Exosome‐Engineered Afterglow Probe for Targeted Imaging of Atherosclerotic Plaques In Vivo

Atherosclerosis is considered one of the primary causes of cardiovascular diseases, and thus assessing the vulnerability of atherosclerotic plaques is significant for timely clinical intervention. However, current probes for assessing vulnerable plaques face the dual challenges of insufficient imaging contrast and limited targeting specificity. Here, these limitations are addressed by applying an exosome-engineered afterglow nanoprobe, which is developed by integrating M2 macrophage-derived exosomes (M2 exosomes) with an afterglow luminescent agent for high-contrast atherosclerotic plaque imaging. The nanoprobe features: 1) M2 exosome-mediated active targeting performance to foam cell-enriched vulnerable plaques through intrinsic inflammation tropism and 2) reactive oxygen species-responsive afterglow amplification via H₂O₂-triggered chemically initiated energy transfer between the oxalate and afterglow agent. This probe could differentiate foam cells from normal macrophages (1.7-fold higher uptake). In vivo results show that it precisely localizes in the plaques of ApoE^-/- mice, demonstrating exceptional specificity. Moreover, imaging with the probe enables the visualization of carotid atherosclerotic plaques in living mouse models, with superior imaging contrast (2.25-fold higher) compared with fluorescence signal. This targeted afterglow imaging agent represents a promising strategy for the non-invasive identification of high-risk atherosclerotic plaques, offering significant potential for guiding precision therapies and improving cardiovascular outcomes.