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Current NIR\u2010II probes are limited by either being \u201calways on\u201d or responding to one stimulus, leading to low signal\u2010to\u2010noise ratios and potential false positives. We introduced a dual\u2010lock\u2010controlled probe,\n                    <jats:bold>HN\u2010PBA<\/jats:bold>\n                    , activated by both H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    and tumor acidic environment. This dual response ensures bright fluorescence at tumor sites, leading to higher tumor\u2010to\u2010normal tissue ratios (T\/NT) compared to conventional \u201calways on\u201d probes and probes activated only by H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    . This strategy allows precise tumor identification and removal of primary and metastatic tumors, achieving superior T\/NT ratios (24.3\/6.4 for orthotopic and lung metastasis, respectively). Our probe also effectively detected lung metastatic foci as small as\u22640.7\u2005mm and showed the capability for accurate lesion localization in clinical breast cancer specimens. This dual\u2010stimuli\u2010responsive strategy could aid future diagnostic probe design.\n                  <\/jats:p>","DOI":"10.1002\/anie.202419191","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T01:49:44Z","timestamp":1731030584000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Metabolic Acidity\/H\n                    <sub>2<\/sub>\n                    O\n                    <sub>2<\/sub>\n                    Dual\u2010Cascade\u2010Activatable Molecular Imaging Platform Toward Metastatic Breast Tumor Malignancy"],"prefix":"10.1002","volume":"64","author":[{"given":"Kun","family":"Dou","sequence":"first","affiliation":[{"name":"Key Laboratory of Haikou Trauma, Key Laboratory of Hainan Trauma and Disaster Rescue, Key Laboratory of Emergency and Trauma Ministry of Education The First Affiliated Hospital of Hainan Medical University Hainan Medical University  Haikou 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