Augmentation of anti-proliferative efficacy of quercetin encapsulated chitosan nanoparticles by induction of cell death via mitochondrial membrane permeabilization in oral cancer

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 improved 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.