Activatable Fluorescence Imaging of Macrophages in Cerebral Aneurysms Using Iron Oxide Nanoparticles Conjugated With Indocyanine Green
Activatable Fluorescence Imaging of Macrophages in Cerebral Aneurysms Using Iron Oxide Nanoparticles Conjugated With Indocyanine Green
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DOI：
10.3389/fnins.2020.00370
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发表时间：
2020-04-22
影响因子：
4.3
通讯作者：
Miyamoto, Susumu
中科院分区：
文献类型：
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作者：
Ikeda, Hiroyuki;Ishii, Akira;Miyamoto, Susumu
背景和目的慢性炎症参与脑动脉瘤（CA）的形成和扩大，巨噬细胞在此过程中发挥关键作用。本研究使用可激活荧光探针（IONP-ICG）评估CA中存在的巨噬细胞的可视化，该探针包含与吲哚菁绿（ICG）缀合的氧化铁纳米颗粒（IONP）。方法将IONP-ICG静脉注射给15周龄CA模型大鼠（n = 8），48小时后对暴露的CA和脑动脉进行离体近红外荧光（NIRF）成像和组织学评估。在对照组中进行了类似的评估，其中包括给予IONP或ICG的CA模型大鼠（n = 8）。结果在三只IONP-ICG组大鼠中检测到ICG衍生的NIRF信号，但在IONP或ICG对照组中未检测到。在表现出信号的三只大鼠中，在两只大鼠的CA和一只大鼠的左大脑后动脉血流动力学应激部位观察到NIRF信号积累。组织学上，NIRF 信号与巨噬细胞定位密切相关。 IONP-ICG 组中总共形成了 13 个 CA。与其余 11 个不显示 NIRF 信号的 CA 相比，显示 NIRF 信号的两个 CA 中 CA 壁中的巨噬细胞数量明显较多 (P = 0.037)。此外，未表现出NIRF信号的所有11个CA均为铁阴性，而表现出NIRF信号的2个CA均为铁阳性（P = 0.013）。结论使用可激活IONP-ICG探针的NIRF成像可用于检测CA和脑动脉壁中巨噬细胞丰富的区域，这被认为是CA形成过程中的早期病变。
Background and PurposeChronic inflammation is involved in the formation and enlargement of cerebral aneurysms (CAs), with macrophages playing a key role in the process. The present study evaluated visualization of macrophages present in CAs using an activatable fluorescent probe (IONP-ICG) comprising an iron oxide nanoparticles (IONPs) conjugated with indocyanine green (ICG).MethodsIONP-ICG was intravenously administered to 15-week-old CA model rats (n = 8), and ex vivo near-infrared fluorescence (NIRF) imaging and histological assessment of exposed CAs and cerebral arteries were performed 48 h later. Similar evaluations were performed in the control group, which included CA model rats given IONPs or ICG (n = 8 each).ResultsICG-derived NIRF signals were detected in three IONP-ICG group rats but not in IONP or ICG control groups. Among the three rats that exhibited signals, NIRF signal accumulation was observed in the CA of two rats and at the site of hemodynamic stress in the left posterior cerebral artery in one rat. Histologically, NIRF signals correlated strongly with macrophage localization. A total of 13 CAs formed in the IONP-ICG group. The number of macrophages in the CA wall was significantly greater in the two CAs that exhibited NIRF signals compared to the remaining 11 CAs that did not (P = 0.037). Moreover, all 11 CAs that did not exhibit NIRF signals were iron-negative, while the two CAs that exhibited NIRF signals were both iron-positive (P = 0.013).ConclusionNIRF imaging using an activatable IONP-ICG probe is feasible for detecting the macrophage-rich regions in CAs and the cerebral artery wall, which is considered an early lesion in the process of CA formation.