D'Achille Anne E, Gonzalez-Rodriguez Roberto, Campbell Elizabeth, Lee Bong Han, Coffer Jeffery L, Naumov Anton V
Department of Chemistry and Biochemistry, Texas Christian University, TCU Box 298860, Fort Worth, Texas 76129, United States.
Department of Physics and Astronomy, Texas Christian University, TCU Box 298840, Fort Worth, Texas 76129, United States.
ACS Biomater Sci Eng. 2020 Dec 14;6(12):6971-6980. doi: 10.1021/acsbiomaterials.0c01193. Epub 2020 Nov 24.
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 (CeO) 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 CeO 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 and a potential for 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 (/), shifting closer to the positive contrast range and suggesting the potential use of the CeO nanocube matrix doped with selected rare-earth ions as a tunable MRI contrast agent with NIR imaging capabilities.
近红外（NIR）荧光为生物医学荧光成像提供了一条新途径，它能够透过几厘米厚的生物组织追踪荧光团。然而，这类荧光团十分稀少，并且由于累积毒性，常常被限制用于临床应用。不仅由近红外荧光团提供，而且传统上由磁共振成像（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性成像解决方案：掺杂镱或钕，并共掺杂钆的氧化铈（CeO）纳米立方体，显示出同时用于近红外（NIR）荧光和磁共振成像（MRI）应用的潜力。这项工作中描述的合成过程能够稳定地掺入镱或钕，二者在近红外区域均具有发射跃迁。作为一种生物相容性纳米材料，CeO纳米立方体是理想的掺杂主体材料，可将镧系元素荧光自猝灭以及与掺杂剂相关的任何潜在毒性降至最低。通过对镱或钕近红外发射的高光谱成像监测HeLa细胞对纳米立方体的摄取，摄取量在12小时时达到最大值，这表明掺杂镧系元素的纳米立方体具有用于荧光成像的能力和潜力。共掺杂的纳米立方体在共掺杂2原子%的钆时，近红外发射强度没有明显损失，并且表现出在已知阴性造影剂范围内的磁化率。然而，钆含量小幅增加至6原子%会显著影响磁化率比（/），使其更接近阳性造影剂范围，这表明掺杂选定稀土离子的CeO纳米立方体基质有可能用作具有近红外成像能力的可调谐MRI造影剂。
