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However, spatiotemporally\u2010controlled manipulation of signal amplification for in situ imaging of the tumor microenvironment remains an outstanding challenge. Here, we demonstrate a DNA\u2010based strategy that can spatial\u2010selectively amplify the acidic signal in the extracellular milieu of the tumor to achieve specific imaging with improved sensitivity. The strategy, termed mild acidosis\u2010targeted amplification (MAT\u2010amp), 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\u2010responsive amplification cascade enables significant fluorescence enhancement in tumors with a reduced background signal in normal tissues, leading to improved signal\u2010to\u2010background ratio. These results highlight the utility of MAT\u2010amp for in situ imaging of the microenvironment characterized by pH disequilibrium.<\/jats:p>","DOI":"10.1002\/anie.202205436","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T06:03:56Z","timestamp":1654149836000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Mild Acidosis\u2010Directed Signal Amplification in Tumor Microenvironment via Spatioselective Recruitment of DNA Amplifiers"],"prefix":"10.1002","volume":"61","author":[{"given":"Zhenghan","family":"Di","sequence":"first","affiliation":[{"name":"CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology  Beijing 100190 China"},{"name":"College of Materials Science and Optoelectronic Technology University of Chinese Academy of Sciences  Beijing 100049 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueguang","family":"Lu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Colloid, Interface and Chemical Thermodynamics Institute of Chemistry Chinese Academy of Sciences  Beijing 100190 China"},{"name":"David H. 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