Neutrophil elastase-activatable ratiometric photoacoustic nanoprobes for imaging atherosclerotic plaque vulnerability

Hui Cao, Xin Meng, Yuan Ma, Zhe Li, Xinyu Xu, Jiaqi Fu, Qingpeng Zhang, Hanlin Wei, Peng Liang, Dingyou Lu, Jinyu Li, Baoli Yin, Shuangyan Huan, Xiao-Bing Zhang () and Guosheng Song ()
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Hui Cao: Hunan University
Xin Meng: Hunan University
Yuan Ma: Hunan University
Zhe Li: Hunan University
Xinyu Xu: Hunan University
Jiaqi Fu: Hunan University
Qingpeng Zhang: Hunan University
Hanlin Wei: Hunan University
Peng Liang: Hunan University
Dingyou Lu: Hunan University
Jinyu Li: Hunan University
Baoli Yin: Hunan University
Shuangyan Huan: Hunan University
Xiao-Bing Zhang: Hunan University
Guosheng Song: Hunan University

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Atherosclerosis is a leading cause of cardiovascular diseases worldwide. Neutrophil elastase, a key protease secreted by neutrophils, contributes significantly to atherosclerosis by degrading the extracellular matrix and destabilizing the fibrous cap of plaques. However, current detection methods for neutrophil elastase lack the ability to monitor its dynamic changes within plaques in a non-invasive and real-time manner. To overcome this limitation, we develop a neutrophil elastase-activated semiconductor polymer nanoprobe with high selectivity, sensitivity, and resistance to interference. We successfully establish a calibration curve correlating the in vivo photoacoustic signal ratio with neutrophil elastase concentration, enabling quantification of intraplaque neutrophil elastase levels. Importantly, we introduce a vulnerability index to assess plaque instability, allowing the nanoprobe to predict the adverse effects of inflammatory responses on the risk of plaque rupture in ApoE-/- male mice. Additionally, the nanoprobe can visualize dynamic changes in neutrophil elastase during intimal hyperplasia under inflammatory conditions. In conclusion, this nanoprobe provides a tool for elucidating the role of neutrophil elastase in cardiovascular disease progression.

Date: 2025
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DOI: 10.1038/s41467-025-64633-2

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