Nature Communications (Oct 2023)
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
Affiliations
- Chi-Ling Chiang
- Department of Chemical and Biomolecular Engineering, The Ohio State University
- Yifan Ma
- Department of Chemical and Biomolecular Engineering, The Ohio State University
- Ya-Chin Hou
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University
- Junjie Pan
- Department of Chemical and Biomolecular Engineering, The Ohio State University
- Sin-Yu Chen
- Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University
- Ming-Hsien Chien
- Genomics Research Center, Academia Sinica
- Zhi-Xuan Zhang
- Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University
- Wei-Hsiang Hsu
- Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University
- Xinyu Wang
- Department of Chemical and Biomolecular Engineering, The Ohio State University
- Jingjing Zhang
- Department of Chemical and Biomolecular Engineering, The Ohio State University
- Hong Li
- Department of Chemical and Biomolecular Engineering, The Ohio State University
- Lili Sun
- Key Laboratory for Ultrafine Materials of Ministry of Education and School of Materials Science and Engineering, East China University of Science and Technology
- Shannon Fallen
- Institute of Systems Biology
- Inyoul Lee
- Institute of Systems Biology
- Xing-Yu Chen
- Brain Research Center, National Yang Ming Chiao Tung University
- Yeh-Shiu Chu
- Brain Research Center, National Yang Ming Chiao Tung University
- Chi Zhang
- College of Pharmacy, The Ohio State University
- Tai-Shan Cheng
- Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University
- Wen Jiang
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center
- Betty Y. S. Kim
- Department of Neurosurgery, The University of Texas MD Anderson Cancer Center
- Eduardo Reategui
- Department of Chemical and Biomolecular Engineering, The Ohio State University
- Robert Lee
- College of Pharmacy, The Ohio State University
- Yuan Yuan
- Department of Chemical and Biomolecular Engineering, The Ohio State University
- Hsiao-Chun Liu
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University
- Kai Wang
- Institute of Systems Biology
- Michael Hsiao
- Genomics Research Center, Academia Sinica
- Chi-Ying F. Huang
- Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University
- Yan-Shen Shan
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University
- Andrew S. Lee
- Institute for Cancer Research, Shenzhen Bay Laboratory
- L. James Lee
- Department of Chemical and Biomolecular Engineering, The Ohio State University
- DOI
- https://doi.org/10.1038/s41467-023-42402-3
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 18
Abstract
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.
