A Redox-Responsive Self-Assembled Nanoprobe for Photoacoustic Inflammation Imaging to Assess Atherosclerotic Plaque Vulnerability

Inflammation triggered by oxidative stress is the main determinant of atherosclerotic plaque disruption, which is the leading cause of myocardial infarctions and strokes. Hence, noninvasive mapping of alterations in redox status in vivo is highly desirable for accurate assessment of plaque inflammatory activity and vulnerability. Herein, two types of near-infrared fluorescence probes, specific for glutathione (GSH)/hydrogen peroxide (H2O2) redox couple, were used to introduce the self-assembly of bovine serum albumin (BSA), forming a BSA-Cy-Mito nanoprobe for in vivo photoacoustic imaging of redox status. Such BSA-based self-assemblies on one hand processed good biocompatibility and long blood circulation for high EPR effect and plaque accumulation and on the other hand displayed strong GSH- and H2O2-dependent absorbance at 765 and 680 nm, which enabled simultaneous photo acoustic detection of GSH/H2O2 with high specificity and sensitivity. Using BSA-Cy-Mito as an in vivo GSH/H2O2 indicator, accurate detection of the redox-related inflammatory process was realized both in oxidized low-density lipoprotein (ox-LDL)-activated macrophages and high fat diet-fed apolipoprotein E-deficient (ApoE(-)/(-)) mice. Systemic administration of BSA-Cy-Mito further enabled differentiation of vulnerable plaques from stable ones based on their different redox states. Therefore, this sensitive redox-responsive PA nanoprobe may be a powerful tool for early identification of rupture-prone plaques and help in implementing successful preventative therapeutic strategies.