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Attenuating Metabolic Competition of Tumor Cells for Favoring the Nutritional Demand of Immune Cells by a Branched Polymeric Drug Delivery System

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机构: [1]Huaxi MR Research Center (HMRRC), Department of Radiology, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, and National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610041, China. [2]Functional and molecular imaging Key Laboratory of Sichuan Province, Key Laboratory of Transplant Engineering and Immunology, NHC, and Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, 610041, China. [3]Amgen Bioprocessing Centre, Keck Graduate Institute, Claremont, CA, 91711, USA. [4]Department of Chemical Engineering, Imperial College London, South Kensington Campus, London, SW7 2AZ, United Kingdom. [5]Department of Radiology, West China Xiamen Hospital of Sichuan University, Xiamen, Fujian, China.
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关键词: metabolic competition branched polymeric prodrug conjugate chemo-immunotherapy tumor immune microenvironment immunogenic cell death

摘要:
Tumor cells are dominant in the nutritional competition in the tumor microenvironment (TME), and their metabolic abnormalities often lead to microenvironmental acidosis and nutrient deprivation, thereby impairing the function of immune cells and diminishing the anti-tumor therapeutic effect. Herein, we report a branched polymeric conjugate and its efficacy in attenuating the metabolic competition of tumor cells. Compared with the control nanoparticles prepared from its linear counterpart, the branched conjugate-based nanoparticles (branched NPs) could more efficiently accumulate in the tumor tissue and interfere with the metabolic processes of tumor cells to increase the concentration of essential nutrients and reduce the level of immunosuppressive metabolites in the TME, thus creating a favorable environment for infiltrated immune cells. Its combined treatment with an immune checkpoint inhibitor (ICI) achieved an enhanced anti-tumor effect. Our work presents a promising approach for targeting the metabolic competition in the TME to enhance the chemo-immunotherapeutic effect against cancers. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.

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出版当年[2022]版:
大类 | 1 区 材料科学
小类 | 1 区 材料科学:综合 1 区 物理化学 1 区 物理:凝聚态物理 1 区 化学:综合 1 区 纳米科技 1 区 物理:应用
最新[2023]版:
大类 | 1 区 材料科学
小类 | 1 区 化学:综合 1 区 物理化学 1 区 材料科学:综合 1 区 纳米科技 1 区 物理:应用 1 区 物理:凝聚态物理
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第一作者机构: [1]Huaxi MR Research Center (HMRRC), Department of Radiology, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, and National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610041, China.
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通讯机构: [1]Huaxi MR Research Center (HMRRC), Department of Radiology, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, and National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610041, China. [2]Functional and molecular imaging Key Laboratory of Sichuan Province, Key Laboratory of Transplant Engineering and Immunology, NHC, and Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, 610041, China. [5]Department of Radiology, West China Xiamen Hospital of Sichuan University, Xiamen, Fujian, China.
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