Balancing and Therapeutic Roles of CXCR4-Inhibiting Nanomedicine via Synergetic Regulation of Hepatic Stellate Cells and Extracellular Matrix in Liver Injury†
Xu Huan
School of Pharmacy, Medical School, Nantong University, Nantong, Jiangsu, 226001 China
Search for more papers by this authorYi Chen
School of Pharmacy, Medical School, Nantong University, Nantong, Jiangsu, 226001 China
Search for more papers by this authorXiaozhen Wu
School of Pharmacy, Medical School, Nantong University, Nantong, Jiangsu, 226001 China
Search for more papers by this authorHui Wang
School of Pharmacy, Medical School, Nantong University, Nantong, Jiangsu, 226001 China
Search for more papers by this authorYing Yang
School of Pharmacy, Medical School, Nantong University, Nantong, Jiangsu, 226001 China
Search for more papers by this authorPengkai Wu
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022 China
Search for more papers by this authorTianqing Liu
NICM Health Research Institute, Western Sydney University, Sydney, NSW, 2145 Australia
Search for more papers by this authorCorresponding Author
Kaikai Wang
School of Pharmacy, Medical School, Nantong University, Nantong, Jiangsu, 226001 China
E-mail: [email protected], [email protected]Search for more papers by this authorCorresponding Author
Dan Ding
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300071 China
E-mail: [email protected], [email protected]Search for more papers by this authorXu Huan
School of Pharmacy, Medical School, Nantong University, Nantong, Jiangsu, 226001 China
Search for more papers by this authorYi Chen
School of Pharmacy, Medical School, Nantong University, Nantong, Jiangsu, 226001 China
Search for more papers by this authorXiaozhen Wu
School of Pharmacy, Medical School, Nantong University, Nantong, Jiangsu, 226001 China
Search for more papers by this authorHui Wang
School of Pharmacy, Medical School, Nantong University, Nantong, Jiangsu, 226001 China
Search for more papers by this authorYing Yang
School of Pharmacy, Medical School, Nantong University, Nantong, Jiangsu, 226001 China
Search for more papers by this authorPengkai Wu
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022 China
Search for more papers by this authorTianqing Liu
NICM Health Research Institute, Western Sydney University, Sydney, NSW, 2145 Australia
Search for more papers by this authorCorresponding Author
Kaikai Wang
School of Pharmacy, Medical School, Nantong University, Nantong, Jiangsu, 226001 China
E-mail: [email protected], [email protected]Search for more papers by this authorCorresponding Author
Dan Ding
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300071 China
E-mail: [email protected], [email protected]Search for more papers by this authorDedicated to the Special Issue of Emerging Themes in Polymer Science.
Comprehensive Summary
Inflammation is associated with different stages of liver disease, including acute injury, fibrosis, cirrhosis, and hepatoma. During the progression of liver inflammation, activation of hepatic stellate cells (HSCs) and extracellular matrix (ECM) deposition are critical pathologies, and thus the combined therapy using HSCs and ECM as targets represents a promising strategy in the treatment of liver injury. Here, a novel CXCR4-inhibiting nanomedicine that can simultaneously deliver AMD3100 (CXCR4 antagonist) and siPAI-1 (siRNA of plasminogen activator inhibitor-1) was designed and developed to reverse liver fibrosis by inhibiting HSCs activation and degrading ECM deposition. With this goal in mind, a Zn(II) coordinated polymeric AMD3100 named PAMD/Zn polymer with siRNA delivery and CXCR4 antagonism capabilities was synthesized. Overall, our results suggest that PAMD/Zn recruits pro-inflammatory cells for fibrogenesis and inhibits the activation of HSCs for fibrolysis at various stages of liver injury. Its use in conjunction with PAI-1 silencing achieved satisfactory therapeutic efficacy in liver injury and fibrosis. The derivative CXCR4-inhibiting nanomedicine is a versatile platform that offers valuable benefits for the treatment of liver diseases.
Supporting Information
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Appendix S1: Supporting Information |
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