Lysosomal pH Decrease in Inflammatory Cells Used To Enable Activatable Imaging of Inflammation with a Sialic Acid Conjugated Profluorophore
Lysosomal pH Decrease in Inflammatory Cells Used To Enable Activatable Imaging of Inflammation with a Sialic Acid Conjugated Profluorophore
复制标题
炎症细胞中溶酶体 pH 值的降低用于通过唾液酸缀合的原荧光团实现可激活的炎症成像
DOI：
10.1021/acs.analchem.5b00847
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发表时间：
2015
影响因子：
7.4
通讯作者：
Han Shoufa
中科院分区：
文献类型：
--
作者：
Yu Mingzhu;Wu Xuanjun;Lin Bijuan;Han Jiahuai;Yang Liu;Han Shoufa
炎症会导致显著的发病率和死亡率，因此有必要对炎症进行有效的体内成像。以前的方法通常依赖于光学试剂与炎症组织中过度表达的蛋白质类生物标记物的特定实体的组合。在这里，我们报告了一种全新的成像炎症的方法，通过靶向通过唾液酸(SIA)结合的近红外前荧光团(PNIR)在炎症细胞中酸化的溶酶体。SIA-pNIR含有一个唾液酸域，用于体内炎症组织的靶向，以及一个pNIR域，它在酸性溶酶体中异构化成荧光和光声物种。在用大肠杆菌、金黄色葡萄球菌或脂多糖治疗的小鼠中，SIA-pNIR显示出高炎症与健康组织信号的对比。此外，在小鼠接受抗生素治疗时，炎症相关的荧光被关闭。这份报告展示了SIA-pNIR在可激活的双模式炎症成像方面的潜力，特别是使用炎症细胞的溶酶体作为以前未被认可的炎症成像的生物标志物。
Inflammation causes significant morbidity and mortality, necessitating effective in vivo imaging of inflammation. Prior approaches often rely on combination of optical agents with entities specific for proteinaceous biomarkers overexpressed in inflammatory tissues. We herein report a fundamentally new approach to image inflammation by targeting lysosomes undergoing acidification in inflammatory cells with a sialic acid (Sia) conjugated near-infrared profluorophore (pNIR). Sia–pNIR contains a sialic acid domain for in vivo targeting of inflamed tissues and a pNIR domain which isomerizes into fluorescent and optoacoustic species in acidic lysosomes. Sia–pNIR displays high inflammation-to-healthy tissue signal contrasts in mice treated withEscherichia coli,Staphylococcus aureus, or lipopolysaccharide. In addition, inflammation-associated fluorescence is switched off upon antibiotics treatment in mice. This report shows the potentials of Sia–pNIR for activatable dual-modality inflammation imaging, and particularly the use of lysosomes of inflamed cells as a previously unappreciated biomarker for inflammation imaging.