State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27th Taiping Road, Haidian District, Beijing 100850, China.
Molecules. 2019 Apr 11;24(7):1438. doi: 10.3390/molecules24071438.
Quercetin (QE) is an attractive natural compound for cancer prevention due to its beneficial anti-oxidative and anti-proliferative effects. However, QE is poorly soluble in water and slightly soluble in oil, which results in its low oral bioavailability and limits its application in the clinic. The aim of this study was to prepare QE nanocrystals (QE-NCs) with improved solubility and high drug loading, furthermore, the size-dependent anti-cancer effects of QE-NCs were studied. We prepared QE-NCs with three different particle sizes by wet milling, then, cell proliferation, migration and invasion were studied in A549 cells. The QE-NCs had antitumor effects in a dose- and size-dependent manner. Compared with the large particles, the small particles had a strong inhibitory impact on cell biological effects ( < 0.05 or < 0.01). Moreover, Western blot assay indicated that QE-NCs may inhibit the migration and invasion of A549 cells by inhibiting the STAT3 signaling pathway, and the particle size may have an effect on this process. In this study, it was proven that NCs could dramatically enhance the anticancer efficacy of QE at the cellular level. In addition, particle size had a considerable influence on the dissolution behavior and antitumor effects of NCs.
槲皮素（QE）由于其有益的抗氧化和抗增殖作用，是一种有吸引力的天然化合物，可用于预防癌症。然而，QE 在水中的溶解度差，在油中的溶解度略高，导致其口服生物利用度低，限制了其在临床上的应用。本研究旨在制备具有改善的溶解度和高载药量的 QE 纳米晶体（QE-NCs），此外，还研究了 QE-NCs 的尺寸依赖性抗癌作用。我们通过湿磨法制备了三种不同粒径的 QE-NCs，然后研究了它们在 A549 细胞中的增殖、迁移和侵袭。QE-NCs 以剂量和尺寸依赖性方式具有抗肿瘤作用。与大颗粒相比，小颗粒对细胞生物学效应具有更强的抑制作用（<0.05 或 <0.01）。此外，Western blot 分析表明，QE-NCs 可能通过抑制 STAT3 信号通路抑制 A549 细胞的迁移和侵袭，而颗粒大小可能对此过程有影响。在这项研究中，证明 NCs 可以在细胞水平上显著增强 QE 的抗癌功效。此外，颗粒大小对 NCs 的溶解行为和抗肿瘤作用有很大影响。
