Redox-activated heavy-atom-free photosensitizers for enhanced photodynamic cancer therapy

In recent years, heavy-atom-free photosensitizers have been recognized as an important class of agents for photodynamic therapy (PDT). In particular, redox-activated heavy-atom-free photosensitizers inspired by the redox imbalance of the tumor microenvironment are emerging as a promising strategy to improve the specificity and therapeutic efficiency of PDT. This review highlights design strategies of redox-activated heavy-atom-free photosensitizers (PSs), including donor-acceptor-based frameworks, thionation, aggregation-induced emission (AIE) driven intersystem crossing enhancement, and the integration of responsive moieties for reactive oxygen species (ROS), glutathione (GSH), cysteine (Cys), and hydrogen sulfide (H₂S). In addition, recent advances in the development of redox-activated heavy-atom-free PSs over the past three years are summarized. Finally, main challenges, including hypoxic tumors, limited tumor-targeting efficiency, and limited light penetration into deep-seated tumors, as well as future prospects for this field, are discussed.