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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.
Nanoscale. 2015 Mar 07; 7(9):3903-14.N

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.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA. omathanu.perumal@sdstate.edu.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25436837

Citation

Venuganti, Venkata Vamsi K., et al. "Topical Gene Silencing By Iontophoretic Delivery of an Antisense Oligonucleotide-dendrimer Nanocomplex: the Proof of Concept in a Skin Cancer Mouse Model." Nanoscale, vol. 7, no. 9, 2015, pp. 3903-14.
Venuganti VV, Saraswathy M, Dwivedi C, et al. Topical gene silencing by iontophoretic delivery of an antisense oligonucleotide-dendrimer nanocomplex: the proof of concept in a skin cancer mouse model. Nanoscale. 2015;7(9):3903-14.
Venuganti, V. V., Saraswathy, M., Dwivedi, C., Kaushik, R. S., & Perumal, O. P. (2015). Topical gene silencing by iontophoretic delivery of an antisense oligonucleotide-dendrimer nanocomplex: the proof of concept in a skin cancer mouse model. Nanoscale, 7(9), 3903-14. https://doi.org/10.1039/c4nr05241b
Venuganti VV, et al. Topical Gene Silencing By Iontophoretic Delivery of an Antisense Oligonucleotide-dendrimer Nanocomplex: the Proof of Concept in a Skin Cancer Mouse Model. Nanoscale. 2015 Mar 7;7(9):3903-14. PubMed PMID: 25436837.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Topical gene silencing by iontophoretic delivery of an antisense oligonucleotide-dendrimer nanocomplex: the proof of concept in a skin cancer mouse model. AU - Venuganti,Venkata Vamsi K, AU - Saraswathy,Manju, AU - Dwivedi,Chandradhar, AU - Kaushik,Radhey S, AU - Perumal,Omathanu P, PY - 2014/12/2/entrez PY - 2014/12/2/pubmed PY - 2016/2/10/medline SP - 3903 EP - 14 JF - Nanoscale JO - Nanoscale VL - 7 IS - 9 N2 - 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. SN - 2040-3372 UR - https://www.unboundmedicine.com/medline/citation/25436837/Topical_gene_silencing_by_iontophoretic_delivery_of_an_antisense_oligonucleotide_dendrimer_nanocomplex:_the_proof_of_concept_in_a_skin_cancer_mouse_model_ L2 - https://doi.org/10.1039/c4nr05241b DB - PRIME DP - Unbound Medicine ER -