Anticancer Activity of Cerium Oxide Nanoparticles Towards Human Lung Cancer Cells

The potential of cerium oxide nanoparticles (nanoceria) for neurodegenerative disease therapy.

Lack of effective pharmacological treatment makes valvular calcification a significant clinical problem in patients with valvular disease and bioprosthetic/mechanical valve replacement therapies. Elevated levels of reactive oxygen species (ROS) in valve tissue have been identified as a prominent hallmark and driving factor for valvular calcification. However, the therapeutic value of ROS-modulating agents for valvular calcification remains elusive. We hypothesized that ROS-modulating shape-specific cerium oxide nanoparticles (CNPs) will inhibit oxidative stress-induced valvular calcification. CNPs are a class of self-regenerative ROS-modulating agents, which can switch between Ce3+ and Ce4+ in response to oxidative microen-vironment. In this work, we developed oxidative stress-induced valve calcification model using two patient-derived stenotic valve interstitial cells (hVICs) and investigated the therapeutic effect of shape-specific CNPs to inhibit hVIC calcification. Human valvular interstitial cells (hVICs) were obtained from a normal healthy donor and two patients with calcified aortic valves. hVICs were characterized for their phenotypic (mesenchymal, myofibroblast and osteoblast) marker expression by qRT-PCR and antioxidant enzymes activity before and after exposure to hydrogen peroxide (H2O2)-induced oxidative stress. Four shape-specific CNPs (sphere, short rod, long rod, and cube) were synthesized via hydrothermal or ultra-sonication method and characterized for their biocompatibility in hVICs by alamarBlue® assay, and ROS scavenging ability by DCFH-DA assay. H2O2 and inorganic phosphate (Pi) were co-administrated to induce hVIC calcification in vitro as demonstrated by Alizarin Red S staining and calcium quantification. The effect of CNPs on inhibiting H2O2-induced hVIC calcification was evaluated. hVICs isolated from calcified valves exhibited elevated osteoblast marker expression and decreased antioxidant enzyme activities compared to the normal hVICs. Due to the impaired antioxidant enzyme activities, acute H2O2-induced oxidative stress resulted in higher ROS levels and osteoblast marker expression in both diseased hVICs when compared to the normal hVICs. Shape-specific CNPs exhibited shape-dependent abiotic ROS scavenging ability, and excellent cytocompatibility. Rod and sphere CNPs scavenged H2O2-induced oxidative stress in hVICs in a shape- and dose-dependent manner by lowering intracellular ROS levels and osteoblast marker expression. Further, CNPs also enhanced activity of antioxidant enzymes in hVICs to combat oxidative stress. Cube CNPs were not effective ROS scavengers. The addition of H2O2 in the Pi-induced calcification model further increased calcium deposition in vitro in a time-dependent manner. Co-administration of rod CNPs with Pi and H2O2 mitigated calcification in the diseased hVICs. We demonstrated that hVICs derived from calcified valves exhibited impaired antioxidant defense mechanisms and were more susceptible to oxidative stress than normal hVICs. CNPs scavenged H2O2-induced oxidative stress in hVICs in a shape-dependent manner. The intrinsic ROS scavenging ability of CNPs and their ability to induce cellular antioxidant enzyme activities may confer protection from oxidative stress-exacerbated calcification. CNPs represent promising antioxidant therapy for treating valvular calcification and deserve further investigation.

This study was to provide a theoretical basis for effective treatment of myocardial ischemia-reperfusion injury (I/R injury) and explore the effect of cerium oxide (CeO2) nanoparticles on myocardial cell apoptosis induced by I/R injury. In this study, 50 healthy male Sprague Dawley (SD) rats were selected and divided into five groups according to the random table method: a sham operation group, an I/R group, a 1 - 10 nm CeO2 nanoparticle group (CeO2-1 group), a 10 - 25 nm CeO2 nanoparticle group (CeO2-2 group), and a 50 nm CeO2 nanoparticle group (CeO2-3 group). Rats in different groups were injected with phosphate buffer solution (PBS) and CeO2 nanoparticles with different diameters, respectively. The rat models of I/R injury were prepared to explore and analyze the superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, glutathione peroxidase (GSH-Px) activity, and myocardial cell apoptosis of rats with I/R injury by CeO2 nanoparticles. The results showed that the cardiomyocyte necrosis, SOD activity, MDA content, GSH-Px activity, and apoptosis index of the three groups of rats injected with CeO2 nanoparticles were much better than those in the I/R group. The effects on SOD activity, MDA content, GSH-Px activity, and apoptosis index of cardiomyocytes in the CeO2-2 group were significantly better than those in the CeO2-1 and CeO2-3 groups, showing statistically great differences (P< 0.05); and effects on SOD activity, MDA content, and GSH-Px activity of cardiomyocytes in CeO2-1 group were better obviously than those in the CeO2-3 groups, showing statistically observable differences (P< 0.05). In addition, the difference between the CeO2-1 group and CeO2-3 on the apoptosis index of cardiomyocytes was not statistically remarkable (P> 0.05). It can be considered that the CeO2 nanoparticles can effectively alleviate the effects of myocardial I/R injury, showing reliable clinical significance.

Neuroprotective effect of cerium oxide nanoparticles in a rat model of experimental diabetic neuropathy.

The effects of cerium oxide nanoparticles on the proliferation, differentiation, and mineralization function of primary osteoblasts in vitro were evaluated. The results showed that the cell biological effects of cerium oxide nanoparticles varied with different diameters. The cytotoxicity of cerium oxide nanoparticles on primary osteoblasts varies with the size and incubation time. Sixty-nanometer cerium oxide nanoparticles show significant cytotoxicity on primary osteoblasts at 48h exposure. Cerium oxide nanoparticles with diameters of 40nm promoted the differentiation of osteoblasts and the promotion rate was enhanced with increasing concentration. Cerium oxide nanoparticles with diameters of 60nm promoted the differentiation of osteoblasts at lower concentrations, but turned to inhibit the differentiation at higher concentrations. Cerium oxide nanoparticles promoted the adipogenic transdifferentiation of osteoblasts at all tested concentrations. Moreover, the effects of 60-nm cerium oxide nanoparticles were stronger than that of 40-nm cerium oxide nanoparticles. Cerium oxide nanoparticles promoted the formation of mineralized matrix nodules of osteoblasts at all tested concentrations in a dose-dependent manner and the promotion rate increased with decreasing size. The results showed that cerium oxide nanoparticles had no acute cytotoxic effects on osteoblasts and could promote the osteogenic differentiation and mineralization of osteoblasts. Moreover, the size, concentration, and culture time of nanoparticles have significant influence on the proliferation, differentiation, and mineralization of osteoblasts.

Background: In recent years, nanoparticles have gained increasing popularity over traditional physicochemical methods for fighting pathogenic microorganisms. Due to their unique properties, cerium oxide nanoparticles (CeO2 NPs) have recently emerged as a promising candidate for biomedical applications. Objectives: This study aimed to investigate the antibacterial effects of CeO2 NPs prepared using alginate, following the disc diffusion method. Methods: For this purpose, four bacterial strains were used in this study: two Gram-positive [Bacillus subtilis (PTCC 1365) and Staphylococcus aureus ATCC 25923] and two Gram-negative [Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 9027]. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were measured using the microdilution method, and the anti-biofilm activity of the synthetic material was also assessed. Results: The results demonstrated the inhibitory effects of the synthesized nanoparticles on gram-positive bacteria, with significant growth inhibition observed in S. aureus and B. subtilis, after exposure to CeO2 NPs. Conclusion: CeO2 NPs synthesized by alginate exhibited significant antibacterial effects against Gram-positive bacteria and could disrupt biofilm structure and prevent further biofilm formation. The findings highlight the potential of CeO2 NPs synthesized by alginate as a novel antibacterial and anti-biofilm therapeutic agent.

Due to its excellent physicochemical properties, cerium oxide (CeO2) has attracted much attention in recent years. CeO2 nanomaterials (nanoceria) are widely being used, which has resulted in them getting released to the environment, and exposure to humans (mostly via inhalation) is a major concern. In the present study, CeO2 nanoparticles were synthesized by hydroxide-mediated method and were further characterized by Scanning Electron Microscopy (SEM), Field Emission Scanning Electron Microscopy (FESEM), Energy Dispersive X-ray Spectroscopy (EDX), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray Diffraction Spectroscopy (XRD). Human lung epithelial (Beas-2B) cells were used to assess the cytotoxicity and biocompatibility activity of CeO2 nanoparticles. 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and Live/Dead assays were performed to determine the cytotoxicity and biocompatibility of CeO2 nanoparticles. Generation of reactive oxygen species (ROS) by cerium oxide nanoparticles was assessed by ROS assay. MTT assay and Live/Dead assays showed no significant induction of cell death even at higher concentrations (100 μg per 100 μL) upon exposure to Beas-2B cells. ROS assay revealed that CeO2 nanoparticles did not induce ROS that contribute to the oxidative stress and inflammation leading to various disease conditions. Thus, CeO2 nanoparticles could be used in various applications including biosensors, cancer therapy, catalytic converters, sunscreen, and drug delivery.

Objective To investigate the effect of cerium oxide (CeO2) nanoparticles on cardiomyocyte apoptosis,and expression of B lymphocytes/leukemia-2 (bcl-2),bcl-2 associated X protein (bax) and Caspase-3 mRNA following myocardial ischemia-reperfusion injury (MIRI) in rats.Methods Forty health male Sprague-Dawley rats were randomly divided into five groups:sham group,I/R group,I/R + CeO2 preconditioning groups with three diverse nano size (1-10,10-25,50 nm).The MIRI model of rats in vivo was established successfully.Hematoxylin-eosin staining (HE) method was used to identify the pathologic changes of myocardial tissue.The apoptotic cardiomyocytes were detected by in situ TdT-media-ted dUTP nick end labeling (TUNEL) method,and the mRNA expression levels of bcl-2,bax and Caspase-3 were detected by using reverse transcription polymerase chain reaction (RT-PCR).Results Compared with the sham group,myocardial ischemia and myocardial infarction areas were significantly increased in I/R group and I/R + CeO2 preconditioning groups.The apoptosis rate of cardiomyocytes in I/R + CeO2 (10-25 nm) group was significantly decreased (P ＜ 0.01 or P ＜ 0.05) as compared other groups except the Sham group.Compared with the I/R group,the mRNA expression level of bcl-2 was increased (P ＜0.01) and that of bax and Caspase-3 was significantly decreased (P ＜ 0.01) in the I/R + CeO2 precondi-tioning groups.Conclusion CeO2 nanoparticles can inhibit the apoptosis of myocardium induced by MIRI,probably through the mechanisms of up-regulating the expression of bcl-2 and down-regulating the expression of bax and Caspase-3.The 10-25 nm CeO2 nanoparticles show the most significant myocardial protective effect. Key words: Cerium oxide ; Myocardial ischemia; Reperfusion injury ; Apoptosis

Protective effects of cerium oxide and yttrium oxide nanoparticles on reduction of oxidative stress induced by sub-acute exposure to diazinon in the rat pancreas

Cerium oxide nanoparticles loaded nanofibrous membranes promote bone regeneration for periodontal tissue engineering

In this paper, the effects of cerium oxide nanoparticles (CeO2 NPs) on the group bacterial behaviors were elaborated. After 36-h cultivation, the biofilm biomass was enhanced by the sub-lethal concentrations of 0.5 and 2mg/L CeO2 NP exposure. Meanwhile, the promoted production of total amino acids in microbes further resulted in the increased surface hydrophobicity and percentage aggregation. To resist the CeO2 NPs stress, the biofilm exhibited a double-layer microstructure, with the protein (PRO) and living cells occupying the bottom, the polysaccharide (PS), and dead cells dominating the top. The bacterial diversity was highly suppressed and Citrobacter and Pseudomonas from the phylum of γ-Proteobacteria strongly dominated the biofilm, indicating the selective and enriched effects of CeO2 NPs on resistant bacteria. The stimulated inherent resistance of biofilm was reflected by the reduced adenosine triphosphate (ATP) content after 4h exposure. The increased levels of reactive oxygen species (ROS) in the treatments of 8h CeO2 NP exposure led to the upregulated quorum sensing signals of acylated homoserine lactone (AHL) and autoinducer 2 (AI-2), beneficial to mitigating the environmental disturbance of CeO2 NPs. These results provide evidences for the accelerating effects of CeO2 NPs on biofilm formation through oxidative stress, which expand the understanding of the ecological effects of CeO2 NPs.

The cardioprotective effects of cerium oxide nanoparticles against the poisoning generated by aluminum phosphide pesticide: Controlling oxidative stress and mitochondrial damage

Occupational heart disease have occurred continuously, making social problems, and increasing the needs for its effective prevention. As natural antioxidants, selenium (Na2SeO3) and cerium oxide (CeO2) nanoparticles, we verified the effect with suspected cardiotoxic chemicals, 1,1,1-trichloroethane (TCEtn) based on the myocardial cell line due to inflammation and oxidative DNA damage, and reliable anti-cardiotoxic effects of selenium and CeO2 nanoparticles. We measured the changes of gene expression with real-time RT-PCR, and oxidative DNA damage with Fragment Length Analysis with Restriction Enzyme (FLARE) assay in H9c2 cell line, and discuss their molecular mechanism from these data. In the result, it has anticytotoxic effect with CeO2 nanoparticles below 100 μM which the particles dispersed well. The early expression of COX2 mRNA is increased with TCEtn but decreased with Na2SeO3, CeO2 nanoparticles, has some anti-inflammatory effect. The PPARγ is much increased with all of TCEtn, Na2SeO3, CeO2 nanoparticles in 36 hour pretreat, are evaluated their activation to cytokines, transcription factors related to overcome and decrease the cardiotoxic effects of test chemical. With the oxidative DNA damage, the CeO2 nanoparticles have more active anti-oxidative effect to selenium.

Cerium oxide (CeO2) nanoparticles (CeNPs) are potent antioxidants that are being explored as potential therapies for diseases in which oxidative stress plays an important pathological role. However, both beneficial and toxic effects of CeNPs have been reported, and the method of synthesis as well as physico-chemical, biological, and environmental factors can impact the ultimate biological effects of CeNPs. In the present study, we explored the effect of different ratios of citric acid (CA) and EDTA (CA/EDTA), which are used as stabilizers during synthesis of CeNPs, on the antioxidant enzyme-mimetic and biological activity of the CeNPs. We separated the CeNPs into supernatant and pellet fractions and used commercially available enzymatic assays to measure the catalase-, superoxide dismutase (SOD)-, and oxidase-mimetic activity of each fraction. We tested the effects of these CeNPs in a mouse hippocampal brain slice model of ischemia to induce oxidative stress where the fluorescence indicator SYTOX green was used to assess cell death. Our results demonstrate that CeNPs stabilized with various ratios of CA/EDTA display different enzyme-mimetic activities. CeNPs with intermediate CA/EDTA stabilization ratios demonstrated greater neuroprotection in ischemic mouse brain slices, and the neuroprotective activity resides in the pellet fraction of the CeNPs. The neuroprotective effects of CeNPs stabilized with equal proportions of CA/EDTA (50/50) were also demonstrated in two other models of ischemia/reperfusion in mice and rats. Thus, CeNPs merit further development as a neuroprotective therapy for use in diseases associated with oxidative stress in the nervous system.

Cerium oxide nanoparticles (CeO2 NPs) are redox-active nanomaterials with promising applications in biomedical engineering. In this study, CeO2 NPs are functionalized with riboflavin to enhance cellular uptake and introduce photoresponsive properties. In vitro studies demonstrate that the resulting riboflavin-modified CeO2 (Rf-CeO2) NPs exhibit low toxicity under dark conditions but exert significantly enhanced cytotoxicity against triple-negative breast cancer (TNBC) MDA-MB-231 cells upon ultraviolet (UV) irradiation. This light-triggered cytotoxic effect is attributed to the photoactive nature of riboflavin, which alters reactive oxygen species (ROS) generation upon UV exposure. Our findings highlight the potential of Rf-CeO2 NPs as a selectively light-activated nanoplatform for targeted cancer therapy that integrates redox functionality and photoactivity into a single engineered nanomaterial, particularly for TNBC and other aggressive cancer subtypes.