Fluorescent-Conjugated ZnO Nanostructures Exhibited 3D Anti-Tumor Efficacy Against Drug-Resistant Cancers Through Cholesterol-Mediated ROS Regulation

ZnO nanoparticles (ZnO NPs) have been widely investigated in the biomedical field, particularly their anti-tumor efficacy. The potential of ZnO hierarchical structures (ZnO HSs) in tumor cell eradication remains largely unexplored in prostate cancer (PCa) and thyroid cancer (TC). In this study, we successfully synthesized and characterized ZnO NPs and ZnO HSs using green tea extract (Camellia sinensis) as a reducing agent and conjugation of FIT-C tracking for both ZnO NPs and ZnO HSs. UV-vis spectrophotometry, Dynamic Light Scattering (DLS), FTIR, XDR, SEM and TEM revealed significant differences in morphology between ZnO NPs and ZnO HSs. Our in vitro experiments demonstrated that SNPs were more effective on aggressive PCa and TC cell lines compared to ZnO NPs. Notably, ZnO HSs exhibited enhanced cytotoxicity in 3D tumor cell spheroid models. Mechanistically, ZnO HSs induced apoptosis through cholesterol-mediated reactive oxygen species (ROS) generation. Our in vivo study revealed no histopathological changes in major organs (liver, kidneys, spleen and lungs), emphasizing the safe administration of both ZnO NPs and ZnO HSs. Our study synthesized FITC-conjugated non-spherical ZnO nanoparticles, providing evidence for a novel treatment strategy for hormone-related cancers and prospective fluorescent-guided nanomedicine.