期刊
NANOMATERIALS
卷 11, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/nano11092312
关键词
cationic polycarbonates; biodegradable; pancreatic cancer; siRNA delivery; K-ras
类别
资金
- National Natural Science Foundation of China [81801859, 51802243, 91859122]
- Natural Science Foundation of Guangdong Province [2019A1515012163, 2021A1515012159]
- University Stable Support Research Funding of Shenzhen [20200813153346001]
- Shenzhen Basic Research Program [JCYJ20180305125254860, JCYJ20180507182025817]
- Shenzhen University [2019136]
- Kaohsiung Veterans General Hospital
- National Sun Yat-sen University/Kaohsiung Medical University [KSVNSU110-011, NSYSUKMU 110-P026]
- Ministry of Science and Technology, Taiwan [MOST 110-2113-M-005-018, MOST 109-2221-E-110-066-MY3, 110-2221-E-110-001-MY3]
The study highlights the potential of CPCHC-mediated siRNA therapies in treating pancreatic cancer by effectively silencing K-ras gene expression and inhibiting cell growth and migration. CPCHCs can protect siRNA from degradation, promote sustained endosomal escape, and induce cell apoptotic program in treated cancer cells.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据