Macrophage membrane-mediated targeted drug delivery for treatment of spinal cord injury regardless of the macrophage polarization states  

作　　者：Wei Tang Yi Yang Ling Yang Mei Tang Ying Chen Chong Li 

机构地区：[1]Medical Research Institute,College of Pharmaceutical Sciences,Southwest University,Chongqing 400715,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2021年第4期459-470,共12页亚洲药物制剂科学（英文）

基　　金：supported by the National Natural Science Foundation of China(No.81673376);the National Natural Science Foundation of Chongqing(cstc2015jcyj BX0100);the project for innovative Research Group at Higher Educational Institutions in Chongqing(CXQT20006)。

摘　　要：Targeted delivery of therapeutics for spinal cord injury(SCI)has been a long-term challenge due to the complexity of the pathological procession.Macrophage,as an immune cell,can selectively accumulate at the trauma site after SCI.This intrinsic targeting,coupled with good immune-escaping capacity makes macrophages an ideal source of biomimetic delivery carrier for SCI.Worth mentioning,macrophages have multiple polarization states,which may not be ignored when designing macrophage-based delivery systems.Herein,we fabricated macrophage membrane-camouflaged liposomes(RM-LIPs)and evaluated their abilities to extend drug circulation time and target the injured spinal cord.Specially,we detected the expression levels of the two main targeted receptors Mac-1 and integrinα4 in three macrophage subtypes,including unactivated(M0)macrophages,classically activated(M1)macrophages and alternatively activated(M2)macrophages,and compared targeting of these macrophage membrane-coated nanoparticles for SCI.The macrophage membrane camouflage decreased cellular uptake of liposomes in RAW264.7 immune cells and strengthened binding of the nanoparticle to the damaged endothelial cells in vitro.RM-LIPs can prolong drug circulation time and actively accumulate at the trauma site of the spinal cord in vivo.Besides,RM-LIPs loaded with minocycline(RM-LIP/MC)showed a comprehensive therapeutic effect on SCI mice,and the anti-pyroptosis was found to be a novel mechanism of RM-LIP/MC treatment of SCI.Moreover,the levels of Mac-1 and integrinα4 in macrophages and the targeting of RM-LIP for SCI were found to be independent of macrophage polarization states.Our study provided a biomimetic strategy via the biological properties of macrophages for SCI targeting and treatment.

关 键 词：Spinal cord injury PYROPTOSIS Macrophage polarization MINOCYCLINE Actively targeted delivery 

分 类 号：R651.2[医药卫生—外科学]