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Academic Journal
Dual targeted extracellular vesicles regulate oncogenic genes in advanced pancreatic cancer
Chi-Ling Chiang, Yifan Ma, Ya-Chin Hou, Junjie Pan, Sin-Yu Chen, Ming-Hsien Chien, Zhi-Xuan Zhang, Wei-Hsiang Hsu, Xinyu Wang, Jingjing Zhang, Hong Li, Lili Sun, Shannon Fallen, Inyoul Lee, Xing-Yu Chen, Yeh-Shiu Chu, Chi Zhang, Tai-Shan Cheng, Wen Jiang, Betty Y. S. Kim, Eduardo Reategui, Robert Lee, Yuan Yuan, Hsiao-Chun Liu, Kai Wang, Michael Hsiao, Chi-Ying F. Huang, Yan-Shen Shan, Andrew S. Lee, L. James Lee
Nature Communications, Vol 14, Iss 1, Pp 1-18 (2023)
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| Title | Dual targeted extracellular vesicles regulate oncogenic genes in advanced pancreatic cancer |
|---|---|
| Authors | Chi-Ling Chiang, Yifan Ma, Ya-Chin Hou, Junjie Pan, Sin-Yu Chen, Ming-Hsien Chien, Zhi-Xuan Zhang, Wei-Hsiang Hsu, Xinyu Wang, Jingjing Zhang, Hong Li, Lili Sun, Shannon Fallen, Inyoul Lee, Xing-Yu Chen, Yeh-Shiu Chu, Chi Zhang, Tai-Shan Cheng, Wen Jiang, Betty Y. S. Kim, Eduardo Reategui, Robert Lee, Yuan Yuan, Hsiao-Chun Liu, Kai Wang, Michael Hsiao, Chi-Ying F. Huang, Yan-Shen Shan, Andrew S. Lee, L. James Lee |
| Publication Year |
2023
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| Source |
Nature Communications, Vol 14, Iss 1, Pp 1-18 (2023)
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| Description |
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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| Document Type |
article
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| Language |
English
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| Publisher Information |
Nature Portfolio, 2023.
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| Subject Terms | |
