Inhibition of Cancer Angiogenesis Using Triptolide Nanoparticles
Inhibition of Cancer Angiogenesis Using Triptolide Nanoparticles
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DOI：
10.1166/jbn.2015.2016
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发表时间：
2015-05-01
影响因子：
2.9
通讯作者：
Xu, Wei
中科院分区：
文献类型：
--
作者：
Wang, Cheng;Shan, Ying;Xu, Wei
肿瘤相关血管生成是由多种血管生成因子触发的。血管内皮生长因子阻滞剂是目前抑制血管生成的主要机制;然而，由于靶向单一血管生成因子而导致的不敏感性或由于非特异性暴露而导致的严重副作用最终导致治疗失败。雷公藤内酯醇（TP）是一种具有抗肿瘤作用的中药化合物。然而，其疏水性和副作用阻碍了其向临床的转化。在这里，我们已经制备了TP-聚合物胶束（TP-PMs）使用甲氧基聚（乙二醇）-嵌段-聚（ε-己内酯）。载药率和包封率可分别达到7.2 ± 0.10%和99.1 ± 1.05%。TP-PM溶液由尺寸为53.1 +/-1.2nm的单分散颗粒（PDI = 0.100 +/-0.023）组成。体外释放实验表明，TP-PM溶液比游离TP溶液具有更好的缓释作用。药代动力学和肿瘤组织分布研究表明，TP-PMs促进TP在肿瘤组织中的积累。TP-PM对B16-F10黑色素瘤小鼠的抑瘤率大于50%，有效延长了荷瘤小鼠的生存时间。此外，TP-PM治疗组的血清VEGF水平和肿瘤发生率均显著降低，组织学分析显示TP-PM治疗组中的肿瘤血管直径和密度远小于对照组中观察到的那些。这些结果表明，TP-PMs作为一个潜在的血管生成抑制剂。
Tumor-associated angiogenesis is triggered by multiple angiogenic factors. Vascular endothelial growth factor blockers are currently a major mechanism of angiogenesis inhibition; however, either insensitivity due to the targeting of single angiogenic factors or serious side effects due to non-specific exposure ultimately leads to the failure of treatment. The herb-derived compound triptolide (TP) can inhibit tumor growth through multiple mechanisms. However, its hydrophobicity and side effects have hindered its translation to the clinic. Here, we have prepared TP-polymeric micelles (TP-PMs) using methoxy poly(ethylene glycol)-block-poly(epsilon-caprolactone). The drug loading efficiency and encapsulation efficiency can reach 7.2 +/- 0.10% and 99.1 +/- 1.05%, respectively. The TP-PM solution consisted of monodispersed particles (PDI = 0.100 +/- 0.023), which were 53.1 +/- 1.2 nm in size. In vitro release profiles indicated that the TP-PM solution exhibited better sustained-release action when compared with free TP solution. Pharmacokinetic and tumor tissue distribution studies showed that TP-PMs facilitated TP accumulation in tumor tissues. The tumor inhibition rate upon treatment with TP-PMs was higher than 50%, and the survival time of B16-F10 melanoma bearing mice was efficiently prolonged after TP-PM administration. In addition, serum VEGF levels and tumor incidence of the TP-PM-treated group were both significantly reduced, and histological analyses revealed that the tumor vessel diameter and density in the TP-PM-treated group were much smaller than those observed in the control groups. These results indicated that TP-PMs serve as a potential angiogenesis inhibitor.