Integrin-targeted AmpRGD sunitinib liposomes as integrated antiangiogenic tools

We report here the preparation, physico-chemical characterization, and biological evaluation of a new liposome formulation as a tool for tumor angiogenesis inhibition. Liposomes are loaded with sunitinib, a tyrosine kinase inhibitor, and decorated with cyclo-aminoprolineRGD units (cAmpRGD), efficient and selective ligands for integrin αVβ3. The RGD units play multiple roles since they target the nanovehicles at the integrin αVβ3-overexpressing cells (e.g. activated endothelial cells), favor their active cell internalization, providing drug accumulation in the cytoplasm, and likely take part in the angiogenesis inhibition by interfering in the αVβ3-VEGFR2 cross-talk. Both in vitro and in vivo studies show a better efficacy of this integrated antiangiogenic tool with respect to the free sunitinib and untargeted sunitinib-loaded liposomes. This system could allow a lower administration of the drug and, by increasing the vector specificity, reduce side-effects in a prolonged antiangiogenic therapy.Graphical AbstractLiposomes decorated with AmpRGD, an αVβ3 integrin-targeted ligand, and loaded with sunitinib, a known tyrosine-kinase inhibitor, were developed. This nanosized system was tested as integrated antiangiogenic tool, and compared to free sunitinib and sunitinib-loaded untargeted liposomes, showing a potentiated activity both in vitro and in vivo.

Source: Nanomedicine: Nanotechnology, Biology and Medicine - March 8, 2019 Category: Nanotechnology Source Type: research