Organic-Inorganic Hybrid Hollow Nanoparticles Suppress Oxidative Stress and Repair Damaged Tissues for Treatment of Hepatic Fibrosis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H03403
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Composite materials/Surface and interface engineering
• Research Institution: Kyushu University
• Principal Investigator: Hayashi Koichiro 九州大学, 歯学研究院, 准教授 (80580886)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ナノ粒子 / ハイブリッド / ナノ医療 / 多機能性 / DDS / 刺激応答性 / ドラッグデリバリー

Outline of Final Research Achievements

We synthesized multifunctional organic-inorganic hybrid hollow nanoparticles (HNPs) containing silibinin. The HNPs were mainly composed of siloxanes and disulfides and had surface thiols. The disulfides were cleaved by intracellular glutathione and reduced to thiols, leading to the deformation of the HNPs. Silibinin molecules were released through the cracks formed by HNP deformation. Furthermore, the HNPs suppressed the generation of hydroxyl radicals, a major cause of liver fibrosis, via sulfenylation reactions of HNP thiols. Retinol-modified HNPs targeted Kupffer cells and hepatic stellate cells, which are essential for hepatic fibrogenesis. The combined suppression of hydroxyl radical generation and release of silibinin using the HNPs decreased the proportion of fibrotic tissues and improved hepatic function. The therapeutic efficacy was greater than can be achieved by the suppression of hydroxyl radical generation alone and the injection of silibinin alone.

Free Research Field

生体材料

Academic Significance and Societal Importance of the Research Achievements

肝硬変は、慢性肝炎やアルコールの過剰摂取、肥満による脂肪肝などにより肝臓が線維化し、本来の機能を果たせなくなった状態である。現在の肝硬変の治療は、食事療法、運動、肝移植であり、肝臓の線維化を引き起こす原因に対して治療を施す療法はなく、線維化した肝臓を正常状態に戻すことはできない(日本消化器学会)。厚労省の発表では、肝硬変の患者は全国で50万人にのぼり、5年生存率は僅か40%である。このような背景から、早期の治療法の開発が求められている。本研究では、ナノ粒子を静脈内注射により投与することで、マウスの肝組織修復、肝機能回復を達成できており、これは新規治療法となる可能性がある。