Dipartimento di Scienze Biomediche, Sperimentali e Cliniche "Mario Serio", Università degli Studi di Firenze, Firenze, Italy.
Dipartimento di Scienze Chimiche, Università degli Studi di Napoli "Federico II", Napoli, Italy.
Nanomedicine. 2019 Jun;18:135-145. doi: 10.1016/j.nano.2019.02.015. Epub 2019 Mar 6.
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 αβ. The RGD units play multiple roles since they target the nanovehicles at the integrin αβ-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 αβ-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.
我们在此报告一种新的脂质体制剂的制备、理化特性鉴定和生物学评价，该制剂可用作肿瘤血管生成抑制的工具。脂质体负载舒尼替尼（一种酪氨酸激酶抑制剂），并通过环氨基丙氨酸精氨酸甘氨酸（cAmpRGD）进行修饰，cAmpRGD 是整合素 αβ 的有效和选择性配体。RGD 单元发挥多种作用，因为它们将纳米载体靶向整合素 αβ 过表达的细胞（例如，活化的内皮细胞），有利于它们的主动细胞内化，使药物在细胞质中积累，并可能通过干扰 αβ-VEGFR2 相互作用参与血管生成抑制。体外和体内研究均表明，与游离舒尼替尼和未靶向的载有舒尼替尼的脂质体相比，这种集成的抗血管生成工具具有更好的疗效。该系统可以允许更低剂量的药物给药，并通过增加载体特异性，减少长期抗血管生成治疗中的副作用。
