Abstract
Head and neck cancer (HNC), the seventh most common cancer type, remains associated with high mortality rates despite the use of current treatment modalities such as surgery, radiotherapy, and chemotherapy. Owing to the side effects and lack of specificity of these standard treatments, polymeric nanoparticles (PNPs) have emerged as promising cancer therapeutics by enabling improved drug delivery to neoplastic sites and reducing off‑target toxicity. This review summarizes advances in PNP‑based therapies for HNC, with a particular focus on major systems such as polycaprolactone (PCL), poly(lactide‑co‑glycolide) (PLGA), chitosan, and polyethyleneimine nanoparticles, as applied in chemotherapy, gene therapy, and combination phototherapies. In oral squamous cell carcinoma (OSCC), PCL copolymers have been shown to induce apoptosis, inhibit tumor growth, and enable dual drug delivery and photothermal/photodynamic therapy. PLGA formulations enhance the efficacy of chemotherapeutics such as paclitaxel and gemcitabine/cisplatin in pharyngeal and nasopharyngeal cancers through controlled and sustained release. Chitosan‑based systems have been reported to provide mucoadhesion, improved residence time at mucosal sites, and efficient gene silencing. Overall, these advances highlight the potential of rationally engineered PNPs to address current therapeutic limitations in HNC. However, further work is required to optimize PNP design, fully characterize long‑term toxicity, and validate clinical benefit in rigorously designed clinical trials.