Characterization of the tumor vasculature in mouse melanoma models. Roles of siRNA- loaded lipid nanocapsules
V Pautu a, P Resniera, N Clereb, C Passirania
aUMR 1066 Inserm – University of Angers, Angers (France);
bUMR 1063 Inserm – University of Angers - Angers (France)
Introduction: 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.
Material and methods: The objective of the present study was to characterize the vascularization of two models (SKMel28 and B16F10) of melanoma xenografted in mice in order to determine a potential variation of EPR effect. Furthermore, the properties of siRNA targeting BCl2 and encapsulated in lipidnanocapsules have been studied in these tumor models.
Results: From immunostaining assay, our work revealed structural difference between vascularization of SKmel28 and B16F10 tumor models. Then, we reported a higher density and a lower integrity of blood vessels in B16F10 model in comparison with SKMel28 model.
Moreover, treatment with BCl2-siRNA- loaded lipid nanocapsules decreased tumor volume in both melanoma models. However, the reduction of tumor volume ratio was 10% higher in B16F10 model than in SKMel28 tumor.
Discussion/Conclusion: Altogether, these findings suggest differences in vascularization of two melanoma models xenografted in mice suggesting a larger EPR effect in B16F10 model compared to SKMel28 tumor. Then, we hypothesized a better distribution of lipid nanocapsules that better reach their target if EPR effect is well expressed.
