Characterization of the tumor vasculature in mouse melanoma models. Roles of siRNA-loaded lipid nanocapsules

A significant increase of reported cutaneous melanoma cases have been observed within the past four decades. Despite numerous therapeutic strategies available and ongoing works on novel therapeutics, the vital prognosis for the diagnosed patients are still poor due to low response rate of the tumors to these treatments. For this reason, the application of interfering RNA (RNAi) as a therapeutic agent allowing reestablishment of physiological process of cellular death seems to be a promising altern ative strategy. The use of nanoparticles enables to i) improve the pharmacokinetic of RNAi, ii) potentialize its efficiency and iii) avoid side effects is essential to improve tumor targeting. Therefore, the structure and density of vascularization in a tumor-site is a crucial factor for determining efficacy of nanovectors. This allows the passive targeting which is due to enhanced permeability and retention (EPR) effect. [...

Melanoma tumour vasculature heterogeneity: from mice models to human

Tumour angiogenesis is defined by an anarchic vasculature and irregularities in alignment of endothelial cells. These structural abnormalities could explain the variability in distribution of nanomedicines in various tumour models. Then, the main goal of this study was to compare and to characterize the tumour vascular structure in different mouse models of melanoma tumours (B16F10 and SK-Mel-28) and in human melanomas from different patients. Tumours were obtained by subcutaneous injection of 106 B16F10 and 3.106 SK-Mel-28 melanoma cells in C57BL/6 and nude mice, respectively. Tumour growth was evaluated weekly, while vasculature was analysed through fluorescent labelling via CD31 and desmin. Significant differences in tumour growth and mice survival were evidenced between the two melanoma models. A fast evolution of tumours was observed for B16F10 melanoma, reaching a tumour size of 100 mm3 in 7 days compared to SK-Mel-28 which needed 21 days to reach the same volumes. Important differences in vascularization were exposed between the melanoma models, characterized by a significant enhancement of vascular density and a significant lumen size for mice melanoma models compared to human. Immunostaining revealed irregularities in endothelium structure for both melanoma models, but structural differences of vasculature were observed, characterized by a stronger expression of desmin in SK-Mel-28 tumours. While human melanoma mainly develops capillaries, structural irregularities are also observed on the samples of this tumour model. Our study revealed an impact of cell type and tumour progression on the structural vasculature of melanoma, which could impact the distribution of drugs in the tumour environment