Dry eye disease (DED) affects a substantial worldwide population with increasing frequency. Current single-targeting DED management is severely hindered by the existence of an oxidative stress-inflammation vicious cycle and complicated intercellular crosstalk within the ocular microenvironment. Here, a nanozyme-based eye drop, namely nanoceria loading cyclosporin A (Cs@P/CeO2), is developed, which possesses long-term antioxidative and anti-inflammatory capacities due to its regenerative antioxidative activity and sustained release of cyclosporin A (CsA). In vitro studies showed that the dual-functional Cs@P/CeO2 not only inhibits cellular reactive oxygen species production, sequentially maintaining mitochondrial integrity, but also downregulates inflammatory processes and repolarizes macrophages. Moreover, using flow cytometric and single-cell sequencing data, the in vivo therapeutic effect of Cs@P/CeO2 was systemically demonstrated, which rebalances the immune-epithelial communication in the corneal microenvironment with less inflammatory macrophage polarization, restrained oxidative stress, and enhanced epithelium regeneration. Collectively, our data proved that the antioxidative and anti-inflammatory Cs@P/CeO2 may provide therapeutic insights into DED management.

In recent years, there has been a notable increase in interest surrounding nanozymes due to their ability to imitate the functions and address the limitations of natural enzymes. The scientific community has been greatly intrigued by the study of nanoceria, primarily because of their distinctive physicochemical characteristics, which include a variety of enzyme-like activities, affordability, exceptional stability, and the ability to easily modify their surfaces. Consequently, nanoceria have found extensive use in various biosensing applications. However, the impact of its redox activity on the enzymatic catalytic mechanism remains a subject of debate, as conflicting findings in the literature have presented both pro-oxidant and antioxidant effects. Herein, we creatively propose a seesaw model to clarify the regulatory mechanism on redox balance and survey possible mechanisms of multienzyme mimetic properties of nanoceria. In addition, this review aims to showcase the latest advancements in this field by systematically discussing over 180 research articles elucidating the significance of ceria-based nanozymes in enhancing, downsizing, and enhancing the efficacy of point-of-care (POC) diagnostics. These advancements align with the ASSURED criteria established by the World Health Organization (WHO). Furthermore, this review also examines potential constraints in order to offer readers a concise overview of the emerging role of nanoceria in the advancement of POC diagnostic systems for future biosensing applications.

Cerium oxide nanoparticles (CeO2NPs) have exceptional catalytic properties, rendering them highly effective in removing excessive reactive oxygen species (ROS) from biological environments, which is crucial in safeguarding these environments against radiation-induced damage. Additionally, the Ce atom\'s high Z number makes it an ideal candidate for utilisation as an X-ray imaging contrast agent. We herein show how the injection of albumin-stabilised 5 nm CeO2NPs into mice revealed substantial enhancement in X-ray contrast, reaching up to a tenfold increase at significantly lower concentrations than commercial or other proposed contrast agents. Remarkably, these NPs exhibited prolonged residence time within the target organs. Thus, upon injection into the tail vein, they exhibited efficient uptake by the liver and spleen, with 85% of the injected dose (%ID) recovered after 7 days. In the case of intratumoral administration, 99% ID of CeO2NPs remained within the tumour throughout the 7-day observation period, allowing for observation of disease dynamics. Mass spectrometry (ICP-MS) elemental analysis confirmed X-ray CT imaging observations.

Nanoparticle (NP) pharmacokinetics significantly differ from traditional small molecule principles. From this emerges the need to create new tools and concepts to harness their full potential and avoid unnecessary risks. Nanoparticle pharmacokinetics strongly depend on size, shape, surface functionalisation, and aggregation state, influencing their biodistribution, accumulation, transformations, and excretion profile, and hence their efficacy and safety. Today, while NP biodistribution and nanoceria biodistribution have been studied often at short times, their long-term accumulation and excretion have rarely been studied. In this work, 3 nm nanoceria at 5.7 mg/kg of body weight was intravenously administrated in a single dose to healthy mice. Biodistribution was measured in the liver, spleen, kidney, lung, brain, lymph nodes, ovary, bone marrow, urine, and faeces at different time points (1, 9, 30, and 100 days). Biodistribution and urinary and faecal excretion were also studied in rats placed in metabolic cages at shorter times. The similarity of results of different NPs in different models is shown as the heterogeneous nanoceria distribution in organs. After the expectable accumulation in the liver and spleen, the concentration of cerium decays exponentially, accounting for about a 50% excretion of cerium from the body in 100 days. Cerium ions, coming from NP dissolution, are most likely excreted via the urinary tract, and ceria nanoparticles accumulated in the liver are most likely excreted via the hepatobiliary route. In addition, nanoceria looks safe and does not damage the target organs. No weight loss or apathy was observed during the course of the experiments.

Deep eutectic solvents (DES) have demonstrated their ability to facilitate skin penetrability of rigid nanoparticles (NPs). Here, we reported a feasible and simple transdermal delivery strategy using mesoporous silica nanoparticles impregnated in DES hydrogels for topical management of rheumatoid arthritis (RA). To achieve this goal, nanoceria was immobilized within a silica nanoparticle matrix (MSN) and encapsulated with methotrexate (MTX). The functionalized nanoparticles were first engineered in an Arginine (Arg)-citric acid (CA) DES and then transferred to the carbomer hydrogel matrix. Due to the strong affinity of DES hydrogels to the skin, combined with solvent-driven \"Drag\" effects, the prepared DES-MSNs hydrogels produced dynamic mobility of MSNs through skin layers, resulting in high skin penetrability. After application to the skin, the hydrogel solvent drove the rigid NPs across the skin barrier in a nonintrusive manner, resulting in sustained penetration and accumulation of MSNs at subcutaneous inflammation sites. Subsequently, the MTX payload exerted a direct therapeutic effect, while nanoceria moderated the inflammatory microenvironment by initiating reactive oxygen species (ROS) scavenging and transformation of the macrophage phenotype. In this way, the synergistic action of the combination of immuno- and chemotherapy of the drug and its carrier on RA was achieved. Our work provides a novel strategy for multisite regulation and controlled management of RA in a noninvasive way.

Wound healing is a programmed process through which tissue restores its integrity after an injury. Advancing age is a risk factor for delayed cutaneous wound healing; however, ideal therapeutic approaches for aged wound have not been developed yet. By dissecting the harsh microenvironment of aged wound, we propose an integrated chemical and biological strategy to mitigate two main hostile factors including oxidative stress and ischemia. Mesenchymal stem cell-derived extracellular vesicles (EVs) are a rising star in regenerative medicine due to their powerful facilitation in tissue repair and regeneration. However, the fragile lipid membrane limits their function under the oxidative stress microenvironment. Nanoceria is an antioxidative nanozyme; here, we reveal that nanoceria-loaded EVs derived from mesenchymal stem cells facilitate cutaneous wound healing in aged mice. DG-CeO2 was prepared via coating CeO2 covalently with d-glucose to promote their cellular endocytosis. DG-CeO2 was packaged into EVs under optimized hypoxic conditions (DG-CeO2 EVsHyp). We further demonstrated that DG-CeO2 EVsHyp had favorable biocompatibility and antioxidative and proangiogenic effects during the cutaneous wound healing in both young and aged mice. Further evidence revealed that DG-CeO2 EVsHyp-transferred miR-92a-3p/125b-5p and their targets associated with aging degeneration may be the potential mechanisms. Collectively, these findings highlight that nanoceria-loaded EVs released by engineered stem cells may represent a potential therapeutic approach for tissue regeneration in aged population.

Designing metal-metal oxide heteronanostructures with synergistic and superior activities (unattainable in the case of a single entity) is of great interest for a wide range of technological applications. Traditional synthetic strategies typically require reducing agents, stabilizing ligands, or high temperature reductive treatment to produce oxide-supported metals. Herein, a facile noble metal deposition strategy is developed to produce silver, gold, and platinum nanocrystals on the surface of hollow mesoporous cerium oxide nanospheres without any pretreatment. Unlike the galvanic replacement reaction, the developed protocol employs the innate reductive potential of CeO2 to produce a high density of ultrafine noble metal nanocrystals homogeneously immobilized onto the surface of CeO2 nanospheres. The multienzyme-like activities (i.e., superoxide dismutase-like and catalase-like) of CeO2@metal nanostructures, originating from CeO2 and metal nanoparticles, were effectively utilized for anti-inflammatory therapies in two in vivo models. This oxygen vacancy-mediated reduction strategy can be generalized to produce diverse metal-metal oxide nanostructures for a wide range of applications.

Release of nanoceria (nCeO2) into the environment has caused much concern about its potential toxicity, which still remains poorly understood for soil microorganisms. In this study, nanoceria and cerium (III) nitrate at different doses (10, 100 and 500 mg/kg) were applied to bok choy (Brassica rapa subsp. chinensis), grown in potting soil, to investigate the responses of soil bacterial communities to nanoceria (NC) and ionic cerium (IC) applications. The results showed that bacterial richness was slightly increased in all cerium treatments relative to the negative control without cerium amendment (CK), but a significant increase was only found in IC500. The patterns of bacterial community composition, predicted functions and phenotypes of all NC treatments were significantly differentiated from IC and CK treatments, which was correlated with the contents of cerium, available potassium and phosphorus in soil. The co-occurrence network of bacterial taxa was more complex after exposure to ionic cerium than to nanoceria. The keystone taxa of the two networks were entirely different. Predicted functions analysis found that anaerobic and Gram-negative bacteria were enriched under nanoceria exposure. Our study implies that Proteobacteria and nitrifying bacteria were significantly enriched after exposure to nanoceria and could be potential biomarkers of soil environmental perturbation from nanoceria exposure.

Tuning morphology and doping additional rare earth (RE) cations are potential techniques to promote the photocatalytic performance of ceria (CeO2), evaluating the collaborative effects of morphology and RE dopants is significant for producing high active ceria-based catalysts. So in this work, cubic, polyhedral and rod-like nanoceria doped with 10 mol % La (lanthanum), Y (yttrium), or Sm (samarium) were synthesized by a facile template-free hydrothermal method. Phases, morphologies, oxygen vacancies (OVs) concentration, energy band structure, photo-carriers separation/recombination, and photodegradation ratio toward methylene blue (MB) dye of as prepared ceria were studied. Results show that doped CeO2 maintains a similar morphology structure with un-doped sample and the band gap narrows slightly. Y-doped nanoceria, with an improved separation and a reduced recombination of photo-excited electrons (e-) and holes (h+), owns a higher MB photodegradation ratio than that of samples doping with La or Sm, which is measured as 79.04, 84.43, and 85.59% for Y-doped cubic, polyhedral, and rod-like CeO2. The collaborative influence of morphology tuning and RE (La, Y, and Sm) doping on photocatalytic performance of nanoceria includes the effects of doped elements and the formation of OVs. The elevation of OVs concentration as well as the separation efficiency of photo-generated e-/h+ are suggested to further enhance the photocatalytic performance of ceria.

Central nervous system (CNS) injury, induced by ischemic/hemorrhagic or traumatic damage, is one of the most common causes of death and long-term disability worldwide. Reactive oxygen and nitrogen species (RONS) resulting in oxidative/nitrosative stress play a critical role in the pathological cascade of molecular events after CNS injury. Therefore, by targeting RONS, antioxidant therapies have been intensively explored in previous studies. However, traditional antioxidants have achieved limited success thus far, and the development of new antioxidants to achieve highly effective RONS modulation in CNS injury still remains a great challenge. With the rapid development of nanotechnology, novel nanomaterials provided promising opportunities to address this challenge. Within these, nanoceria has gained much attention due to its regenerative and excellent RONS elimination capability. To promote its practical application, it is important to know what has been done and what has yet to be done. This review aims to present the opportunities and challenges of nanoceria in treating CNS injury. The physicochemical properties of nanoceria and its interaction with RONS are described. The applications of nanoceria for stroke and neurotrauma treatment are summarized. The possible directions for future application of nanoceria in CNS injury treatment are proposed.