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Targeted Clearance of Senescent Cells Via Engineered Extracellular Vesicles Reprograms Tumor Immunosuppressive Microenvironment.
Ji, Panpan; Wang, Chen; Liu, Yang; Guo, Xin; Liang, Yuan; Wei, Jiangpeng; Liu, Zhaoyou; Gong, Li; Yang, Guodong; Ji, Gang.
Afiliación
  • Ji P; Department of Digestive Surgery, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China.
  • Wang C; Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
  • Liu Y; Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
  • Guo X; Department of Digestive Surgery, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China.
  • Liang Y; Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
  • Wei J; Department of Digestive Surgery, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China.
  • Liu Z; Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
  • Gong L; Department of Pathology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
  • Yang G; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Department of Biochemistry and Molecular Biology, Military Medical Innovation Center, Fourth Military Medical University, Xi'an, 710032, China.
  • Ji G; Department of Digestive Surgery, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China.
Adv Healthc Mater ; 13(23): e2400945, 2024 Sep.
Article en En | MEDLINE | ID: mdl-38794820
ABSTRACT
Unravelling the mechanisms for the immunosuppressive tumor microenvironment and developing corresponding therapeutic strategies are of great importance to improve the cancer immunotherapy. This study has revealed that there are abundant senescent cells accumulated in the colon cancer tissue, which contributes greatly to the immunosuppressive microenvironment. Oral delivery of Dasatinib and Quercetin (D+Q) eliminates the senescent cells with compromised efficiency due to the poor tumor penetration and short half-life. To improve the efficacy of senescent cell clearance, this work has developed an extracellular vesicle (EV) based senolytic strategy. The engineered senolytic EVs have anti-GPNMB (a senescent cell surface marker) displayed on the surface and D+Q loaded on the membrane. In a syngeneic mouse model, senolytic EVs efficiently and selectively eradicate the senescent cells and in turn unleashes the antitumor immunity. With the antitumor immunity boosted, cancer growth is inhibited and the survival is prolonged. In summary, this work has illuminated that senescent cells contribute to the immunosuppressive microenvironment in colon cancer and proposes a novel strategy to conquer the problem by EV-based senolytics.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Quercetina / Senescencia Celular / Neoplasias del Colon / Microambiente Tumoral / Vesículas Extracelulares / Dasatinib Límite: Animals / Humans Idioma: En Revista: Adv Healthc Mater Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Quercetina / Senescencia Celular / Neoplasias del Colon / Microambiente Tumoral / Vesículas Extracelulares / Dasatinib Límite: Animals / Humans Idioma: En Revista: Adv Healthc Mater Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania