World Cardiology Conference 2026

Abstract

Introduction: Inflammation plays a critical role in the progression and rupture of atherosclerotic plaques, making it a key target for non-invasive detection of vulnerable plaques. Although conventional optical imaging offers advantages such as high spatial resolution and rapid acquisition, its clinical translation is hampered by limited tissue penetration and significant background autofluorescence. Recently, fluorescence imaging (FLI) and photoacoustic imaging (PAI) in the second near-infrared window (NIR-II, 1000–1700 nm) have emerged as promising alternatives due to reduced autofluorescence, deeper penetration, and higher permissible laser exposure. Herein, this study aimed to develop a novel 1064 nm NIR-II FLI/PAI platform that specifically targets myeloperoxidase (MPO), a potential inflammatory marker of vulnerable plaques, to identify high-risk plaques in vivo.

Method: The MPO-targeted micellar nanoprobe (MPO-MNPs) was synthesized via self-assembly of an NIR-II cyanine dye (IR-1061) and 5-HT-conjugated PEG-DSPE and systematically characterized in vitro. To demonstrate in vivo MPO-targeting specificity, a localized inflammation model was established in C57BL/6 mice by intramuscular LPS injection. A vulnerable plaque model was generated in Apoe mice fed a high-fat diet for 12 weeks, followed by tandem stenosis (TS) surgery. To assess the correlation between probe signals and plaque vulnerability, TS-operated Apoe mice received either colchicine (to modulate plaque vulnerability) or PBS control. For large-animal validation, New Zealand rabbits fed a high-fat diet underwent balloon-induced aortic injury to establish atherosclerotic plaques, then received targeted or control probes for intravascular photoacoustic/intravascular ultrasound (IVPA/IVUS) imaging. Following intravenous administration of probes, NIR-II FLI/PAI at 1064 nm was performed in mice, while ex vivo IVPA/IVUS imaging was performed in rabbit specimens. Histopathological analysis assessed MPO expression and plaque vulnerability.

Result: The MPO-MNPs probe exhibited excellent stability, NIR-II FLI/PAI capability, high MPO specificity, and good biocompatibility. In the murine inflammation model, significantly stronger FLI/PAI signals were detected in LPS-injected limbs, confirming specific MPO targeting in vivo. In Apoe mice with TS-induced atherosclerosis, the probe effectively accumulated in carotid vulnerable plaques, enabling clear lesion delineation via NIR-II FLI/PAI. In colchicine-treated mice, the NIR-II FLI/PAI signals showed a positive correlation with histopathological vulnerability indices and MPO expression, confirming that the probe signals can reflect plaque vulnerability. In the rabbit model, IVPA/IVUS imaging detected clear photoacoustic signals in plaque regions only in the targeted probe group, and segments positive for photoacoustic signals corresponded to vulnerable plaques with high MPO expression on histopathology, including increased macrophage infiltration, larger necrotic core, and reduced collagen content.

Conclusion: We developed a novel MPO-targeted NIR-II nanoprobe, MPO-MNPs, enabling noninvasive dual-modal FLI/PAI imaging of inflammatory activity in atherosclerotic plaques in mice and IVPA/IVUS imaging in rabbits. The probe demonstrated high MPO specificity and strong correlation with plaque vulnerability across species, highlighting its value for vulnerable plaque detection and risk assessment.