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Dysprosium-Modified Tobacco Mosaic Virus Nanoparticles for Ultra-High-Field Magnetic Resonance and Near-Infrared Fluorescence Imaging of Prostate Cancer
ACS Nano ( IF 15.8 ) Pub Date : 2017-09-06 00:00:00 , DOI: 10.1021/acsnano.7b04472
He Hu 1 , Yifan Zhang 1 , Sourabh Shukla 1 , Yuning Gu 1 , Xin Yu 1 , Nicole F. Steinmetz 1, 2, 3
Affiliation  

The increasing prevalence of ultra-high-field magnetic resonance imaging (UHFMRI) in biomedical research and clinical settings will improve the resolution and diagnostic accuracy of MRI scans. However, better contrast agents are needed to achieve a satisfactory signal-to-noise ratio. Here, we report the synthesis of a bimodal contrast agent prepared by loading the internal cavity of tobacco mosaic virus (TMV) nanoparticles with a dysprosium (Dy3+) complex and the near-infrared fluorescence (NIRF) dye Cy7.5. The external surface of TMV was conjugated with an Asp-Gly-Glu-Ala (DGEA) peptide via a polyethylene glycol linker to target integrin α2β1. The resulting nanoparticle (Dy-Cy7.5-TMV-DGEA) was stable and achieved a high transverse relaxivity in ultra-high-strength magnetic fields (326 and 399 mM–1 s–1 at 7 and 9.4 T, respectively). The contrast agent was also biocompatible (low cytotoxicity) and targeted PC-3 prostate cancer cells and tumors in vitro and in vivo as confirmed by bimodal NIRF imaging and T2-mapping UHFMRI. Our results show that Dy-Cy7.5-TMV-DGEA is suitable for multiscale MRI scanning from the cellular level to the whole body, particularly in the context of UHFMRI applications.

中文翻译:

s修饰的烟草花叶病毒纳米粒子用于前列腺癌的超高场磁共振和近红外荧光成像

在生物医学研究和临床环境中,超高场磁共振成像(UHFMRI)的普及率将提高MRI扫描的分辨率和诊断准确性。然而,需要更好的造影剂来达到令人满意的信噪比。在这里,我们报告了通过将mosaic(Dy 3+)复合物和近红外荧光(NIRF)染料Cy7.5加载到烟草花叶病毒(TMV)纳米颗粒的内腔中而制备的双峰造影剂的合成。TMV的外表面用天冬氨酸-甘氨酸-谷氨酸-丙氨酸(DGEA)缀合的肽通过聚乙二醇接头到目标整合素α 2 β 1。所得的纳米粒子(Dy-Cy7.5-TMV-DGEA)稳定并在超高强度磁场(分别在7和9.4 T时分别为326和399 mM –1 s –1)中实现了较高的横向弛豫性。如双峰NIRF成像和T 2映射UHFMRI所证实,造影剂在体外体内也具有生物相容性(低细胞毒性)并靶向PC-3前列腺癌细胞和肿瘤。我们的结果表明,Dy-Cy7.5-TMV-DGEA适用于从细胞水平到全身的多尺度MRI扫描,特别是在UHFMRI应用的情况下。
更新日期:2017-09-07
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