A novel nanomaterial-based system for the removal of antibodies in the blood through macrophages

• Project/Area Number: 17K01386
• 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: 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, 生命工学領域, 主任研究員 (40611554)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 生体材料 / 血液浄化療法 / 炎症性自己免疫疾患 / ナノ材料

Outline of Final Research Achievements

A novel nanomaterial-based system that could selectively recognize macrophages and effectively remove antibodies in the blood through macrophages was developed. This system consisted of a main body that could target macrophages and a grafted protein that could bind with blood antibodies such as immunoglobulin G. Injection of system into mouse models of experimental autoimmune myocarditis decreased the levels of blood immunoglobulin G compared with those in the phosphate-buffered saline (PBS)-injected group, although this treatment failed to show a statistically significant difference.

Academic Significance and Societal Importance of the Research Achievements

装置に頼らない、より簡便で、持ち運びや保存に便利な血中抗体の除去システムは自然災害など免疫吸着療法の実施が困難な緊急時にも使用可能である。患者の生体内に存在するマクロファージに血中抗体を選択的に運んで分解・除去するシステムの開発は非常に独創的な研究であり、心筋炎動物モデルを用いた評価でその可能性を確認したことに大きな意義がある。

Research Products

• [Journal Article] Protective and healing effects of apoptotic mimic-induced M2-like macrophage polarization on pressure ulcers in young and middle-aged mice (2021)
  • Author(s): Riki Toita, Eiko Shimizu, Masaharu Murata, Jeong-Hun Kang
  • Journal Title: Journal of Controlled Release Volume: 330 Pages: 705-714
  • Peer Reviewed
• [Journal Article] Effect of Fetal Bovine Serum Concentration on Lysophosphatidylcholine-mediated Proliferation and Apoptosis of Human Aortic Smooth Muscle Cells (2020)
  • Author(s): Asai, D, Kawano, T, Murata, M, Nakashima, H, Toita, R, Kang, J.H
  • Journal Title: Journal of Oleo Science Volume: 69 Issue: 3 Pages: 255-260
  • DOI: 10.5650/jos.ess19268
  • NAID: 130007804109
  • ISSN: 1345-8957, 1347-3352
  • Peer Reviewed / Open Access
• [Journal Article] Unique cellular interaction of macrophage-targeted liposomes potentiates anti-inflammatory activity (2020)
  • Author(s): Riki Toita, Eiko Shimizu, Jeong-Hun Kang
  • Journal Title: Chemical Communications Volume: 56 Issue: 59 Pages: 8253-8256
  • DOI: 10.1039/d0cc03320k
  • Peer Reviewed
• [Journal Article] Suppression of lysophosphatidylcholine-induced human aortic smooth muscle cell calcification by protein kinase A inhibition (2019)
  • Author(s): Riki Toita, Daisuke Asai, Kentaro Otani, Takahito Kawano, Masaharu Murata, Jeong-Hun Kang
  • Journal Title: Lipids Volume: 54 Issue: 8 Pages: 465-470
  • DOI: 10.1002/lipd.12178
  • Peer Reviewed
• [Journal Article] A high-affinity peptide substrate for G protein-coupled receptor kinase 2 (GRK2) (2019)
  • Author(s): Daisuke Asai, Masaharu Murata, Riki Toita, Takahito Kawano, Hideki Nakashima, Jeong-Hun Kang
  • Journal Title: Amino acids Volume: 51 Issue: 6 Pages: 973-976
  • DOI: 10.1007/s00726-019-02735-0
  • Peer Reviewed
• [Journal Article] Macrophage Uptake Behavior and Anti-inflammatory Response of Bovine Brain- or Soybean-derived Phosphatidylserine Liposomes (2018)
  • Author(s): Riki Toita, Satoshi Fujita, Jeong-Hun Kang
  • Journal Title: Journal of Oleo Science Volume: 67 Issue: 9 Pages: 1131-1135
  • DOI: 10.5650/jos.ess18097
  • NAID: 130007479574
  • ISSN: 1345-8957, 1347-3352
  • Peer Reviewed / Open Access
• [Journal Article] Protein kinase A (PKA) inhibition reduces human aortic smooth muscle cell calcification stimulated by inflammatory response and inorganic phosphate (2018)
  • Author(s): Riki Toita, Kentaro Otani, Takahito Kawano, Satoshi Fujita, Masaharu Murata, Jeong-Hun Kang
  • Journal Title: Life Sciences Volume: 209 Pages: 466-471
  • DOI: 10.1016/j.lfs.2018.08.051
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Increased hepatic inflammation in a normal-weight mouse after long-term high-fat diet feeding (2017)
  • Author(s): Riki TOITA, Takahito KAWANO, Satoshi FUJITA, Masaharu MURATA, Jeong-Hun KANG
  • Journal Title: Journal of Toxicologic Pathology Volume: 31 Issue: 1 Pages: 43-47
  • DOI: 10.1293/tox.2017-0038
  • NAID: 130006318210
  • ISSN: 0914-9198, 1881-915X
  • Peer Reviewed / Open Access
• [Presentation] 炎症性細胞の機能変換能を有するナノ分子による心筋炎の治療 (2019)
  • Author(s): 姜貞勲、戸井田力
  • Organizer: 第35回日本DDS学会学術集会
• [Presentation] マクロファージ表現型に着目した癒着治療 (2019)
  • Author(s): 戸井田力、姜貞勲
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] マクロファージ標的型ナノメディシンによる自己免疫性心筋炎の治療 (2018)
  • Author(s): 姜貞勲、戸井田力
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] NAFLD治療を目ざしたマクロファージ指向性ナノメディシン (2018)
  • Author(s): 戸井田力、藤田聡史、姜貞勲
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] マクロファージを標的とするIL-10修飾リポソーム (2017)
  • Author(s): 姜貞勲、河野喬仁、村田正治、戸井田力
  • Organizer: 第33回日本DDS学会学術集会