Silica-coated Gd(DOTA)-loaded protein nanoparticles enable magnetic resonance imaging of macrophages
Silica-coated Gd(DOTA)-loaded protein nanoparticles enable magnetic resonance imaging of macrophages
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DOI：
10.1039/c5tb01014d
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发表时间：
2015-01-01
影响因子：
7
通讯作者：
Steinmetz, Nicole F.
中科院分区：
文献类型：
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作者：
Bruckman, Michael A.;Randolph, Lauren N.;Steinmetz, Nicole F.
体内靶标的分子成像允许非侵入性疾病诊断。纳米颗粒为分子成像提供了一个有前途的平台，因为它们可以将大量有效载荷的成像试剂运送到疾病部位。磁共振成像（MRI）通常是临床诊断的首选，因为它使用非电离辐射，并提供高空间分辨率和良好的穿透力。我们已经探索了使用植物病毒作为MRI造影剂的基础，特别是烟草花叶病毒（TMV），它可以组装成硬杆或球体。我们加载TMV颗粒与顺磁性Gd离子，增加离子弛豫相比，自由Gd离子。然后用二氧化硅涂覆负载的TMV颗粒，保持高弛豫率。有趣的是，我们发现当Gd（DOTA）被加载到TMV的内部通道中并且外部被二氧化硅涂覆时，与未涂覆的Gd加载的TMV相比，在60 MHz下T-1弛豫率从10.9 mm（-1）s（-1）增加到29.7 mm（-1）s（-1）。为了测试造影剂在生物学环境中的性能，我们专注于与巨噬细胞的相互作用，因为主动或被动靶向免疫细胞是研究与炎症相关的疾病进展中涉及的细胞成分的流行策略。体外测定和体模MRI实验表明巨噬细胞的有效靶向和成像，通过形状工程（SNP 4 TMV）和二氧化硅涂覆（Si-TMV/SNP > TMV/SNP）观察到增强的对比噪声比。由于植物病毒存在于食物链中，因此抗体可能在人群中普遍存在。因此，我们研究了二氧化硅涂层是否可以阻止抗体识别;事实上，我们的数据表明，矿化可以用作隐形涂层选项，以减少清除。因此，我们得出结论，二氧化硅涂层的蛋白质为基础的造影剂可以提供一个有趣的候选材料，通过巨噬细胞成像在体内描绘疾病的进一步调查。
The molecular imaging of in vivo targets allows non-invasive disease diagnosis. Nanoparticles offer a promising platform for molecular imaging because they can deliver large payloads of imaging reagents to the site of disease. Magnetic resonance imaging (MRI) is often preferred for clinical diagnosis because it uses non-ionizing radiation and offers both high spatial resolution and excellent penetration. We have explored the use of plant viruses as the basis for MRI contrast reagents, specifically tobacco mosaic virus (TMV), which can assemble to form either stiff rods or spheres. We loaded TMV particles with paramagnetic Gd ions, increasing the ionic relaxivity compared to free Gd ions. The loaded TMV particles were then coated with silica maintaining high relaxivities. Interestingly, we found that when Gd(DOTA) was loaded into the interior channel of TMV and the exterior was coated with silica, the T-1 relaxivities increased by three-fold from 10.9 mm(-1) s(-1) to 29.7 mm(-1) s(-1) at 60 MHz compared to uncoated Gd-loaded TMV. To test the performance of the contrast agents in a biological setting, we focused on interactions with macrophages because the active or passive targeting of immune cells is a popular strategy to investigate the cellular components involved in disease progression associated with inflammation. In vitro assays and phantom MRI experiments indicate efficient targeting and imaging of macrophages, an enhanced contrast-to-noise ratio was observed by shape-engineering (SNP 4 TMV) and silica-coating (Si-TMV/SNP > TMV/SNP). Because plant viruses are in the food chain, antibodies may be prevalent in the population. Therefore we investigated whether the silica-coating could prevent antibody recognition; indeed our data indicate that mineralization can be used as a stealth coating option to reduce clearance. Therefore, we conclude that the silica-coated protein-based contrast agent may provide an interesting candidate material for further investigation of in vivo delineation of disease through macrophage imaging.