Significance
Our work introduces an innovative antifibrotic drug system that is developed upon the active targeting of CPT and aims for the fate reversal of HSCs. Through HSC-targeted delivery achieved by PEG-PCL polymeric micelles decorated with vitamin A-derivatives, CPT significantly suppressed the expressions of HIF-1α and glycolytic enzymes in MF-HSCs, as well as their pathologic expansion in mouse livers. It effectively ameliorated chronic liver fibrosis in mice induced by CCl4 injection or BDL and restored the damaged liver structure and function. These compelling findings demonstrate the therapeutic potential of glycolytic HSC-targeting in combating fibrosis and related disorders and thus provide new promise for future clinical management of such prevalent and life-threatening conditions.
Statement of significance
Our work introduces an innovative antifibrotic drug system that is developed upon the active targeting of CPT and aims for the fate reversal of HSCs. Through HSC-targeted delivery achieved by PEG-PCL polymeric micelles decorated with vitamin A-derivatives, CPT significantly suppressed the expressions of HIF-1α and glycolytic enzymes in MF-HSCs, as well as their pathologic expansion in mouse livers. It effectively ameliorated chronic liver fibrosis in mice induced by CCl4 injection or BDL and restored the damaged liver structure and function. These compelling findings demonstrate the therapeutic potential of glycolytic HSC-targeting in combating fibrosis and related disorders and thus provide new promise for future clinical management of such prevalent and life-threatening conditions.