Abstract 2667: Intrinsically radiolabeled multifunctional cerium oxide nanoparticles for in vivo studies.
Authors: Yang Likun , Sundaresan Gobalakrishnan , Sun Minghao , Jose Purnima , McDonagh Philip R. , Zweit Jamal 
Published: August 2014

Cerium oxide nanopaticles (CONP) have unique properties in free radical scavenging. The CONP is a rare-earth metal oxide nanoparticle of the lanthanide series, which is widely used in ultraviolet absorbance, oxygen sensing and automotive catalytic convertors. This nanoparticle has both Ce3+ and Ce4+ oxidation states that could result in an auto-regenerative redox cycle between Ce3+ and Ce4+, accompanied by creation of oxygen defects on their surface and offers many active sites for free radical scavenging. CONP have demonstrated protection properties against oxidation damages in various cells and tissues. The mechanism of this, however, is poorly understood. Monitoring the interaction of CONP with biological compartments ‘in situ’ is crucial in order to understand their biochemical and physiological properties in vivo. In this study, a multifunctional nanoparticle platform was developed through an intrinsic radiolabeling strategy and extrinsic surface functionalization to combine dual imaging components such as Single Photon Emission Computed Tomography and Optical Imaging (SPECT/OI) in single nanoparticle. The cell viability, cell uptake and overall in vivo biodistribution of CONP were also manipulated through surface functionalization. The intrinsic radiolabeling strategy is demonstrated by incorporation of various radionuclides (141Ce, 111In, 65Zn) into CONP and these radiolabeled CONP (rCONP) were coated with biocompatible polymers including Dextran T10 (DT10), Poly(acrylic acid) (PAA), or functionalized DT10 (DT10-NH2, DT10-PEG and DT10-sulfobetaine). This intrinsic labeling strategy enabled quantitative in vivo SPECT imaging. Fluorescent CONP was obtained through conjugation of fluorescein isothiocynate (FITC) with DT10-NH2 rCONP and used for cell imaging. The DT10 and DT10-NH2 rCONP didn't show decreased viability up to 120 μg/ml of Cerium whilst the PAA rCONP showed decreased viability at Cerium concentrations above 40 μg/ml. Variations in blood circulation and renal/hepatic clearance of rCONP were demonstrated and were found to be dependent on surface coating and hydrodynamic size of these nanoparticles. The results of ex vivo biodistribution were reflected in SPECT imaging of 141Ce-rCONP, showing accumulation in the liver and spleen in a living mouse over a one-week period. Together, the intrinsic and extrinsic multifunctional strategy allows the determination of the biophysical properties of CONP, opening the door for their future applications for in vivo studies and biomedical imaging.

Citation Format: Likun Yang, Gobalakrishnan Sundaresan, Minghao Sun, Purnima Jose, Philip R. McDonagh, Jamal Zweit. Intrinsically radiolabeled multifunctional cerium oxide nanoparticles for in vivo studies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2667. doi:10.1158/1538-7445.AM2013-2667