Modification of Hypoxic States in Photodynamic Therapy
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Modification of Hypoxic States in Photodynamic Therapy A. B. Gapeyeva, * and T. G. Shcherbatyukb, c aInstitute
b
of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow oblast, 142290 Russia Privolzhsky Research Medical University, Ministry of Health of the Russian Federation, Nizhny Novgorod, 603950 Russia c Pushchino State Institute of Natural Science, Pushchino, Moscow oblast, 142290 Russia *e-mail: [email protected] Received May 28, 2019; revised October 14, 2019; accepted October 29, 2019
Abstract—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. Keywords: photodynamic therapy, photosensitizers, reactive oxygen species, carcinogenesis, hypoxia, antitumor effect DOI: 10.1134/S1990747820020051
INTRODUCTION At the present time, cancer is the second leading cause of death in many countries [1]. Surgery, radiotherapy and chemotherapy are the main methods of treatment of malignant tumors. These traditional methods of treatment have significant side effects, bad tolerance and do not guarantee a complete recovery. Therefore, the search for new, more effective and safe methods of treating cancer, as well as ways to reduce the side effects of traditional therapies is an urgent problem. The search for effective and sparing methods of cancer treatment is conducted in different directions, one of which is photodynamic therapy (PDT) of malignant neoplasms (MNPs) [2–4]. Photodynamic therapy differs from traditional methods of treatment in its minimal invasiveness, convenience and flexibility, efficiency and good patient tolerance, which are of important clinical significance [5, 6]. Analysis of the literature has shown that physical impacts of antitumor direction, such as PDT [4], hyperbaric oxygenation [7], and the main method of MNP therapy, radiotherapy [8], have common mechanisms of action associated with the development of free-radical reactions [9]. Due to the fa
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