A nanosystem as an alternative to immunoadsorption plasmapheresis and its application in the treatment of dilated cardiomyopathy

• Project/Area Number: 15K12531
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: KANG JEONG-HUN 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (50423512)
• Co-Investigator(Kenkyū-buntansha): 戸井田 力 国立研究開発法人産業技術総合研究所, その他部局等, 研究員 (40611554)
• 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: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 生体制御・治療 / 生体材料 / ナノ材料 / 免疫吸着療法 / 自己免疫 / 拡張型心筋症 / 自己抗体 / ナノ分子

Outline of Final Research Achievements

The ultimate aim of this study is to develop a nanosystem that can remove blood immunoglobulin (IgG) and to apply the treatment of dilated cardiomyopathy. The eat-me signal phosphatidylserine was involved in nanosystems for their specific recognition by macrophage, and the protein G was grafted on the surface of nanosystems for the IgG-specific binding. The nanosystem showed high-affinity binding to macrophage cells. After intravenous injection into myocarditis model mice, nanosystems inhibited the occurrence of myocarditis and dilated cardiomyopathy.

Research Products

• [Journal Article] Anti-obesity and anti-inflammatory effects of macrophage-targeted interleukin-10-conjugated liposomes in obese mice (2016)
  • Author(s): iki Toita, Takahito Kawano, Masaharu Murata, Jeong-Hun Kang
  • Journal Title: Biomaterials Volume: 110 Pages: 81-88
  • DOI: 10.1016/j.biomaterials.2016.09.018
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Role of amino acid residues surrounding the phosphorylation site in peptide substrates of G protein-coupled receptor kinase 2 (GRK2) (2016)
  • Author(s): Asai, D., Murata, M., Toita, R., Kawano, T., Nakashima, H., and Kang, J.H.
  • Journal Title: Amino Acids Volume: 48 Issue: 12 Pages: 2875-2880
  • DOI: 10.1007/s00726-016-2345-6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Modulation of the osteoconductive property and immune response of poly(ether ether ketone) by modification with calcium ions (2015)
  • Author(s): Riki Toita, Sunarso, Ahmed Nafis Rashid, Kanji Tsuru, Kunio Ishikawa
  • Journal Title: Journal of Materials Chemistry B Volume: 3 Issue: 44 Pages: 8738-8746
  • DOI: 10.1039/c5tb01679g
  • Peer Reviewed
• [Presentation] マクロファージを標的とするIL-10修飾リポソームの抗肥満・抗炎症効果 (2016)
  • Author(s): 姜貞勲、河野喬仁、村田正治、戸井田力
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2016-11-30
• [Presentation] 炎症性疾患治療を指向したマクロファージ機能制御剤の基礎評価 (2016)
  • Author(s): 戸井田力、藤田聡史、姜貞勲
  • Organizer: 第68回日本生物工学会大会
  • Place of Presentation: 富山国際会議場（富山）
  • Year and Date: 2016-09-28
• [Presentation] マクロファージを標的とするeat-meシグナルナノ分子 (2016)
  • Author(s): 姜貞勲、戸井田力、浅井大輔、村田正治
  • Organizer: 第32回日本DDS学会学術集会
  • Place of Presentation: グランシップ（静岡）
  • Year and Date: 2016-06-30
• [Presentation] マクロファージを選択的に認識する機能性ナノ分子の創製 (2015)
  • Author(s): 姜貞勲、戸井田力、浅井大輔、村田正治
  • Organizer: BMB2015(第38回日本分子生物学会念会、第88回日本生化学会 合同大会）
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Patent(Industrial Property Rights)] リポソーム組成物及び炎症性疾患用治療剤 (2016)
  • Inventor(s): 姜貞勲、村田正治
  • Industrial Property Rights Holder: 姜貞勲、村田正治
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-252224
  • Filing Date: 2016-12-27