Department of Chemistry, Jinan University, Guangzhou 510632, China.
Biomaterials. 2013 Jan;34(1):171-80. doi: 10.1016/j.biomaterials.2012.09.031. Epub 2012 Oct 8.
Anti-angiogenesis is an effective strategy for cancer treatment because uncontrolled tumor growth depends on tumor angiogenesis and sufficient blood supply. Thus, blocking angiogenesis could be a strategy to arrest tumor growth. The function and mechanism of luminescent ruthenium-modified selenium nanoparticles (Ru-SeNPs) in angiogenesis have not been elucidated to date. Here, we found that Ru-SeNPs significantly inhibited human umbilical vascular endothelial cell (HUVEC) proliferation, migration and tube formation. Ru-SeNPs was also tested in vivo in the chicken chorioallantoic membrane (CAM) assay and found to inhibit bFGF-treated CAMs development like suramin. Moreover, we showed that Ru-SeNPs inhibited the activations of FGFR1 and its downstream protein kinases, such ErK and AKT. Furthermore, by using fluorescence confocal microscopy and TEM imaging studies, we have demonstrated their cellular uptake and localization within the cytoplasm of HepG2 and HUVEC cells. These findings indicate that Ru-SeNPs inhibits angiogenesis and may be a viable drug candidate in anti-angiogenesis and anticancer therapies.
抗血管生成是癌症治疗的有效策略,因为不受控制的肿瘤生长依赖于肿瘤血管生成和充足的血液供应。因此,阻断血管生成可能是阻止肿瘤生长的一种策略。迄今为止,发光钌修饰硒纳米粒子(Ru-SeNPs)在血管生成中的功能和机制尚未阐明。在这里,我们发现 Ru-SeNPs 可显著抑制人脐静脉内皮细胞(HUVEC)的增殖、迁移和管腔形成。还在鸡胚尿囊膜(CAM)试验中对 Ru-SeNPs 进行了体内测试,发现其可抑制 bFGF 处理的 CAM 发育,作用与苏拉明类似。此外,我们表明 Ru-SeNPs 抑制 FGFR1 及其下游蛋白激酶的激活,如 ErK 和 AKT。此外,通过使用荧光共聚焦显微镜和 TEM 成像研究,我们已经证明了它们在 HepG2 和 HUVEC 细胞的细胞质中的细胞摄取和定位。这些发现表明 Ru-SeNPs 抑制血管生成,可能是抗血管生成和抗癌治疗中有前途的药物候选物。