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We herein report a 5\u2010\n                    <jats:italic>exo\u2010trig<\/jats:italic>\n                    cyclization strategy to create diverse activatable heptamethine cyanine probes with \u201czero\u201d intrinsic background fluorescence for high\u2010contrast bioimaging. This intramolecular ring\u2010closure approach imparts a built\u2010in switch to regulate the fluorescence of cyanine dyes, which predominantly exist in the nonfluorescent closed\u2010loop form at pH over 5.0 and are not affected by environmental polarity and protein interaction, thereby reducing false\u2010positive fluorescent signals. Upon reaction with various biomarkers, including methylglyoxal (MGO), hydroxyl radical (\u00b7OH), and adenosine triphosphate (ATP), they could rapidly transform into fluorescent open\u2010loop structures, showing significant NIR fluorescence enhancement (up to 184\u2010fold). Furthermore, we extended this strategy to develop a variety of NIR\u2010II ATP\u2010activatable cyanine probes for the first time, as well as a theranostic probe\n                    <jats:bold>57<\/jats:bold>\n                    using host\u2013guest chemistry. Probe\n                    <jats:bold>57<\/jats:bold>\n                    not only sensitively monitored ATP levels in inflammatory bowel disease (IBD) with a high signal\u2010to\u2010background ratio of 48\/1, but it also precisely detected extracellular ATP in stools. This work opens a new avenue to develop stimuli\u2010responsive NIR cyanine probes for improving disease diagnosis.\n                  <\/jats:p>","DOI":"10.1002\/anie.202423059","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T04:15:06Z","timestamp":1748405706000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Access to Diverse Activatable Heptamethine Cyanine Probes with Low Intrinsic Fluorescence via 5\u2010\n                    <i>exo\u2010trig<\/i>\n                    Cyclization Strategy for High\u2010Contrast Bioimaging In Vivo"],"prefix":"10.1002","volume":"64","author":[{"given":"Fapu","family":"Wu","sequence":"first","affiliation":[{"name":"Research Center for Analytical Sciences Tianjin Key Laboratory of Biosensing and Molecular Recognition Frontiers Science Center for New Organic Matter College of Chemistry Nankai University  94 Weijin Road, Nankai District 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