Nanoplatform-Enhanced Photodynamic Therapy in Head and Neck Squamous Cell Carcinoma: Advances and Future Directions

Photodynamic therapy (PDT) has become a promising treatment for head and neck squamous cell carcinoma over the past 25 years, with nanotechnology accelerating its development. This study aimed to systematically map research trends, thematic evolutions, and technological advances in nano-enhanced PDT for head and neck squamous cell carcinoma.

A bibliometric and trend analysis was performed on 736 English-language publications from January 2000 to June 2025, sourced from the Web of Science Core Collection. CiteSpace/VOSviewer, BICOMB, gCLUTO, and related visualization tools were applied to analyse global research contributions, collaboration networks, keyword clusters, and technological breakthroughs.

Annual publications increased from fewer than 30 (2000-2011) to over 50 (2022-2025), with China, the United States, and the United Kingdom as leading contributors. International collaborations have become more multipolar over time. Three major thematic clusters emerged: (1) fundamental PDT mechanisms, (2) nano-enhanced delivery systems and modulation of the tumour microenvironment, and (3) multimodal combination therapies. Recent growth in publications has been driven by nanoplatforms employing passive and active tumour targeting, along with oxygen-generating strategies.

Although nano-enhanced PDT has achieved substantial preclinical progress, its clinical translation remains limited by manufacturing variability, regulatory uncertainty, and cost-effectiveness concerns. Progress will require well-designed multicentre trials, standardized nanomaterial characterization, and early incorporation of health-economic evaluation. By charting the integration of nanotechnology into PDT and identifying opportunities for synergistic and theranostic approaches, this research provides a structured reference to support future clinical translation.

Nano-enhanced PDT holds strong potential to improve treatment precision, reduce side effects, and address resistance in HNSCC, offering new strategies for both early-stage lesions and advanced tumours. By clarifying global research patterns and identifying key innovation areas, this study supports more effective clinical translation and evidence-based adoption of nano-enhanced PDT into head and neck cancer care pathways.