Modification of Hypoxic States in 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 the generation of reactive oxygen species upon irradiation of a photosensitizer with light. Reactive oxygen species cause direct destruction of tumor cells, vascular damage, and activate anti-tumor immunity. Hypoxia of tumor tissue significantly reduces the efficacy of PDT and is a serious obstacle for this method. In addition, oxygen consumption in PDT may further aggravate tumor hypoxia that leads to undesirable consequences, such as multidrug resistance, angiogenesis, tumor invasiveness, and metastasis. The purpose of this work was to review the current literature on the progress in overcoming tumor hypoxia or its use to increase the therapeutic efficacy of PDT. The following strategies for overcoming tumor hypoxia were considered: the modification of tumor microenvironment to improve oxygenation; the development of oxygen delivery systems or oxygen generation in situ; an oxygen-independent PDT; and the inhibition of the proteins associated with hypoxia. The existing approaches to use tumor hypoxia in drug release and bioreductive therapy were summarized.