期刊
JOURNAL OF MATERIALS CHEMISTRY B
卷 3, 期 10, 页码 2163-2172出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c4tb01623h
关键词
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资金
- Nanyang Technological University [M4080141.040]
- Singapore Ministry of Education [M4010360.040 RG29/10]
- Singapore Ministry of Education under Tier 2 Research Grant [MOE2010-T2-2-010 (4020020.040 ARC2/11)]
- National Natural Science Foundation of China (NSFC) [81301318, 61107017, 81400591]
- Department of Fiber and Composite Materials at Feng Chia University
- Ministry of Science and Technology of Taiwan, Republic of China [MOST 103-2218-E-035-010]
RNA interference (RNAi) targeting the K-ras oncogene mutation in pancreatic cancer mediated by small interfering RNA (siRNA) transfection is a very promising treatment. However, the rapid degradation and negative charge of naked siRNAs restrict their direct delivery into cells. In this contribution, we propose a safe and effective transmembrane transport nanocarrier formulation based on a newly developed biodegradable charged polyester-based vector (BCPV) for K-ras siRNA delivery into pancreatic cancer cells. Our results have shown that these biodegradable and biocompatible vectors are able to transfect siRNAs targeting mutant K-ras into MiaPaCa-2 cells with high transfection and knockdown efficiency. More importantly, the RNAi process initiated a cascade gene regulation of the downstream proteins of K-ras associated with cell proliferation, migration, invasion and apoptosis. We observed that after the mutant K-ras siRNA transfection, the growth, migration and invasion of the MiaPaCa-2 cells were significantly reduced; also, the apoptosis of the pancreatic cancer cells was promoted. Although in vivo testing data are limited, we propose that the BCPV based nanoparticle formulation could be a promising candidate as non-viral vectors for gene therapy in clinical settings.
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