Non-covalently functionalized single-walled carbon nanotube for topical siRNA delivery into melanoma

King Sun Siu; Di Chen; Xiufen Zheng; Xusheng Zhang; Nathan Johnston; Yanling Liu; Ken Yuan; James Koropatnick; Elizabeth R Gillies; Wei-Ping Min

doi:10.1016/j.biomaterials.2013.12.079

Non-covalently functionalized single-walled carbon nanotube for topical siRNA delivery into melanoma

Biomaterials. 2014 Mar;35(10):3435-42. doi: 10.1016/j.biomaterials.2013.12.079. Epub 2014 Jan 11.

Authors

Affiliations

¹ 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.
² 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.
³ Jiangxi Academy of Medical Sciences, and Institute of Immunomodulation and Immunotherapy of Nanchang University, Nanchang, China.
⁴ 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.
⁵ Department of Chemistry, Chemical and Biochemical Engineering, Western University, London, Canada.
⁶ 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.

PMID: 24424208
DOI: 10.1016/j.biomaterials.2013.12.079

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.

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.

Publication types

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

MeSH terms

Animals
Gene Silencing
Melanoma, Experimental / drug therapy*
Melanoma, Experimental / genetics
Mice
Mice, Inbred C57BL
Nanotubes, Carbon*
RNA, Small Interfering / administration & dosage*
RNA, Small Interfering / therapeutic use

Substances

Nanotubes, Carbon
RNA, Small Interfering

Grants and funding

Canadian Institutes of Health Research/Canada