Development of multifunctional polyplexes without polycations

• Project/Area Number: 26350532
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Nihon University
• Principal Investigator: ISHIHARA Tsutomu 日本大学, 工学部, 教授 (70349554)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 核酸デリバリー / ポリプレックス / ナノ粒子 / siRNA / 薬物送達システム / ポリ乳酸 / DDS / 遺伝子治療

Outline of Final Research Achievements

To achieve the silence specific genes, a novel type of polyplexes was developed in the absence of polycations in this study. The polyplexes were prepared from poly(lactic acid) with a terminal amino group by the solvent diffusion method. The polyplexes exhibited stable nucleic acids retention in the serum, compared with conventional polyplexes formed from polycations, and sustained release of nucleic acids along with degrade of the polymer. The polyplexes also exhibited low cytotoxicity, long retention of nucleic acids in the cultured cells and gene silencing activity. These results suggested that the polyplexes could help to advance the clinical application for gene therapy.

Research Products

• [Journal Article] Alkyne-functionalized cationic polysiloxane polymers conjugated with targeting molecules by click reactions for DNA delivery (2017)
  • Author(s): Kihara Y, Maeda R, Imaizumi A, Ichikawa T, Nemoto N, Ishihara T, Hirano N, and Haruki M.
  • Journal Title: J. Nanosci. Nanotechnol. Volume: 17 Pages: 5081-5089
  • DOI: 10.1166/jnn.2017.13121
  • Peer Reviewed
• [Journal Article] Scavenging of superoxide anions by lecithinized superoxide dismutase in HL-60 cells (2016)
  • Author(s): Ishihara T, Shibui M, Hoshi T, Mizushima T
  • Journal Title: Molecular BioSystems Volume: 12 Pages: 274-282
  • DOI: 10.1039/c5mb00631g
  • Peer Reviewed
• [Journal Article] Encapsulation of beraprost sodium in nanoparticles: Analysis of sustained release properties, targeting abilities and pharmacological activities in animal models of pulmonary arterial hypertension. (2015)
  • Author(s): Ishihara, T., Hayashi, E., Yamamoto, S., Kobayashi, C., Tamura, Y., Sawazaki, R., Tamura, F., Tahara, K., Kasahara, T., Ishihara, T., Takenaga, M., Fukuda, K. and Mizushima, T
  • Journal Title: J Control Release Volume: 97 Pages: 97-104
  • DOI: 10.1016/j.jconrel.2014.10.029
  • Peer Reviewed
• [Journal Article] Synthesis of alkyne-functionalized amphiphilic polysiloxane polymers and formation of nanoemulsions conjugated with bioactive molecules by click reactions. (2014)
  • Author(s): Kihara Y, Ichikawa T, Abe S, Nemoto N, Ishihara T, Hirano N, Haruki M.
  • Journal Title: Polymer Journal Volume: 46 Pages: 175-183
  • DOI: 10.1038/pj.2013.86
  • Peer Reviewed
• [Journal Article] Interactions of Lecithinized Superoxide Dismutase with Serum Proteins and Cells. (2014)
  • Author(s): Ishihara T, Nara S, Mizushima T.
  • Journal Title: J Pharm Sci. Volume: 103 Pages: 1987-1994
  • DOI: 10.1002/jps.24031
  • Peer Reviewed
• [Journal Article] Development of biodegradable nanoparticles for liver-specific ribavirin delivery (2014)
  • Author(s): Ishihara, T., Kaneko, K., Ishihara, T. and Mizushima, T
  • Journal Title: J Pharm Sci. Volume: 103 Pages: 4005-4011
  • DOI: 10.1002/jps.24219
  • Peer Reviewed
• [Presentation] 肝星細胞特異的薬物デリバーを目指した生分解性ナノ粒子の開発 (2017)
  • Author(s): 山下勇一、齋藤菜美恵、石原務
  • Organizer: 第66回高分子学会年次大会
  • Place of Presentation: 幕張メッセ（千葉県千葉市）
  • Year and Date: 2017-05-29
• [Presentation] 肝硬変治療を目指したセレコキシブ封入ナノ粒子の開発 (2016)
  • Author(s): 山下勇一、齋藤菜美恵、石原務
  • Organizer: 第59回日本大学工学部学術研究報告会
  • Place of Presentation: 日本大学（福島県郡山市）
  • Year and Date: 2016-12-03
• [Presentation] ポリカチオンを用いない核酸内包高分子ナノ粒子の開発 (2016)
  • Author(s): 佐藤佳純、石原務
  • Organizer: 2016高分子学会東北支部研究発表会
  • Place of Presentation: 山形大学（山形県米沢市）
  • Year and Date: 2016-11-10
• [Presentation] 肝指向性高分子ナノ粒子の開発 (2015)
  • Author(s): 金子昂平、石原務
  • Organizer: 第64回高分子学会討論会
  • Place of Presentation: 東北大学
  • Year and Date: 2015-09-15
• [Presentation] 肝炎治療を目指したリバビリン封入高分子ナノ粒子の開発 (2015)
  • Author(s): 金子昂平、石原務、水島徹
  • Organizer: 第31回日本DDS学会
  • Place of Presentation: 京王プラザホテル
  • Year and Date: 2015-07-03
• [Presentation] 肝炎治療を目指したリバビリン封入高分子ナノ粒子の開発 (2014)
  • Author(s): 金子昂平,石原務
  • Organizer: 平成26年度化学系学協会東北大会
  • Place of Presentation: 山形
  • Year and Date: 2014-09-21 – 2014-09-22
• [Presentation] 薬物放出速度を制御可能な生分解性高分子ナノ粒子の開発 (2014)
  • Author(s): 石原務
  • Organizer: 第３０回日本DDS学会
  • Place of Presentation: 東京
  • Year and Date: 2014-07-30 – 2014-07-31
  • Invited