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基于 MARCO 靶向上转换发光探针的动脉粥样硬化斑块 M1 巨噬细胞极化的光学/MRI 双模态成像

Optical/MRI dual-modality imaging of M1 macrophage polarization in atherosclerotic plaque with MARCO-targeted upconversion luminescence probe.

机构信息

Department of Cardiology & National Clinical Research Center of Geriatric Disease, 2nd Medical Center of Chinese PLA General Hospital, Beijing, 100853, China; Department of Cardiology, Chinese Eastern Theatre Naval Hospital, Zhejiang, 316000, China.

Department of Cardiology & National Clinical Research Center of Geriatric Disease, 2nd Medical Center of Chinese PLA General Hospital, Beijing, 100853, China; TEDA International Cardiovascular Hospital, Tianjin, 300457, China.

出版信息

Biomaterials. 2019 Oct;219:119378. doi: 10.1016/j.biomaterials.2019.119378. Epub 2019 Jul 27.

Abstract

Pro-inflammatory M1 macrophage is identified as a prominent component initializing the progress of vulnerable atherosclerotic plaque. Here, we constructed anti-MARCO NaGdF:Yb,Er@NaGdF upconversion nanoparticles (UCNPs) by conjugating polyclonal MARCO antibody to the surface of NaGdF:Yb,Er@NaGdFvia condensation reaction. UCNPs displayed highly mono-dispersion with average sizes of 26.7 ± 0.8 nm and favorable biocompatibility. In vivo upconversion optical imaging revealed that distinctive fluorescence signal could be observed in the regions of carotid artery 10 min post-injection, reached peak value at 1 h and decreased back to baseline at 24 h post-injection. The carotid artery wall demonstrated high signal intensity on T1-weighted MR images after anti-MARCO UCNPs injection, as determined by 7.0T MRI. Immunofluorescence staining of tissue section of carotid artery revealed that MARCO was highly abundant in shoulder regions of plaque. Anti-MARCO UCNPs is a promising optical/MRI dual-modality imaging probe which can non-invasively reflect M1 phenotype macrophages behavior in vivo.

摘要

促炎型 M1 巨噬细胞被认为是启动易损动脉粥样硬化斑块进展的主要成分。在此,我们通过缩合反应将多克隆 MARCO 抗体结合到 NaGdF:Yb,Er@NaGdF 的表面,构建了抗-MARCO NaGdF:Yb,Er@NaGdF 上转换纳米粒子(UCNPs)。UCNPs 表现出高度的单分散性,平均粒径为 26.7±0.8nm,具有良好的生物相容性。体内上转换光学成像显示,在注射后 10min 即可在颈动脉区域观察到独特的荧光信号,在 1h 时达到峰值,并在注射后 24h 恢复到基线。注射抗-MARCO UCNPs 后,通过 7.0T MRI 测定,颈动脉壁在 T1 加权 MR 图像上显示出高信号强度。颈动脉组织切片的免疫荧光染色显示,MARCO 在斑块肩部区域高度丰富。抗-MARCO UCNPs 是一种有前途的光学/MRI 双模式成像探针,可在体无创地反映 M1 表型巨噬细胞的行为。

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