Development of MRI/NIRF 'activatable' multimodal imaging probe based on iron oxide nanoparticles
Development of MRI/NIRF 'activatable' multimodal imaging probe based on iron oxide nanoparticles
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DOI：
10.1016/j.jconrel.2011.07.019
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发表时间：
2011-10-30
影响因子：
10.8
通讯作者：
Ahn, Cheol-Hee
中科院分区：
文献类型：
--
作者：
Cha, Eui-Joon;Jang, Eue Soon;Ahn, Cheol-Hee
本报告描述了一种Cy5.5-MMP衬底和PEG共轭氧化铁纳米颗粒与薄二氧化硅涂层（PCM-CS）的制造方法及其作为肿瘤成像“可激活”双成像探针的潜力。动态光散射显示，PCM-CS在7天内强度平均直径为43.1 +/- 6.3 nm，无明显聚集。Cy5.5在纳米颗粒表面的荧光被完全猝灭，猝灭效率为97.2%。PCM-CS显示出由MMP-2特异性肽切割引起的蛋白酶特异性荧光恢复，探针在0.5 nM或更低的酶浓度下显示出灵敏度。在体内通过静脉注射PCM-CS成功地通过NIRF和MRI显示肿瘤。注射后12 h，肿瘤的NIRF信号逐渐增强，肿瘤强度约为正常组织的3-4倍。在MMP-2抑制剂处理的肿瘤中，由于肽切割不足，NIRF信号明显低于未加抑制剂的肿瘤。切除肿瘤处的NIRF信号比其他器官强5-10倍。注射PCM-CS后12 h，肿瘤区域磁共振图像明显变暗，图像逐渐变暗。肿瘤区域与健康肌肉的最大信号差异为34%。(C) 2011 Elsevier B.V.版权所有
A fabrication method of Cy5.5-MMP substrate and PEG conjugated iron oxide nanoparticles with thin silica coating (PCM-CS) and its potential as an 'activatable' dual imaging probe for tumor imaging is described in this report. PCM-CS showed an intensity-averaged diameter of 43.1 +/- 6.3 nm by dynamic light scattering without any noticeable aggregation over 7 days. Fluorescence of Cy5.5 on the surface of nanoparticles was fully quenched and the quenching efficiency was 97.2%. PCM-CS showed protease specific fluorescence recovery in vitro caused from the specific peptide cleavage by MMP-2 and the probe displayed the sensitivity on 0.5 nM or less enzyme concentration. Tumor was successfully visualized by NIRF and MRI in vivo by intravenously injected PCM-CS. NIRF signal of tumor was gradually increased up to 12 h post injection and the intensity of tumor was about 3-4 times higher than normal tissue. NIRF signal at MMP-2 inhibitor treated tumor was clearly lower than tumor without inhibitor due to the insufficient peptide cleavage. NIRF signal at excised tumor was 5-10 times stronger than other organs. Noticeable darkening in magnetic resonance image was observed at the tumor region and the image was gradually darkened at 12 h post injection of PCM-CS. The maximum signal difference between tumor region and healthy muscle was 34%. (C) 2011 Elsevier B.V. All rights reserved.