Emerging Metallic Nanoparticle Modalities in Oral Squamous Cell Carcinoma: A Comprehensive Review on Theranostic Strategies and Future Perspectives

Oral cancer remains a significant global health concern, with aggressive progression and high mortality rates due to late diagnosis and limited treatment efficacy. Surgical ablation, radio-, and chemotherapy are the primary standalone treatment regimens for oral cancer; however, their success is often hindered by late-stage diagnosis, chemoresistance, and debilitating side effects, underscoring the demand for more precise and effective alternatives. In modern cancer treatment, multifunctional metallic nanoparticles are being developed as promising carriers in cancer therapy owing to their ability to selectively target tumor cells via active and passive mechanisms and effectively reduce the off-target toxicity of the chemotherapeutics. Different types of metallic nanoparticles offer distinct therapeutic advantages. Gold nanoparticles leverage strong surface plasmon resonance, enabling photothermal therapy and imaging; silver nanoparticles possess inherent oxidative stress-inducing and antimicrobial properties that enhance cytotoxicity, and the magnetic properties of iron oxide nanoparticles support magnetic resonance imaging, facilitating magnetic field-driven targeting and magnetothermal therapeutic applications. These intrinsic features lead to their broad utilization in drug delivery, sensing, phototherapy, imaging, and integrated theranostic applications. The agenda of the current review article is to explore the pathogenesis of oral cancer and elucidate how the metallic nanoparticles can revolutionize its diagnosis and treatment. This article also seeks to uncover the diverse fabrication methods and biomedical applications of metallic nanoparticles, showcasing their transformative synergy with conventional therapies to overcome the limitations such as chemoresistance, nonspecific toxicity, and inadequate imaging precision. Moreover, the article addresses the barriers to clinical implementation, the regulatory landscape, and critical toxicity evaluations. Collectively, the article underscores the transformative potential of MNPs in advancing oral cancer management and delineates key avenues for future developments.