Abstract
Activated hepatic stellate cells(aHSCs),the main source of extracellular matrix deposition,are key targets in liver fibrosis.However,no effective drug specific to aHSCs has been clinically applied due to poor drug delivery efficiency.Herein,we designed a CXC chemokine receptor 4(CXCR4)-targeted reactive oxygen species(ROS)-responsive platform AMD-Dex-ROS-responsive-sorafenib(ARS)based on natural polysac-charide and thioctic acid frame,which can deliver anti-fibrosis drug represented by sorafenib specifically to aHSCs on account of CXCR4 over-expression on aHSCs,and smartly disassemble via ROS-responsive thioketal rupture relying on high intracellular ROS in HSCs,realized on-demand drug release and effec-tive liver fibrosis reversion.Notably,in this platform,the CXCR4 antagonist AMD3100 not only enhanced aHSCs targeting efficiency of sorafenib but also effectively magnified the aHSCs elimination of sorafenib by blocking stroma cell derived factor-1(SDF-1)/CXCR4-induced aHSCs protection,resulting in synergis-tic anti-fibrosis effect.The platform provided a new approach for drug delivery system design and liver fibrosis treatment.
基金项目
Jiangsu Agriculture Science and Technology Innovation Fund(CX223174)
国家自然科学基金(82102202)
江苏省自然科学基金(BK20210424)
Postgraduate Research & Practice Innovation Program of Jiangsu Province(KYCX23_0849)
维普
万方数据