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

Abstract

Background: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia that is effectively treated with arsenic trioxide (ATO) in combination with all-trans retinoic acid. However, the toxic effects of ATO necessitate exploring safer therapeutic combinations. Nanotechnology offers potential strategies to enhance drug efficacy and safety. Zinc oxide quantum dots (ZnO Q-dots) exhibit properties such as biocompatibility, selectivity, and the ability to induce reactive oxygen species (ROS), which may potentiate anticancer drug effects. Objectives: This study investigated the combined use of ZnO Q-dots and ATO to improve anticancer outcomes in NB4 APL-derived cells. Methods: NB4 cells were treated with varying concentrations of ZnO Q-dots and ATO, either alone or in combination. Cell viability was assessed using the trypan blue exclusion assay and the MTT assay. Proliferation was evaluated using the BrdU assay, and cell cycle distribution was analyzed by flow cytometry. Apoptosis- and autophagy-related markers were assessed using quantitative real-time PCR (qRT-PCR), and ROS levels were measured using a fluorogenic dye. Results: ZnO Q-dots enhanced the antiproliferative and apoptotic effects of ATO in a dose- and time-dependent manner. Combined treatment reduced metabolic activity to 39.7 ± 2.6%, corresponding to approximately 60.3% inhibition relative to controls. Significant upregulation of apoptotic genes (e.g., p53, Bax) and downregulation of anti-apoptotic genes (e.g., Bcl-2) were observed. ROS production was markedly increased, accompanied by induction of autophagy-related genes (ATG-7, Beclin-1). Conclusions: The combination of ZnO Q-dots and ATO enhances anticancer efficacy in APL-derived NB4 cells, primarily by increasing ROS production, apoptosis, and autophagy. These findings suggest a promising therapeutic strategy with improved efficacy compared with that of single-agent treatments.