活性氧
光动力疗法
单线态氧
光化学
激进的
光子上转换
芬顿反应
羟基自由基
DNA
线粒体ROS
线粒体
癌细胞
肿瘤微环境
体内
DNA损伤
氧气
化学
癌症研究
生物物理学
材料科学
癌症
生物
生物化学
肿瘤细胞
发光
光电子学
有机化学
生物技术
遗传学
作者
Ping Hu,Tong Wu,Wenpei Fan,Lei Chen,Yanyan Liu,Dalong Ni,Wenbo Bu,Jianlin Shi
出处
期刊:Biomaterials
[Elsevier]
日期:2017-10-01
卷期号:141: 86-95
被引量:221
标识
DOI:10.1016/j.biomaterials.2017.06.035
摘要
The strong dependence on oxygen level, low ultraviolet/visible (UV/vis) light penetration depth and the extremely short lifetime of reactive oxygen species (ROS) are the major challenges of photodynamic therapy (PDT) for tumors. Fenton reaction can produce abundant ROS such as reactive hydroxyl radicals (OH) with significantly higher oxidation performance than singlet oxygen (1O2), which, however, has been rarely used in biomedical fields due to strict reaction conditions (favorably in pH range of 3-4, mostly under UV/vis light catalysis). Herein we propose and demonstrate a photochemotherapy (PCT) strategy of cancer therapy using near-infrared (NIR)-assisted tumor-specific Fenton reactions. NIR light-upconverted UV/vis light by upconversion nanoparticles (UCNPs) catalyze the intra-mitochondrial Fenton reaction between the delivered Fe2+ and H2O2 species over-expressed in cancer cell's mitochondria to in-situ kill the cancer cells. The intra-mitochondrial ROS generation of enabled by directly targeting the mitochondrial DNA (mtDNA) helix minimized the distance between the ROS and mtDNA molecules, thus the present PCT strategy showed much enhanced and tumor-specific therapeutic efficacy, as demonstrated by the intratumoral-accelerated OH burst and elevated cytotoxicity. Following the direct intratumoral injection, the PCT revealed marked tumor regression effect in vivo. This constructed PCT-agent is the first paradigm of NIR-upconversion catalyzed intra-mitochondrial Fenton reaction in response to tumoral microenvironment, establishing a novel photochemotherapy strategy for efficient cancer therapy.
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