Improving the anti-colon cancer activity of curcumin with biodegradable nano-micelles
Improving the anti-colon cancer activity of curcumin with biodegradable nano-micelles
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DOI：
10.1039/c3tb21091j
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发表时间：
2013-01-01
影响因子：
7
通讯作者：
Wei, Yu-quan
中科院分区：
文献类型：
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作者：
Gao, Xiang;Zheng, Fengjin;Wei, Yu-quan
姜黄素（Curcumin，Cur）通过抑制血管生成和诱导细胞凋亡发挥抗肿瘤作用。然而，姜黄素的疏水性限制了其临床应用。因此，提高姜黄素的水溶性和抗肿瘤作用具有重要意义。本研究采用可生物降解的单甲氧基聚乙二醇聚乳酸共聚物（MPEG-PLA）胶束，通过自组装的方法将姜黄素释放到载体中。所制备的姜黄素聚合物胶束（Cur/MPEG-PLA）粒径约为30 nm，载药量为8%，呈单分散性，在体外和体内均能较长时间释放姜黄素。此外，Cur/MPEG-PLA在体外对细胞生长的抑制作用和诱导细胞凋亡的作用均大于游离姜黄素。此外，详细评价了Cur/MPEG-PLA对结肠癌小鼠模型的治疗效率。Cur/MPEG-PLA对结肠癌细胞的生长抑制作用明显优于相同剂量的游离姜黄素（P < 0.05或P < 0.05），表明Cur/MPEG-PLA可增强姜黄素的体内抗肿瘤作用。免疫组化和免疫荧光分析显示，Cur/MPEG-PLA能诱导更多的肿瘤细胞凋亡，抑制更多的血管生成。此外，Cur/MPEG-PLA在体内具有较强的抗血管生成作用。最后，评价Cur/MPEG-PLA对结肠癌模型的抗肺转移效率。Cur/MPEG-PLA对肺转移的抑制作用明显优于相同剂量的游离姜黄素（P < 0.05），表明Cur/MPEG-PLA能增强姜黄素的体内抗肺转移作用。我们的数据表明Cur/MPEG-PLA可能在结肠癌治疗中具有潜在的临床应用。
Curcumin (Cur) showed an antitumor effect by anti-angiogenesis and the induction of apoptosis. However, curcumin is limited in clinical applications by its hydrophobicity. Therefore, improving the water-solublilty and antitumor effect of curcumin are very meaningful. In this work, biodegradable monomethoxy poly(ethylene glycol) poly(lactide) copolymer (MPEG-PLA) micelles were employed to deliver curcumin by a self-assembly method. The obtained curcumin loaded polymeric micelles (Cur/MPEG-PLA) with a drug loading of 8% were monodisperse and similar to 30 nm in diameter, which could release curcumin in an extended period in vitro and in vivo. In addition, Cur/MPEG-PLA showed a larger effect on cell growth inhibition and the induction of cell apoptosis than free curcumin in vitro. Furthermore, the therapy efficiency of Cur/MPEG-PLA on a colon cancer mouse model was evaluated in detail. Cur/MPEG-PLA could cause a more significant inhibitory effect on colon tumor growth than free curcumin with the same dose (P < 0.05 or P < 0.05, respectively), which indicated that Cur/MPEG-PLA could improve the antitumor effect of curcumin in vivo. Immunohistochemical and immunofluorescent analysis showed that Cur/MPEG-PLA could induce more tumor cell apoptosis, and inhibit more angiogenesis than the free drug group. Besides, Cur/MPEG-PLA exhibited a larger anti-angiogenesis effect in vivo. Finally, the anti-lung metastasis efficiency of Cur/MPEG-PLA on the colon cancer model was evaluated. Cur/MPEG-PLA could cause a more significant inhibitory effect on lung metastasis than free curcumin with the same dose (P < 0.05), which indicates that Cur/MPEG-PLA could improve the anti-lung metastasis effect of curcumin in vivo. Our data suggested Cur/MPEG-PLA may have potential clinical applications in colon cancer therapy.