ZnO Q-Dots Nanoparticles: Intensifying ROS Stress to Improve Anticancer Drug Efficacy

Abstract

Abstract Zinc oxide quantum dot Nanoparticles (ZnO Q-Dots NPs) are a conducive and versatile nano-platform with extraordinary biological applications. Despite a legion of studies, ZnO's biological and pharmacological activities have yet to be utilized in therapeutic applications. Recently, arsenic trioxide (ATO), an anti-cancer missile with multiple warheads, has shown harbinger therapeutic potential for acute promyelocytic leukemia (APL) by selectively instigating reactive oxygen species (ROS) stress in cancer cells. However, determining how best to lessen the toxic effects of ATO while increasing its therapeutic efficacy is a severe subject. In this study, we report that ZnO can synergize with ATO and escalate the ROS stress in NB4 cells, thereby greatly enhancing the apoptotic cell death and not only up-regulated the effect the ATO on the expression of anti-apoptotic target genes but also significantly elevating the expression of pro-apoptotic molecules in NB4 cells, as compared to either agent alone. We found that when ATO combined with ZnO, even the lower concentrations could induce flagrantly inhibitory effects on the survival of NB4 through retreating the cells to replicate DNA in the S phase of cell cycle. Moreover, our study indicated for the first time that the anti-leukemic effect of dual therapy combination of ZnO and ATO was coupled with the up-regulation of p21 and, thereby, G2/M cell cycle arrest. Our data suggest that incorporating ZnO with ATO can potentially ameliorate anti-leukemic effect in NB4 cells, thereby providing a synergistic strategy in the development of theranostic nanomedicine in APL patients.