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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish
Article number6692
JournalNature Communications
Volume14
Issue number1
DOIs
StatePublished - Dec 2023

Fingerprint

Dive into the research topics of 'Dual targeted extracellular vesicles regulate oncogenic genes in advanced pancreatic cancer'. Together they form a unique fingerprint.

Cite this