Nanoparticle to Nanoparticle Bioorthogonal Detection of Atherosclerosis

In vivo identification and characterization of atherosclerosis is a promising approach for the development of novel therapies and personalized treatments. Among the methods for this in vivo identification, the use of pretargeted imaging shows very large probe uptakes and excellent selectivity. However, this approach relies on the use of antibodies which may limit their usability. In this study, we introduce a pretargeting imaging approach for atherosclerosis detection using PET that only employs nanomaterials. Here we develop the concept of nanoparticle-to-nanoparticle pretargeted imaging for atherosclerosis. Sphingomyelin solid lipid nanoparticles (sphNP) functionalized with trans-cyclooctene (TCO) were used as targeting agents and accumulated in atherosclerotic plaques. This was followed by the injection of ⁶⁸Ga-doped nanotracers functionalized with tetrazine ([⁶⁸Ga]Ga-IONP-Tz), which binds to the accumulated sphNP-TCO via bioorthogonal click chemistry. In vivo PET imaging showed clear uptake in the aortic arch of mice receiving the full pretargeting approach, while the control groups showed no significant signal. This nanoparticle-based pretargeting strategy enables noninvasive PET imaging of atherosclerosis without using antibodies. This approach expands the use of bioorthogonal imaging and may have potential for targeted drug delivery to atherosclerotic plaques.