肿瘤微环境
荧光
DNA
信号(编程语言)
生物物理学
化学
荧光原位杂交
生物
生物化学
癌症研究
肿瘤细胞
基因
计算机科学
物理
程序设计语言
量子力学
染色体
作者
Zhenghan Di,Xueguang Lu,Jian Zhao,Ana Jaklenec,Ye Zhao,Róbert Langer,Lele Li
标识
DOI:10.1002/anie.202205436
摘要
DNA biotechnology offers intriguing opportunities for amplification-based sensitive detection. However, spatiotemporally-controlled manipulation of signal amplification for in situ imaging of the tumor microenvironment remains an outstanding challenge. Here, we demonstrate a DNA-based strategy that can spatial-selectively amplify the acidic signal in the extracellular milieu of the tumor to achieve specific imaging with improved sensitivity. The strategy, termed mild acidosis-targeted amplification (MAT-amp), leverages the specific acidic microenvironment to engineer tumor cells with artificial DNA receptors through a pH (low) insertion peptide, which permits controlled recruitment of fluorescent amplifiers via a hybridization chain reaction. The acidosis-responsive amplification cascade enables significant fluorescence enhancement in tumors with a reduced background signal in normal tissues, leading to improved signal-to-background ratio. These results highlight the utility of MAT-amp for in situ imaging of the microenvironment characterized by pH disequilibrium.
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