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

Current therapeutic options for the treatment of liver fibrosis are limited, and transplantation is often the only effective option for end‐stage fibrotic diseases. To overcome this problem, a nanoparticle‐based treatment as an alternative to transplantation is developed. Multifunctional organic–inorganic hybrid hollow nanoparticles (HNPs) containing silibinin are synthesized by mixing precursors in ammonia water at 60 °C for 1 min. The HNPs are mainly composed of siloxanes and disulfides and have surface thiols. The disulfides are cleaved by intracellular glutathione and reduced to thiols, leading to the deformation of the HNPs. Silibinin molecules are released through the cracks formed by HNP deformation. Furthermore, the HNPs suppress the generation of hydroxyl radicals, a major cause of liver fibrosis, via sulfenylation reactions of HNP thiols. Retinol‐modified HNPs target 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 decreases the proportion of fibrotic tissues and improves hepatic function. The therapeutic efficacy is greater than can be achieved by the suppression of hydroxyl radical generation alone and the injection of silibinin alone. Thus, HNPs are promising for the treatment of liver fibrosis.