Supramolecular hybrids of carbon dots and dihydroartemisinin for enhanced anticancer activity and mechanism analysis
Supramolecular hybrids of carbon dots and dihydroartemisinin for enhanced anticancer activity and mechanism analysis
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DOI：
10.1039/d0tb01826k
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发表时间：
2020-11-14
影响因子：
7
通讯作者：
Feng, Xianmin
中科院分区：
文献类型：
--
作者：
Li, Yawei;Shi, Nianqiu;Feng, Xianmin
双氢青蒿素（DHA）是近年来发现的一种潜在的抗癌药物。然而，由于DHA的固有特性，如水溶性差、不稳定、清除快等，严重限制了其临床应用。本文通过碳量子点（CD）和DHA的超分子组装成功制备了一种荧光纳米颗粒。所制备的CDs-DHA荧光纳米粒不仅显著提高了DHA的溶解性和稳定性，而且具有良好的生物相容性和pH依赖性药物释放行为。特别地，CD和DHA的杂化物作为纳米载体可以有效地促进DHA的内吞，并且与游离DHA相比在体外和体内表现出增强的抗肿瘤作用。此外，我们还通过流式细胞仪检测、转染和western blot分析，探讨了CDs-DHA可能的作用机制。结果表明，CDs-DHA纳米粒通过诱导细胞凋亡和抑制糖代谢抑制肝癌进展，其机制与下调PKM 2表达和抑制Akt/mTOR信号通路有关，可能为肝癌的治疗提供潜在的治疗靶点。本工作强调了利用CD作为一种安全、方便的平台来递送DHA用于有效的癌症治疗的巨大潜力，并且对DHA的抗癌机制的研究也可以为DHA的临床应用提供理论支持。
Dihydroartemisinin (DHA) has been regarded as a potential anticancer agent in recent years. Nevertheless, the clinical applications of DHA are seriously restricted as a result of its intrinsic characteristics, such as poor water solubility, instability, and fast clearance. Herein, a type of fluorescent nanoparticles was successfully fabricated via supramolecular assembling of carbon dots (CDs) and DHA. The formulated CDs-DHA fluorescent nanoparticles not only significantly improve the solubility and stability of DHA, but also possess favorable biocompatibility and pH-dependent drug release behavior. In particular, the hybrids of CDs and DHA as nanocarriers can effectively promote the endocytosis of DHA and exhibit enhanced antitumor effects compared with free DHA in vitro and in vivo. In addition, we also explore the possible action mechanism of CDs-DHA through flow cytometric assay, transfection and western blot analysis. The results indicate that CDs-DHA nanoparticles suppress the progression of hepatic carcinoma through inducing apoptosis and inhibiting glucose metabolism, and the mechanism is related to the downregulation of PKM2 expression and the suppression of the Akt/mTOR signaling pathway, which may provide a potential therapeutic target for hepatic carcinoma treatment. This work emphasizes the great potential of utilizing CDs as a safe and convenient platform to deliver DHA for efficient cancer therapy, and the study on the anticancer mechanism can also offer theoretical support for the clinical application of DHA.