Photodynamic therapy for oral mucosal lesions: photosensitizer evolution, pharmacological mechanisms, and clinical translation.

Oral mucosal lesions (OMLs) comprise a diverse group of diseases affecting the oral mucosal tissues. Traditional treatments such as medication, surgery, laser therapy, and cryotherapy often produce significant side effects, including high recurrence rates due to drug resistance-associated recurrence and considerable tissue trauma, leading to unsatisfactory clinical outcomes. Photodynamic therapy (PDT), which uses photosensitizers, light at specific wavelengths, and oxygen to generate cytotoxic effects that induce cell apoptosis and necrosis, cause immunogenic cell death and microcirculation damage, and trigger local immune responses, has emerged as a promising minimally invasive alternative. PDT offers advantages including strong selectivity, minimal invasiveness, high targeting capability, and repeatable administration. However, clinical translation remains constrained by pharmacological barriers including restricted tissue penetration depth of therapeutic light, absence of standardized treatment protocols, and insufficient long-term efficacy data. This comprehensive review systematically examines the evolutionary development of photosensitizer generations, explores synergistic combination strategies integrating PDT with complementary therapeutic modalities, and critically evaluates current clinical applications across common OMLs types. By synthesizing current evidence and identifying knowledge gaps regarding drug-target interactions, this review aims to provide a robust foundation for advancing therapeutic agent development and guiding future research directions in PDT-based management of OMLs.