Zinc oxide nanoparticles from drug delivery to immunomodulation: progress and challenges

INTRODUCTION: Over the last decades, zinc oxide nanoparticles (ZnO NPs) have emerged as promising nanoplatforms for various biomedical applications. This critical perspective summarizes the main uses of ZnO NPs in cancer therapy, focusing on their roles in advanced drug delivery, stimuli-responsive systems, and immunomodulatory treatments targeting tumor tissues. AREAS COVERED: Due to their intrinsic physicochemical properties, ZnO NPs can dissolve in the acidic tumor microenvironment and generate radical oxygen species, causing metabolic dysregulations that lead to cancer cell apoptosis. When engineered into multimodal nanoplatforms, the combination of ZnO with standard cancer therapies, such as chemotherapy and immunotherapy, or with energy-activated treatments like photodynamic and sonodynamic therapy, achieves synergistic antitumor effects, overcoming many limitations of current standards of care. EXPERT OPINION: Crucially, ZnO demonstrates a strong immunomodulatory capability, promoting T-cell activation and dendritic cell maturation necessary to reverse the 'cold' tumor microenvironment often associated with solid and deep-seated tumors. Overall, ZnO NPs offer revolutionary therapeutic prospects for novel anticancer treatments, provided that challenges regarding long-term stability and controlled degradability are addressed in future works for clinical translation.