工学系研究科(工学部), 准教授 (10533911)
• Co-Investigator(Renkei-kenkyūsha): KATAOKA Kazunori 公益財団法人川崎市産業振興財団, ナノ医療イノベーションセンター, 主幹研究員 (00130245)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ドラッグデリバリーシステム / 高分子ミセル / がんの標的治療 / 金属錯体 / 酸化還元反応 / ビタミンC / 白金制がん剤 / 化学療法 / がん治療

Outline of Final Research Achievements

In this study, we developed novel oxidized polymeric micelles with low side effect and high anticancer efficacy by oxidizing polymeric micelles incorporating platinum anticancer drugs. These oxidized polymeric micelles showed prolonged blood circulation and increased drug accumulation in the tumor tissues, which led to significant anticancer efficacy against colon cancer models, while minimizing the distribution of the anticancer drugs to the healthy tissues. Moreover, stronger anticancer efficacy was observed when the oxidized polymeric micelles were given in combination with parenteral vitamin C.

Research Products

• [Journal Article] Block copolymer-boron cluster conjugate for effective boron neutron capture therapy of solid tumors. (2017)
  • Author(s): P. Mi, H. Yanagie, N. Dewi, H.-C. Yen, X. Liu, M. Suzuki, Y. Sakurai, K. Ono, H. Takahashi, H. Cabral, K. Kataoka,
  • Journal Title: J. Control. Release Volume: 254 Pages: 1-9
  • DOI: 10.1016/j.jconrel.2017.03.036
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Polymeric micelles for targeted tumor therapy of platinum anticancer drugs (2017)
  • Author(s): Y. Mochida, H. Cabral, K. Kataoka
  • Journal Title: Expert Opin. Drug Deliv. Volume: -
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Enhanced Efficacy against Cervical Carcinomas through Polymeric Micelles Physically Incorporating the Proteasome Inhibitor MG132. (2016)
  • Author(s): Matsumoto Y, Miyamoto Y, Cabral H, Matsumoto Y, Nagasaka K, Nakagawa S, Yano T, Maeda D, Oda K, Kawana K, Nishiyama N, Kataoka K, Fujii T
  • Journal Title: Cancer Sci Volume: in press Issue: 6 Pages: 773-781
  • DOI: 10.1111/cas.12926
  • NAID: 120007089072
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Nanomedicines eradicating cancer stem-like cells in vivo by pH-triggered intracellular cooperative action of loaded drugs. (2016)
  • Author(s): H. Kinoh, Y. Miura, T. Chida, X. Liu, K. Mizuno, S. Fukushima, Y. Morodomi, N. Nishiyama, H. Cabral, K. Kataoka
  • Journal Title: ACS Nano Volume: 10 Issue: 6 Pages: 5643-5655
  • DOI: 10.1021/acsnano.6b00900
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Lipid- and polyion complex-based micelles as agonist platforms for TNFR superfamily receptors (2016)
  • Author(s): R. N. Gilbreth, S. Novarra, L. Wetzel, S. Florinas, H. Cabral, K. Kataoka, J. RiosDoria, R. J. Christie, M. Baca
  • Journal Title: J. Control. Release Volume: 230 Pages: 104-114
  • DOI: 10.1016/j.jconrel.2016.05.041
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A pH-activatable nanoparticle with signal-amplification capabilities for non-invasive imaging of tumour malignancy. (2016)
  • Author(s): P. Mi, D. Kokuryo, H. Cabral, H. Wu, Y. Terada, T. Saga, I. Aoki, N. Nishiyama, K. Kataoka,
  • Journal Title: Nat. Nanotechnol. Volume: 11 Issue: 8 Pages: 724-730
  • DOI: 10.1038/nnano.2016.72
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Vascular bursts enhance permeability of tumour blood vessels and improve nanoparticle delivery (2016)
  • Author(s): Yu Matsumoto, Joseph W. Nichols, Kazuko Toh, Takahiro Nomoto, Horacio Cabral, Yutaka Miura, R. James Christie, Naoki Yamada, Tadayoshi Ogura, Mitsunobu R. Kano, Yasuhiro Matsumura, Nobuhiro Nishiyama, Tatsuya Yamasoba, You Han Bae, Kazunori Kataoka
  • Journal Title: Nature Nanotechnology Volume: - Issue: 6 Pages: 533-538
  • DOI: 10.1038/nnano.2015.342
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Hydroxychloroquine-conjugated gold nanoparticles for improved siRNA activity (2016)
  • Author(s): Federico Perche, Yu Yi, Louise Hespel, Peng Mi, Anjaneyulu Dirisala, Horacio Cabral, Kanjiro Miyata, Kazunori Kataoka
  • Journal Title: Biomaterials Volume: 90 Pages: 62-71
  • DOI: 10.1016/j.biomaterials.2016.02.027
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Eradication of CD44-variant positive population in head and neck tumors through controlled intracellular navigation of cisplatin-loaded nanomedicines (2016)
  • Author(s): Ming Wang, Yutaka Miura, Kenji Tsuchihashi, Kazuki Miyano, Osamu Nagano, Momoko Yoshikawa, Ami Tanabe, Jun Makino, Yuki Mochida, Nobuhiro Nishiyama, Hideyuki Saya, Horacio Cabral, Kazunori Kataoka
  • Journal Title: Journal of Controlled Release Volume: 230 Pages: 26-33
  • DOI: 10.1016/j.jconrel.2016.03.038
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A Nanoparticle platform to evaluate bioconjugation and receptor-mediated cell uptake using crosslinked polyion complex micelles bearing antibody fragments (2016)
  • Author(s): Stelios Florinas, Marc Liu, Ryan Fleming, Lilian Van Vlerken-Ysla, Joanne Ayriss, Ryan Gilbreth, Nazzareno Dimasi, Changshou Gao, Herren Wu, Ze-Qi Xu, Shanoyi Chen, Anjaneyulu Dirisala, Kazunori Kataoka, Horacio Cabral, R. James Christie
  • Journal Title: Biomacromolecules Volume: 17 Issue: 5 Pages: 1818-1833
  • DOI: 10.1021/acs.biomac.6b00239
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] In vivo evaluation of neutron capture therapy effectivity using calcium phosphate-based nanoparticles as Gd-DTPA delivery agent (2016)
  • Author(s): Novriana Dewi, Peng Mi, Hironobu Yanagie, Yuriko Sakurai, Yasuyuki Morishita, Masashi Yanagawa, Takayuki Nakagawa, Atsuko Shinohara, Takehisa Matsukawa, Kazuhito Yokoyama, Horacio Cabral, Minoru Suzuki, Yoshinori Sakurai, Hiroki Tanaka, Koji Ono, Nobuhiro Nishiyama, Kazunori Kataoka, Hiroyuki Takahashi
  • Journal Title: Journal of Cancer Research and Clinical Oncology Volume: 142 Issue: 4 Pages: 767-775
  • DOI: 10.1007/s00432-015-2085-0
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Intracellular Delivery of Charge-Converted Monoclonal Antibodies by Combinatorial Design of Block/Homo Polyion Complex Micelles (2016)
  • Author(s): Ahram Kim, Yutaka Miura, Takehiko Ishii, Omer F. Mutaf, Nobuhiro Nishiyama, Horacio Cabral, Kazunori Kataoka
  • Journal Title: Biomacromolecules Volume: 17 Issue: 2 Pages: 446-453
  • DOI: 10.1021/acs.biomac.5b01335
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] cRGD-installed polymeric micelles loading platinum anticancer drugs enable cooperative treatment against lymph node metastasis (2016)
  • Author(s): Jun Makino, Horacio Cabral, Yutaka Miura, Yu Matsumoto, Ming Wang, Hiroaki Kinoh, Yuki Mochida, Nobuhiro Nishiyama, Kazunori Kataoka
  • Journal Title: Journal of Controlled Release Volume: 220 PartB Pages: 783-791
  • DOI: 10.1016/j.jconrel.2015.10.017
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Polymeric Micelle Platform for Multimodal Tomographic Imaging to Detect Scirrhous Gastric Cancer (2015)
  • Author(s): Yutaka Miura, Atsushi B. Tsuji, Aya Sugyo, Hitomi Sudo, Ichio Aoki, Masayuki Inubushi, Masakazu Yashiro, Kosei Hirakawa, Horacio Cabral, Nobuhiro Nishiyama, Tsuneo Saga, Kazunori Kataoka
  • Journal Title: ACS Biomaterials Science & Engineering Volume: 1 Issue: 11 Pages: 1067-1076
  • DOI: 10.1021/acsbiomaterials.5b00142
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Overcoming biological barriers through rational design of polymeric micelles incorporating anticancer drugs (2017)
  • Author(s): Yuki Mochida, Horacio Cabral, Hhiroaki Kinoh, Sabina Quader, Yutaka Miura, Nobuhiro Nishiyama, Kazunori Kataoka
  • Organizer: 11th Annual Symposium on Nanobiotechnology 2017
  • Place of Presentation: Kawasaki City Industrial Promotion Hall, Kawasaki, Kanagawa
  • Year and Date: 2017-02-27
  • Int'l Joint Research / Invited
• [Presentation] Assembly of α-helical polymer chains plays a key role in tumor-targeting performance of platinum-loaded polymeric micelles (2016)
  • Author(s): Y. Mochida, H. Cabral, Y. Miura, K. Osada, N. Nishiyama, K. Kataoka
  • Organizer: 3rd Internatioal Conference on Biomaterials Science in Tokyo(ICBS2016)
  • Place of Presentation: Ito Hall located at The University of Tokyo, Tokyo, Japan
  • Year and Date: 2016-11-28
  • Int'l Joint Research
• [Presentation] 環状RGDペプチドを修飾した白金制がん剤内包高分子ミセルを用いたリンパ節転移／治療抵抗性がんの治療 (2016)
  • Author(s): 持田祐希、H. Cabral、牧野惇、三浦裕、M. Wang、西山伸宏、片岡一則
  • Organizer: 第65回高分子討論会
  • Place of Presentation: 神奈川大学横浜キャンパス、横浜市、神奈川県
  • Year and Date: 2016-09-14
• [Presentation] 環状RGDペプチドを修飾した白金制がん剤内包ミセルのがん幹細胞治療への応用 (2016)
  • Author(s): 持田祐希、M. Wang、H. Cabral、三浦裕、西山伸宏、片岡一則
  • Organizer: 第65回高分子学会年次大会
  • Place of Presentation: 神戸国際会議場・展示場、神戸市、兵庫県
  • Year and Date: 2016-05-25
• [Presentation] Highly ordered core structure enhances drug delivery performance of polymeric micelles incorporating platinum anticencer agents (2016)
  • Author(s): Y. Mochida, H. Cabral, Y. Miura, A. Francesco, K. Osada, N. Nishiyama, K. Kataoka
  • Organizer: 10th World Biomaterials Congress
  • Place of Presentation: Montreal Convention Center, Montreal, Canada
  • Year and Date: 2016-05-17
  • Int'l Joint Research
• [Presentation] Secondary Structures in the Core of Platinum-Loaded Polymeric Micelles Improve Tumor-Targeted Drug Delivery (2016)
  • Author(s): Yuki Mochida, Horacio Cabral, Yutaka Miura, Albertini Francesco, Kensuke Osada, Nobuhiro Nishiyama, Kazunori Kataoka
  • Organizer: 2016 International Symposium on Nanobiotechnology
  • Place of Presentation: University of California, Los Angeles
  • Year and Date: 2016-02-03
  • Int'l Joint Research
• [Presentation] Higher-Order Structure of Poly(glutamic acid) Enhances Drug Delivery Performance of Anticancer Platinum-Loaded Polymeric Micelles (2015)
  • Author(s): Yuki Mochida, Horacio Cabral, Yutaka Miura, Albertini Francesco, Kensuke Osada, Nobuhiro Nishiyama, Kazunori Kataoka
  • Organizer: IUPAC 11th International Conference on Advanced Polymers via Macromolecular Engineering
  • Place of Presentation: Pacifico Yokohama
  • Year and Date: 2015-10-18
  • Int'l Joint Research
• [Presentation] 白金制がん剤を内包する高分子ミセルの安定性及び機能を決定する内核高次構造 (2015)
  • Author(s): 持田祐希, Horacio Cabral, 三浦裕, Francesco Albertini, 長田健介, 西山伸宏, 片岡一則
  • Organizer: 第64回高分子討論会
  • Place of Presentation: 東北大学川内キャンパス
  • Year and Date: 2015-09-15
• [Presentation] 環状RGDペプチドを搭載した白金錯体制がん剤内包ミセルの がん幹細胞治療への展開 (2015)
  • Author(s): ○持田祐希, Ming Wang, 三浦裕, Horacio Cabral, 西山伸宏, 片岡一則
  • Organizer: 第64回高分子学会年次大会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2015-05-27
• [Patent(Industrial Property Rights)] 金属とブロック共重合体との錯体を含むミセルを安定化させる方法および安定化されたミセル、並びにミセルからの金属の放出制御法 (2016)
  • Inventor(s): 持田祐希、片岡一則、カブラル オラシオ
  • Industrial Property Rights Holder: 持田祐希、片岡一則、カブラル オラシオ
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-08-26