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Delivery of Engineered Primary Tumor-Derived Exosomes Effectively Suppressed the Colorectal Cancer Chemoresistance and Liver Metastasis.
Huang, Chengzhi; Zhou, Yue; Feng, Xingyu; Wang, Junjiang; Li, Yong; Yao, Xueqing.
Afiliación
  • Huang C; Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510000, China.
  • Zhou Y; School of Medicine, South China University of Technology, Guangzhou 510006, China.
  • Feng X; Department of General Surgery, Guangdong Provincial People's Hospital Ganzhou Hospital (Ganzhou Municipal Hospital), Ganzhou 341000, China.
  • Wang J; Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510000, China.
  • Li Y; Department of General Surgery, Guangdong Provincial People's Hospital Ganzhou Hospital (Ganzhou Municipal Hospital), Ganzhou 341000, China.
  • Yao X; The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510000, China.
ACS Nano ; 17(11): 10313-10326, 2023 06 13.
Article en En | MEDLINE | ID: mdl-37141393
Liver metastasis is one of the major causes of colorectal cancer (CRC)-related morbidity and mortality. Delivering small interfering RNAs (siRNAs) or noncoding RNAs has been reported as a promising method to target liver metastasis and chemoresistance in CRC. Here, we report a noncoding RNA delivery system using exosomes derived from primary patient cells. Coiled-coil domain-containing protein 80 (CCDC80) was strongly associated with CRC liver metastasis and chemoresistance, a finding validated by bioinformatic analysis and clinical specimens. Silencing CCDC80 significantly increased sensitivity to chemotherapy agents in OXA-resistant cell lines and a mouse model. The primary cell-derived exosome delivery system was designed to simultaneously deliver siRNAs targeting CCDC80 and increase chemotherapy sensitivity in the distant CRC liver metastasis mouse models and patient-derived xenograft mouse models. We further validated the antitumor effect in an ex vivo model of chemoresistant CRC organoids and a patient-derived organoid xenograft model. Tumor-bearing mice treated with the siRNA-delivering exosomes and hepatectomy showed ideal overall survival. Our results provide a therapeutic target and represent a possible therapeutic alternative for patients with CRC and distant metastasis and in cases of chemoresistance.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / MicroARNs / Exosomas / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: ACS Nano Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / MicroARNs / Exosomas / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: ACS Nano Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos