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HERO ID
4367577
Reference Type
Journal Article
Title
PEG conjugated VEGF siRNA for anti-angiogenic gene therapy
Author(s)
Kim, SH; Jeong, JH; Lee, SH; Kim, SW; Park, TG
Year
2006
Is Peer Reviewed?
Yes
Journal
Journal of Controlled Release
ISSN:
0168-3659
EISSN:
1873-4995
Publisher
ELSEVIER SCIENCE BV
Location
AMSTERDAM
Volume
116
Issue
2
Page Numbers
123-129
Language
English
PMID
16831481
DOI
10.1016/j.jconrel.2006.05.023
Web of Science Id
WOS:000245332000004
Abstract
A novel siRNA delivery system based on polyelectrolyte complex (PEC) micelles was introduced in this study. Vascular endothelial growth factor (VEGF) siRNA was conjugated to poly(ethylene glycol) (PEG) via a disulfide linkage (siRNA-PEG). The siRNA-PEG conjugate could form PEC micelles by interacting with cationic polyethylenimine (PEI) as a core forming agent. The VEGF siRNA-PEG/PEI PEC micelles showed greater stability than naked VEGF siRNA against enzymatic degradation. Under a reductive condition similar to cytosolic environment, an intact form of siRNA was released from the siRNA-PEG conjugate by cleavage of the disulfide linkage. The VEGF siRNA-PEG/PEI PEC micelles effectively silenced VEGF gene expression in prostate carcinoma cells (PC-3) up to 96.5% under an optimized formulation condition. They also showed a far superior VEGF gene silencing effect than VEGF siRNA/PEI complexes even in the presence of serum. This study suggests that the siRNA delivery system using VEGF siRNA-PEG/PEI PEC micelles could be potentially applied to RNAi-based anti-angiogenic treatment of cancer in vivo.
Conference Name
9th European Symposium on Controlled Drug Delivery
Conference Location
Noordwijk, NETHERLANDS
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