Natural photosensitizers with relevance to traditional medicine in photodynamic therapy

Photodynamic therapy (PDT) uses a photosensitizer (PS), light of a specific wavelength, and molecular oxygen to generate reactive oxygen species that destroy target cells.Currently approved photodynamic agents have practical limitations, including prolonged skin photosensitivity, limited tumor selectivity, and high cost.Natural compounds with photosensitizing activity have been investigated as alternative candidates.This review summarizes and critically discusses four natural PSs that have historical roles in, or relevance to, traditional medicine: Hypocrellins A and B (from Hypocrella bambusae), Berberine (from Coptis chinensis), Curcumin (from Curcuma longa), and Hypericin (from Hypericum perforatum).For each compound, photophysical properties (absorption wavelength, singlet-oxygen quantum yield), biological mechanisms, preclinical findings, and clinical status were reviewed.Nanocarrier strategies addressing their shared limitations, including poor aqueous solubility, aggregation, and suboptimal activation wavelengths, were evaluated by functional category.Among these candidates, Hypericin has been most extensively evaluated in clinical trials, while Curcumin has been explored in antimicrobial PDT settings.Hypocrellin and Berberine remain at the preclinical stage.For all four compounds, further formulation optimization, pharmacokinetic characterization, dosimetry standardization, and well-designed clinical trials are needed before clinical utility can be established.