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. KimEduardo 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*

*此作品的通信作者

研究成果: Article同行評審

13 引文 斯高帕斯(Scopus)

摘要

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.

原文English
文章編號6692
期刊Nature Communications
14
發行號1
DOIs
出版狀態Published - 12月 2023

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