In Vivo Imaging of Hypoxia Associated with Inflammatory Bowel Disease by Cytoplasmic Protein-Powered Fluorescence Cascade Amplifier
In Vivo Imaging of Hypoxia Associated with Inflammatory Bowel Disease by Cytoplasmic Protein-Powered Fluorescence Cascade Amplifier
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通过细胞质蛋白驱动的荧光级联放大器对与炎症性肠病相关的缺氧进行体内成像
DOI：
10.1021/acs.analchem.9b05278
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发表时间：
2020
影响因子：
7.4
通讯作者：
Ronghua Yang
中科院分区：
文献类型：
--
作者：
Yibo Zhou;Sheng Yang;Jingru Guo;Hao Dong;Keyi Yin;Wei Tao Huang;Ronghua Yang
炎症性肠病（IBD）相关缺氧的准确和敏感成像对于该疾病的精确诊断和治疗具有重要意义，但由于IBD期间的缺氧状态比其他病理状态更温和，因此传统的缺氧激活荧光探针仍然是一个挑战。为了解决这个问题，我们设计了一个缺氧激活的细胞质蛋白驱动的荧光级联放大器，命名为HCFA，来成像体内与IBDin相关的缺氧。在我们的设计中，以4-氨基苯甲酸（偶氮）修饰的介孔二氧化硅纳米颗粒（MSN）作为容器，装载黑洞猝灭剂2 （BHQ2）和细胞质蛋白结合方英染料（SQ）；然后，β-环糊精聚合物（β-CDP）通过主客体相互作用与偶氮结合形成HCFA。在IBD炎症组织中被动滞留后，偶氮带在缺氧微环境下断裂，释放SQ激活HCFA的荧光。此外，不受约束的SQ可以与细胞质蛋白结合，表现出强烈的荧光强度增强，实现荧光信号放大，用于缺氧成像。当人们利用MSN的大负载能力和SQ的独特性能时，HCFA可以在0%到10%的范围内检测氧气水平。同时，荧光成像结果表明，HCFA可以灵敏地区分不同水平的细胞缺氧，并监测体内缺氧的变化，突出了HCFA在IBD相关缺氧检测中的应用前景。
Accurate and sensitive imaging of hypoxia associated with inflammatory bowel disease (IBD) is significant for the precise diagnosis and treatment of this disease, but it remains a challenge for traditional hypoxia-activatable fluorescence probes because of a more moderate hypoxic state during IBD than under other pathological conditions. To address this issue, herein, we designed a hypoxia-activatable and cytoplasmic protein-powered fluorescence cascade amplifier, named HCFA, to image hypoxia associated with IBDin vivo. In our design, a 4-aminobenzoic acid (azo)-modified mesoporous silica nanoparticle (MSN) was used as a container to load black hole quencher 2 (BHQ2) and cytoplasmic protein-binding squarylium dye (SQ); then, the β-cyclodextrin polymer (β-CDP) combined with azo through a host–guest interaction to form HCFA. Upon passive stagnation in the inflamed tissue of IBD, the azo band would be cleaved under a hypoxic microenvironment, and SQ was released to activate the fluorescence of HCFA. Moreover, the unconstrained SQ can bind with cytoplasmic protein to exhibit drastic fluorescence intensity enhancement, realizing the fluorescence signal amplification for imaging of hypoxia. When one takes advantage of the large load capacity of MSN and the unique property of SQ, HCFA can sense oxygen levels in the range of 0% to 10%. Meanwhile, the fluorescence imaging results demonstrate that HCFA can sensitively distinguish different levels of cellular hypoxia and monitor the variations of hypoxiain vivo, highlighting HCFA as a promising tool for the detection of hypoxia associated with IBD.