Dumont Matthieu F, Hoffman Hilary A, Yoon Pryscilla R S, Conklin Laurie S, Saha Shanta R, Paglione Johnpierre, Sze Raymond W, Fernandes Rohan
The Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Medical Center , 111 Michigan Avenue NW, Washington, DC 20010, United States.
Bioconjug Chem. 2014 Jan 15;25(1):129-37. doi: 10.1021/bc4004266. Epub 2013 Dec 20.
Molecular imaging agents enable the visualization of phenomena with cellular and subcellular level resolutions and therefore have enormous potential in improving disease diagnosis and therapy assessment. In this article, we describe the synthesis, characterization, and demonstration of core-shell, biofunctionalized, gadolinium-containing Prussian blue nanoparticles as multimodal molecular imaging agents. Our multimodal nanoparticles combine the advantages of MRI and fluorescence. The core of our nanoparticles consists of a Prussian blue lattice with gadolinium ions located within the lattice interstices that confer high relaxivity to the nanoparticles providing MRI contrast. The relaxivities of our nanoparticles are nearly nine times those observed for the clinically used Magnevist. The nanoparticle MRI core is biofunctionalized with a layer of fluorescently labeled avidin that enables fluorescence imaging. Biotinylated antibodies are attached to the surface avidin and confer molecular specificity to the nanoparticles by targeting cell-specific biomarkers. We demonstrate our nanoparticles as multimodal molecular imaging agents in an in vitro model consisting of a mixture of eosinophilic cells and squamous epithelial cells. Our nanoparticles specifically detect eosinophilic cells and not squamous epithelial cells, via both fluorescence imaging and MRI in vitro. These results suggest the potential of our biofunctionalized Prussian blue nanoparticles as multimodal molecular imaging agents in vivo.
分子成像剂能够以细胞和亚细胞水平分辨率实现现象可视化，因此在改善疾病诊断和治疗评估方面具有巨大潜力。在本文中，我们描述了核壳结构、生物功能化的含钆普鲁士蓝纳米颗粒作为多模态分子成像剂的合成、表征及演示。我们的多模态纳米颗粒结合了磁共振成像（MRI）和荧光的优势。我们纳米颗粒的核心由普鲁士蓝晶格组成，钆离子位于晶格间隙中，赋予纳米颗粒高弛豫率，从而提供MRI对比度。我们纳米颗粒的弛豫率几乎是临床使用的马根维显的九倍。纳米颗粒的MRI核心用一层荧光标记的抗生物素蛋白进行生物功能化，从而实现荧光成像。生物素化抗体附着在表面抗生物素蛋白上，通过靶向细胞特异性生物标志物赋予纳米颗粒分子特异性。我们在由嗜酸性细胞和鳞状上皮细胞混合物组成的体外模型中展示了我们的纳米颗粒作为多模态分子成像剂的性能。我们的纳米颗粒通过体外荧光成像和MRI特异性检测嗜酸性细胞，而非鳞状上皮细胞。这些结果表明我们生物功能化的普鲁士蓝纳米颗粒在体内作为多模态分子成像剂的潜力。
