Zhu Wen-Ting, Liu Sheng-Yao, Wu Lei, Xu Hua-Li, Wang Jun, Ni Guo-Xin, Zeng Qing-Bing
Biomaterial Research Center, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
Int J Nanomedicine. 2017 Apr 3;12:2621-2634. doi: 10.2147/IJN.S128921. eCollection 2017.
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.
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.
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.
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.
已有广泛报道称姜黄素（CUR）具有抗癌活性，并能触发人A549非小细胞肺癌（NSCLC）细胞凋亡。然而，由于其溶解度和生物利用度较差，其应用受到限制。因此，迫切需要开发一种具有更高水溶性和更好生物相容性的新型CUR制剂，以便将来用于临床应用。
在本研究中，采用薄膜水化法制备了载姜黄素的甲氧基聚乙二醇-聚丙交酯（CUR/mPEG-PLA）聚合物胶束。随后对其特性和抗肿瘤效果进行了评估。
CUR/mPEG-PLA胶束的平均粒径为34.9±2.1nm，其多分散指数（PDI）在0.067-0.168范围内。包封率和载药量分别为90.2%±0.78%和9.1%±0.07%。CUR从CUR/mPEG-PLA胶束中持续释放，其在A549细胞中的细胞摄取显著增加。还发现CUR/mPEG-PLA胶束抑制A549细胞增殖，增加细胞毒性，诱导G2/M期阻滞并促进细胞凋亡。此外，CUR/mPEG-PLA胶束比游离CUR更明显地抑制A549细胞的迁移和侵袭。另外，CUR/mPEG-PLA胶束抑制人脐静脉内皮细胞迁移、侵袭及相应的管腔形成，这意味着其具有抗血管生成能力。其增强的抗肿瘤机制可能与血管内皮生长因子、基质金属蛋白酶（MMP）-2、MMP-9和Bcl-2表达降低以及Bax表达增加有关。
mPEG-PLA共聚物胶束可作为CUR的有效载体。CUR/mPEG-PLA胶束在治疗NSCLC方面具有广阔的临床应用前景。
