title: Topical and Targeted Delivery of siRNAs to Melanoma Cells Using a Fusion Peptide Carrier.
abstract: 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.
authors.affiliation: Center for Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui 230027, China.|Department of Electronic Science and Technology, Hefei, Anhui 230027, China.|School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.|Fujian Longsheng Biotechnology (Group) Co., Ltd., Longyan, Fujian 364000, China.
authors.forename: Renquan
authors.initials: R
authors.lastname: Ruan
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.|Department of Pharmacology, Anhui University of Chinese Medicine, Hefei, Anhui 230038, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Sijie
authors.initials: S
authors.lastname: Sun
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Wei
authors.affiliation: Center for Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui 230027, China.|Department of Electronic Science and Technology, Hefei, Anhui 230027, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zou
authors.affiliation: Center for Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui 230027, China.|Department of Electronic Science and Technology, Hefei, Anhui 230027, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Mechanical Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Dayong
authors.initials: D
authors.lastname: Gao
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Longping
authors.initials: L
authors.lastname: Wen
authors.affiliation: Center for Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui 230027, China.|Department of Electronic Science and Technology, Hefei, Anhui 230027, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Ding
mesh_terms: D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000378:metabolism; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D008099:Liver / Q000473:pathology; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology*; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000737:chemistry*; D010539:Permeability; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism
chemical_list: D010455:Peptides; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D004815:Epidermal Growth Factor