Cascade-Activatable Nanoprobes for NIR-II Fluorescence/Photoacoustic Dual-Modal Imaging of Atherosclerotic Plaques

The rupture of atherosclerotic plaques is a crucial event leading to acute cardiovascular incidents like myocardial infarction and stroke, and accurate imaging of atherosclerotic plaques is of great significance. Currently, early and precise diagnosis of atherosclerosis (AS) is still a challenge because of the lack of suitable diagnostic methods and probes. Herein, we develop a novel cascade-activatable nanoprobe IR820-PDA@BSA-T, which can sequentially respond to AS-overexpressed protein disulfide isomerase (PDI) and high viscosity microenvironment, for second near-infrared window (NIR-II) fluorescence/photoacoustic imaging of AS. IR820-PDA@BSA-T was prepared by encapsulating a small-molecular dye IR820-PDA with bovine serum albumin (BSA), and then conjugating AS-targetable peptide VVGS onto its surface. Upon the activation of PDI, the NIR-II fluorescence intensity and ratiometric photoacoustic signal (PA₈₄₀/PA₆₇₀) of IR820-PDA are significantly enhanced. The high viscosity restricts the intramolecular rotation of activated IR820-PDA, leading to the further elevation of NIR-II fluorescence signal. In atherosclerotic mouse model, IR820-PDA@BSA-T accurately targets plaque regions, achieving a total 8.3- and 13.9-fold increases of PA₈₄₀/PA₆₇₀ and NIR-II fluorescence signal, respectively, compared with normal vessels. Therefore, this research establishes IR820-PDA@BSA-T as a smart and multi-modality nanoprobe for AS imaging with high sensitivity and resolution, providing novel thoughts for precise imaging of cardiovascular diseases.