Development of Novel Therapeutic Angiogenesis Method by Combination of Nanotechnology and siRNA Targeting PHD2

2011 Fiscal Year Final Research Report

• Project/Area Number: 21659299
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: General surgery
• Research Institution: The University of Tokyo
• Principal Investigator: NISHIYAMA Nobuhiro 東京大学, 大学院・医学系研究科, 准教授 (10372385)
• Co-Investigator(Kenkyū-buntansha): ITAKA Keiji 東京大学, 大学院・医学系研究科, 特任准教授 (60292926)
• Project Period (FY): 2009 – 2011
• Keywords: ドラッグデリバリー / siRNA / 遺伝子治療 / 虚血性疾患 / 血管再生

Research Abstract

To establish the effective strategy for therapeutic angiogenesis of ischemic diseases, in this project, we revealed the efficacy of siRNA-mediated knockdown of PHD2, which lead to enhanced expression of angiogenic factors regulated by HIF-1α, in a mouse ischemic limb model. For this purpose, we also developed polymeric nanocarriers for in vivo delivery of plasmid DNA and siRNA.

Research Products

• [Journal Article] Rational design of smart supramolecular assemblies for gene delivery : Chemical challenges in the creation of artificial viruses (2012)
  • Author(s): K. Miyata, N. Nishiyama, K. Kataoka
  • Journal Title: Chem. Soc. Rev Volume: 41(7) Pages: 2562-2574
  • DOI: DOI:10.1039/C1CS15258K
  • Peer Reviewed
• [Journal Article] Enhanced stability and gene silencing ability of siRNA-loaded polyion complexes formulated from polyaspartamide derivatives with a repetitive array of amino groups in the side chain (2012)
  • Author(s): T. Suma, K. Miyata, T. Ishii, S. Uchida, H. Uchida, K. Itaka, N. Nishiyama, K. Kataoka
  • Journal Title: Biomaterials Volume: 33(9) Pages: 2770-2779
  • DOI: DOI:10.1016/j.biomaterials.2011.12.022
  • Peer Reviewed
• [Journal Article] Gene transfer using micellar nanovectors inhibits choroidal neovascularization in vivo (2011)
  • Author(s): A. Iriyama, M. Oba, T. Ishii, N. Nishiyama, K. Kataoka, Y. Tamaki, Y. Yanagi
  • Journal Title: PLoS One Volume: 6(12) Pages: e28560
  • DOI: DOI:10.1371/journal.pone.0028560
  • Peer Reviewed
• [Journal Article] Gene transfer using micellar nanovectors inhibits corneal neovascularization in vivo (2011)
  • Author(s): A. Iriyama, T. Usui, Y. Yanagi, S. Amano, M. Oba, K. Miyata, N. Nishiyama, K. Kataoka
  • Journal Title: Cornea Volume: 30(12) Pages: 1423-1427
  • DOI: DOI:10.1097/ICO.0b013e318206c893
  • Peer Reviewed
• [Journal Article] PEG-detachable cationic polyaspartamide detivatives bearing stearoyl moieties for systemic siRNA delivery toward subcutaneous BxPC3 pancreatic tumor (2011)
  • Author(s): H.-J. Kim, M. Oba, F. Pittella, T. Nomoto, H. Cabral, Y. Matsumoto, K. Miyata, N. Nishiyama, K. Kataoka
  • Journal Title: J. Drug Target Volume: 20(1) Pages: 33-42
  • DOI: DOI:10.3109/1061186X.2011.632010
  • Peer Reviewed
• [Journal Article] Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size (2011)
  • Author(s): H. Cabral, Y. Matsumoto, K. Mizuno, Q. Chen, M. Murakami, M. Kimura, Y. Terada, M. R. Kano, K. Miyazono, M. Uesaka, N. Nishiyama, K. Kataoka
  • Journal Title: Nature Nanotech Volume: 6(12) Pages: 815-823
  • DOI: DOI:10.1038/nnano.2011.166
  • Peer Reviewed
• [Journal Article] Effect of integrin targeting and PEG shielding on polyplex micelle internalization studied by live-cell imaging (2011)
  • Author(s): F. M. Mickler, Y. Vachutinsky, M. Oba, K. Miyata, N. Nishiyama, K. Kataoka, C. Brachle, N. Ruthardt
  • Journal Title: J. Control. Release Volume: 156(3) Pages: 364-373
  • DOI: DOI:10.1016/j.jconrel.2011.08.003
  • Peer Reviewed
• [Journal Article] Supramolecular nanodevices : From design validation to theranostic nanomedicine. Acc (2011)
  • Author(s): H. Cabral, N. Nishiyama, K. Kataoka
  • Journal Title: Chem. Res Volume: 44(10) Pages: 999-1008
  • DOI: DOI:10.1021/ar200094a
  • Peer Reviewed
• [Journal Article] Odd-even effect of repeating aminoethylene units in the side chain of N-substituted polyaspartamides on gene transfection profiles (2011)
  • Author(s): H. Uchida, K. Miyata, M. Oba, T. Ishii, T. Suma, K. Itaka, N. Nishiyama, K. Kataoka
  • Journal Title: J. Am. Chem. Soc Volume: 133(39) Pages: 15524-15532
  • DOI: DOI:10.1021/ja204466y
  • Peer Reviewed
• [Journal Article] Effect of polymer structure on micelles formed between siRNA and cationic block copolymer Comprising thiols and amidines (2011)
  • Author(s): R. J. Christie, K. Miyata, Y. Matsumoto, T. Nomoto, D. Menasco, T.-C. Lai, M. Pennisi, K. Osada, S. Fukushima, N. Nishiyama, Y. Yamasaki, K. Kataoka
  • Journal Title: Biomacromolecules Volume: 12(9) Pages: 3174-3185
  • DOI: DOI:10.1021/bm2006714
  • Peer Reviewed
• [Journal Article] Enhanced endosomal escape of siRNA-incorporating hybrid nanoparticles from calcium phosphate and PEG-block charge-conversional polymer for efficient gene knockdown with negligible cytotoxicity (2011)
  • Author(s): F. Pittella, M. Zhang, Y. Lee, H.-J. Kim, T. Tockary, K. Osada, T. Ishii, K. Miyata, N. Nishiyama
  • Journal Title: Biomaterials Volume: 32(11) Pages: 3106-3114
  • DOI: DOI:10.1016/j.biomaterials.2010.12.057
  • Peer Reviewed
• [Journal Article] Antiangiogenic gene therapy of experimental pancreatic tumor by sFlt-1 plasmid DNA carried by RGD-modified crosslinked polyplex micelles (2011)
  • Author(s): Y. Vachutinsky, M. Oba, K. Miyata, S. Hiki, M. R. Kano, N. Nishiyama, H. Koyama, K. Miyazono, K. Kataoka
  • Journal Title: J. Control. Release Volume: 149(1) Pages: 51-57
  • DOI: DOI:10.1016/j.jconrel.2010.02.002
  • Peer Reviewed
• [Journal Article] Improving drug potency and efficacy by nanocarrier-mediated subcellular targeting (2011)
  • Author(s): M. Murakami, H. Cabral, Y. Matsumoto, S. Wu, M. R. Kano, T. Yamori, N. Nishiyama, K. Kataoka
  • Journal Title: Science Transl. Med Volume: 3(64) Pages: 64
  • DOI: DOI:10.1126/scitranslmed.3001385
  • Peer Reviewed
• [Journal Article] Polyplex micelles prepared fromω-cholesteryl PEG-polycation blockcopolymers for systemic gene delivery (2011)
  • Author(s): M. Oba, K. Miyata, K. Osada, R. J. Christie, M. Sanjoh, W. Li, S. Fukushima, T. Ishii, M. R. Kano, N. Nishiyama, H. Koyama, K. Kataoka
  • Journal Title: Biomaterials Volume: 32(2)
  • DOI: DOI:10.1016/j.biomaterials.2010.09.022
  • Peer Reviewed
• [Journal Article] Visible-drug delivery by supra-molecular nanocarriers directing to single-platformed diagnosis and therapy of pancreatic tumor model (2010)
  • Author(s): S. Kaida, H. Cabral, M. Kumagai, A. Kishimura, Y. Terada, M. Sekino, I. Aoki, N. Nishiyama, T. Tani, K. Kataoka
  • Journal Title: Cancer Res Volume: 70(18) Pages: 7031-7041
  • DOI: DOI:10.1158/0008-5472.CAN-10-0303
  • Peer Reviewed
• [Journal Article] siRNA-grafted polymer for polyion complex(PIC)-based siRNA delivery : Enhancement of PIC stability and gene silencing efficiency (2010)
  • Author(s): H. Takemoto, A. Ishii, K. Miyata, M. Nakanishi, M. Oba, T. Ishii, Y. Yamasaki, N. Nishiyama, K. Kataoka
  • Journal Title: Biomaterials Volume: 31(31) Pages: 8097-8105
  • DOI: DOI:10.1016/j.biomaterials.2010.07.015
  • Peer Reviewed
• [Journal Article] Introduction of stearoyl moieties into a biocompatible cationic polyaspartamide derivative, PAsp(DET), with endosomal escaping function for enhanced siRNA-mediated gene knockdown (2010)
  • Author(s): H.-J. Kim, A. Ishii, K. Miyata, Y. Lee, S. Wu, M. Oba, N. Nishiyama, K. Kataoka
  • Journal Title: J. Control. Release Volume: 145(2) Pages: 141-148
  • DOI: DOI:10.1016/j.jconrel.2010.03.019
  • Peer Reviewed
• [Journal Article] Enhanced transfection with silica-coated polyplexes loading plasmid DNA (2010)
  • Author(s): K. Miyata, N. Gouda, H. Takemoto, M. Oba, Y. Lee, H. Koyama, Y. Yamasaki, K. Itaka, N. Nishiyama, K. Kataoka
  • Journal Title: Biomaterials Volume: 31(17) Pages: 4764-4770
  • DOI: DOI:10.1016/j.biomaterials.2010.02.033
  • Peer Reviewed
• [Journal Article] Antiangiogenic gene therapy of solid tumor by systemic injection of polyplex micelles loading plasmid DNA encoding soluble Flt-1 (2010)
  • Author(s): M. Oba, Y. Vachutinsky, K. Miyata, M. R. Kano, S. Ikeda, N. Nishiyama, K. Itaka, K. Miyazono, H. Koyama, K. Kataoka
  • Journal Title: Mol. Pharm Volume: 7(2) Pages: 501-509
  • DOI: DOI:10.1021/mp9002317
  • Peer Reviewed
• [Journal Article] siRNA-based therapy ameliorates glomerulonephritis (2010)
  • Author(s): H. Shimizu, Y. Hori, S. Kaname, K. Yamada, N. Nishiyama, S. Matsumoto, K. Miyata, M. Oba, A. Yamada, K. Kataoka, T. Fujita
  • Journal Title: J. Am. Soc. Nephrol Volume: 21(4) Pages: 622-633
  • DOI: DOI:10.1681/ASN.2009030295
  • Peer Reviewed
• [Journal Article] Efficient delivery of bioactive antibodies into thecytoplasm of living cells by charge-conversional polyion complex micelles. Angew (2010)
  • Author(s): Y. Lee, T. Ishii, H.-J. Kim, N. Nishiyama, Y. Hayakawa, K. Itaka, K. Kataoka
  • Journal Title: Chem. Int. Ed Volume: 49(14) Pages: 2552-2555
  • DOI: DOI:10.1002/anie.200905264
  • Peer Reviewed
• [Journal Article] Enhanced percolation and gene expression in tumor hypoxia by PEGylated polyplex micelles (2009)
  • Author(s): M. Han, M. Oba, N. Nishiyama, M. R. Kano, S. Kizaka-Kondoh, K. Kataoka
  • Journal Title: Mol. Ther Volume: 17(8) Pages: 1404-1410
  • DOI: DOI:10.1038/mt.2009.119
  • Peer Reviewed
• [Journal Article] Intratracheal gene transfer of adrenomedullin using polyplex nanomicelles attenuates monocrotaline-induced pulmonary hypertension in rats (2009)
  • Author(s): M. Harada-Shiba, I. Takamisawa, K. Miyata, T. Ishii, N. Nishiyama, K. Itaka, K. Kangawa, F. Yoshihara, Y. Asada, K. Hatakeyama, N. Nagaya, K. Kataoka
  • Journal Title: Mol. Ther Volume: 17(7) Pages: 1180-1186
  • DOI: DOI:10.1038/mt.2009.63
  • Peer Reviewed
• [Journal Article] PEGylated calcium phosphate nanocomposites as smart environment-sensitive carriers for siRNA delivery (2009)
  • Author(s): M. Zhang, A. Ishii, N. Nishiyama, S. Matsumoto, T. Ishii, Y. Yamasaki, K. Kataoka
  • Journal Title: Adv. Mater Volume: 21(34) Pages: 3520-3525
  • DOI: DOI:10.1002/adma.200800448
  • Peer Reviewed
• [Journal Article] Charge-conversional polyionic complex micelles-efficient nanocarriers for protein delivery into cytoplasm (2009)
  • Author(s): Y. Lee, T. Ishii, H. Cabral, H.-J. Kim, J.-H. Seo, N. Nishiyama, H. Oshima, K. Osada, K. Kataoka
  • Journal Title: Angew. Chem. Int. Ed Volume: 48(29) Pages: 5309-5312
  • DOI: DOI:10.1002/anie.200900064
  • Peer Reviewed
• [Journal Article] Environment-responsive block copolymer micelles with a disulfide cross-linked core for enhanced siRNA delivery (2009)
  • Author(s): S. Matsumoto, R. J. Christie, N. Nishiyama, K. Miyata, A. Ishii, M. Oba, H. Koyama, Y. Yamasaki, K. Kataoka
  • Journal Title: Biomacromolecules Volume: 10(1) Pages: 119-127
  • DOI: DOI:10.1021/bm800985e
  • Peer Reviewed
• [Presentation] Development of functional polymeric micelles for cancer diagnosis and therapy (2011)
  • Author(s): N. Nishiyama
  • Organizer: The 14th Asian Chemical Congress(14-ACC)
  • Place of Presentation: Bangkok, Thailand
  • Year and Date: 20110905-08
• [Presentation] Polymeric micelles for photodynamic diagnosis and therapy (2011)
  • Author(s): N. Nishiyama, Y. Morimoto, K. Kataoka
  • Organizer: The 15th International Symposium on Recent Advances in Drug Delivery Systems
  • Place of Presentation: Sheraton Hotel, Salt Lake City, Utah, USA
  • Year and Date: 20110213-16
• [Presentation] Development of functional polymeric micelles for cancer diagnosis and therapy (2011)
  • Author(s): N. Nishiyama
  • Organizer: Singapore-Japan "Bioelectronics" Workshop
  • Place of Presentation: Keihanna plaza, Kyoto, Japan
  • Year and Date: 2011-08-12
• [Presentation] Development of photosensitizer drug delivery system for cancer theranostics (2011)
  • Author(s): N. Nishiyama
  • Organizer: 28th International Conference of Photopolymer Science and Technology
  • Place of Presentation: University Convention Hall, Chiba University, Chiba
  • Year and Date: 2011-06-24
• [Presentation] Design of smart nanocarriers for photosensitizer delivery (2011)
  • Author(s): N. Nishiyama, K. Kataoka
  • Organizer: 13^<th> World Congress of International Photodynamic Association(IPA)
  • Place of Presentation: Innsbruck, Austria
  • Year and Date: 2011-05-12
• [Presentation] Development of functional polymeric micelles for cancer diagnosis and therapy (2011)
  • Author(s): N. Nishiyama
  • Organizer: 2011 International Symposium on Intelligent Drug Delivery Systems
  • Place of Presentation: KIST, Seoul, Korea, April
  • Year and Date: 2011-04-28
• [Presentation] Nanocarrier-mediated photodynamic diagnosis and therapy of malignant tumors, New Directions In Nanotheranostics : Imaging, Biosensors, Materials and DNA Technologies (2010)
  • Author(s): N. Nishiyama, Y. Morimoto, K. Kataoka
  • Organizer: 4^<th> Annual Symposium on Nanobiotechnology
  • Place of Presentation: Ludwig-Maximilians University, Munich, Germany
  • Year and Date: 2010-10-06
• [Presentation] Development of smart polymeric micelles for innovative cancer therapy (2010)
  • Author(s): N. Nishiyama, H. Cabral, K. Kataoka
  • Organizer: World Congress of Pharmacy and Pharmaceutical Sciences
  • Place of Presentation: Lisbon, Portugal
  • Year and Date: 2010-09-01
• [Presentation] Block copolymer micelles as smart supramolecular nanodevices for tumor targeting (2009)
  • Author(s): N. Nishiyama
  • Organizer: The 36th Annual Meeting and Exposition of the Controlled Release Society
  • Place of Presentation: Bella Center, Copenhagen Denmark
  • Year and Date: 2009-07-19
• [Presentation] Development of dendirimer phthalocyanine-loaded polymericmicelles for diagnosis and treatment of microcarcinoma (2009)
  • Author(s): N. Nishiyama, Y. Morimoto, K. Miyazaki, K. Urano, S. Horie, M. Kumagai, S. Fukushima, W.-D. Jang, K. Kataoka
  • Organizer: The 36th Annual Meeting and Exposition of the Controlled Release Society
  • Place of Presentation: Bella Center, Copenhagen Denmark
  • Year and Date: 2009-07-12
• [Remarks]
  • URL: http://www.bmw.t.u-tokyo.ac.jp/
• [Patent(Industrial Property Rights)] 核酸送達用組成物及び担体組成物、それを用いた医薬組成物、並びに核酸送達方法 (2010)
  • Inventor(s): 片岡一則,フレデリコピテラシルバ,ミンゼンジャン,西山伸宏,宮田完二郎,ヤンイー
  • Industrial Property Rights Holder: 国立大学法人,東京大学
  • Industrial Property Number: 特許、特願2010-102880
  • Filing Date: 2010-04-28