Cholinized-Polymer\nFunctionalized Lipid-Based Drug\nCarriers Facilitate Liver Fibrosis Therapy via Ultrafast Liver-Targeting\nDelivery

Here,\nwe report novel cholinized-polymer functionalized lipid-based\nnanoparticles (CP-LNPs) for rapid and highly effective delivery of\ndrugs to the liver, achieving targeting within 10 min and nearly 100%\nefficiency. In this study, CP-LNPs loaded with a promising antifibrotic\nagent curcumin (CP-LNPs/Cur) significantly improved the stability\nof curcumin under physiological conditions and its distribution in\nthe liver. In vitro experiments demonstrated that CP-LNPs/Cur effectively\nsuppressed the proliferation and migration of activated hepatic stellate\ncells (aHSCs), as evidenced by the decreased expression of α-SMA.\nMoreover, CP-LNPs/Cur attenuated oxidative stress levels in hepatocytes\nwhile improving mitochondrial physiological activity. In vivo antifibrosis\nstudies have shown that CP-LNPs/Cur only require a low dose to significantly\nalleviate liver injury and collagen deposition, thereby preventing\nthe progression of liver fibrosis. These findings indicated that CP-LNPs\nexhibit great potential in liver fibrosis therapy benefiting from\nthe novel targeting strategy.