Development of therapeutically active nanomaterials: lipoprotein structure/function-based therapeutic strategies to treat intractable ocular diseases

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H03821
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 90120:Biomaterials-related
• Research Institution: Toyama Prefectural University
• Principal Investigator: Tatsuya Murakami 富山県立大学, 工学部, 教授 (90410737)
• Co-Investigator(Kenkyū-buntansha): 小倉 正恒 順天堂大学, 医療科学部, 教授 (30532486) ; 須田 謙史 京都大学, 医学研究科, 助教 (70779157)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 脂質ナノ粒子 / 高密度リポタンパク質 / 吸収促進 / 温度応答性 / 血管内皮接着

Outline of Final Research Achievements

We have conducted multifaceted research on reconstituted high-density lipoprotein nanoparticles (HDL) for medical applications and obtained the following important results; (1) a variant of HDL, bearing a cell-penetrating peptide and a neovasculature-targeting peptide, was prepared, and by its eye drop instillation to a mouse model of age-related macular degeneration a significant therapeutic effect was observed; (2) among the partial peptides of the HDL constituent protein, apoA-1, which correspond to single α helix regions of apoA-I, a peptide capable of forming temperature-responsive and anti-inflammatory lipid nanoparticles was discovered; (3) a live imaging method in zebrafish larvae to evaluate the vascular endothelial adhesion of lipid nanoparticles was developed, and a vascular endothelial cell-adhesive variant of HDL was obtained by the above imaging method.

Free Research Field

生物化学、薬物送達学

Academic Significance and Societal Importance of the Research Achievements

加齢黄斑変性に対する点眼剤が強く望まれている。新生血管ペプチドが角膜吸収促進剤としても機能し、かつそれを含むＨＤＬ改変体が有意な治療効果を示すという今回の発見は、世界初の点眼剤開発に向けた大きな前進である。
我々が見いだした温度応答性脂質ナノ粒子は、有効成分吸収促進や部位特異的薬物輸送に利用できる可能性が高く、将来、医薬品だけでなく化粧品分野での利用が期待される。
敗血症では血中毒素の除去および血管内皮保護が治療標的であり、両機能を有するＨＤＬはそれ自体が治療薬候補である。血管内皮接着性を付与することで、血管内皮選択的薬物送達キャリアとしても利用できる。