Developments in PDT Sensitizers for Increased Selectivity and Singlet Oxygen Production

Photodynamic therapy (PDT) is a minimally-invasive procedure that has been clinically approved for treating certain types of cancers. This procedure takes advantage of the cytotoxic activity of singlet oxygen (¹O₂) and other reactive oxygen species (ROS) produced by visible and NIR light irradiation of dye sensitizers following their accumulation in malignant cells. The main two concerns associated with certain clinically-used PDT sensitizers that have been influencing research in this arena are low selectivity toward malignant cells and low levels of ¹O₂ production in aqueous media. Solving the selectivity issue would compensate for photosensitizer concerns such as dark toxicity and aggregation in aqueous media. One main approach to enhancing dye selectivity involves taking advantage of key methods used in pharmaceutical drug delivery. This approach lies at the heart of the recent developments in PDT research and is a point of emphasis in the present review. Of particular interest has been the development of polymeric micelles as nanoparticles for delivering hydrophobic (lipophilic) and amphiphilic photosensitizers to the target cells. This review also covers methods employed to increase ¹O₂ production efficiency, including the design of two-photon absorbing sensitizers and triplet forming cyclometalated Ir(III) complexes.