| Budget Amount *help |
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2017: ¥12,610,000 (Direct Cost: ¥9,700,000、Indirect Cost: ¥2,910,000)
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| 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.
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