Abstract We113: Intravascular Theranostic Photoactivation Guided By OCT-NIRF Dual-Modal Imaging Facilitates Inflammation Resolution of High-Risk Plaque

Abstract

Introduction and Hypothesis: Photoactivation eliminates inflammatory cells and promotes healing, paving the way for atherosclerosis intervention. We hypothesized that intravascular macrophage-targeted near-infrared fluorescence (NIRF) emitting photoactivation could facilitate inflammation resolution and stabilize the inflamed high-risk plaques. Method and Results: We newly fabricated a Dectin-1-targeted photoactivatable theranostic agent through the chemical conjugation of the NIRF-emitting photosensitizer chlorin e6 (Ce6) and the Dectin-1 ligand laminarin (LAM-Ce6). By intravascular OCT-NIRF structural-molecular imaging at 0- vs 4 weeks, LAM-Ce6 under light irradiation through a customized intravascular fiber effectively attenuated inflammatory NIRF signals, resulting in replacement of fibrotic composition in the targeted plaques (Figure A, P <0.01). Mechanistically, one hour after the light irradiation, autophagy was strongly augmented with the formation of autophagolysosomes (Figure B, P <0.001) and an increase of CD206-positive cells at 7 days. Furthermore, TUNEL/RAM11- and CD206/MerTK-positive cells were prominently increased at 1 day, suggestive of enhanced efferocytosis in the treated plaques (Figure C, the white arrow: macrophage associated apoptotic cells, P <0.05). In line with inflammation resolution, photoactivation enhanced the cholesterol efflux regulatory protein ABCA1 and induced TGF-β in macrophages, which subsequently stimulated smooth muscle cells and produced collagen within the lesions (Figure D). Conclusions: The macrophage Dectin-1 targetable intravascular photoactivation assisted by OCT-NIRF catheter imaging could ultimately transit the plaque phenotype to collagen-rich fibrotic one by autophagy-mediated inflammation resolution with a fibrotic replacement. This novel targeted photoactivation is expected to offer new opportunity for the catheter-based theranostic strategy in patients with macrophage/lipid-rich inflamed coronary plaques.