Ambidextrous approach of silver decorated polydopamine-zinc oxide nanohybrid for long-lasting ROS generation and...

Zinc oxide (ZnO) nanoparticles have shown considerable promise in cancer therapy due to their unique and tunable physicochemical characteristics. Integrating with nanotechnology-driven combination therapies offers significant potential for treating metastatic tumors by facilitating targeted drug delivery through selective interaction with specific cell surface receptors. Herein, we have synthesized folate-targeted silver-polydopamine functionalized eco-friendly ZnO NPs loaded with paclitaxel with zeta potential of around -25.7 ± 1.65 mV and a diameter 186 ± 5.32 nm. Presence of FA moieties over nanoparticle surface facilitates targeted delivery of paclitaxel to folic acid overexpressing breast cancer cells. Moreover, paclitaxel-loaded ZnO@PDA/Ag-FA nanohybrid showed pH-sensitive drug release behavior due to its acid-responsive degradation. It demonstrated a substantial release of up to 80 % in an acidic environment, whereas only 20 % in a neutral environment. Results suggested that ZnO-PTX@PDA/Ag-FA effectively triggers apoptotic cell death in human breast cancer cells by promoting oxidative stress and mitochondrial dysfunction. Cellular studies further revealed that the co-delivery of Ag, ZnO, and PTX significantly enhances reactive oxygen species generation and disrupts the glucose metabolism of tumor cells, thereby promoting apoptosis and inhibiting tumor growth. Collectively, these results underscore the strong chemotherapeutic potential of this novel nanohybrid, suggesting its promise for future clinical applications in cancer treatment.