# Nanoparticle to Nanoparticle Bioorthogonal Detection of Atherosclerosis

## TL;DR

This paper introduces a new method for detecting atherosclerosis in mice using nanoparticles and PET imaging, avoiding the need for antibodies.

## Contribution

A novel nanoparticle-to-nanoparticle pretargeting strategy for atherosclerosis imaging using bioorthogonal chemistry is developed.

## Key findings

- PET imaging showed clear uptake in aortic arches of mice using the nanoparticle pretargeting approach.
- Control groups showed no significant signal, confirming the method's specificity.
- The strategy enables noninvasive imaging of atherosclerosis without antibodies.

## Abstract

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.