Evaluating the mechanisms and therapeutic potential of ZnO nanoparticles as selective anticancer agents for lung malignancies

Lung cancer's high mortality necessitates refined, targeted therapeutic interventions. Zinc oxide nanoparticles (ZnO NPs) have emerged as promising anticancer agents owing to their distinctive physicochemical characteristics, particularly their pH-dependent solubility, and their preferential toxicity toward malignant cells. This review critically examines the mechanisms, advantages, and limitations of ZnO NPs as a novel therapeutic strategy for lung cancer. The primary antitumor mechanism involves the generation of reactive oxygen species (ROS), which disrupts the cellular redox balance and induces apoptosis. ZnO NPs are shown to trigger apoptosis by compromising mitochondrial integrity, activating caspase cascades, and altering the expression of Bax and Bcl-2 proteins. Furthermore, they impede cancer cell growth by enforcing a G2/M cell cycle arrest. Selectivity is achieved via the enhanced permeation and retention (EPR) effect and electrostatic affinity, wherein their positive surface charge (at physiological pH) promotes binding to anionic cancer cell membranes. Despite these advantages, significant challenges in biocompatibility, long-term toxicity, and in vivo stability must be addressed to facilitate clinical translation. This review underscores the critical need for further research to unlock the full therapeutic potential of ZnO NPs.