Type I Photosensitizers Revitalizing Photodynamic Oncotherapy

Photodynamic therapy (PDT) has shown great potential for tumor treatment with merits of non-invasiveness, high selectivity, and minimal side effects. However, conventional type II PDT relying on ¹O₂ presents poor therapeutic efficacy for hypoxic tumors due to the oxygen-dependent manner. Alternatively, emerging researches have demonstrated that type I PDT exhibits superiority over type II PDT in tumor treatment owing to its diminished oxygen-dependence. In this review, state-of-the-art studies concerning recent progress in type I photosensitizers are scrutinized, emphasizing the strategies to construct highly effective type I photosensitizers. As the foundation, basic principles of type I PDT are presented, and up-to-date type I photosensitizers are summarized and classified based on their attributes. Then, a literature review of representative type I photosensitizers (including nanomaterials and small molecules) is presented with impetus to delineate their novel designs, action mechanisms, as well as anticancer PDT applications. Finally, the remaining challenges and development directions of type I photosensitizers are outlined, highlighting key scientific issues toward clinical translations.