Surface charge-convertible quaternary ammonium salt-based micelles for in vivo infection therapy  

作　　者：Dengfeng He Yifeng Tan Pengfei Li Yadong Luo Yuhong Zhu Yunlong Yu Jiali Chen Ning Ning Shiyong Zhang 

机构地区：[1]National Engineering Research Center for Biomaterials and College of Chemistry,Sichuan University,Chengdu 610064,China [2]West China Hospital,Sichuan University,Chengdu 610041,China

出　　处：《Chinese Chemical Letters》2021年第5期1743-1746,共4页中国化学快报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(Nos.21975165,51703145 and 51673130);China Postdoctoral Science Foundation(Nos.2017M620426 and 2019T12084).

摘　　要：Quaternary ammonium salts(QASs) are excellent candidates for treating stubborn bacterial infections caused by biofilms due to their high sterilization efficiency and potential inhibition of the development of drug resistance.However,the inherent toxicity of QASs,including cytotoxicity,protein absorption and hemolysis,severely limits their applications in vivo.Herein,a charge-co nvertible quaternary ammonium salt-based micelle(QAS-SL@CM) was constructed by co-assembly of two amphiphiles with opposite charges and shell cross-linking strategy.The toxicity of the QAS-SL@CM could be greatly reduced towa rds human cells contrast to the corresponding QASs.By response to the acidic environment at infection sites,the surface charge of QAS-SL@CM could be immediately changed to positive and then target to negatively charged bacteria.Furthermo re,β-thiopropionate bonds on QAS-SL@CM could also be disintegrated under acid environment to release QASs to kill bacteria.Importantly,the QAS-SL@CM showed significant therapeutic effect in mice subcutaneous abscesses models without interference with normal cells.Therefore,a surface adaptive micelle constructed by charge-convertible strategy has been developed to ove rcome the cytotoxicity of QAS s,and could intelligently respond to the microenvironment of infected wound for in vivo infection therapy,which shows promising application in clinic.

关 键 词：Quaternary ammonium salt Co-assembled micelle BIOFILM Biological safety In vivo infection 

分 类 号：TQ460.1[化学工程—制药化工]