Targeted photodynamic therapy in head and neck squamous cell carcinoma: heading into the future

The aim of this article is to give an insight into the future of photodynamic therapy (PDT) in head and neck squamous cell carcinoma (HNSCC). Through the combination of a photosensitizing agent with light and oxygen, PDT produces highly cytotoxic reactive oxygen species leading to selective tumor eradication. PDT is an attractive treatment for focal therapy of localized tumors, especially in the case of unresectable tumors. In HNSCC, over 1500 patients have been treated by PDT, and the majority of them responded quite favorably to this treatment. However, the non-negligible photosensitization of healthy tissue is a major limitation for the clinical application of PDT. Improvement in tumor selectivity is the main challenge that can be taken up by the use of a new generation of photosensitizing nanoparticles. Passive targeting, by using functionalised nanocarriers to target to overexpressed transmembrane receptors afford attractive solutions. To this day, epidermal growth factor receptor (EGFR) remains the only validated molecular target for HNSCC, and photosensitizer immunoconjugates to EGFR have been developed for the intracellular delivery of photosensitizing agents. Depending on coordinated research between biomarkers, specific ligands, and photosensitizers, similar approaches could be rapidly developed. In addition, some photosensitizers hold high fluorescence yield and therefore could emerge as theranostic agents.