Wang Jiao, Liu Qiang, Yang Linnan, Xia Xiaofei, Zhu Rongrong, Chen Shengguang, Wang Mei, Cheng Liming, Wu Xianzheng, Wang Shilong
J Biomed Nanotechnol. 2017 Dec 1;13(12):1631-1646. doi: 10.1166/jbn.2017.2442.
Cervical cancer is the fourth most common cancer in women worldwide, and existing treatments cause severe side effects and great burdens. Thus, the development of safe, inexpensive therapeutic agents is necessary. Curcumin (Cur), a well-known natural product, exerts promising anti-cancer activities against various cancer types. However, its therapeutic efficacy is severely restrained due to rapid degradation, poor aqueous solubility, and low bioavailability. The objective of this study was to investigate the therapeutic potential of novel curcumin-loaded TPGS/F127/P123 mixed polymeric micelles (Cur@NPT100) for cervical cancer treatment. The Cur@NPT100 exhibited an average size of approximately 19 nm, a zeta potential of around -4 mV, a drug loading of 8.18 ± 0.36%, and an encapsulation efficiency of 79.38 ± 4.65%. Unlike free Cur, Cur@NPT100 are readily dispersed in aqueous medium, showing enhanced stability and a sustained release profile over a 6-day period. In vitro cell culture experiments revealed that TPGS/F127/P123 mixed polymeric micelles (NPT100) based nanocarriers substantially promoted the selective cellular uptake of Cur into HeLa cells rather than by non-cancerous NIH3T3 cells, inducing higher cytotoxicity and greater apoptosis and significantly increasing the percentage of cells arrested at the G2/M phase of the cell cycle. Additionally, the Cur@NPT100 facilitated more Cur accumulation in the mitochondria and decreased the mitochondrial membrane potential. In addition, western blot assays demonstrated that Cur@NPT100 were more potent than free Cur at activating the mitochondria-mediated apoptosis pathway. In vivo results further confirmed that Cur@NPT100 exhibited a much higher antitumor efficacy than free Cur and had excellent biocompatibility. In conclusion, Cur@NPT100 might be an effective therapeutic agent for cervical cancer.
宫颈癌是全球女性中第四大常见癌症，现有治疗方法会引起严重的副作用和巨大负担。因此，开发安全、廉价的治疗药物很有必要。姜黄素（Cur）是一种著名的天然产物，对多种癌症类型具有有前景的抗癌活性。然而，由于其快速降解、水溶性差和生物利用度低，其治疗效果受到严重限制。本研究的目的是研究新型载姜黄素的TPGS/F127/P123混合聚合物胶束（Cur@NPT100）用于宫颈癌治疗的潜力。Cur@NPT100的平均粒径约为19nm，zeta电位约为 -4mV，载药量为8.18±0.36%，包封率为79.38±4.65%。与游离Cur不同，Cur@NPT100易于分散在水性介质中，在6天内显示出增强的稳定性和持续释放特性。体外细胞培养实验表明，基于TPGS/F127/P123混合聚合物胶束（NPT100）的纳米载体显著促进Cur选择性地被HeLa细胞摄取，而非被非癌性NIH3T3细胞摄取，诱导更高的细胞毒性和更大程度的凋亡，并显著增加细胞周期G2/M期停滞的细胞百分比。此外，Cur@NPT100促进更多的Cur在线粒体中积累并降低线粒体膜电位。另外，蛋白质印迹分析表明，Cur@NPT100在激活线粒体介导的凋亡途径方面比游离Cur更有效。体内结果进一步证实，Cur@NPT100比游离Cur表现出更高的抗肿瘤功效，并且具有优异的生物相容性。总之，Cur@NPT100可能是一种有效的宫颈癌治疗药物。
