Zinc Oxide Nanoparticles as Drug Delivery Tools

Abstract

Zinc oxide nanoparticles (ZnO-NPs) have emerged as promising inorganic nanocarriers for drug delivery due to their unique physicochemical properties, pH-responsive biodegradability, high surface area, and intrinsic biological activity. Their dissolution under acidic conditions enables controlled drug release within the tumor microenvironment and intracellular compartments, improving therapeutic selectivity while aiming to reduce off-target exposure. Surface functionalization with polyethylene glycol (PEG), chitosan, hyaluronic acid, and folic acid has further improved nanoparticle stability, prolonged circulation, and promoted receptor-mediated cellular uptake in targeted tissues. Beyond serving as drug carriers, ZnO-NPs exhibit intrinsic anticancer, antimicrobial, and anti-inflammatory activities, primarily through the generation of reactive oxygen species and controlled release of Zn2+ ions, which can contribute to activity in addition to that of the loaded drug. Despite promising preclinical results, challenges continue to limit clinical translation of ZnO-NP-based drug delivery systems, including reproducible large-scale synthesis, long-term colloidal stability and biosafety, pharmacokinetic behavior, and regulatory requirements. Continued optimization of nanoparticle engineering, functionalization, and in vivo validation is essential for advancing ZnO-NPs toward clinical use. This review summarizes the synthesis methods, physicochemical properties, functionalization strategies, and biomedical applications of ZnO-NPs, and discusses remaining challenges and future clinical perspectives.