Shape Effect of Carbon Nanovectors on Angiogenesis
Shape Effect of Carbon Nanovectors on Angiogenesis
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DOI：
10.1021/nn901465h
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发表时间：
2010-01-01
期刊：
影响因子：
17.1
通讯作者：
Sengupta, Shiladitya
中科院分区：
文献类型：
--
作者：
Chaudhuri, Padmaparna;Harfouche, Rania;Sengupta, Shiladitya
物理上不同的碳纳米结构；正在越来越多地被研究在癌症化疗中的潜在应用。然而，当它们被用作药物输送的纳米载体时，关于它们的形状在调节生物结果方面的影响的了解有限。在这项研究中，我们评估了阿霉素偶联的单壁碳纳米管(CNT-Dox)和阿霉素偶联的球形多羟基富勒烯或富勒烯醇(Full-Dox)对血管生成的影响。我们报道了碳纳米管在体外和体内都具有促血管生成的作用。相比之下，富勒烯醇或阿霉素偶联的富勒烯醇在斑马鱼和小鼠肿瘤血管生成模型中发挥了截然不同的抗血管生成活性。将血管生成表型分解成不同的细胞步骤显示，富勒烯醇抑制内皮细胞的增殖，而碳纳米管则减弱阿霉素对内皮细胞的细胞毒作用。有趣的是，碳纳米管促进了血管生成的晚期阶段--内皮小管生成。此外，机制研究表明，碳纳米管，而不是富勒烯醇，诱导整合素聚集和激活粘着斑激酶和下游的磷脂酰肌醇-3-激酶(PI3K)。内皮细胞中的信号，这可以解释不同的血管生成结果。这项研究的结果突出了纳米粒子的物理参数在确定其在生物环境中的活性方面的作用。
Physically diverse carbon nanostructures; are increasingly being studied for potential applications in cancer chemotherapy. However, limited knowledge exists on the effect of their shape in tuning the biological outcomes when used as nanovectors for drug delivery. In this study, we evaluated the effect of doxorubicin-conjugated single walled carbon nanotubes (CNT-Dox) and doxorubicin-conjugated spherical polyhydroxylated fullerenes or fullerenols (Ful-Dox) on angiogenesis. We report that CNTs exert a pro-angiogenic effect in vitro and in vivo. In contrast, the fullerenols or doxorubicin-conjugated fullerenols exerted a dramatically opposite antiangiogenic activity in zebrafish and murine tumor angiogenesis models. Dissecting the angiogenic phenotype into discrete cellular steps revealed that fullerenols inhibited endothelial (ell proliferation, while,CNTs attenuated the cytotoxic effect of doxorubicin on the endothelial cells. Interestingly, CNT promoted endothelial tubulogenesis, a late step during angiogenesis. Further, mechanistic studies revealed that CNTs, but not fullerenols, induced, integrin clustering and activated focal adhesion kinase and downstream phosphoinositide-3-kinase (PI3K). signaling in endothelial cells, which can explain the distinct angiogenic outcomes. The results of the study highlight the function of physical parameters of nanoparticles in determining their activity in biological, settings.