Rare-Earth-Doped Cerium Oxide Nanocubes for Biomedical Near-Infrared and Magnetic Resonance Imaging
Rare-Earth-Doped Cerium Oxide Nanocubes for Biomedical Near-Infrared and Magnetic Resonance Imaging
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DOI：
10.1021/acsbiomaterials.0c01193
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发表时间：
2020-12-01
影响因子：
5.8
通讯作者：
Naumov, Anton, V
中科院分区：
文献类型：
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作者：
D'Achille, Anne E.;Gonzalez-Rodriguez, Roberto;Naumov, Anton, V
近红外（NIR）荧光为生物医学荧光成像提供了一条新的途径，它允许通过几厘米的生物组织跟踪荧光团。然而，这样的荧光团是罕见的，并且由于积累衍生的毒性，通常限制临床应用。不仅由近红外荧光团提供而且常规地由磁共振成像（MRI）或计算机断层扫描（CT）进行的深部组织成像也受到造影剂毒性的阻碍。这项工作提供了一种生物相容的成像解决方案：掺杂镱或钕的氧化铈（CeO 2）纳米立方体，并与钆共掺杂，同时显示出近红外（NIR）荧光和磁共振成像（MRI）应用的潜力。在这项工作中描述的合成过程允许稳定掺入镱或钕，两者都具有发射转换在近红外作为一种生物相容性纳米材料，CeO 2纳米立方体作为一个理想的主体材料掺杂，最大限度地减少镧系元素荧光自猝灭以及任何潜在的毒性与掺杂剂。通过镱或钕近红外发射的高光谱成像来监测HeLa细胞对纳米立方体的吸收在12小时达到最大化，这表明镧系元素掺杂的纳米立方体具有体外荧光成像的能力和体内荧光成像的潜力。共掺杂的纳米立方体在与2原子%的钆共掺杂时没有表现出NIR发射强度的显著损失，并且在已知的负性造影剂的范围内表现出磁性。然而，少量增加到6原子%的钆显著影响磁化率比（r（2）/r（1）），更接近正对比度范围，并表明掺杂有所选稀土离子的CeO 2纳米立方体基质作为具有NIR成像能力的可调MRI造影剂的潜在用途。
Near-infrared (NIR) fluorescence provides a new avenue for biomedical fluorescence imaging that allows for the tracking of fluorophore through several centimeters of biological tissue. However, such fluorophores are rare and, due to accumulation-derived toxicity, are often restricted from clinical applications. Deep tissue imaging not only provided by near-infrared fluorophores but also conventionally carried out by magnetic resonance imaging (MRI) or computed tomography (CT) is also hampered by the toxicity of the contrast agents. This work offers a biocompatible imaging solution: cerium oxide (CeO2) nanocubes doped with ytterbium or neodymium, and co-doped with gadolinium, showing simultaneous potential for near-infrared (NIR) fluorescence and magnetic resonance imaging (MRI) applications. A synthetic process described in this work allows for the stable incorporation of ytterbium or neodymium, both possessing emissive transitions in the NIR As a biocompatible nanomaterial, the CeO2 nanocubes act as an ideal host material for doping, minimizing lanthanide fluorescence self-quenching as well as any potential toxicity associated with the dopants. The uptake of nanocubes by HeLa cells maximized at 12 h was monitored by hyperspectral imaging of the ytterbium or neodymium NIR emission, indicating the capacity of the lanthanide-doped nanocubes for in vitro and a potential for in vivo fluorescence imaging. The co-doped nanocubes demonstrate no significant loss of NIR emission intensity upon co-doping with 2 atomic % gadolinium and exhibit magnetic susceptibilities in the range of known negative contrast agents. However, a small increase to 6 atomic % gadolinium significantly affects the magnetic susceptibility ratio (r(2)/r(1)), shifting closer to the positive contrast range and suggesting the potential use of the CeO2 nanocube matrix doped with selected rare-earth ions as a tunable MRI contrast agent with NIR imaging capabilities.