Near-infrared uncaging or photosensitizing dictated by oxygen tension.
Near-infrared uncaging or photosensitizing dictated by oxygen tension.
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DOI：
10.1038/ncomms13378
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发表时间：
2016-11-17
影响因子：
16.6
通讯作者：
Schnermann MJ
中科院分区：
文献类型：
--
作者：
Anderson ED;Gorka AP;Schnermann MJ
使用组织渗透近红外光进行癌症靶向治疗的现有策略通常依赖于活性氧簇的局部产生。这种方法可能会受到缺氧的阻碍，缺氧经常发生在肿瘤微环境中。在这里，我们表明，轴向不对称的硅酞菁uncage小分子优先在低氧环境中，同时有效地产生活性氧在常氧条件下。解开反应的机理研究暗示了光氧化还原途径，涉及光诱导电子转移，以产生一个关键的自由基阴离子中间体。细胞研究表明，生物学作用机制是O2依赖性的，在常氧条件下活性氧介导的光毒性和缺氧条件下的小分子释放。这些研究提供了一种近红外光靶向治疗策略，有可能通过两种不同的机制来解决复杂的肿瘤景观，这两种机制对局部O2环境的反应不同。 光动力学癌症治疗中活性氧（ROS）的产生受到低的腔内氧可用性的限制。在这里，作者表明，硅酞菁的照射导致生物活性分子的释放或以氧依赖性方式形成ROS。
Existing strategies that use tissue-penetrant near-infrared light for the targeted treatment of cancer typically rely on the local generation of reactive oxygen species. This approach can be impeded by hypoxia, which frequently occurs in tumour microenvironments. Here we demonstrate that axially unsymmetrical silicon phthalocyanines uncage small molecules preferentially in a low-oxygen environment, while efficiently generating reactive oxygen species in normoxic conditions. Mechanistic studies of the uncaging reaction implicate a photoredox pathway involving photoinduced electron transfer to generate a key radical anion intermediate. Cellular studies demonstrate that the biological mechanism of action is O2-dependent, with reactive oxygen species-mediated phototoxicity in normoxic conditions and small molecule uncaging in hypoxia. These studies provide a near-infrared light-targeted treatment strategy with the potential to address the complex tumour landscape through two distinct mechanisms that vary in response to the local O2 environment. The generation of reactive oxygen species (ROS) in photodynamic cancer treatments is limited by low intraturmoural oxygen availability. Here the authors show that irradiation of a silicon phthalocyanine leads to uncaging of a biologically active molecule or to ROS formation in an oxygen-dependent manner.