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‐π‐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. Right on target: Targeted activation allows activatable photosensitizers (PSs) capable of distinguishing healthy cells from diseased ones, thus relieving off‐target damage to the skin and neighboring healthy cells during photodynamic therapy (PDT). This Minireview highlights advances in organic activatable PSs over the past five years, in particular those based on the fluorescence turn‐on design. It discusses how conventional fluorophores were modified to produce efficient PSs as scaffolds for activatable compounds that target a variety of disease biomarkers.