Enhanced Anti-Cancer Efficacy of Quercetin Encapsulated Chitosan Nanoparticles by Induction of Cell Death Via Mitochondrial Membrane Permeabilization

Abstract

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.