From Nature to Nanomedicine: Green-Synthesized Metal Oxide Nanoparticles for Oral Cancer Drug Delivery

Oral cancer represents one of the most prevalent malignancies worldwide, characterized by high morbidity and mortality rates primarily due to late diagnosis, limited therapeutic efficacy, systemic toxicity, and recurrence following conventional treatments. Traditional chemotherapeutic drugs, while effective to a certain extent, often suffer from poor bioavailability, nonspecific targeting, and multidrug resistance, highlighting the importance of innovative therapeutic strategies. Nanomedicine has emerged as a promising alternative, providing site-specific delivery, enhanced drug stability, and improved therapeutic outcomes. Among various nanoparticles (NPs), metal oxide nanoparticles (MONPs), such as zinc oxide, titanium dioxide, and copper oxide, have demonstrated potent anticancer activity due to their high surface area, tunable physicochemical properties, and ability to generate reactive oxygen species (ROS). Recent progress in green synthesis approaches, employing plant extracts, microbes, and biopolymers as reducing and stabilizing agents, has further advanced the development of biocompatible and eco-friendly NPs. These green-synthesized NPs minimize toxic byproducts and allow their functionalization with herbal compounds and conventional drugs, offering synergistic effects against oral cancer. This review highlights the limitations of traditional treatments, examines the role of nanomedicine, and discusses the application of green-synthesized MONPs as drug delivery platforms for oral cancer management. It also addresses challenges such as standardization, scalability, safety concerns, and regulatory barriers, while outlining future perspectives that integrate green nanotechnology with precision medicine. Collectively, green nanomedicine offers a sustainable and innovative paradigm with the potential to revolutionize oral cancer therapy.