Advanced nanotechnology in enhancing immune checkpoint inhibitors (ICIs) for head and neck cancer therapy.

The sixth most prevalent malignancy in the world, head and neck cancer (HNC), is associated with high mortality rate. Several risk factors, such as Helicobacter pylori and human papillomavirus (HPV) infection, alcohol and tobacco consumption, enhance the chance of developing these malignancies. Given its high prevalence and severe clinical manifestations, timely and appropriate therapeutic approaches are essential. The disease stage and the precise location of the tumor determine whether conventional treatment modalities—surgery, chemotherapy, radiation, immunotherapy, and targeted therapy—are used. Immunotherapy is designed to enhance the immune system’s activity against tumors. Due to its superior efficacy and minimal impact on healthy cells, immunotherapy has gained considerable attention. One category of immunotherapy is immune checkpoint inhibitors (ICIs), which target overexpressed checkpoint proteins in cancer, such as TIGIT, CTLA-4, TIM-3, LAG-3, PD-L1, and PD-1. By inhibiting these proteins, ICIs enhance immune cell activity. However, these treatments face challenges, including weak T-cell responses and adverse effects of ICI systemic administration. The combination of ICIs with nanotechnology has been explored to overcome these limitations. Nanotechnology can improve drug delivery, reduce systemic toxicity, enhance pharmacokinetics, and prolong drug circulation time. This review first addresses the use of ICIs in HNCs treatment and subsequently examines their combination with nanotechnology to overcome existing limitations and improve therapeutic efficacy. Additionally, the combination of these approaches (ICIs-NP) with conventional treatments is explored.