Real‐Time Monitoring of Atherosclerotic Plaque Using β‐Galactosidase‐Activated Photoacoustic Tomography

Abstract The early monitoring and risk assessment of atherosclerotic progression is crucial yet challenging due to its intricate and dynamic pathological process. A lipo‐nanoprobe incorporating chlorophyll derivatives is developed, which enables enzyme‐triggered in situ J‐aggregation‐induced red‐shift, allowing detection at 710 nm with a linear relationship to senescence‐associated β‐galactosidase (SA‐β‐gal), an essential marker of atherosclerotic formation and progression. The photoacoustic histological analysis conducted using the nanoprobe confirmed the accurate visualization of plaque microenvironment SA‐β‐gal activity, enabling semi‐quantitation of plaque progression at different time points. By employing dynamic multi‐wavelength imaging, the nanoprobe presented a specific SA‐β‐gal‐dependent absorption at 710 nm 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‐β‐gal‐responsive photoacoustic imaging for detecting plaque pathological progression and highlights its advantage for early monitor plaque formation in individuals at risk of developing atherosclerosis.