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

Acta Pharmaceutica Sinica B 2023年第1期13卷 327-343页

作者： Zimo Liu Xuefei Zhou Qi Li Youqing Shen Tianhua Zhou Xiangrui Liu Department of Pharmacology and Department of Gastroenterology of the Second Affiliated Hospital Zhejiang University School of MedicineHangzhou 310058China College of Chemical and Biological Engineering Zhejiang UniversityHangzhou 310027China International Institutes of Medicine The Fourth Affiliated Hospital of Zhejiang University School of MedicineYiwu 322000China Cancer Center Zhejiang UniversityHangzhou 310058China Department of Cell Biology School of MedicineZhejiang UniversityHangzhou 310058China

Extended circulation of anticancer nanodrugs in blood stream is essential for their clinical ***,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 *** 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 ***,this membrane coating specifically induced tumor cell apoptosis via the interaction of TRAIL and its cognate death ***,the encapsulated chloroquine(CQ)further suppressed the uptake of nanoparticles by macrophages,and synergized with TRAIL to induce tumor cell *** vigorous antitumor efficacy in two mice tumor models confirmed our nanosystem was an effective approach to address the MPS challenge for cancer ***,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

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