Delivery of curcumin by directed self-assembled micelles enhances therapeutic treatment of non-small-cell lung cancer.
Delivery of curcumin by directed self-assembled micelles enhances therapeutic treatment of non-small-cell lung cancer.
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通过定向自组装胶束递送姜黄素可增强非小细胞肺癌的治疗效果
DOI：
10.2147/ijn.s128921
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发表时间：
2017
影响因子：
8
通讯作者：
Zeng QB
中科院分区：
文献类型：
--
作者：
Zhu WT;Liu SY;Wu L;Xu HL;Wang J;Ni GX;Zeng QB
研究背景姜黄素（curcumin，CUR）对人非小细胞肺癌（non-small-cell lung cancer，NSCLC）A549细胞具有抗肿瘤活性和诱导凋亡作用。但由于其溶解性差、生物利用度低，限制了其应用。因此，未来迫切需要开发一种水溶性更好、生物相容性更好的CUR新剂型用于临床应用。材料与方法采用薄膜水化法制备了负载CUR的甲氧基聚乙二醇-聚乳酸（CUR/mPEG-PLA）聚合物胶束。并对其特性及抗肿瘤作用进行了评价。结果CUR/mPEG-PLA胶束的平均粒径为（34.9±2.1）nm，多分散指数（PDI）在0.067 ~ 0.168之间。包封率和载药量分别为90.2%±0.78%和9.1%± 0.07%。CUR/mPEG-PLA胶束能持续释放CUR，并能显著增加A549细胞对CUR的摄取。CUR/mPEG-PLA胶束抑制A549细胞增殖，增加细胞毒性，诱导细胞G2/M期阻滞，促进细胞凋亡。CUR/mPEG-PLA胶束对A549细胞的迁移和侵袭能力的抑制作用明显强于游离CUR。此外，CUR/mPEG-PLA胶束对人脐静脉内皮细胞的迁移、侵袭及相应的管腔形成有抑制作用，提示CUR/mPEG-PLA胶束具有抗血管生成的作用。其抗肿瘤作用机制可能与降低血管内皮生长因子、基质金属蛋白酶（MMP）-2、MMP-9和Bcl-2的表达，增加Bax的表达有关。结论mPEG-PLA共聚物胶束可作为CUR的有效载体。CUR/mPEG-PLA胶束具有良好的临床应用前景。
Background It has been widely reported that curcumin (CUR) exhibits anticancer activity and triggers the apoptosis of human A549 non-small-cell lung cancer (NSCLC) cells. However, its application is limited owing to its poor solubility and bioavailability. Therefore, there is an urgent need to develop a new CUR formulation with higher water solubility and better biocompatibility for clinical application in the future. Materials and methods In this study, CUR-loaded methoxy polyethylene glycol–polylactide (CUR/mPEG–PLA) polymeric micelles were prepared by a thin-film hydration method. Their characteristics and antitumor effects were evaluated subsequently. Results The average size of CUR/mPEG–PLA micelles was 34.9±2.1 nm with its polydispersity index (PDI) in the range of 0.067–0.168. The encapsulation efficiency and drug loading were 90.2%±0.78% and 9.1%±0.07%, respectively. CUR was constantly released from the CUR/mPEG–PLA micelles, and its cellular uptake in A549 cells was significantly increased. It was also found that CUR/mPEG–PLA micelles inhibited A549 cell proliferation, increased the cell cytotoxicity, induced G2/M stage arrest and promoted cell apoptosis. Moreover, the CUR/mPEG–PLA micelles suppressed the migration and invasion of A549 cells more obviously than free CUR. Additionally, CUR/mPEG–PLA micelles inhibited human umbilical vein endothelial cells migration, invasion and corresponding tube formation, implying the antiangiogenesis ability. Its enhanced antitumor mechanism may be related to the reduced expression of vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, MMP-9 and Bcl-2 as well as the increased expression of Bax. Conclusion The mPEG–PLA copolymer micelles can serve as an efficient carrier for CUR. The CUR/mPEG–PLA micelles have promising clinical potential in treating NSCLC.