Photodynamic therapy (PDT) is an approved procedure using a photosensitizer (PS) activated by light to selectively destroy malignant/premalignant cells. Transition metal complexes, such as Ru(II)- and Os(II)-based PSs (Theralase Technologies Inc., Ontario. Canada), are activated in a wide range of wavelengths, are resistant to photobleaching and have a high singlet oxygen quantum yield and ability to produce cytotoxic reactive oxygen species (ROS). Their design allows fine-tuning of the photophysical and photochemical properties. They demonstrate Type I and II photoreactions, and some are activated in hypoxia. High PDT potency and activation under NIR light and even X-ray may provide an advantage over the approved PSs. Their ability to associate with transferrin (Tf) as an endogenous delivery system increases photobleaching resistance, ROS production, selective cellular uptake, and PDT efficacy in combination with a decreased systemic toxicity. This makes these PSs attractive for systemic therapy of recurrent/progressive cancers. Their PDT efficacy has been demonstrated in various in vitro and in vivo clinically relevant models. The unique properties of the mentioned PSs allow bypassing such limitations of PDT as low specific uptake ratio, insufficiently broad absorption band, and low efficacy in hypoxia. One of these PSs (TLD-1433) was successful against non-muscle invasive urinary bladder cancer unresponsive to contemporary anticancer therapies.
Part of the book: Tumor Progression and Metastasis