Strategies to construct efficient singlet oxygen-generating photosensitizers

•The state-of-the-art strategies to improve the 1O2 quantum yield are summarized.•The advantages and disadvantages of these strategies are highlighted and compared.•The challenges and obstacles encountered in clinical PDT are discussed. Singlet oxygen (1O2) generation is an essential function of photosensitizer (PS) as applied to photodynamic therapy (PDT) of cancer. As illustrated in the Jablonski diagram, the generation of 1O2 is directly related to the process of intersystem crossing (ISC), in which a high ISC efficiency typically correlates with a high quantum yield (QY) of 1O2. In recent years, multiple strategies have been adopted to improve ISC efficiency, including tuning chemical structures and reducing aggregation-caused quenching (ACQ), thus increase the 1O2 QY of PS. Here, we systematically summarize and compare the advantages and disadvantages of these strategies through analysis of some representative examples. In addition, we also discuss the challenges and obstacles encountered in the development of PS with high 1O2 generation efficiency and propose directions for future clinical applications of PDT.