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Cuproptosis-immunotherapy using PD-1 overexpressing T cell membrane-coated nanosheets efficiently treats tumor

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机构: [1]Med-X Center for Materials, College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China [2]State Key Laboratory of Polymer Materials Engineering Polymer Research Institute of Sichuan University, College of Polymer Science and Engineering, Chengdu 610065, China [3]Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China [4]Key Laboratory of Drug Targeting and Drug Delivery Systems of Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610065, China
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关键词: Biomimetic system Nanosheets Cuproptosis Immunotherapy

摘要:
The cuproptosis cell death pathway brings fresh opportunities for tumor therapy. However, efficient and targeted cuproptosis induction in tumors is still a challenge. Unfortunately, the well-known cuproptosis initiator, disulfiram and copper complex (DSF/Cu2+), also increases PD-L1 level in tumors, which may diminish the final therapeutic outcome. In this study, DSF/Cu2+-loading MXene nanosheets are coated with PD-1 overexpressing T cell membrane to generate CuX-P system. CuX-P could recognize and stick to PD-L1 on tumor cells like a patch, which promotes the endocytosis of both CuX-P and PD-L1 by tumor cells. Following internalization and release of DSF/Cu2+ in the cytoplasm, PD-L1 expression is upregulated. However, due to the presence of CuX-P in the tumor microenvironment, the then supplemented PD-L1 on tumor surface again binds CuX-P for internalization. This feedback loop keeps blocking and consuming the PD-L1 on tumor surface and promotes the enrichment of CuX-P in tumors to induce cuproptosis. After CuX-P treatment with laser irradiation, strong anti-tumor immune responses are stimulated in a mouse model with triple-negative breast cancer. Thus, this study develops a tumor-targeted biomimetic system that offers simultaneous cuproptosis killing, photothermal therapy (PTT) and immunotherapy in mice.Copyright © 2023 Elsevier B.V. All rights reserved.

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出版当年[2023]版:
大类 | 1 区 医学
小类 | 1 区 化学:综合 1 区 药学
最新[2023]版:
大类 | 1 区 医学
小类 | 1 区 化学:综合 1 区 药学
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第一作者机构: [1]Med-X Center for Materials, College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China
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