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

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.

Computational models of melanoma

“…However, the transport from the blood vessels or skin surface to the melanoma cells depends on the diffusion coefficient of the microanatomical structure. Drug delivery models are available for both the penetration of spherical tumors with melanin-binding antibodies for radioimmunotherapy [160] and SPACE-EGF mediated transdermal delivery of siRNA against the MYC proto-oncogene, bHLH transcription factor (MYC) [161]. However, the impact of biomechanics and tumor physiology on drug delivery is not considered by those models but discussed for MU89 melanoma in mice [162,163].…”