| 1 | Engineering SIRPα cellular membrane-based nanovesicles for combination immunotherapy显示文摘Immune checkpoint inhibitors(ICIs)have revolutionized cancer treatment for their unprecedented clinical efficacy.Signal regulatory proteinα(SIRPα)is a phagocytic checkpoint expressed on macrophages,dendritic cells,other myeloid cells.Cancer cells inhibit macrophage phagocytosis through the interaction of the CD47-SIRPαaxis.Disrupting the CD47-SIRPαaxis has therefore been a promising strategy in restoring the immune attack against cancer.Herein,we engineered cellular membrane nanovesicles(NVs)presenting SIRPαreceptors for phagocytosis checkpoint blockade to augment the antitumor immune response.Furthermore,zebularine(Zeb),an inhibitor of DNA methyltransferase,was encapsulated into SIRPαNVs to reprogram the immunosuppressive tumor microenvironment together with blockade of phagocytosis checkpoint.It is demonstrated that SIRPα@Zeb can improve tumor immunogenicity,the polarization of tumor-associated macrophages to the M1 phenotype,increase the infiltration of CD8^(+)T lymphocytes in tumors.The robust antitumor immune response induced by SIRPα@Zeb significantly suppressed tumor growth and extended mice-bearing melanoma xenograft survival. | Mingyue Wang Yanfang Wang Yeteng Mu Fuxu Yang Zebin Yang Yuxuan Liu Lili Huang Shi Liu Xingang Guan Zhigang Xie Zhen Gu | 2023 | Nano Research2023，16，5： | 0 |
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