槲皮素（Quercetin，简称QCT）是一种抗氧化的植物黄酮类化合物，已知具有显著的抗癌特性。然而，由于其亲水性差、代谢广泛、吸收率低和快速消除，其临床应用作为潜在药物受到了阻碍。纳米技术基于药物传递系统可以解决这些植物化学治疗的缺点。本研究旨在开发壳聚糖纳米颗粒（chitosan nanoparticles，简称CSNPs）作为携带槲皮素（QCT-CSNPs）的药物载体，并进一步研究其对人口腔癌细胞株Cal33的抗肿瘤潜力。我们的研究发现，所制备的壳聚糖纳米颗粒平均粒径约为100 nm，其形状为球形，这与透射电子显微镜和场发射扫描电镜图像所示一致。结晶衍射（XRD）、紫外-可见光谱（UV-Vis spectrophotometry）、傅里叶红外光谱（FTIR）和差示扫描量热（DSC）分析证实槲皮素高效地被诱导进入壳聚糖纳米颗粒的基质中。对Cal33口腔癌细胞的体外细胞毒性研究表明，在经过24小时处理后，QCT-CSNPs相比于游离QCT表现出更高的毒性。QCT-CSNPs的卓越抗癌效果通过增强的细胞凋亡、抑制的集落形成、抑制的迁移以及染色质凝聚进一步得到证实。此外，线粒体功能紊乱和增强的活性氧（ROS，reactive oxygen species）产生表明QCT-CSNPs处理后的Cal33细胞发生了线粒体介导的细胞死亡。总之，我们的数据表明，封装槲皮素的壳聚糖纳米颗粒可能成为一种治疗口腔癌的潜在药物候选物。版权所有 © 2023 Elsevier B.V.出版。

Quercetin (QCT), an antioxidant plant flavonoid, is known to impart prominent anti-cancer properties. However, its clinical application as a potential drug is hindered owing to its hydrophobicity, extensive metabolism, low absorption, and rapid elimination. The drawbacks of these phytochemical-based therapies can be addressed using nanotechnology-based drug delivery systems. In this study, we sought to develop chitosan nanoparticles (CSNPs) as the drug vehicle for encasing quercetin (QCT-CSNPs) and further investigate its anti-tumor potential against human oral cancer cell line Cal33. Our findings indicate that the average particle diameter of the formulated chitosan nanoparticles was around 100 nm, and they had a spherical structure, as per the TEM and FESEM images. The efficient entrapment of quercetin inside the CSNPs matrix is confirmed by XRD, UV-Vis spectrophotometry, FTIR, and DSC analysis. The in vitro cell cytotoxicity study against Cal33 oral cancer cells revealed that QCT-CSNPs exhibited superior toxicity compared to free QCT post-24-hour treatment. The superior anti-cancer efficacy of QCT-CSNPs was further confirmed by enhanced cellular apoptosis, colony formation inhibition, migration inhibition, and chromatin condensation. Moreover, the mitochondrial dysfunction and enhanced ROS (Reactive oxygen species) production indicated mitochondrial-mediated cell death in QCT-CSNPs treated Cal33 cells. In conclusion, our data suggest that quercetin-encapsulated chitosan nanoparticles may serve as a potential drug candidate against oral cancer.Copyright © 2023. Published by Elsevier B.V.