A Theoretical Study on Inhibition of Melanoma with Controlled and Targeted Delivery of siRNA via Skin Using SPACE-EGF

Ann Biomed Eng. 2017 Jun;45(6):1407-1419. doi: 10.1007/s10439-017-1825-5. Epub 2017 Mar 27.

Abstract

Melanoma is a potentially lethal skin cancer with high mortality rate. Recently, the peptide-mediated transdermal delivery of small interference RNA (siRNA) emerges as a promising strategy to treat melanoma by inducing the apoptosis of tumor cells, but the related theoretical model describing the delivery of siRNA under the effect of SPACE-EGF, the growth inhibition of melanoma and the dynamic expanding of the bump on the skin due to the growth of melanoma has not been reported yet. In this article, a theoretical model is developed to describe the percutaneous siRNA delivery mediated by SPACE-EGF to melanoma and the growth inhibition of melanoma. The results present the spatial-temporal distribution of siRNA and the growth of melanoma under the inhibition of siRNA, which shows a good consistency with the experimental results. In addition, this model represents the uplift process of tumors on the skin surface. The model presented here is a useful tool to understand the whole process of the SPACE-EGF-mediated delivery of the siRNA to melanoma through skin, to predict the therapeutic effect, and to optimize the therapeutic strategy, providing valuable references for the treatment of melanoma.

Keywords: Melanoma; Peptide carrier; Transdermal drug delivery; Tumor growth inhibition; siRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Cell Line, Tumor
  • Cell-Penetrating Peptides / administration & dosage*
  • Cell-Penetrating Peptides / therapeutic use
  • Epidermal Growth Factor / administration & dosage*
  • Epidermal Growth Factor / therapeutic use
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology
  • Melanoma, Experimental / therapy*
  • Mice, Inbred C57BL
  • Models, Biological
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / therapeutic use
  • Skin / metabolism
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy*

Substances

  • Cell-Penetrating Peptides
  • RNA, Small Interfering
  • Epidermal Growth Factor