PreS1-Derived Peptide-Engineered Cell Membrane-Coated Nanoparticles Enhance Liver-Directed Curcumin Delivery in Acute Liver Injury

Background: Liver injury remains a major clinical challenge, and the therapeutic performance of many candidate drugs is limited by poor bioavailability and insufficient tissue selectivity. Methods: This study proposes a biomimetic delivery strategy based on genetically engineered cell membrane camouflage. Briefly, curcumin-loaded PLGA nanoparticles were co-ultrasonicated with genetically modified 293T cell membranes displaying a hepatocyte-binding peptide that originates from the preS1 region of the hepatitis B virus large surface protein, allowing the membrane-coated particles to self-assemble into a core–shell structure designated HBVP-MPNs, thereby achieving active hepatocyte-targeted delivery of curcumin. The resulting HBVP-MPNs were designed to engage sodium taurocholate cotransporting polypeptide (NTCP) and improve liver-directed delivery. Results: HBVP-MPNs exhibited a mean particle diameter of approximately 197.9 nm, a core–shell morphology, high curcumin encapsulation efficiency, and slower cumulative curcumin release over 24 h than uncoated PNs (35.1% versus 51.6%). They showed approximately threefold higher cell-associated fluorescence in HepG2-NTCP cells and approximately 50% lower fluorescence in RAW264.7 macrophages than PNs in vitro. Following intravenous administration in mice, HBVP-MPNs displayed prolonged blood-associated fluorescence and increased liver accumulation. Upon therapeutic evaluation in a CCl₄-triggered murine model of acute hepatic injury, HBVP-MPNs elicited markedly lower circulating ALT and AST activities and conferred superior protection against histopathological abnormalities in liver tissue relative to free curcumin and non-targeted control formulations. Cytotoxicity, hemolysis, hematological, serum biochemical, and histological assessments indicated favorable tolerability within the present experimental settings. Conclusions: Collectively, these data warrant further investigation of preS1 peptide-engineered cell membrane-coated nanoparticles as a biomimetic platform for liver-directed curcumin delivery in acute liver injury.