Dual-modal magnetic resonance and fluorescence imaging of atherosclerotic plaques in vivo using VCAM-1 targeted tobacco mosaic virus.
Dual-modal magnetic resonance and fluorescence imaging of atherosclerotic plaques in vivo using VCAM-1 targeted tobacco mosaic virus.
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DOI：
10.1021/nl404816m
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发表时间：
2014-03-12
期刊：
影响因子：
10.8
通讯作者：
Steinmetz NF
中科院分区：
文献类型：
--
作者：
Bruckman MA;Jiang K;Simpson EJ;Randolph LN;Luyt LG;Yu X;Steinmetz NF
主要心血管事件，如心肌梗塞和中风的根本原因是动脉粥样硬化。为了准确诊断这种炎症性疾病，需要分子成像。为了实现这一目标，我们试图开发一种基于纳米颗粒的高纵横比分子靶向磁共振（MR）成像造影剂。具体而言，我们设计了植物病毒纳米颗粒平台烟草花叶病毒（TMV），以靶向血管细胞粘附分子（VCAM）-1，该分子在动脉粥样硬化斑块的活化内皮细胞上高度表达。为了在动脉粥样硬化ApoE-/-小鼠模型中实现双重光学和MR成像，将TMV修饰为携带近红外染料和螯合Gd离子。我们的研究结果表明动脉粥样硬化斑块的分子靶向。基于多价性和多功能性，靶向的基于TMV的MR探针显著提高了检测限;与建议的临床使用相比，Gd离子的注射剂量可以进一步减少400倍，证明了靶向纳米颗粒货物递送的实用性。
The underlying cause of major cardiovascular events, such as myocardial infarctions and strokes, is atherosclerosis. For accurate diagnosis of this inflammatory disease, molecular imaging is required. Toward this goal, we sought to develop a nanoparticle-based, high aspect ratio, molecularly targeted magnetic resonance (MR) imaging contrast agent. Specifically, we engineered the plant viral nanoparticle platform tobacco mosaic virus (TMV) to target vascular cell adhesion molecule (VCAM)-1, which is highly expressed on activated endothelial cells at atherosclerotic plaques. To achieve dual optical and MR imaging in an atherosclerotic ApoE–/– mouse model, TMV was modified to carry near-infrared dyes and chelated Gd ions. Our results indicate molecular targeting of atherosclerotic plaques. On the basis of the multivalency and multifunctionality, the targeted TMV-based MR probe increased the detection limit significantly; the injected dose of Gd ions could be further reduced 400x compared to the suggested clinical use, demonstrating the utility of targeted nanoparticle cargo delivery.
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