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Carbon Dioxide-Derived Biodegradable and Cationic Polycarbonates as a New siRNA Carrier for Gene Therapy in Pancreatic Cancer.
Zhang, Xinmeng; Lin, Zheng-Ian; Yang, Jingyu; Liu, Guan-Lin; Hu, Zulu; Huang, Haoqiang; Li, Xiang; Liu, Qiqi; Ma, Mingze; Xu, Zhourui; Xu, Gaixia; Yong, Ken-Tye; Tsai, Wei-Chung; Tsai, Tzu-Hsien; Ko, Bao-Tsan; Chen, Chih-Kuang; Yang, Chengbin.
Afiliación
  • Zhang X; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China.
  • Lin ZI; Polymeric Biomaterials Laboratory, Department of Materials and Optoelectronic Science, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan.
  • Yang J; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China.
  • Liu GL; Department of Chemistry, National Chung Hsing University, Taichung 402, Taiwan.
  • Hu Z; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China.
  • Huang H; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China.
  • Li X; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China.
  • Liu Q; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China.
  • Ma M; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China.
  • Xu Z; Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen 518055, China.
  • Xu G; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China.
  • Yong KT; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China.
  • Tsai WC; School of Biomedical Engineering, The University of Sydney, Sydney, NSW 2006, Australia.
  • Tsai TH; The University of Sydney Nano Institute, The University of Sydney, Sydney, NSW 2006, Australia.
  • Ko BT; Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.
  • Chen CK; Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.
  • Yang C; Department of Chemistry, National Chung Hsing University, Taichung 402, Taiwan.
Nanomaterials (Basel) ; 11(9)2021 Sep 06.
Article en En | MEDLINE | ID: mdl-34578632
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: Nanomaterials (Basel) Año: 2021 Tipo del documento: Article País de afiliación: China
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: Nanomaterials (Basel) Año: 2021 Tipo del documento: Article País de afiliación: China