title: Non-covalently functionalized single-walled carbon nanotube for topical siRNA delivery into melanoma.
abstract: RNAi can specifically regulate gene expression, but efficient delivery of siRNA in vivo is difficult while it has been shown that modified carbon nanotubes (CNT) protect siRNA, facilitate entry into cells and enhance transdermal drugs delivery. Single-walled carbon nanotubes (SWCNT) were functionalized non-covalently with succinated polyethyleimine (PEI-SA). In this study, the water soluble CNT, PEI-SA/CNT (IS/C) were isolated and characterized, the gene silencing induced by IS/C/siRNA complexes was achieved in vitro in B16-F10 cells. In vivo delivery was topically applied to shaved mouse skin, as well as topically to a C57BL/6 mice melanoma model. We found significant uptake of Cy3-labeled siRNA specific to Braf (siBraf) and gene silencing in the tumor tissue. Treatment with IS/C/siBraf resulted in attenuation of tumor growth over a 25-day period. This new delivery method has provided a new possibility for future siRNA delivery and therapy, which providing insight for the potential application and development of CNT-based siRNA delivery.
authors.affiliation: Department of Pathology, Western University, London, Canada; Department of Surgery, Western University, London, Canada; Department of Oncology, Western University, London, Canada; Department of Microbiology and Immunology, Western University, London, Canada; Department of Physiology and Pharmacology, Western University, London, Canada.
authors.forename: King Sun
authors.initials: KS
authors.lastname: Siu
authors.affiliation: Department of Pathology, Western University, London, Canada; Department of Surgery, Western University, London, Canada; Department of Oncology, Western University, London, Canada; Department of Microbiology and Immunology, Western University, London, Canada; Department of Physiology and Pharmacology, Western University, London, Canada.
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Pathology, Western University, London, Canada; Department of Surgery, Western University, London, Canada; Department of Oncology, Western University, London, Canada; Department of Microbiology and Immunology, Western University, London, Canada; Department of Physiology and Pharmacology, Western University, London, Canada.
authors.forename: Xiufen
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Pathology, Western University, London, Canada; Department of Surgery, Western University, London, Canada; Department of Oncology, Western University, London, Canada; Department of Microbiology and Immunology, Western University, London, Canada; Department of Physiology and Pharmacology, Western University, London, Canada.
authors.forename: Xusheng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Western University, London, Canada; Department of Surgery, Western University, London, Canada; Department of Oncology, Western University, London, Canada; Department of Microbiology and Immunology, Western University, London, Canada; Department of Physiology and Pharmacology, Western University, London, Canada.
authors.forename: Nathan
authors.initials: N
authors.lastname: Johnston
authors.affiliation: Department of Pathology, Western University, London, Canada; Department of Surgery, Western University, London, Canada; Department of Oncology, Western University, London, Canada; Department of Microbiology and Immunology, Western University, London, Canada; Department of Physiology and Pharmacology, Western University, London, Canada; Jiangxi Academy of Medical Sciences, and Institute of Immunomodulation and Immunotherapy of Nanchang University, Nanchang, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Jiangxi Academy of Medical Sciences, and Institute of Immunomodulation and Immunotherapy of Nanchang University, Nanchang, China.
authors.forename: Ken
authors.initials: K
authors.lastname: Yuan
authors.affiliation: Department of Pathology, Western University, London, Canada; Department of Surgery, Western University, London, Canada; Department of Oncology, Western University, London, Canada; Department of Microbiology and Immunology, Western University, London, Canada; Department of Physiology and Pharmacology, Western University, London, Canada; Lawson Health Research Institute, London, Canada; London Regional Cancer Program, London, Canada.
authors.forename: James
authors.initials: J
authors.lastname: Koropatnick
authors.affiliation: Department of Chemistry, Chemical and Biochemical Engineering, Western University, London, Canada.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Gillies
authors.affiliation: Department of Pathology, Western University, London, Canada; Department of Surgery, Western University, London, Canada; Department of Oncology, Western University, London, Canada; Department of Microbiology and Immunology, Western University, London, Canada; Department of Physiology and Pharmacology, Western University, London, Canada; Jiangxi Academy of Medical Sciences, and Institute of Immunomodulation and Immunotherapy of Nanchang University, Nanchang, China; Lawson Health Research Institute, London, Canada; London Regional Cancer Program, London, Canada. Electronic address: weiping.min@uwo.ca.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Min
mesh_terms: D000818:Animals; D020868:Gene Silencing; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D037742:Nanotubes, Carbon; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D037742:Nanotubes, Carbon; D034741:RNA, Small Interfering
keywords: (1)H NMR; Braf; CNT; IS/C; MAPK; Melanoma; PEI; RNA interference; RNAi; Topical delivery; carbon nanotubes; mitogen-activated protein kinase; poly(ethylenimine); proton nuclear magnetic resonance; siBraf; siRNA; siRNA specific to Braf; small interfering RNA; succinated-polyethylenimine/carbon nanotube; v-raf murine sarcoma viral oncogene homolog B