期刊
JOURNAL OF CONTROLLED RELEASE
卷 118, 期 3, 页码 357-363出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2006.12.026
关键词
RNA interference; VEGF; anti-angiogenesis; gene therapy; polyethylenimine
资金
- NCI NIH HHS [CA 107070] Funding Source: Medline
We examined the potential application of a non-viral gene carrier, water soluble lipopolymer (WSLP) for delivering siRNA targeting vascular endothelial growth factor (VEGF) in vitro and in vivo. WSLP was complexed with siRNA designed to inhibit human VEGF expression or scrambled siRNA as a control. WSLP readily formed nano-sized complexes (similar to 100 nm) with siRNA and protected siRNAs from enzymatic degradation in serum conditioned media. WSLP/siRNA complexes were transfected in PC-3 cells derived from human prostate adenocarcinomas and, then the siRNA delivery efficiency of the complexes was evaluated by VEGF production inhibition assay. VEGF production was efficiently inhibited by the WSLP/siRNA complexes, while complexes of WSLP with scrambled siRNA did not show this inhibitory effect. WSLP/siRNA complexes reduced the VEGF production by 40% when compared to unmodified branched polyethylenimine (bPEI, MW = 1800). Moreover, WSLP/siRNA complexes reduced tumor volume by 55% at 21 days, and by 65% at 28 days when compared to controls. These results indicate that WSLP has potential as a siRNA delivering agent and can be applied for anti-angiogenic tumor therapy. (c) 2007 Elsevier B.V. All rights reserved.
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