Macrophage-evading and tumor-specific apoptosis inducing nanoparticles for targeted cancer therapy  

作　　者：Zimo Liu Xuefei Zhou Qi Li Youqing Shen Tianhua Zhou Xiangrui Liu 

机构地区：[1]Department of Pharmacology and Department of Gastroenterology of the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310058,China [2]College of Chemical and Biological Engineering,Zhejiang University,Hangzhou 310027,China [3]International Institutes of Medicine,The Fourth Affiliated Hospital of Zhejiang University School of Medicine,Yiwu 322000,China [4]Cancer Center,Zhejiang University,Hangzhou 310058,China [5]Department of Cell Biology,School of Medicine,Zhejiang University,Hangzhou 310058,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第1期327-343,共17页药学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.32101128,21975218,and 51773176);the National Key Research and Development Program of China(2019YFA0802202);the 111 Project(B13026,China)。

摘　　要：Extended circulation of anticancer nanodrugs in blood stream is essential for their clinical applications.However,administered nanoparticles are rapidly sequestered and cleared by cells of the mononuclear phagocyte system(MPS).In this study,we developed a biomimetic nanosystem that is able to efficiently escape MPS and target tumor tissues.The fabricated nanoparticles(TM-CQ/NPs)were coated with fibroblast cell membrane expressing tumor necrosis factor(TNF)-related apoptosis inducing ligand(TRAIL).Coating with this functionalized membrane reduced the endocytosis of nanoparticles by macrophages,but increased the nanoparticle uptake in tumor cells.Importantly,this membrane coating specifically induced tumor cell apoptosis via the interaction of TRAIL and its cognate death receptors.Meanwhile,the encapsulated chloroquine(CQ)further suppressed the uptake of nanoparticles by macrophages,and synergized with TRAIL to induce tumor cell apoptosis.The vigorous antitumor efficacy in two mice tumor models confirmed our nanosystem was an effective approach to address the MPS challenge for cancer therapy.Together,our TM-CQ/NPs nanosystem provides a feasible approach to precisely target tumor tissues and improve anticancer efficacy.

关 键 词：TRAIL FIBROBLAST NANOPARTICLES Mononuclear phagocyte system Membrane coating CHLOROQUINE Cancer therapy Drug delivery 

分 类 号：R730.5[医药卫生—肿瘤]