Molecular Mechanisms in extravasation of nanoDDS

• Project/Area Number: 23790433
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Okayama University (2012-2013); The University of Tokyo (2011)
• Principal Investigator: KANO Mitsunobu 岡山大学, 医歯(薬)学総合研究科, 教授 (80447383)
• Project Period (FY): 2011-04-28 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 腫瘍血管 / ナノDDS / 新生血管 / 血管透過性 / ナノ薬剤 / ナノ粒子 / 血管内皮細胞 / 血管壁細胞 / ナノテクノロジー

Outline of Final Research Achievements

We have shown that characteristics of tumor vasculature can determine the intractability of tumors, and that manipulation of the vasculature characteristics can improve the efficacy of nanoDDS in the animal models of pancreatic and gastric cancers. In this study we focused on a protein, known to be expressed in neovasculature and stabilizing endothelial-mural cell attachment. The protein was suggested to play an important role in the mechanism of extravasation of nanoDDS from tumor vasculature.

Research Products

• [Journal Article] Targeted gene delivery by polyplex micelles with crowded PEG palisade and cRGD moiety for systemic treatment of pancreatic tumors (2014)
  • Author(s): Z. Ge, Q. Chen, K. Osada, X. Liu, T. A. Tockary, S. Uchida, A. Dirisala, T. Ishii, T. Nomoto, K. Toh, Y. Matsumoto, M. Oba, M. R. Kano, K. Itaka, K. Kataoka
  • Journal Title: Biomaterials Volume: 35 Issue: 10 Pages: 3416-3426
  • DOI: 10.1016/j.biomaterials.2013.12.086
  • Peer Reviewed
• [Journal Article] Nanotechnology and tumor microcirculation. (2013)
  • Author(s): Kano MR.
  • Journal Title: Adv Drug Deliv Rev. Volume: 印刷中 Pages: 2-11
  • DOI: 10.1016/j.addr.2013.08.010
  • Peer Reviewed
• [Journal Article] Targeted therapy of spontaneous murine pancreatic tumors by polymeric micelles prolongs survival and prevents peritoneal metastasis (2013)
  • Author(s): H. Cabral, N. Nishiyama, et al.
  • Journal Title: Proc. Natl. Acad. Sci. USA. Volume: 110 Issue: 28 Pages: 11397-11402
  • DOI: 10.1073/pnas.1301348110
  • Peer Reviewed
• [Journal Article] Pericyte-coverage of human tumor vasculature and nanoparticle permeability. (2012)
  • Author(s): Zhang L, Nishihara H, Kano MR.
  • Journal Title: Biol Pharm Bull. Volume: 35 Pages: 761-766
  • Peer Reviewed
• [Journal Article] Polymeric micelles incorporating (1,2-diaminocyclohexane)platinum (II) suppress the growth of orthotopic scirrhous gastric tumors and their lymph node metastasis (2012)
  • Author(s): M. Rafi
  • Journal Title: J. Control. Release Volume: 159 Issue: 2 Pages: 189-196
  • DOI: 10.1016/j.jconrel.2012.01.038
  • Peer Reviewed
• [Journal Article] Homo-catiomer integration into PEGylated polyplex micelle from block-catiomer for systemic antiangiogenic gene therapy for fibrotic pancreatic tumors (2012)
  • Author(s): Q.Chen, K.Osada, T.Ishii, M.Oba, S.Uchida, T.A.Tockary, T.Endo, Z.Ge, H.Kinoh, M.R.Kano, K.Itaka, K.Kataoka
  • Journal Title: Biomaterials Volume: (in press) Issue: 18 Pages: 4722-4730
  • DOI: 10.1016/j.biomaterials.2012.03.017
  • Peer Reviewed
• [Journal Article] NC-6301, a polymeric micelle rationally optimized for effective release of docetaxel, is potent but is less toxic than native docetaxel in vivo (2012)
  • Author(s): Harada M, Iwata C, Saito H, Ishii K, Hayashi T, Yashiro M,, Hirakawa K, Miyazono K, Kato Y, Kano MR
  • Journal Title: Int J Nanomedicine Volume: 7 Pages: 2713-27
  • DOI: 10.2147/ijn.s31247
  • Peer Reviewed
• [Journal Article] Pericyte-coverage of human tumor vasculature and nanoparticle permeability (2012)
  • Author(s): Liuzhe Zhang, Hiroshi Nishihara, Mitsunobu R Kano
  • Journal Title: Biol. Pharm. Bull. Volume: （印刷中）掲載確定
  • Peer Reviewed
• [Presentation] Use of nanoparticle to analyze vasculature in diseases (2013)
  • Author(s): Kano MR
  • Organizer: 国際膵臓フォーラム
  • Place of Presentation: 仙台
  • Invited
• [Presentation] Use of nanoparticle to analyze vasculature in diseases (2013)
  • Author(s): Kano MR
  • Organizer: The 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC’13)
  • Place of Presentation: 大阪
  • Invited
• [Presentation] Use of nanoparticle to analyze vasculature in diseases (2013)
  • Author(s): 狩野 光伸
  • Organizer: 第90会日本生理学会大会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Use of nanoparticle to analyze vasculature in diseases (2012)
  • Author(s): Mitsunobu Kano
  • Organizer: IEEE nanomed 2012
  • Place of Presentation: タイ王国バンコク
  • Invited
• [Presentation] Use of nanoparticle to analyze vasculature in intractable tumors
  • Author(s): Mitsunobu R Kano
  • Organizer: The 9th Japan-Korea Joint Symposium on Vascular Biology
  • Place of Presentation: 大韓民国 釜山
  • Invited
• [Remarks] 岡山大学大学院医歯薬学総合研究科 医薬品臨床評価学 ホームページ
  • URL: http://www.pharm.okayama-u.ac.jp/lab/ph_biomed/