首页|Natural polysaccharide-based smart CXCR4-targeted nano-system for magnified liver fibrosis therapy
Natural polysaccharide-based smart CXCR4-targeted nano-system for magnified liver fibrosis therapy
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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.
Liqiong Sun、Xinping Luo、Chenxi Zhou、Zhanwei Zhou、Minjie Sun
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College of Horticulture,Nanjing Agricultural University,Nanjing 210095,China
NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients,State Key Laboratory of Natural Medicines,Department of Pharmaceutics,China Pharmaceutical University,Nanjing 210009,China
Jiangsu Agriculture Science and Technology Innovation Fund国家自然科学基金江苏省自然科学基金Postgraduate Research & Practice Innovation Program of Jiangsu Province
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