Smart molecular designs and applications of activatable organic photosensitizers

초록

Photodynamic therapy (PDT) - which combines light, oxygen and photosensitizers (PS) to generate reactive oxygen species - has emerged as an effective approach for targeted ablation of pathogenic cells with reduced risk of inducing resistance. Some organic PS are now being applied for PDT in the clinic or undergoing evaluation in clinical trials. A limitation of the first-generation organic PS was their potential off-target toxicity. This shortcoming prompted the design of constructs that can be activated by the presence of specific biomolecules - from small biomolecules to large enzymes - in the target cells. Here, we review advances in the design and synthesis of activatable organic PS and their contribution to PDT in the past decade. Important areas of research include novel synthetic methodologies to engineer smart PS with tuneable singlet oxygen generation, their integration into larger constructs such as bioconjugates, and finally, representative examples of their translational potential as antimicrobial and anticancer therapies. Advances in activatable organic photosensitizers for photodynamic therapy are reviewed, highlighting novel synthetic methodologies, their integration into bioconjugates, and their potential in antimicrobial and anticancer treatments, addressing off-target toxicity and enhancing targeted ablation of pathogenic cells. Activatable organic photosensitizers (PS) are designed for targeted photodynamic therapy (PDT), reducing off-target toxicity by activating only at disease sites.Chemical activation strategies include pH-responsive, redox-mediated, and enzyme-activatable PS, enhancing selectivity and efficacy in anticancer and antibacterial treatments.Near-infrared (NIR) PS improve tissue penetration and targeting for clinical translatability, with modifications such as extended conjugation and heavy atom inclusion to increase the excitation wavelengths.Successful biomedical applications demonstrate the potential of activatable PS in treating cancers and infectious diseases, with ongoing challenges in clinical adaptation.Future directions focus on optimizing PS formulations for better biodistribution, developing NIR PS for deeper tissue penetration, and exploring sonodynamic activation.

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