Modification of Hypoxic States at Photodynamic Therapy

Photodynamic therapy (PDT) is regarded as a promising approach to the treatment of malignant tumors, the effect of which is achieved due to generation of reactive oxygen species when the photosensitizer is irradiated with light. Reactive oxygen species cause direct destruction of tumor cells and vascular damage and activate anti-tumor immunity. Hypoxia of tumor tissue, significantly reducing the efficacy of PDT, creates a serious obstacle to this method. In addition, oxygen consumption in PDT may further aggravate tumor hypoxia, which leads to undesirable consequences, such as multidrug resistance, angiogenesis, tumor invasiveness, and metastasis. The purpose of this work is to review the current literature on the achievements in overcoming or using tumor hypoxia to increase the therapeutic efficacy of PDT. We consider strategies for overcoming of tumor hypoxia by modifying the tumor microenvironment to improve oxygenation, development of the means of oxygen delivery or oxygen generation in situ, oxygen-independent PDT, and inhibition of proteins associated with hypoxia. The existing approaches to usage of tumor hypoxia upon drug release and bioreductive therapy are summarized.