Acute liver failure is a life-threatening syndrome, for which liver transplantation is presently the most effective treatment. Unfortunately, such treatment is extremely limited by a shortage of donor organs. Stem cell therapy offers a promising treatment strategy for acute liver failure. Yet, therapeutic efficacy and potential are hampered by administration route and safety concerns. In this work, we fabricated menstrual blood-derived stem cells-conditioned medium/polymersome hybrid nanoparticles that were self-assembled from amphiphilic block copolymers via the direct hydration method and encapsulated therapeutic bioactive factors within the aqueous core of vesicles. The merit of vesicular architecture enabled the loading capacity of distinct proteins and the maintenance of biological activity. These hybrid nanoparticles can be steadily taken up into cytoplasm and promote hepatocyte proliferation in vitro. Prolonged in vivo circulation time brought higher accumulation in livers. The therapeutic nanoparticles alleviated hepatic injury and promoted liver recovery in mice with carbon tetrachloride-induced liver failure. Considering the feasibility and benefit of the hybrid nanoparticle therapy, it provided a potential strategy to treat acute liver failure.
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