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Penetration and efficacy of VEGF siRNA using polyelectrolyte complex micelles in a human solid tumor model in-vitro

Title
Penetration and efficacy of VEGF siRNA using polyelectrolyte complex micelles in a human solid tumor model in-vitro
Authors
Al-Abd A.M.Lee S.H.Kim S.H.Cha J.-H.Park T.G.Lee S.J.Kuh H.-J.
Ewha Authors
이승진
SCOPUS Author ID
이승진scopus
Issue Date
2009
Journal Title
Journal of Controlled Release
ISSN
0168-3659JCR Link
Citation
vol. 137, no. 2, pp. 130 - 135
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
A polyelectrolyte complex(PEC) micelle-based siRNA delivery system has been developed for vascular endothelial growth factor (VEGF), and its antitumor efficacy has been demonstrated using in-vivo animal models. Penetration and distribution through the avascular regions of human solid tumors after extravasation are important issues for antitumor efficacy, especially for macromolecules such as VEGF siRNA PEC micelles. Using an in-vitro solid tumor model, multicellular layers(MCL) culture of human colorectal cancer cells, we evaluated the penetration kinetics and efficacy of VEGF siRNA PEC micelles(PEC-siRNA) in comparison to unmodified siRNA(N-siRNA). The PEC-siRNA showed full penetration (15-17 layers of cells) with a unique punctuated distribution pattern at 48 h following initial accumulation in the top layers and a significant suppression of mRNA and protein expression in a dose-dependent manner after 72 h exposure. Although the initial penetration of N-siRNA was faster than that of PEC-siRNA, N-siRNA showed complete loss of activity due to its instability within 24 h. Our data support the idea that PEC micelle formulation may provide stable penetration tool through the multilayers of cancer cells and ensure the gene silencing effect of VEGF. This study also demonstrated that MCL could serve as a useful in-vitro model to evaluate the dose- and time-dependent profiles of penetration and efficacy of macromolecular delivery systems in human solid tumor avascular regions. © 2009 Elsevier B.V. All rights reserved.
DOI
10.1016/j.jconrel.2009.03.009
Appears in Collections:
약학대학 > 약학과 > Journal papers
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