Photodynamic therapy for hypoxic tumors: Advances and perspectives

Photodynamic therapy (PDT) has been a preferred clinical technology for treating superficial tumors due to its advantages of high selectivity, non-invasiveness and negligible drug resistance. However, the hypoxic tumor microenvironment weakens the efficiency of O₂-dependent PDT. Moreover, the PDT process consumes a large amount of O₂ and destroys the tumor blood vessels and further blocks the O₂ supply to tumor sites. Therefore, developing more advanced materials and methods for PDT of the hypoxic tumor is an essential scientific significance. This tutorial review summarizes the strategies for improving the efficacy of PDT in hypoxic tumor therapy, which is categorized into three sections: (I) enhancing O₂ concentration in the tumor; (II) disregarding hypoxia; and (III) exploiting hypoxia. The advantages of combining PDT with other therapeutics, such as chemotherapy, chemo-dynamic therapy, gas therapy, immunotherapy and gene therapy, are also demonstrated. Finally, the existing challenges and future perspectives on clinical PDT for hypoxic tumors are discussed.