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Dual targeted extracellular vesicles regulate oncogenic genes in advanced pancreatic cancer.
Chiang, Chi-Ling; Ma, Yifan; Hou, Ya-Chin; Pan, Junjie; Chen, Sin-Yu; Chien, Ming-Hsien; Zhang, Zhi-Xuan; Hsu, Wei-Hsiang; Wang, Xinyu; Zhang, Jingjing; Li, Hong; Sun, Lili; Fallen, Shannon; Lee, Inyoul; Chen, Xing-Yu; Chu, Yeh-Shiu; Zhang, Chi; Cheng, Tai-Shan; Jiang, Wen; Kim, Betty Y S; Reategui, Eduardo; Lee, Robert; Yuan, Yuan; Liu, Hsiao-Chun; Wang, Kai; Hsiao, Michael; Huang, Chi-Ying F; Shan, Yan-Shen; Lee, Andrew S; James Lee, L.
  • Chiang CL; Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, 43210, USA.
  • Ma Y; Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA.
  • Hou YC; Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, 43210, USA.
  • Pan J; Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA.
  • Chen SY; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan.
  • Chien MH; Division of General Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan.
  • Zhang ZX; Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, 43210, USA.
  • Hsu WH; Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 11221, Taiwan.
  • Wang X; Genomics Research Center, Academia Sinica, Taipei, 11529, Taiwan.
  • Zhang J; Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 11221, Taiwan.
  • Li H; Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 11221, Taiwan.
  • Sun L; Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, 43210, USA.
  • Fallen S; Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, 43210, USA.
  • Lee I; Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, 43210, USA.
  • Chen XY; Key Laboratory for Ultrafine Materials of Ministry of Education and School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, PR China.
  • Chu YS; Institute of Systems Biology, Seattle, WA, 98109, USA.
  • Zhang C; Institute of Systems Biology, Seattle, WA, 98109, USA.
  • Cheng TS; Brain Research Center, National Yang Ming Chiao Tung University, Taipei, 11221, Taiwan.
  • Jiang W; Brain Research Center, National Yang Ming Chiao Tung University, Taipei, 11221, Taiwan.
  • Kim BYS; College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA.
  • Reategui E; Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 11221, Taiwan.
  • Lee R; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • Yuan Y; Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • Liu HC; Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, 43210, USA.
  • Wang K; College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA.
  • Hsiao M; Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, 43210, USA.
  • Huang CF; Key Laboratory for Ultrafine Materials of Ministry of Education and School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, PR China.
  • Shan YS; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan.
  • Lee AS; Division of General Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan.
  • James Lee L; Institute of Systems Biology, Seattle, WA, 98109, USA.
Nat Commun ; 14(1): 6692, 2023 10 23.
Article en En | MEDLINE | ID: mdl-37872156
ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) tumours carry multiple gene mutations and respond poorly to treatments. There is currently an unmet need for drug carriers that can deliver multiple gene cargoes to target high solid tumour burden like PDAC. Here, we report a dual targeted extracellular vesicle (dtEV) carrying high loads of therapeutic RNA that effectively suppresses large PDAC tumours in mice. The EV surface contains a CD64 protein that has a tissue targeting peptide and a humanized monoclonal antibody. Cells sequentially transfected with plasmid DNAs encoding for the RNA and protein of interest by Transwell®-based asymmetric cell electroporation release abundant targeted EVs with high RNA loading. Together with a low dose chemotherapy drug, Gemcitabine, dtEVs suppress large orthotopic PANC-1 and patient derived xenograft tumours and metastasis in mice and extended animal survival. Our work presents a clinically accessible and scalable way to produce abundant EVs for delivering multiple gene cargoes to large solid tumours.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático / Vesículas Extracelulares Límite: Animals / Humans Idioma: En Año: 2023 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático / Vesículas Extracelulares Límite: Animals / Humans Idioma: En Año: 2023 Tipo del documento: Article