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.

中文翻译：

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光动力疗法中缺氧状态的改变

摘要

光动力疗法（PDT）被认为是治疗恶性肿瘤的一种有前途的方法，其效果是由于光敏剂照射光后产生的活性氧而产生的。活性氧会直接破坏肿瘤细胞，破坏血管并激活抗肿瘤免疫力。肿瘤组织缺氧显着降低了PDT的功效，并且是该方法的严重障碍。另外，PDT中的氧气消耗可能会进一步加重肿瘤缺氧，从而导致不良后果，例如多药耐药性，血管生成，肿瘤浸润和转移。这项工作的目的是回顾有关克服肿瘤缺氧的进展或将其用于增加PDT的治疗功效的最新文献。考虑了以下克服肿瘤缺氧的策略：改变肿瘤微环境以改善氧合；氧气输送系统的开发或现场氧气的产生；不依赖氧气的PDT；以及与缺氧有关的蛋白质的抑制作用。总结了利用肿瘤缺氧进行药物释放和生物还原治疗的现有方法。