<br>用于缺氧/ROS/pH 三重响应货物释放的金属有机框架,Advanced Healthcare Materials

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用于缺氧/ROS/pH 三重响应货物释放的金属有机框架
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2023-08-17 , DOI: 10.1002/adhm.202301785
Wenyu Chen ₁ , Huixin He ₁ , Pengfei Jiao ₁ , Lefei Han ₁ , Jianchun Li ₁ , Xiu Wang ₁ , Xuliang Guo ₁

Affiliation

纳米颗粒抗肿瘤光动力疗法（PDT）存在寿命短、活性氧（ROS）扩散距离有限的问题。在此，设计了一种缺氧/ROS/pH三重响应金属有机框架（MOF），以促进光敏剂的按需释放，从而增强PDT功效。定制的含偶氮咪唑配体与锌配位形成 MOF，其中封装有光敏剂 (Chlorin e6/Ce6)。缺氧肿瘤细胞中过度表达的偶氮还原酶可以还原偶氮，导致谷胱甘肽 (GSH) 和硫氧还蛋白 (Trx) 消耗，这两种物质是 PDT 中对抗 ROS 氧化损伤的主要抗氧化剂，从而导致快速药物释放和额外的功效放大。咪唑电离引起质子海绵效应，确保纳米载体在酸性细胞器中崩解，从而使 Ce6 通过溶酶体逃逸快速释放。在光照射下，Ce6产生的ROS可以将咪唑氧化成尿素，从而导致货物快速释放。所有触发因素预计将显示出交互协同作用。 pH 和缺氧响应性可以提高 Ce6 的释放速率，从而增强 PDT 治疗，而 PDT 消耗的氧气可能会导致缺氧加剧，从而增强药物释放。这项工作强调了三重响应纳米载体在触发光敏剂释放和提高抗肿瘤 PDT 功效方面的作用。

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Metal–Organic Framework for Hypoxia/ROS/pH Triple-Responsive Cargo Release

Nanoparticulate antitumor photodynamic therapy (PDT) is suffering from a very short lifetime, limited diffusion distance of reactive oxygen species (ROS). Herein, a hypoxia/ROS/pH triple-responsive metal–organic framework (MOF) is designed to facilitate the on-demand release of photosensitizers and hence enhanced PDT efficacy. Tailored azo-containing imidazole ligand is coordinated with zinc to form MOF where photosensitizer (Chlorin e6/Ce6) is encapsulated. Azo can be reduced by overexpressed azoreductase in hypoxic tumor cells, resulting in depletion of glutathione (GSH) and thioredoxin (Trx) which are major antioxidants against ROS oxidative damage in PDT, resulting in rapid cargo release and additional efficacy amplification. The imidazole ionization causes a proton sponge effect to ensure the disintegration of the nanocarriers in acidic organelles, allowing the rapid release of Ce6 through lysosome escape. Under light irradiation, ROS produced by Ce6 may oxidize imidazole to urea, resulting in rapid cargo release. All of the triggers are expected to show interactive synergism. The pH- and hypoxia-responsiveness can improve the release rate of Ce6 for enhanced PDT therapy, whereas the consumption of oxygen by PDT may induce elevated hypoxia and hence in turn enhanced cargo release. This work highlights the role of triple-responsive nanocarriers for triggered photosensitizer release and improved antitumor PDT efficacy.

更新日期：2023-08-17

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