Rare-Earth-Doped Cerium Oxide Nanocubes for Biomedical Near-Infrared and Magnetic Resonance Imaging.

Abstract

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 (r2/r1), 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.