Large animal models for investigating the applications of photodynamic therapy

Photodynamic therapy (PDT) is an emerging minimally invasive therapeutic modality that relies on the activation of a photosensitizing agent by light of a specific wavelength in the presence of molecular oxygen, leading to the generation of reactive oxygen species (ROS). This mechanism facilitates selective cytotoxic effects within pathological tissues and has demonstrated therapeutic potential across diverse disease contexts. However, the broader clinical applications remain limited by photosensitizer selectivity, shallow light penetration, and the risk of off-target cytotoxicity. Recent advancements in PDT have focused on the development of next-generation photosensitizers, the integration of nanotechnology for enhanced delivery and targeting, and the strategic combination of PDT with complementary therapeutic approaches. Experimental animal models play a crucial role in validating the efficacy and safety of PDT, optimizing its therapeutic parameters, and determining its mechanisms of action. This review provides a comprehensive overview of PDT applications in various disease models, including oncological, infectious, and nonconventional indications. Special emphasis is placed on the importance of large animal models in PDT research, such as rabbits, pigs, dogs, and non-human primates, which provide experimental platforms that more closely resemble human physiological and pathological states. The use of these models for understanding the mechanisms of PDT, optimizing therapeutic regimens, and evaluating clinical outcomes is also discussed. This review aims to inform future directions in PDT research and emphasizes the importance of selecting appropriate preclinical animal models to facilitate successful clinical translation.