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A lipo\u2010nanoprobe incorporating chlorophyll derivatives is developed, which enables enzyme\u2010triggered in situ J\u2010aggregation\u2010induced red\u2010shift, allowing detection at 710\u00a0nm with a linear relationship to senescence\u2010associated \u03b2\u2010galactosidase (SA\u2010\u03b2\u2010gal), an essential marker of atherosclerotic formation and progression. The photoacoustic histological analysis conducted using the nanoprobe confirmed the accurate visualization of plaque microenvironment SA\u2010\u03b2\u2010gal activity, enabling semi\u2010quantitation of plaque progression at different time points. By employing dynamic multi\u2010wavelength imaging, the nanoprobe presented a specific SA\u2010\u03b2\u2010gal\u2010dependent absorption at 710\u00a0nm in vivo. Utilizing photoacoustic tomography imaging, 3D images of plaques were reconstructed and quantitative analysis was performed on the extent and distribution of senescence in the total aortic vascular wall. The monitored signal revealed significant trends in relation to cellular senescence phenotype, particularly in vascular smooth muscle cells (VSMCs), which are crucial for clinically assessing the impact of cellular processes that contribute to plaque formation and expansion during the progression of atherosclerosis. This study demonstrates the utility of SA\u2010\u03b2\u2010gal\u2010responsive photoacoustic imaging for detecting plaque pathological progression and highlights its advantage for early monitor plaque formation in individuals at risk of developing atherosclerosis.<\/jats:p>","DOI":"10.1002\/smll.202506731","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T09:21:13Z","timestamp":1757668873000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Real\u2010Time Monitoring of Atherosclerotic Plaque Using \u03b2\u2010Galactosidase\u2010Activated Photoacoustic Tomography"],"prefix":"10.1002","volume":"21","author":[{"given":"Yifan","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Neurology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 P. R. 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