BACKGROUND Atherosclerosis is a chronic inflammatory disease causing a fatal plaque rupture, and its key aspect is a failure to resolve inflammation. We hypothesize that macrophage-targeted near-infrared fluorescence emitting photoactivation could simultaneously assess macrophage/lipid-rich plaques in vivo and facilitate inflammation resolution. METHODS We fabricated a Dectin-1-targeted photoactivatable theranostic agent through the chemical conjugation of the near-infrared fluorescence-emitting photosensitizer chlorin e6 and the Dectin-1 ligand laminarin (laminarin-chlorin e6 [LAM-Ce6]). Intravascular photoactivation by a customized fiber-based diffuser after administration of LAM-Ce6 effectively reduced inflammation in the targeted plaques of atherosclerotic rabbits in vivo as serially assessed by dual-modal optical coherence tomography-near-infrared fluorescence structural-molecular catheter imaging after 4 weeks. RESULTS The number of apoptotic macrophages peaked at 1 day after laser irradiation and then resolved until 4 weeks. Autophagy was strongly augmented 1 hour after the light therapy, with the formation of autophagolysosomes. LAM-Ce6 photoactivation increased the terminal deoxynucleotidyl transferase dUTP (deoxyuridine triphosphate) nick end labeling/RAM11 (rabbit monocyte/macrophage antibody)- and MerTK (c-Mer tyrosine kinase)-positive cells in the plaques, suggesting enhanced efferocytosis. In line with inflammation resolution, photoactivation reduced the plaque burden through fibrotic replacement via the TGF (transforming growth factor)-β/CTGF (connective tissue growth factor) pathway. CONCLUSIONS Optical coherence tomography-near-infrared fluorescence imaging-guided macrophage Dectin-1-targetable photoactivation could induce the transition of macrophage/lipid-rich plaques into collagen-rich lesions through autophagy-mediated inflammation resolution and TGF-β-dependent fibrotic replacement. This novel strategy offers a new opportunity for the catheter-based theranostic strategy.

中文翻译：

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多模态成像辅助血管内治疗光激活动脉粥样硬化斑块。


背景技术动脉粥样硬化是一种导致致命性斑块破裂的慢性炎症性疾病，其关键方面是无法解决炎症。我们假设巨噬细胞靶向的近红外荧光发射光激活可以同时评估体内巨噬细胞/富含脂质的斑块并促进炎症消退。方法 我们通过近红外荧光发射光敏剂二氢卟酚 e6 和 Dectin-1 配体昆布多糖（昆布多糖-二氢卟酚 e6 [LAM-Ce6]）的化学结合，制备了一种 Dectin-1 靶向光激活治疗剂。 4周后，通过双模态光学相干断层扫描-近红外荧光结构分子导管成像进行连续评估，给予LAM-Ce6后，定制的基于纤维的扩散器的血管内光活化有效地减少了动脉粥样硬化兔子体内目标斑块的炎症。结果 凋亡巨噬细胞的数量在激光照射后 1 天达到峰值，然后直到 4 周才消退。光疗后 1 小时，自噬强烈增强，并形成自噬溶酶体。 LAM-Ce6 光活化增加了斑块中末端脱氧核苷酸转移酶 dUTP（脱氧尿苷三磷酸）缺口末端标记/RAM11（兔单核细胞/巨噬细胞抗体）和 MerTK（c-Mer 酪氨酸激酶）阳性细胞，表明胞吞作用增强。与炎症消退一致，光激活通过 TGF（转化生长因子）-β/CTGF（结缔组织生长因子）途径进行纤维化替代，从而减少斑块负担。 结论光学相干断层扫描-近红外荧光成像引导巨噬细胞Dectin-1靶向光激活可以通过自噬介导的炎症消退和TGF-β依赖性纤维化替代，诱导巨噬细胞/富含脂质的斑块转变为富含胶原蛋白的病变。这种新颖的策略为基于导管的治疗诊断策略提供了新的机会。