Insights into the organic semiconducting photosensitizers for hypoxia-tolerant type I photodynamic therapy

Photodynamic therapy (PDT) is a promising approach to treat cancer and microbial infections due to its minimal invasiveness, high spatiotemporal selectivity, tissue specificity, and low toxicity. Depending on the reactive oxygen species generation mechanisms, PDT can be classified as type I and type II. To date, most reported photosensitizers are based on the type II PDT mechanism, which produces toxic singlet oxygen and requires an abundant and continuous supply of oxygen molecules. Unfortunately, in typical solid tumor microenvironments, vascular abnormalities and rapid metabolisms lead to oxygen deficiency, severely compromising type II PDT's effectiveness. To address this issue, type I PDT with less oxygen consumption has been developed as an effective way to overcome the limitations of traditional type II PDT. In this contribution, we focus on the recent advances in type I organic semiconducting photosensitizers (OSPs), including organic semiconducting small molecules, conjugated polymers, and covalent organic frameworks for advanced hypoxia-tolerant PDT. The conceptual framework and general properties of these OSPs are firstly introduced, followed by introducing OSPs with different chemical structures for type I PDT. Finally, the overall conclusion, insightful perspective, and future direction of the efforts of OSPs for advanced biological applications are outlined.