Topical and Targeted Delivery of siRNAs to Melanoma Cells Using a Fusion Peptide Carrier
Autor: | Weiping Ding, Dayong Gao, Jing Liu, Renquan Ruan, Pengfei Wei, Sijie Sun, Longping Wen, Ming Chen, Lili Zou |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Small interfering RNA Melanoma Experimental Apoptosis Biology Permeability Article Proto-Oncogene Proteins c-myc Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine In vivo Epidermal growth factor medicine Animals Gene silencing Gene Silencing RNA Small Interfering Cell Proliferation Skin Multidisciplinary Cell Death Epidermal Growth Factor Cell growth Melanoma Gene Transfer Techniques medicine.disease Molecular biology Mice Inbred C57BL 030104 developmental biology Liver 030220 oncology & carcinogenesis Cancer cell Cancer research Peptides Drug carrier |
Zdroj: | Scientific Reports |
ISSN: | 2045-2322 |
DOI: | 10.1038/srep29159 |
Popis: | Topical application of siRNAs through the skin is a potentially effective strategy for the treatment of melanoma tumors. In this study, we designed a new and safe fusion peptide carrier SPACE-EGF to improve the skin and cell penetration function of the siRNAs and their targeting ability to B16 cells, such that the apoptosis of B16 cells can be induced. The results show that the carrier is stable and less toxic. The EGF motif does not affect the skin and cell penetration function of the SPACE. Because EGF can strongly bind EGFR, which is overexpressed in cancer cells, the targeting ability of the SPACE-EGF-siRNA complex is increased. In vitro experiments indicate that GAPDH siRNAs conjugated with SPACE-EGF can significantly reduce the GAPDH concentration in B16 cells and c-Myc siRNAs can cause the gene silencing of c-Myc and thus the apoptosis of cells. In vivo experiments show that the topical application of c-Myc siRNAs delivered by SPACE-EGF through the skin can significantly inhibit the growth of melanoma tumors. This work may provide insight into the development of new transdermal drug carriers to treat a variety of skin disorders. |
Databáze: | OpenAIRE |
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