单位：[1]Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China[2]Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE), Wuhan University, Wuhan 430072, China[3]Key Laboratory of Coal Conversion and New Carbon Materials of Hubei Province & Institute of Advanced Materials and Nanotechnology, College of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, China[4]Hubei Jiangxia Laboratory, Wuhan 430200, China[5]Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China内科学系血液内科华中科技大学同济医学院附属同济医院[6]Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan 430030, China[7]State Key Laboratory of Separation Membrane and Membrane Process & Tianjin Key Laboratory of Green Chemical Technology and Process Engineering, School of Chemistry and Chemical Engineering, Tiangong University, Tianjin 300387, China[8]Hubei Key Laboratory of Radiation Chemistry and Functional Materials, Hubei University of Science and Technology, Xianning 437100, China
Chimeric antigen receptor (CAR) T cell therapy holds great promise in the treatment of hematological malignancies but performs poorly in solid tumors due to the tumor immunosuppressive microenvironment. Herein, a multifunctional nanocatalyst (APHA@CM) was prepared by encapsulating horseradish peroxidase (HRP)-loaded Au/polydopamine nanoparticles (Au/PDA NPs) and Ag2S quantum dots with CAR T cell membranes to improve the CAR T cell therapy in solid tumors. The APHA@CM has excellent multimodal imaging capability to precisely guide the scope and time window for nanocatalyst-induced tumor microenvironment regulation and CAR T cell therapy. The oxidase-like activity of Au NPs inhibited the glycolytic metabolism of tumor cells, reducing lactate efflux, reprogramming tumor immunosuppression, and ultimately increasing CAR T cell activation within the tumors. Additionally, the hypoxia environment of tumors could be relieved by HRP to enhance the Au/PDA NPs-induced synergistic sonodynamic/photothermal therapy (SDT/PTT), thereby promoting the immunogenic cell death of NALM 6 cells and enhancing CAR T cell-mediated immune microenvironment reprogramming. When this strategy was utilized to treat NALM 6 solid tumors, it not only completely eliminated tumors but also formed a long-term immune memory effect to inhibit tumor metastasis and recurrence. This work offers a strategy for CAR T cell therapy in solid tumor.
第一作者单位：[1]Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China[2]Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE), Wuhan University, Wuhan 430072, China[3]Key Laboratory of Coal Conversion and New Carbon Materials of Hubei Province & Institute of Advanced Materials and Nanotechnology, College of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, China[4]Hubei Jiangxia Laboratory, Wuhan 430200, China
通讯作者：
通讯机构：[1]Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China[2]Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE), Wuhan University, Wuhan 430072, China[3]Key Laboratory of Coal Conversion and New Carbon Materials of Hubei Province & Institute of Advanced Materials and Nanotechnology, College of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, China[4]Hubei Jiangxia Laboratory, Wuhan 430200, China[5]Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China[6]Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan 430030, China[7]State Key Laboratory of Separation Membrane and Membrane Process & Tianjin Key Laboratory of Green Chemical Technology and Process Engineering, School of Chemistry and Chemical Engineering, Tiangong University, Tianjin 300387, China[8]Hubei Key Laboratory of Radiation Chemistry and Functional Materials, Hubei University of Science and Technology, Xianning 437100, China[*1]Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China[*2]Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE), Wuhan University, Wuhan 430072, China[*3]Hubei Jiangxia Laboratory, Wuhan 430200, China[*4]Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China[*5]Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan 430030, China[*6]Key Laboratory of Coal Conversion and New Carbon Materials of Hubei Province & Institute of Advanced Materials and Nanotechnology, College of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, China[*7]State Key Laboratory of Separation Membrane and Membrane Process & Tianjin Key Laboratory of Green Chemical Technology and Process Engineering, School of Chemistry and Chemical Engineering, Tiangong University, Tianjin 300387, China[*8]Hubei Key Laboratory of Radiation Chemistry and Functional Materials, Hubei University of Science and Technology, Xianning 437100, China
推荐引用方式(GB/T 7714)：
Li Haimei,Yang Xiuxiu,Wang Zichen,et al.A Near-Infrared-II Fluorescent Nanocatalyst for Enhanced CAR T Cell Therapy against Solid Tumor by Immune Reprogramming[J].ACS NANO.2023,11749-11763.doi:10.1021/acsnano.3c02592.
APA：
Li Haimei,Yang Xiuxiu,Wang Zichen,She Wenyan,Liu Yi...&Jiang Peng.(2023).A Near-Infrared-II Fluorescent Nanocatalyst for Enhanced CAR T Cell Therapy against Solid Tumor by Immune Reprogramming.ACS NANO,,
MLA：
Li Haimei,et al."A Near-Infrared-II Fluorescent Nanocatalyst for Enhanced CAR T Cell Therapy against Solid Tumor by Immune Reprogramming".ACS NANO .(2023):11749-11763
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