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Issue 9, 2015
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Topical gene silencing by iontophoretic delivery of an antisense oligonucleotide–dendrimer nanocomplex: the proof of concept in a skin cancer mouse model

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Abstract

The study was aimed at investigating the feasibility of using a poly (amidoamine) (PAMAM) dendrimer as a carrier for topical iontophoretic delivery of an antisense oligonucleotide (ASO). Bcl-2, an anti-apoptotic protein implicated in skin cancer, was used as the model target protein to demonstrate the topical gene silencing approach. Confocal laser scanning microscopy studies demonstrated that the iontophoretically delivered ASO–dendrimer complex can reach the viable epidermis in porcine skin. In contrast, passively delivered free or dendrimer complexed ASO was mainly localized to the stratum corneum. The cell uptake of ASO was significantly enhanced by the dendrimer complex and the complex suppressed Bcl-2 levels in the cell. In the skin cancer mouse model, the iontophoretically delivered ASO–dendrimer complex reduced the tumor volume by 45% and was consistent with the reduction in Bcl-2 protein levels. The iontophoretically delivered ASO–dendrimer complex caused significant apoptosis in skin tumor. Overall, the findings from this study demonstrate that dendrimers are promising nanocarriers for developing topical gene silencing approaches for skin diseases.

Graphical abstract: Topical gene silencing by iontophoretic delivery of an antisense oligonucleotide–dendrimer nanocomplex: the proof of concept in a skin cancer mouse model

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Supplementary files

Article information


Submitted
10 Sep 2014
Accepted
14 Nov 2014
First published
17 Nov 2014

Nanoscale, 2015,7, 3903-3914
Article type
Paper
Author version available

Topical gene silencing by iontophoretic delivery of an antisense oligonucleotide–dendrimer nanocomplex: the proof of concept in a skin cancer mouse model

V. V. K. Venuganti,, M. Saraswathy, C. Dwivedi, R. S. Kaushik and O. P. Perumal, Nanoscale, 2015, 7, 3903
DOI: 10.1039/C4NR05241B

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