Journal
BIOMATERIALS
Volume 34, Issue 4, Pages 1391-1401Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.10.072
Keywords
siRNA; Delivery system; Magnetic mesoporous silica nanoparticles (M-MSNs) Polyethyleneimine (PEI); KALA peptide; VEGF
Funding
- ERC from Science and Technology Commission of Shanghai [11DZ2211000]
- NNSF China [30900756, 81000656]
- SJTU [YG2009ZD203, YG2010ZD102, YG2011MS44, AE4160003, Z-416-001]
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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. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.
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