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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\u2010activatable nanoprobe IR820\u2010PDA@BSA\u2010T, which can sequentially respond to AS\u2010overexpressed protein disulfide isomerase (PDI) and high viscosity microenvironment, for second near\u2010infrared window (NIR\u2010II) fluorescence\/photoacoustic imaging of AS. IR820\u2010PDA@BSA\u2010T was prepared by encapsulating a small\u2010molecular dye IR820\u2010PDA with bovine serum albumin (BSA), and then conjugating AS\u2010targetable peptide VVGS onto its surface. Upon the activation of PDI, the NIR\u2010II fluorescence intensity and ratiometric photoacoustic signal (PA\n                    <jats:sub>840<\/jats:sub>\n                    \/PA\n                    <jats:sub>670<\/jats:sub>\n                    ) of IR820\u2010PDA are significantly enhanced. The high viscosity restricts the intramolecular rotation of activated IR820\u2010PDA, leading to the further elevation of NIR\u2010II fluorescence signal. In atherosclerotic mouse model, IR820\u2010PDA@BSA\u2010T accurately targets plaque regions, achieving a total 8.3\u2010 and 13.9\u2010fold increases of PA\n                    <jats:sub>840<\/jats:sub>\n                    \/PA\n                    <jats:sub>670<\/jats:sub>\n                    and NIR\u2010II fluorescence signal, respectively, compared with normal vessels. Therefore, this research establishes IR820\u2010PDA@BSA\u2010T as a smart and multi\u2010modality nanoprobe for AS imaging with high sensitivity and resolution, providing novel thoughts for precise imaging of cardiovascular diseases.\n                  <\/jats:p>","DOI":"10.1002\/smll.74268","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T10:10:22Z","timestamp":1781777422000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cascade\u2010Activatable Nanoprobes for NIR\u2010II Fluorescence\/Photoacoustic Dual\u2010Modal Imaging of Atherosclerotic Plaques"],"prefix":"10.1002","volume":"22","author":[{"given":"Xiaowen","family":"He","sequence":"first","affiliation":[{"name":"State Key Laboratory of Flexible Electronics (LoFE) and Institute of Advanced Materials (IAM) Nanjing University of Posts and Telecommunications  Nanjing 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