Highly NIR-II Scattering Gold Superclusters for Intravascular Optical Coherence Tomography Molecular Imaging

In North America, intravascular optical coherence tomography (IV-OCT) is performed every few minutes to evaluate atherosclerotic plaques and guide stent placement. Currently, IV-OCT is limited to anatomical imaging, providing structural information about atherosclerotic plaque morphology, thrombus, and dissection. Earlier detection and risk stratification would be possible through molecular characterization of endothelium but necessitates a purpose-engineered IV-OCT contrast agent. We developed gold superclusters (AuSC) tailored to clinical instrumentation and integrated into clinically relevant workflows. AuSC are aqueously dispersible clusters of closely packed small gold nanoparticles, affording plasmon hybridization to maximize light scattering at the IV-OCT laser line (~1350 nm). A polymer coating fosters AuSC uniformity and provides a functionalizable handle, which we targeted to intravascular P-selectin, an early vascular endothelial marker of inflammation. In a rat model of intravascular inflammation, P-selectin-targeted AuSC facilitated IV-OCT molecular imaging, where the strength of the signal correlates with the severity of vascular inflammation. AuSC thus enable in vivo molecular imaging, advancing IV-OCT into the molecular age.