Ludovica Lucchesi Palli, Cinzia Scialabba, Gennara Cavallaro
Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral cavity and is still associated with a poor prognosis today. Although surgery, radiotherapy, chemotherapy, and more recently immunotherapy and targeted therapies have improved the clinical management of the disease, their efficacy is often limited by poor selectivity, systemic toxicity, and the development of therapeutic resistance. In this context, nanotheranostics has emerged as one of the most promising strategies in the field of precision medicine, thanks to the development of multifunctional nanoplatforms capable of integrating diagnostic and therapeutic functions within a single system. In addition to improving the delivery and controlled release of anticancer agents, these nanosystems can enable real-time monitoring of biodistribution and therapeutic response through integrated imaging techniques, supporting imaging-guided and personalized treatment. In particular, the integration of photothermal therapy (PTT) and photodynamic therapy (PDT) with other therapeutic strategies has led to the development of increasingly multifunctional platforms capable of exploiting synergistic mechanisms to enhance antitumor efficacy. This review provides a state of overview of the major theranostic nanoplatforms developed for the treatment of OSCC, critically analyzing lipid, polymeric, inorganic, carbon-based, biomimetic, and multifunctional hydrogel-based nanosystems, with a focus on targeting strategies, various integrated imaging modalities, stimulus-responsive drug delivery systems, and PTT/PDT-based combination therapies.