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Fluorescence imaging is emerging as a promising alternative to traditional visual inspection by surgeons for intraoperative imaging. However, traditional probes lack accuracy in tumor diagnosis, making it difficult to depict tumor boundaries accurately. Herein, we proposed an offensive and defensive integration (ODI) strategy based on the \u201cattack systems (invasive peptidase) and defense systems (reductive microenvironment)\u201d of multi\u2010dimensional tumor characteristics to design activatable fluorescent probes for imaging tumor boundaries precisely. Screened out from a series of ODI strategy\u2010based probes,\n                    <jats:bold>ANQ<\/jats:bold>\n                    performed better than traditional probes based on tumor unilateral correlation by distinguishing between tumor cells and normal cells and minimizing false\u2010positive signals from living metabolic organs. To further improve the signal\u2010to\u2010background ratio in vivo, derivatized\n                    <jats:bold>FANQ<\/jats:bold>\n                    , was prepared and successfully applied to distinguish orthotopic hepatocellular carcinoma tissues from adjacent tissues in mice models and clinical samples. This work highlights an innovative strategy to develop activatable probes for rapid diagnosis of tumors and high\u2010precision imaging of tumor boundaries, providing more efficient tools for future clinical applications in intraoperative assisted resection.\n                  <\/jats:p>","DOI":"10.1002\/anie.202406332","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T13:14:03Z","timestamp":1716470043000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Dual\u2010Locked Fluorescent Probes Activated by Aminopeptidase N and the Tumor Redox Environment for High\u2010Precision Imaging of Tumor Boundaries"],"prefix":"10.1002","volume":"63","author":[{"given":"Yang","family":"Shen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Chemo\/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Hunan University  Changsha 410082 P.\u2005R. 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