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Current AIE\u2010active probes primarily focus on improving their water solubility to resist aggregation, thereby achieving an initial fluorescence\u2010off state. However, the complex biological environment can cause undesirable aggregation, resulting in false signals. To address this issue, we have ingeniously introduced an azo group into the AIE luminogen (AIEgen), developing a reductase\u2010activated AIE probe, Azo\u2010quinoline\u2010malononitrile (QM)\u2010PN, for imaging hypoxic environments. In this probe, the azo group promotes intramolecular motion through rapid <jats:italic>E<\/jats:italic>\/<jats:italic>Z<\/jats:italic> isomerization, causing the excited state energy to dissipate via non\u2010radiative decay, thus turning off the initial fluorescence. In the presence of reductase, Azo\u2010QM\u2010PN is reduced and cleaved to produce the hydrophobic AIEgen NH<jats:sub>2<\/jats:sub>\u2010QM\u2010PN, which subsequently aggregates and generates an in situ AIE signal, thereby imaging the hypoxic environment with reductase. Encapsulation of Azo\u2010QM\u2010PN with DSPE\u2010PEG<jats:sub>2000<\/jats:sub> results in the formation of the nanoprobe Azo\u2010QM\u2010PN NPs, which can effectively penetrate cell membranes, specifically illuminate tumor cells, monitor fluctuations in azo reductase levels, and deeply penetrate and image multicellular tumor spheroids, demonstrating potential for hypoxic tumor imaging. Additionally, the nanoprobe Azo\u2010QM\u2010PN NPs can selectively image hypoxic atherosclerotic plaque tissues, showing potential for detecting atherosclerosis. Therefore, in this study, we successfully developed an enzyme\u2010activated AIE probe for imaging hypoxic environments, laying the foundation for further clinical applications.<\/jats:p>","DOI":"10.1002\/smo.20240028","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T01:23:58Z","timestamp":1725499438000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["An azo substituted quinoline\u2010malononitrile enzyme\u2010activable aggregation\u2010induced emission nanoprobe for hypoxia imaging"],"prefix":"10.1002","volume":"3","author":[{"given":"Zhirong","family":"Zhu","sequence":"first","affiliation":[{"name":"School of Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Key Laboratory for Advanced Materials and Institute of Fine Chemicals Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Feringa Nobel 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