Photodynamic therapy using metal-conjugated novel photosensitizer with the expectation of heavy atom effects

Abstract Photodynamic therapy (PDT) is a relatively non-invasive anti-cancer therapy that employs a photosensitizer with a specific wavelength of light, causing a photochemical reaction that releases free radicals, thereby inducing tumor cell necrosis via oxidative stress. The oxygen molecule reaches the singlet excited state through efficient energy transfer from an excited triplet state of the photosensitizer. Heavy atoms are frequently introduced in photosensitizers for efficiently generating reactive oxygen species (ROS) in PDT, known as the heavy atom effect. However, metal-complexed photosensitizers often show low water-solubility. Here, we established maltotriose (Mal 3 )-conjugation with heavy metallochlorins (M (Mal 3 -chlorin), M = Pt or Pd)) to improve its solubility and evaluated its anti-tumor effect. M (Mal 3 -chlorin) showed effective ROS production and singlet oxygen induction as a result of the heavy-atom effect. Consequently, these cytotoxic factors caused effective anti-tumor effects and induced morphological changes, followed by cell death in vitro . In a xenograft tumor mouse model, PDT with M (Mal 3 -chlorin) showed tumor growth suppression. Thereby, M (Mal 3 -Chlorin) might be an excellent glucose-conjugated chlorin because of its strong anti-tumor PDT effect.