科研之友
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摘要
RNA interference (RNAi) is widely regarded as a promising technology for disease treatment, yet one major obstacle for its clinical application is the lack of efficient siRNA delivery vehicles. In this study, we described a magnetic mesoporous silica nanoparticles (M-MSNs)-based, polyelectrolyte (polyethylenimine, PEI) and fusogenic peptide (KALA)-functionalized siRNA delivery system (denoted as M-MSN_siRNA@PEI-KALA), which was highly effective for initiating target gene silencing both in vitro and in vivo. The construction of this delivery system began with the encapsulation of siRNA within the mesopores of M-MSNs, followed by the coating of PEI on the external surface of siRNA-loaded M-MSNs and the chemical conjugation of KALA peptides. The as-prepared delivery vehicles, with notable siRNA protective effect and negligible cytotoxicity, could be easily internalized into cells, readily escape from the endolysosomes and release the loaded siRNA into the cytoplasm. As a result, the knockdown of enhanced green fluorescent protein (EGFP) and vascular endothelial growth factor (VEGF) in tumor cells were observed, both with excellent RNAi efficiencies. In the following in vivo experiments, the intratumoral injection of M-MSN_VEGF siRNA@PEI-KALA significantly inhibited the tumor growth, possibly by the suppression of neovascularization in tumors. To sum up, we have established a highly effective MSNs-based delivery system, which has great potential to serve as therapeutic siRNA formulation for cancer treatment.
- 出版日期2013-1
- 单位上海交通大学
