PluS Nanoparticles Loaded with Sorafenib: Synthetic Approach and Their Effects on Endothelial Cells.

Silica nanostructures are widely investigated for theranostic applications since relatively mild and easy synthetic methods allow the fabrication of multicompartment nanoparticles (NPs) and fine modulation of their properties. Here, we report the optimization of a synthetic strategy leading to brightly fluorescent silica NPs with a high loading ability, up to 45 molecules per NP, of Sorafenib, a small molecule acting as an antiangiogenic drug. We demonstrate that these NPs can efficiently release the drug and they are able to inhibit endothelial cell proliferation and migration and network formation. Their lyophilization can endow them with long shelf stability, whereas, once in solution, they show a much slower release compared to analogous micellar systems. Interestingly, Sorafenib released from Pluronic silica NPs completely prevented endothelial cell responses and postreceptor mitogen-activated protein kinase signaling ignited by vascular endothelial growth factor, one of the major players of tumor angiogenesis. Our results indicate that these theranostic systems represent a promising structure for anticancer applications since NPs alone have no cytotoxic effect on cultured endothelial cells, a cell type to which drugs and exogenous material are always in contact once delivered.