A chemical biology toolbox to overcome the hypoxic tumor microenvironment for photodynamic therapy: a review

Cancer is a disease that seriously threatens human health. Over the past few decades, researchers have continued to find ways to cure cancer. Currently, the most commonly used clinical techniques are surgery, chemotherapy, radiotherapy and so on. Among them, photodynamic therapy (PDT) has received extensive attention due to its better therapeutic effect and lower side effects. However, the inherent microenvironmental hypoxia of tumor tissue leads to unsatisfactory therapeutic effects. Therefore, researchers have conducted in-depth research on the hypoxia problem in PDT therapy. This review classified photodynamic therapy according to the response mechanism and summarized the strategies developed to overcome tumor hypoxia in recent years. Among them, research strategies can be divided into five types: type I PDT photosensitizers, introducing exogenous oxygen, O-2 carriers using nanomaterials, generating endogenous oxygen by catalytic reactions, and combination with prodrugs that inhibit the consumption of endogenous oxygen. Finally, we also list some studies using combination therapy, such as microbes, photothermal therapy, etc. It can be guaranteed that the review can provide theoretical guidance for the development of anti-hypoxic PDT tools.