Cerium oxide nanoparticles with antioxidant capabilities and gadolinium integration for MRI contrast enhancement

Abstract

The chelating gadolinium-complex is routinely used as magnetic resonance imaging (MRI) -contrast enhancer. However, several safety issues have recently been reported by FDA and PRAC. There is an urgent need for the next generation of safer MRI-contrast enhancers, with improved local contrast and targeting capabilities. Cerium oxide nanoparticles (CeNPs) are designed with fractions of up to 50% gadolinium to utilize the superior MRI-contrast properties of gadolinium. CeNPs are well-tolerated in vivo and have redox properties making them suitable for biomedical applications, for example scavenging purposes on the tissue- and cellular level and during tumor treatment to reduce in vivo inflammatory processes. Our near edge X-ray absorption fine structure (NEXAFS) studies show that implementation of gadolinium changes the initial co-existence of oxidation states Ce3+ and Ce4+ of cerium, thereby affecting the scavenging properties of the nanoparticles. Based on ab initio electronic structure calculations, we describe the most prominent spectral features for the respective oxidation states. The as-prepared gadolinium-implemented CeNPs are 3–5 nm in size, have r1-relaxivities between 7–13 mM−1 s−1 and show clear antioxidative properties, all of which means they are promising theranostic agents for use in future biomedical applications.

<p>Antioxidant and toxicity studies of biosynthesized cerium oxide nanoparticles in rats</p>

“…[33][34][35] Antioxidants could be harmful per se, because of pro-oxidant activity. [36][37][38] For example, Srinivas et al suggested that acute exposure of CNPs through inhalation route may induce cytotoxicity via oxidative stress and may lead to a chronic inflammatory response. 39 Adebayo et al also showed that administration of 100-300 mg/kg CNPs thrice in a week for 5 consecutive weeks to mice induces testicular dysfunction via disruption of antioxidant/oxidant balance and endocrine suppression.…”

Synthesis of Cerium Oxide Nanoparticles Using Various Methods: Implications for Biomedical Applications

“…Researchers have investigated and reported on the precipitation method for the synthesis of cerium oxide nanoparticles using various chemical ingredients. Some of the reagents that are used in the precipitation method include precursors such as cerium nitrate hexahydrate and sodium hydroxide [26,65,66]. Metal oxide powders are acquired by the addition of a ligand such as ammonia into solution of metal ions.…”

“…Changes in nanoparticle sizes directly affect their characteristics and behavior. These changes influence biological parameters such as the biological half-life, diffusivity, and immunogenicity [26]. Decreases in the sizes of the particles increases the surface area to volume ratio.…”

“…A study by Morones and coworkers demonstrated that the smaller the size of the nanoparticles the more potent the bacterial properties of silver nanoparticles [30]. Eriksson and coworkers demonstrated that cerium oxide nanoparticles between 3-5 nm offer exceptional antioxidative properties when doped into gadolinium for MRI imaging [26]. Studies have also identified size as one of the causes of nanoparticle toxicity.…”

Responses of seed germination and shoot metabolic profiles of maize (Zea maysL.) to Y2O3nanoparticle stress

“…Rare earth nanoparticles (RENPs), as a type of articial nanoparticles, have excellent physicochemical properties and extensive applications, and are considered as a treasury of opportunities for new light sources, magnetic sources, energy sources, and materials. [5][6][7] With the widespread use of RENPs, the potential risks of their accumulation and migration in the environment are expanding. 8 The phytotoxicity of RENPs has been conrmed by some laboratory simulations.…”