Recent Advances in Activatable Organic Photosensitizers for Specific Photodynamic Therapy

Photodynamic therapy is an alternative modality for the therapy of diseases such as cancer in a minimally invasive manner. The essential photosensitizer, which acts as a catalyst when absorbing light, converts oxygen into cytotoxic reactive oxygen species that ablate malignant cells through apoptosis and/or necrosis, destroy tumor microvasculature, and stimulate immunity. An activatable photosensitizer whose photoactivity could be turned on by a specific disease biomarker is capable of distinguishing healthy cells from diseased cells, thereby reducing off-target photodamage. In this Minireview, we highlight progress in activatable organic photosensitizers over the past five years, including: (i) biorthogonal activatable BODIPYs; (ii) activatable Se-rhodamine with single-cell resolution; (iii) silicon phthalocyanine targeting oxygen tension; (iv) general D-pi-A scaffolds; and (v) AIEgens. The potential challenges and opportunities for developing new types of activatable organic photosensitizers to overcome the hypoxia dilemmas of photodynamic therapy are discussed.