Activatable fluorescence imaging of macrophages in atherosclerotic plaques using iron oxide nanoparticles conjugated with indocyanine green
Activatable fluorescence imaging of macrophages in atherosclerotic plaques using iron oxide nanoparticles conjugated with indocyanine green
复制标题
DOI：
10.1016/j.atherosclerosis.2018.05.028
复制
发表时间：
2018-08-01
期刊：
影响因子：
5.3
通讯作者：
Miyamoto, Susumu
中科院分区：
文献类型：
--
作者：
Ikeda, Hiroyuki;Ishii, Akira;Miyamoto, Susumu
背景和目的：巨噬细胞是不稳定动脉粥样硬化斑块形成的关键因素，可以通过巨噬细胞成像来识别。我们测试了由生物相容性试剂组成的氧化铁纳米粒子（IONP）与吲哚菁绿（ICG）缀合的可激活荧光探针（IONP-ICG）是否可以可视化动脉粥样硬化斑块中存在的巨噬细胞。方法：合成了与不同数量的ICG分子缀合的基于IONP的探针。六周龄自发性高脂血症（SHL）小鼠采用西方或正常饮食喂养 14 周，并静脉注射 IONP-ICG（55.8 mg Fe/kg）。 48小时后收获主动脉，并对含有动脉粥样硬化斑块的主动脉进行成像。结果：使用IONP-ICG溶液的幻影成像研究表明，向IONP-ICG溶液中添加表面活性剂会产生荧光激活。巨噬细胞与 IONP-ICG 一起孵育导致 IONP-ICG 内化和近红外荧光 (NIRF) 激活。在NIRF成像研究中，强烈的荧光信号主要在动脉粥样硬化斑块的边缘清晰可见，而斑块内部的信号相对较弱，证明了在动脉粥样硬化斑块处检测NIRF信号的可行性。在 NIRF 的定量评估中，施用与更多 ICG 分子缀合的探针导致 NIRF 信号显着增加，表明具有更多 ICG 分子的探针对于灵敏的 NIRF 检测是有效的。与给予西方饮食的小鼠相比，给予低胆固醇正常饮食的 SHL 小鼠显示出显着较低的 NIRF 信号。从组织学角度来看，动脉粥样硬化斑块中的 NIRF 信号与巨噬细胞的位置密切相关，这表明使用 IONP-ICG 进行 NIRF 巨噬细胞成像的可能性。结论：使用可激活的 NIRF 探针 IONP-ICG 可以实现动脉粥样硬化斑块中巨噬细胞的定位。 (C) 2018 Elsevier B.V. 保留所有权利。
Background and aims: Macrophages are key factors in the formation of unstable atherosclerotic plaques, which may be identified through macrophage imaging. We tested whether activatable fluorescence probes of iron oxide nanoparticles (IONPs) conjugated with indocyanine green (ICG) (IONP-ICG), consisting of biocompatible reagents, can visualize macrophages present in atherosclerotic plaques.Methods: IONP-based probes conjugated with different numbers of ICG molecules were synthesized. Sixweek-old spontaneously hyperlipidemic (SHL) mice were fed either a Western or normal diet for 14 weeks, and were intravenously injected with IONP-ICG (55.8 mg Fe/kg). Aortas were harvested 48 h later, and aortas containing atherosclerotic plaques were imaged.Results: Phantom imaging studies using IONP-ICG solution demonstrated that the addition of surfactants to IONP-ICG solutions yielded fluorescence activation. Incubation of macrophages with IONP-ICG led to internalization of IONP-ICG and near infrared fluorescence (NIRF) activation. In NIRF imaging studies, intense fluorescence signals were clearly visible primarily at the margins of atherosclerotic plaques, and relatively weak signals were evident inside the plaques, demonstrating the feasibility of detection of NIRF signals at atherosclerotic plaques. In the quantitative evaluation of NIRF, administration of a probe conjugated with more ICG molecules led to a significant increase in the NIRF signal, indicating that probes with greater numbers of ICG molecules are effective for sensitive NIRF detection. SHL mice given a low-cholesterol normal diet showed a significantly lower NIRF signal compared with mice given the Western diet. Histologically, NIRF signals in atherosclerotic plaques strongly correlated with the location of macrophages, suggesting the possibility of NIRF macrophage imaging using IONP-ICG.Conclusions: Localization of macrophages in atherosclerotic plaques may be achieved using the activatable NIRF probe, IONP-ICG. (C) 2018 Elsevier B.V. All rights reserved.