A Non‐Invasive Nanoprobe for In Vivo Photoacoustic Imaging of Vulnerable Atherosclerotic Plaque

Vulnerable atherosclerotic (AS) plaque is the major cause of cardiovascular death. However, clinical methods cannot directly identify the vulnerable AS plaque at molecule level. Herein, osteopontin antibody (OPN Ab) and NIR fluorescence molecules of ICG co‐assembled Ti3C2 nanosheets are reported as an advanced nanoprobe (OPN Ab/Ti3C2/ICG) with enhanced photoacoustic (PA) performance for direct and non‐invasive in vivo visual imaging of vulnerable AS plaque. The designed OPN Ab/Ti3C2/ICG nanoprobes successfully realize obvious NIR fluorescence imaging toward foam cells as well as the vulnerable AS plaque slices. After intravenous injection of OPN Ab/Ti3C2/ICG nanoprobes into AS model mice, in vivo imaging results show a significantly enhanced PA signal in the aortic arch accumulated with vulnerable plaque, well indicating the remarkable feasibility of OPN Ab/Ti3C2/ICG nanoprobes to distinguish the vulnerable AS plaque. The proposed OPN Ab/Ti3C2/ICG nanoprobes not only overcome the clinical difficulty to differentiate vulnerable plaque, but also achieve the non‐invasively specific in vivo imaging of vulnerable AS plaque at molecule level, greatly promoting the innovation of cardiovascular diagnosis technology. Direct identification of vulnerable atherosclerotic plaque at the molecular level is critical to prevent cardiovascular death. Osteopontin antibody (OPN Ab)/Ti3C2/indocyanine green nanoprobes with excellent photoacoustic performance well realize the non‐invasive in vivo imaging of vulnerable plaque through the targeted recognition of OPN‐overexpressed foam cells that are the main ingredients of vulnerable plaque, significantly advancing the innovation of cardiovascular disease diagnosis technology.