Twinkling Peptide Nanoemulsions Enable Precision Ultrasound Detection of Atherosclerotic Plaques

Non-invasive imaging modalities that identify rupture-prone atherosclerotic plaques hold promise to improve patient risk stratification and advance early intervention strategies. Here, phase-changing peptide nanoemulsions are developed as theranostic contrast agents for synchronous ultrasound detection and therapy of at-risk atherosclerotic lesions. By targeting lipids within atherogenic foam cells, and exploiting characteristic features of vulnerable plaques, these nanoemulsions preferentially accumulate within lesions and are retained by intraplaque macrophages. It is demonstrated that acoustic vaporization of intracellular nanoemulsions promotes lipid efflux from foam cells and generates echogenic microbubbles that provide contrast-enhanced ultrasound identification of lipid-rich anatomical sites. In Doppler mode, stably oscillating peptide nanoemulsions induce random amplitude and phase changes of the echo wave to generate transient color imaging features, referred to as 'twinkling'. Importantly, acoustic twinkling is unique to these peptide emulsions, and not observed from endogenous tissue bubble nuclei, generating diagnostic features that offer unprecedented spatial precision of lesion identification in 3D.