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Review

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

Jul 2026 · Advanced Drug Delivery Reviews · Vol 237, pp. 115937 · 2 citations · 89 references
Medicine

TL;DR

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, cysteine, and hydrogen sulfide are highlighted.

Abstract

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.

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