Metal-conjugated Maltotriose Chlorins as Novel Photosensitizers for Photodynamic Therapy

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. To overcome this limitation and produce ROS effectively, we focused on the better solubility of photosensitizers with heavy metals bound within the chlorin skeleton and conjugated with glucose in this study.

We established maltotriose (Mal₃)-conjugation with heavy metallochlorins [M (Mal₃-chlorin), M=Pt or Pd)] and evaluated its anti-tumor effect.

M (Mal₃-chlorin) showed effective ROS production and singlet oxygen induction. 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 (Mal₃-chlorin) showed tumor growth suppression.

M (Mal₃-Chlorin) might be an excellent glucose-conjugated chlorin because of its strong anti-tumor PDT effect.