Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 18, Issue -, Pages 135-145Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2019.02.015
Keywords
Liposomes; Integrin alpha(v)beta(3); RGD; Tumor angiogenesis; Sunitinib
Funding
- Italian Ministry of Education, University and Research (MIUR) [20157WW5EH]
- Ente Cassa di Risparmio di Firenze
- Istituto Toscano Tumori
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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 alpha(v)beta(3). The RGD units play multiple roles since they target the nanovehicles at the integrin alpha(v)beta(3)-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 alpha(v)beta(3)-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. (C) 2019 Elsevier Inc. All rights reserved.
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