Carbon Dioxide-Derived Biodegradable and Cationic Polycarbonates as a New siRNA Carrier for Gene Therapy in Pancreatic Cancer

Xinmeng Zhang; Zheng-Ian Lin; Jingyu Yang; Guan-Lin Liu; Zulu Hu; Haoqiang Huang; Xiang Li; Qiqi Liu; Mingze Ma; Zhourui Xu; Gaixia Xu; Ken-Tye Yong; Wei-Chung Tsai; Tzu-Hsien Tsai; Bao-Tsan Ko; Chih-Kuang Chen; Chengbin Yang

doi:10.3390/nano11092312

Nanomaterials (Sep 2021)

Carbon Dioxide-Derived Biodegradable and Cationic Polycarbonates as a New siRNA Carrier for Gene Therapy in Pancreatic Cancer

Xinmeng Zhang,
Zheng-Ian Lin,
Jingyu Yang,
Guan-Lin Liu,
Zulu Hu,
Haoqiang Huang,
Xiang Li,
Qiqi Liu,
Mingze Ma,
Zhourui Xu,
Gaixia Xu,
Ken-Tye Yong,
Wei-Chung Tsai,
Tzu-Hsien Tsai,
Bao-Tsan Ko,
Chih-Kuang Chen,
Chengbin Yang

Affiliations

Xinmeng Zhang: Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China
Zheng-Ian Lin: Polymeric Biomaterials Laboratory, Department of Materials and Optoelectronic Science, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan
Jingyu Yang: Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China
Guan-Lin Liu: Department of Chemistry, National Chung Hsing University, Taichung 402, Taiwan
Zulu Hu: Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China
Haoqiang Huang: Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China
Xiang Li: Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China
Qiqi Liu: Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China
Mingze Ma: Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China
Zhourui Xu: Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China
Gaixia Xu: Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China
Ken-Tye Yong: School of Biomedical Engineering, The University of Sydney, Sydney, NSW 2006, Australia
Wei-Chung Tsai: Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
Tzu-Hsien Tsai: Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
Bao-Tsan Ko: Department of Chemistry, National Chung Hsing University, Taichung 402, Taiwan
Chih-Kuang Chen: Polymeric Biomaterials Laboratory, Department of Materials and Optoelectronic Science, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan
Chengbin Yang: Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China

DOI: https://doi.org/10.3390/nano11092312
Journal volume & issue: Vol. 11, no. 9
p. 2312

Abstract

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Pancreatic cancer is an aggressive malignancy associated with poor prognosis and a high tendency in developing infiltration and metastasis. K-ras mutation is a major genetic disorder in pancreatic cancer patient. RNAi-based therapies can be employed for combating pancreatic cancer by silencing K-ras gene expression. However, the clinical application of RNAi technology is appreciably limited by the lack of a proper siRNA delivery system. To tackle this hurdle, cationic poly (cyclohexene carbonate) s (CPCHCs) using widely sourced CO2 as the monomer are subtly synthesized via ring-opening copolymerization (ROCOP) and thiol-ene functionalization. The developed CPCHCs could effectively encapsulate therapeutic siRNA to form CPCHC/siRNA nanoplexes (NPs). Serving as a siRNA carrier, CPCHC possesses biodegradability, negligible cytotoxicity, and high transfection efficiency. In vitro study shows that CPCHCs are capable of effectively protecting siRNA from being degraded by RNase and promoting a sustained endosomal escape of siRNA. After treatment with CPCHC/siRNA NPs, the K-ras gene expression in both pancreatic cancer cell line (PANC-1 and MiaPaCa-2) are significantly down-regulated. Subsequently, the cell growth and migration are considerably inhibited, and the treated cells are induced into cell apoptotic program. These results demonstrate the promising potential of CPCHC-mediated siRNA therapies in pancreatic cancer treatment.

Published in Nanomaterials

ISSN: 2079-4991 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry
Website: https://www.mdpi.com/journal/nanomaterials

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