Targeted Intravascular Photoactivation Guided by Multimodal Optical Coherence Tomography-Nearinfrared Fluorescence Imaging on Atherosclerotic Plaque

초록

Background Atherosclerosis is a chronic inflammatory disease characterized by unresolved inflammation, leading to potentially fatal plaque rupture. We hypothesized that macrophage-targeted near-infrared fluorescence (NIRF) emitting photoactivation could accurately detect inflamed high-risk plaques and resolve inflammation. Methods The macrophage-targeted photoactivatable theranostic agent was synthesized by conjugating the NIRF-emitting photosensitizer chlorin e6 (Ce6) with the macrophage Dectin-1 ligand laminarin (LAM-Ce6). Results Four weeks after LAM-Ce6 administration, intravascular photoactivation effectively attenuated inflammatory NIRF signals, converting them into fibrotic tissue as monitored by optical coherence tomography (OCT)-NIRF imaging (Figure 1A, P < 0.01). LAM-Ce6 photoactivation activated autophagic flux early and induced apoptosis through complex cross-talk, all successfully terminated 28 days post-treatment. In addition, photoactivation triggered M2 differentiation and enhanced efferocytosis via MerTK expression. In line with inflammation resolution, photoactivation reduced plaque burden through cholesterol efflux and induced the transition of inflamed high-risk plaque into fibrotic plaque via the TGF-β/CTGF dependent pathway, confirmed by corroborative immunostainings (Figure 1B, P < 0.01). Conclusion Macrophage-targeted photoactivation guided by OCT-NIRF catheter imaging could facilitate autophagy-mediated inflammation resolution and stabilize inflamed high-risk plaques through fibrotic replacement.