Treatment of chronic arterial occlusion with biodegradable nanoparticles encapsulating anti-miRNA oligonucleotides

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K12654
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 90120:Biomaterials-related
• Research Institution: Nihon University
• Principal Investigator: ISHIHARA Tsutomu 日本大学, 工学部, 教授 (70349554)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ナノ粒子 / 生分解性ポリマー / アンチmiRNAオリゴ核酸 / 血管新生

Outline of Final Research Achievements

In this study, we attempted to develop an oligonucleotide therapeutic that can induce angiogenesis for the treatment of chronic arterial occlusion. Anti-miRNA oligonucletides (AMO) were selected as nucleic acid molecules, and nanoparticles consisting of biodegradable polymers were prepared as a carrier of AMO to enhance its accumulation in lesion sites. These nanoparticles were able to efficiently accumulate AMO on vascular endothelial cells via RGD peptides on the surfaces. From wound healing assay and tube formation assay using vascular endothelial cells, three types of AMO with high angiogenesis induction ability were screened. Furthermore, it was found that the nanoparticles with AMO could significantly induce angiogenesis.

Free Research Field

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Academic Significance and Societal Importance of the Research Achievements

下肢慢性動脈閉塞症は、患肢切断に至るなどQOLは著しく低い。しかし、現在の薬物療法では劇的な改善効果がなく、遺伝子治療薬/核酸医薬のような新たな作用機序に基づく新薬が切望されている。本研究では、既存薬の課題を克服した新たな核酸医薬を作製した。この医薬は、AMOにより血管新生を誘導し、標的細胞(血管内皮細胞)に高い集積性を示す。本成果は、miRNAを標的とした核酸医薬の先駆けとなる可能性を秘めており、学術的な意義も大きいと考えられる。