Gadolinium Doping Modulates the Enzyme-like Activity and Radical-Scavenging Properties of CeO 2 Nanoparticles.

Their unique physicochemical properties and multi-enzymatic activity make CeO 2 nanoparticles (CeO 2 NPs) the most promising active component of the next generation of theranostic drugs. When doped with gadolinium ions, CeO 2 NPs constitute a new type of contrast agent for magnetic resonance imaging, possessing improved biocatalytic properties and a high level of biocompatibility. The present study is focused on an in-depth analysis of the enzyme-like properties of gadolinium-doped CeO 2 NPs (CeO 2 :Gd NPs) and their antioxidant activity against superoxide anion radicals, hydrogen peroxide, and alkylperoxyl radicals. Using an anion-exchange method, CeO 2 :Gd NPs (~5 nm) with various Gd-doping levels (10 mol.% or 20 mol.%) were synthesized. The radical-scavenging properties and biomimetic activities (namely SOD- and peroxidase-like activities) of CeO 2 :Gd NPs were assessed using a chemiluminescent method with selective chemical probes: luminol, lucigenin, and L-012 (a highly sensitive luminol analogue). In particular, gadolinium doping has been shown to enhance the radical-scavenging properties of CeO 2 NPs. Unexpectedly, both bare CeO 2 NPs and CeO 2 :Gd NPs did not exhibit SOD-like activity, acting as pro-oxidants and contributing to the generation of reactive oxygen species. Gadolinium doping caused an increase in the pro-oxidant properties of nanoscale CeO 2 . At the same time, CeO 2 :Gd NPs did not significantly inhibit the intrinsic activity of the natural enzyme superoxide dismutase, and CeO 2 :Gd NPs conjugated with SOD demonstrated SOD-like activity. In contrast to SOD-like properties, peroxidase-like activity was observed for both bare CeO 2 NPs and CeO 2 :Gd NPs. This type of enzyme-like activity was found to be pH-dependent. In a neutral medium (pH = 7.4), nanoscale CeO 2 acted as a prooxidant enzyme (peroxidase), while in an alkaline medium (pH = 8.6), it lost its catalytic properties; thus, it cannot be regarded as a nanozyme. Both gadolinium doping and conjugation with a natural enzyme were shown to modulate the interaction of CeO 2 NPs with the key components of redox homeostasis.