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.
A cysteine-inspired conjugated polymer photosensitizer was developed to integrate enhanced tumor accumulation, hydrogen sulfide generation, photodynamic therapy (PDT), and photothermal therapy (PTT), achieving an 89% tumor inhibition rate without detectable skin injury or systemic toxicity.
Yan Yuan, Zhi-Jie Fang, Wei-Qing Yue et al.· ACS Applied Materials and In...· 0 citations
Photodynamic therapy (PDT) is an established clinically approved treatment; however, the development of next-generation photosensitizers remains constrained by the reliance on scarce precious-metal scaffolds and poor pharmacological properties. Earth-abundant first−row transition metals offer an attractive alternativ...
Zisis Papadopoulos, Aimée Marie Irgel, Alexandra König-Schäfer et al.· Journal of Medicinal Chemist...· 0 citations
This study compares natural ligand-metal complexes with conventional Ru(II)/Ir(III) complexes and clinical PSs to assess their translational potential as immune-activating agents in PDT oncology, as well as focusing on the integration of nanotechnology with natural ligand-metal complexes to enhance delivery, biocompati...
Siu Kan Law, Albert Wingnang Leung, Chuan-Shan Xu· International Journal of Mol...· 0 citations
This work provides an oxygen-unrestricted synergistic strategy to compensate for the limitations of standalone Type II PSs or HAPs monotherapy, offering valuable insights for clinical cancer treatment.
Porphyrin-based photosensitizers (PSs) are among the most widely explored agents for photodynamic therapy (PDT), yet their clinical translation is severely limited by poor biocompatibility, aggregation-induced quenching, insufficient tumor selectivity, and the intrinsic reactive oxygen species (ROS) resistance of cance...
Yi-Hui Ai, Chong-Zhi Wu, Zhi-Yao Li et al.· Small· 0 citations
Photodynamic therapy (PDT), as a promising anticancer strategy, has attracted much attention due to the advantages of non-invasiveness, temporal-spatial selectivity, and low tendency to induce drug resistance. However, the clinical translation of PDT faces severe challenges, owing to the oxygen-demanding nature of ROS...