Combination Therapy with LXW7 and Ceria Nanoparticles Protects against Acute Cerebral Ischemia/Reperfusion Injury in Rats

Ischemia/reperfusion is known to greatly increase oxidative stress in the penumbra,which results in brain damage.Integrinαvβ3 is selectively up-regulated with ischemic injury to the brain and remains elevated throughout reperfusion.We determined whether or not a new compound biotinylated-LXW7-ceria nanoparticle(Ce NP)(b LXW7-Ce NP)plays a role in brain protection in the rat model of middle cerebral artery occlusion/reperfusion and shows better effects than Ce NPs alone in improving the outcomes of focal oxidative stress and apoptosis more effectively.Male Sprague-Dawley rats were subjected to focal cerebral ischemia for 2 h followed by a 24-h reperfusion.Drug treatment was intravenously administered via the caudal vein 1 h after occlusion.Rats were randomly divided into the following 4 groups:b LXW7-Ce NP treatment group(0.5 mg/kg);Ce NP treatment group(0.5 mg/kg);control saline group;and sham group.Brains were harvested 24 h after reperfusion,and the neurologic deficit scores,infarction volume,blood-brain barrier(BBB)disruption,and the level of oxidative stress and apoptosis were determined.Results showed that the b LXW7-Ce NP and Ce NP treatments could improve neurologic deficit scores,infarction volume,BBB disruption,and the level of oxidative stress and apoptosis.Compound b LXW7-Ce NP treatment exhibited better effects than Ce Np treatment and showed remarkable statistical differences in the infarction volume,the degree of BBB breakdown,the apoptosis and oxidative stress,apart from neurologic deficit scores.Thus,we concluded that b LXW7-Ce NP protects against acute cerebral ischemia/reperfusion injury.BLXW7,as a ligand of integrinαvβ3,may be able to effectively localize the anti-oxidant Ce NPs to the ischemic penumbra region,which may provide more adequate opportunities for Ce NPs to exert anti-oxidative stress effects and subsequently reduce apoptosis in acute cerebral ischemia/reperfusion.

Synthesis and characterization of ceria nanoparticles by complex-precipitation route

Ceria(CeO_(2))nanoparticles were successfully synthesized via a simple complex-precipitation route that employs cerium chloride as cerium source and citric acid as precipitant.The elemental analysis results of carbon,hydrogen,oxygen,and cerium in the precursors were calculated,and the results revealed that the precursors were composed of Ce(OH)_(3),Ce(H_(2)Cit)_(3),or CeCit.X-ray diffraction analysis showed that all ceria nanoparticles had a face-centered cubic structure.With the molar ratio of citric acid to Ce^(3)+(n)of 0.25 and pH of 5.5,the specific surface area of the sample reached the maximum value of 83.17 m^(2)/g.Ceria nanoparticles were observed by scanning electron microscopy.Selected area electron diffraction patterns of several samples were obtained by transmission electron microscopy,and the crystal plane spacing of each low-exponent crystal plane was calculated.The ultraviolet(UV)–visible transmittance curve showed that ceria can absorb UV light and pass through visible light.Among all samples,the minimum average transmittance of ultraviolet radiation a(UVA)was 4.42%,and that of ultraviolet radiation b(UVB)was 1.56%.

Ceria nanoparticles: biomedical applications and toxicity

Ceria nanoparticles(CeO_(2) NPs)have become popular materials in biomedical and industrial fields due to their potential applications in anti-oxidation,cancer therapy,photocatalytic degradation of pollutants,sensors,etc.Many methods,including gas phase,solid phase,liquid phase,and the newly proposed green synthesis method,have been reported for the synthesis of CeO_(2) NPs.Due to the wide application of CeO_(2) NPs,concerns about their adverse impacts on human health have been raised.This review covers recent studies on the biomedical applications of CeO_(2) NPs,including their use in the treatment of various diseases(e.g.,Alzheimer's disease,ischemic stroke,retinal damage,chronic inflammation,and cancer).CeO_(2) NP toxicity is discussed in terms of the different systems of the human body(e.g.,cytotoxicity,genotoxicity,respiratory toxicity,neurotoxicity,and hepatotoxicity).This comprehensive review covers both fundamental discoveries and exploratory progress in CeO_(2) NP research that may lead to practical developments in the future.

Application of biocompatible custom ceria nanoparticles in improving the quality of liver grafts for transplantation

Liver transplantation(LT),an ultimate and vital method for treating end-stage liver disease,is often accompanied by ischemiareperfusion injury(IRI)resulting from warm or cold ischemia of the donor liver.Organ protection techniques are used to improve the quality of liver grafts(from retrieval to implantation).Reactive oxygen species(ROS)cause oxidative stress,which is considered a crucial factor in IRI after LT.Nano antioxidants capable of scavenging ROS alleviate IRI in multiple types of organs and tissues.In this study,we synthesized ceria nanoparticles(NPs)with antioxidant properties using a pyrolysis method and covered them with phospholipid-polyethylene glycol to improve their biocompatibility in vivo.We investigated the potential organprotective effect of ceria NPs and the underlying mechanisms.Ceria NPs promoted liver function recovery after LT by attenuating IRI in liver grafts in vivo.The protective effect of ceria NPs on liver grafts was investigated by applying hypothermic oxygenated machine perfusion ex vivo.Ceria NPs attenuated hypoxia reoxygenation-or H_(2)O_(2)-induced hepatocyte injury by enhancing mitochondrial activity and ROS scavenging in vitro.These effects may be associated with the activation of the nuclear factor erythroid-derived 2-related factor 2(Nrf2)/Kelch-like ECH-associated protein 1(Keap1)/heme oxygenase 1(HO-1)signaling pathway.In conclusion,ceria NPs may serve as a promising antioxidant agent for the treatment of hepatic IRI after LT.

Biocompatible custom ceria nanoparticles against reactive oxygen species resolve acute inflammatory reaction after intracerebral hemorrhage

Intracerebral hemorrhage （ICH） is a devastating subtype of stroke with a high mortality rate, for which there currently is no effective treatment. A perihematomal edema caused by an intense inflammatory reaction is more deleterious than the hematoma itself and can result in neurological deterioration and death. Ceria nanoparticles （CeNPs） are potent free radical scavengers with potential for biomedical applications. As oxidative stress plays a major role in post-ICH inflammation, we hypothesized that CeNPs might protect against ICH. To test this hypothesis, core CeNPs were synthesized using a modified reverse micelle method and covered with phospholipid-polyethylene glycol （PEG） to achieve biocompatibility. We investigated whether our custom-made biocompatible CeNPs have protective effects against ICH. The CeNPs reduced oxidative stress, hemin-induced cytotoxicity, and inflammation in vitro. In a rodent ICH model, intravenously administered CeNPs were mainly distributed in the hemorrhagic hemisphere, suggesting that they could diffuse through the damaged blood-brain barrier. Moreover, CeNPs attenuated microglia/macrophage recruitment around the hemorrhagic lesion and inflammatory protein expression. Finally, CeNP treatment reduced the brain edema by 68.4% as compared to the control. These results reveal the great potential of CeNPs as a novel therapeutic agent for patients with ICH.

Customized lipid-coated magnetic mesoporous silica nanoparticle doped with ceria nanoparticles for theragnosis of intracerebral hemorrhage

Intracerebral hemorrhage （ICH）, caused by the sudden rupture of an artery within the brain, is a devastating subtype of stroke, which currently has no effective treatment. Intense inflammatory reactions that occur in the peri-hematomal area after ICH are more deleterious than the hematoma itself, resulting in subsequent brain edema and neurologic deterioration. Thus, we developed lipid-coated magnetic mesoporous silica nanoparticles doped with ceria nanoparticles （CeNPs）, abbreviated as LMCs, which have both potent anti-inflammatory therapeutic effects via scavenging reactive oxygen species and help in increasing the efficacy of magnetic resonance imaging enhancement in the peri-hematomal area. LMCs consist of mesoporous silica nanopartide-supported lipid bilayers, which are loaded with large amounts of CeNPs for scavenging of reactive oxygen species, and iron oxide nanoparticles for magnetic resonance imaging contrast. LMCs loaded with CeNPs exhibited strong anti-oxidative and anti-inflammatory activities in vitro. In the rodent ICH model, intracerebraUy injected LMCs reached the peri-hematomal area and were engulfed by macrophages, which were clearly visualized by magnetic resonance imaging of the brain. Moreover, LMCs reduced inflammatory macrophage infiltration, and thus significantly reduced brain edema. Finally, LMC treatment markedly improved neurologic outcomes of the animals with ICH. Thus, LMC is the first nanobiomaterial that successfully showed theragnostic effects in ICH.

Fabrication and ultraviolet-shielding properties of silica-coated titania-doped ceria nanoparticles

A series of well-dispersed titania-doped ceria nanoparticles Ce1–xTixO2 were rapidly prepared by a novel salt-assisted solution combustion process using correspondent metal nitrates as oxidizers and ethyl glycol as fuel, and then coated with amorphous silica by seeded polymerization using tetraethyl orthoslicate （TEOS）. The as-prepared samples were characterized by transmission electron microscopy （TEM）, X-ray diffraction （XRD）, Fourier-transform infrared spectroscopy （FTIR）, and ultraviolet-visible light （UV-Vis） diffuse reflectance spectroscopy. The results indicated that compared with the as-prepared pure ceria nanoparticles, the red-shift phenomenon occurred for Ti-doped ceria nanoparticles with Ti incorporation. Meanwhile, the absorption intensity in the UV light region slightly decreased and transmission rate in visible light region was somewhat enhanced. In comparison with the silica-coated CeO2 nanopowders, the silica-coated Ce0.95Ti0.05O2 nanopowders displayed the same absorption intensity in the UV light region, broader UV absorption band and higher transmission rate in visible light region.

Shape and size effects of ceria nanoparticles on the impact strength of ceria/epoxy resin composites

Ceria nanoparticles with various shapes （rods, cubes, and plates） and sizes were controllably synthesized and then introduced into epoxy resin. Subsequently, we investigated correlations between the shape and size of ceria nanostructures and the mechanical performance of composites. The samples were character- ized by transmission electron microscopy, scanning electron microscopy, and X-ray diffraction. Compared with commercial ceria filled composites, the composites made with morphology-controlled ceria nanos- tructures show a higher impact strength. It is found that epoxy resins made with high-aspect-ratio ceria nanorods show the highest impact strength, up to 17.27 kJ/m2, which is about four times that of the neat epoxy resin.

Study on application of CeO_2 and CaCO_3 nanoparticles in lubricating oils

The ceria （CeO2） nanoparticles and calcium carbonate （CaCO3） nanoparticles were chosen as additives of anti-wear and extreme pressure for lubricating oils, and the morphology and sizes of nanoparticles were examined using Transmission Electron Microscope （TEM）. The tribological performance of lubricating oils containing combined nanoparticles were determined by four-ball friction and wear tester, and the chemical composition of steel ball with worn surface were analyzed by X-ray Photoelectron Spectrurn（XPS）. The results showed that the lubricating oils containing combined nanoparticles had good anti-wear and friction reducing effects, and the tribological properties were optimal when WCeO2＋CaCO3=0.6%, WCeO2：WCaCO3=1：1. The extreme pressure value increased by 40.25%, the wear spot diameter reduced by 33.5%, and friction coefficient reduced by 32% compared with 40CD oil. The coordinated action of big and small particles made anti-wear and friction reducing effective. Tribological chemical reactions resulting from the friction surface formed metal calcium, metal cerium and oxides film, and they could fill up the concave surface and protect the worn surface.

Gold nanoparticles-embedded ceria with enhanced antioxidant activities for treating inflammatory bowel disease

The excessive reactive oxygen species(ROS)is a hallmark associated with the initiation and progression of inflammatory bowel disease(IBD),which execrably form a vicious cycle of ROS and inflammation to continually promote disease progression.Here,the gold nanoparticles-embedded ceria nanoparticles(Au/CeO_(2))with enhanced antioxidant activities are designed to block this cycle reaction for treating IBD by scavenging overproduced ROS.The Au/CeO_(2) with core-shell and porous structure exhibits significantly higher enzymatic catalytic activities compared with commercial ceria nanoparticles,likely due to the effective exposure of catalytic sites,higher content of Ce(III)and oxygen vacancy,and accelerated reduction from Ce(IV)to Ce(III).Being coated with negatively-charged hyaluronic acid,the Au/CeO_(2)@HA facilitates accumulation in inflamed colon tissues via oral administration,reduces pro-inflammatory cytokines,and effectively alleviates colon injury in colitis mice.Overall,the Au/CeO_(2)@HA with good biocompatibility is a promising nano-therapeutic for treating IBD.

CeO_2/Zn NANOCOMPOSITE COATING BY ELECTRODEPOSITION

The nanocomposite coating is obtained by electrochemical deposition of the zinc plating solution with ceria nanoparticles (mean diameter 30 nm). The effect of ceria nanoparticles on the electrodeposited zinc coating is stu died by weight loss test, inductively copuled plasma quantometer (ICP), scanning electron microscopy (SEM) and X ray diffraction (XRD), respectively. It is found that under the same electrodeposition conditions, the corrosion resistance of the nanocomposite coating increases obviously while that of the micron composite coating only improves slightly; The ceria content of the nanocomposite coating is more than that of the micron composite coating. Ceria nanoparticles modify the surface morphology and crystal structure of the zinc matrix in correlation with the increase of corrosion resistance.

CeO2/Zn NANOCOMPOSITE COATING BY ELECTRODEPOSITION

The nanocomposite coating is obtained by electrochemical deposition of the zinc plating solution with ceria nanoparticles (mean diameter 30 nm). The effect of ceria nanoparticles on the electrodeposited zinc coating is stu died by weight loss test, inductively copuled plasma quantometer (ICP), scanning electron microscopy (SEM) and X ray diffraction (XRD), respectively. It is found that under the same electrodeposition conditions, the corrosion resistance of the nanocomposite coating increases obviously while that of the micron composite coating only improves slightly; The ceria content of the nanocomposite coating is more than that of the micron composite coating. Ceria nanoparticles modify the surface morphology and crystal structure of the zinc matrix in correlation with the increase of corrosion resistance.

Surface oxidation of Ni-cermet electrodes by CO_(2) and H_(2)O and how to moderate it

The oxidation of porous Ni-yttria-stabilized zirconia(YSZ)and Ni-gadolinia-doped ceria(GDC)ceramicmetal(cermet)electrodes in H_(2)O and CO_(2)atmospheres was studied by near-ambient pressure X-ray photoelectron spectroscopy(NAP-XPS).We show that the oxidation of nickel by the two gases is not similar,as is commonly believed,but it depends on the ceramic type.Nickel is vulnerable to oxidation in H_(2)O but it resists to CO_(2)in Ni-GDC,as compared to the Ni-YSZ electrode.Inspired by this observation we conceptualize and fabricate Ni-YSZ electrodes modified by ceria nanoparticles,which show significantly higher resistance to CO_(2)oxidation as compared with conventional Ni-YSZ electrodes.The preparation of tailormade cermet electrodes with identical bulk/mechanical characteristics but very different surface properties offers a promising fabrication strategy for high-performance and durability solid oxide electrolysis cells for CO_(2)conversion.