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Cuproptosis-immunotherapy using PD-1 overexpressing T cell membrane-coated nanosheets efficiently treats tumor.
Liu, Tiantian; Zhou, Zehang; Zhang, Mengxing; Lang, Puxin; Li, Jing; Liu, Zhenmi; Zhang, Zhirong; Li, Lin; Zhang, Ling.
Afiliación
  • Liu T; Med-X Center for Materials, College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China.
  • Zhou Z; State Key Laboratory of Polymer Materials Engineering Polymer Research Institute of Sichuan University, College of Polymer Science and Engineering, Chengdu 610065, China.
  • Zhang M; Med-X Center for Materials, College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China.
  • Lang P; Med-X Center for Materials, College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China.
  • Li J; Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China.
  • Liu Z; Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China.
  • Zhang Z; Key Laboratory of Drug Targeting and Drug Delivery Systems of Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610065, China.
  • Li L; Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China. Electronic address: lilin93@scu.edu.cn.
  • Zhang L; Med-X Center for Materials, College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China. Electronic address: zhangling83@scu.edu.cn.
J Control Release ; 362: 502-512, 2023 Oct.
Article en En | MEDLINE | ID: mdl-37652367
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos