In vivo magnetomotive optical molecular imaging using targeted magnetic nanoprobes

In vivo magnetomotive optical molecular imaging using targeted magnetic nanoprobes
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DOI:
10.1073/pnas.0913679107
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发表时间:
2010-05-04
影响因子:
11.1
通讯作者:
Boppart, Stephen A.
Boppart, Stephen A.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
John, Renu;Rezaeipoor, Robabeh;Boppart, Stephen A.

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磁动光学相干断层扫描(MMOCT)检测的磁性纳米粒子(MNP)的动态磁运动代表了一种新的方法,在分子成像中的对比度增强和治疗干预。在这项研究中,我们证明了在临床前乳腺肿瘤模型中使用MM-OCT的动态功能化氧化铁MNP的体内成像。使用靶向MNP,体内MM-OCT图像在乳腺肿瘤中表现出强磁动信号,并且从注射非靶向MNP或盐水的大鼠肿瘤中没有测量到显著信号。体内MM-OCT的结果通过MRI、离体MM-OCT、组织切片的普鲁士蓝染色以及切除的肿瘤和内脏的免疫组织化学分析来验证。MNP是抗体功能化的,以靶向人表皮生长因子受体2(HER 2 neu)蛋白。抗体与MNP的Fc定向缀合有助于减少网状内皮系统中巨噬细胞的摄取,从而增加血液中的循环时间。这些工程磁性纳米探针具有多功能功能,使其能够在MM-OCT和MRI中用作动态造影剂。
Dynamic magnetomotion of magnetic nanoparticles (MNPs) detected with magnetomotive optical coherence tomography (MMOCT) represents a new methodology for contrast enhancement and therapeutic interventions in molecular imaging. In this study, we demonstrate in vivo imaging of dynamic functionalized iron oxide MNPs using MM-OCT in a preclinical mammary tumor model. Using targeted MNPs, in vivo MM-OCT images exhibit strong magnetomotive signals in mammary tumor, and no significant signals were measured from tumors of rats injected with nontargeted MNPs or saline. The results of in vivo MM-OCT are validated by MRI, ex vivo MM-OCT, Prussian blue staining of histological sections, and immunohistochemical analysis of excised tumors and internal organs. The MNPs are antibody functionalized to target the human epidermal growth factor receptor 2 (HER2 neu) protein. Fc-directed conjugation of the antibody to the MNPs aids in reducing uptake by macrophages in the reticulo-endothelial system, thereby increasing the circulation time in the blood. These engineered magnetic nanoprobes have multifunctional capabilities enabling them to be used as dynamic contrast agents in MM-OCT and MRI.