Activity Of Nanoceria Research Articles

Unveiling the mechanism of superior phosphatase-like activity of nanoceria supported on titania nanotubes for accelerating biomineralization

Implant surface immobilization of alkaline phosphatase aims at utilization of biomineralization-enhancing functions at the implant-bone interface. Nanoceria (NC) with phosphatase-mimetic activity shows potential for accelerating biomineralization. However, the strong adsorption of phosphate ions on NC in physiological environments severely limits its catalytic performance. In this work, titania nanotube supported NC (TNT-NC) retained phosphatase-mimetic activities in phosphate-buffered saline compared with Ti supported NC. Moreover, Ce3+-rich TNT-NC1 possessed higher activity than Ce4+-rich TNT-NC2. More importantly, NC supported on TNT exhibited Ce3+- and pH-dependent catalytic performance and achieved greater phosphatase-mimetic activity when increasing the nucleophile attack of surface hydroxyl species formed from cofeeding water. Consistent with the results of phosphatase-mimetic activity, TNT-NC1 showed the best effect on enhancing osteoblast mineralization as evidenced by alizarin red staining results. Thus, this study presents the mechanism of superior phosphatase-like activity of NC supported on TNT for the design of advanced implant surface with biomineralization-enhancing properties.

The preparation temperature influences the physicochemical nature and activity of nanoceria.

Cerium oxide nanoparticles, so-called nanoceria, are engineered nanomaterials prepared by many methods that result in products with varying physicochemical properties and applications. Those used industrially are often calcined, an example is NM-212. Other nanoceria have beneficial pharmaceutical properties and are often prepared by solvothermal synthesis. Solvothermally synthesized nanoceria dissolve in acidic environments, accelerated by carboxylic acids. NM-212 dissolution has been reported to be minimal. To gain insight into the role of high-temperature exposure on nanoceria dissolution, product susceptibility to carboxylic acid-accelerated dissolution, and its effect on biological and catalytic properties of nanoceria, the dissolution of NM-212, a solvothermally synthesized nanoceria material, and a calcined form of the solvothermally synthesized nanoceria material (ca. 40, 4, and 40 nm diameter, respectively) was investigated. Two dissolution methods were employed. Dissolution of NM-212 and the calcined nanoceria was much slower than that of the non-calcined form. The decreased solubility was attributed to an increased amount of surface Ce4+ species induced by the high temperature. Carboxylic acids doubled the very low dissolution rate of NM-212. Nanoceria dissolution releases Ce3+ ions, which, with phosphate, form insoluble cerium phosphate in vivo. The addition of immobilized phosphates did not accelerate nanoceria dissolution, suggesting that the Ce3+ ion release during nanoceria dissolution was phosphate-independent. Smaller particles resulting from partial nanoceria dissolution led to less cellular protein carbonyl formation, attributed to an increased amount of surface Ce3+ species. Surface reactivity was greater for the solvothermally synthesized nanoceria, which had more Ce3+ species at the surface. The results show that temperature treatment of nanoceria can produce significant differences in solubility and surface cerium valence, which affect the biological and catalytic properties of nanoceria.

Therapeutic Efficacy of Lactonic Sophorolipids: Nanoceria-Assisted Combination Therapy of NSCLC using HDAC and Hsp90 Inhibitors.

Purpose: Non-Small-Cell Lung Cancer (NSCLC) has gained resistance to common chemo- and radiotherapy due to the oncogenic K-RAS mutations. In this work, lactonic sophorolipids (LSL), a constituent of natural sophorolipids known to inhibit histone deacetylase (HDAC) activity, is used to evaluate its potential anticancer property for the treatment of NSCLC. In addition, ganetespib (GT), a Hsp90 inhibitor, is used for its known antitumor activity in several K-RAS mutant NSCLC cells. We propose, a functional anti-oxidant nanomedicine composed of nanoceria (NC) encapsulated with two-drug cocktail LSL and GT for the assessment of therapeutic efficacy of LSL and targeted combination therapy of NSCLC. NC is an excellent redox platform specifically used to supplement the therapeutic potency of these drugs to target both HDAC inhibition and Hsp90 signaling pathways in NSCLC.Methods: Polyacrylic acid-coated nanoceria (PNC) was formulated and folic acid was conjugated on the surface of PNC using “click” chemistry to target NSCLC and to minimize adverse side effects. Solvent diffusion method was used for the encapsulation of individual drugs and co-encapsulation of drug-cocktail along with an optical dye DiI for diagnosis. We hypothesized that the therapeutic efficacy of LSL will be synergistically accelerated by the inhibition of Hsp90 mechanism of GT and redox activity of NC.Results: For the targeted therapy of NSCLC, A549 cells were used and Chinese hamster ovary (CHO) cells were used as healthy control cells. Results showed more than 40% cells were dead within 24 h when treated with LSL nanodrug. When combined with GT, enhanced ROS signals were detected and more than 80% reduction in cell viability was recorded within 24 h of incubation. Treatments with NC without any drug showed minimal toxicity. Migration assays indicate that the highly metastatic nature of NSCLC is successfully restricted by this combination approach. To validate the effectiveness of this combination therapy various cell-based assays including detection of apoptosis, necrosis and HDAC inhibition of LSL were performed.Conclusion: Functional nanoceria with drug-cocktail LSL and GT is successfully developed for the targeted treatment of undruggable NSCLC. The fluorescence modality helps monitoring the drugs delivery. Results demonstrate the potential therapeutic efficacy of LSL, which is synergistically accelerated by the Hsp90 inhibition mechanism of GT and redox activity of NC.

Promotion and Inhibition of the Oxidase‐Mimicking Activity of Nanoceria by Phosphate, Polyphosphate, and DNA

Nanoceria (CeO2 nanoparticles) is an extensively studied nanozyme with interesting oxidase-mimicking activity. As they can work in the absence of toxic and unstable H2 O2 , CeO2 nanoparticles have been widely used in biosensing. CeO2 nanoparticles often encounter phosphate-containing molecules that can affect their catalytic activity, and various reports exist in the literature showing both promoted and inhibited activity. In this work, we systematically studied five types of phosphate: orthophosphate, pyrophosphate, triphosphate, trimetaphosphate, and a polyphosphate with 25 phosphate units (Pi25 ). In addition, DNA oligonucleotides of various length and sequence. DNA was included as they contain a phosphate backbone that can strongly adsorb on nanoceria. We observed that a high concentration of DNA in acetate buffer inhibited activity, whereas a low concentration of DNA in phosphate buffer increased activity. The change of activity was also related to the type of substrate and related to the aggregation of CeO2 . These discoveries provide an important understanding for the further use of CeO2 nanoparticles in biosensor development, materials science, and nanotechnology.

Evaluation of the oxidase like activity of nanoceria and its application in colorimetric assays

Nanomaterial-based enzyme mimics have attracted considerable interest in chemical analysis as alternative catalysts to natural enzymes. However, the conditions in which such particles can replace biological catalysts and their selectivity and reactivity profiles are not well defined. This work explored the oxidase like properties of nanoceria particles in the development of colorimetric assays for the detection of dopamine and catechol. Selectivity of the system with respect to several phenolic compounds, the effect of interferences and real sample analysis are discussed. The conditions of use such as buffer composition, selectivity, pH, reaction time and particle type are defined. Detection limits of 1.5 and 0.2μM were obtained with nanoceria for dopamine and catechol. The same assay could be used as a general sensing platform for the detection of other phenolics. However, the sensitivity of the method varies significantly with the particle type, buffer composition, pH and with the structure of the phenolic compound. The results demonstrate that nanoceria particles can be used for the development of cost effective and sensitive methods for the detection of these compounds. However, the selection of the particle system and experimental conditions is critical for achieving high sensitivity. Recommendations are provided on the selection of the particle system and reaction conditions to maximize the oxidase like activity of nanoceria.

Production of cerium-141 using ceria and nanoceria powder: a potential radioisotope for simultaneous therapeutic and diagnostic applications

Cerium-141 [T 1/2 = 32.5 days, β 1 = 580.4 keV (30 %), β 2 = 435.0 keV (70 %), γ = 145.4 keV (48 %)], has been introduced as a radionuclide for therapy while can be used in diagnosis as well. In this study, nuclear model calculation on 141Ce production was investigated via the 140Ce(d,p)141Ce, 142Ce(d,dn)141Ce, 141Pr(n,p)141Ce, and 140Ce(n,γ)141Ce nuclear reactions. 140Ce was irradiated by thermal neutron at the Tehran Research Reactor according to the 140Ce(n,γ)141Ce reaction. In addition, the obtained activity of the produced 141Ce was compared with the theoretical calculations. The results showed that the end of bombardment activities of 141Ce is 631.64 MBq theoretically and 611.60 MBq experimentally for ceria powder. The activities of similar samples of ceria (CeO2) powder in two forms of nano-particles (nanoceria) and bulk were compared after bombardment by thermal neutrons. The results showed that activities of nanoceria were less than the bulk form of ceria.

Nucleoside Triphosphates as Promoters to Enhance Nanoceria Enzyme‐like Activity and for Single‐Nucleotide Polymorphism Typing

Nucleoside triphosphates (NTPs) can improve the oxidase‐like activity of nanoceria and the enhancement is correlated with the type of NTP. This effect is demonstrated to be as a result of the coupling of the oxidative reaction with the NTP hydrolysis reactions, as the nanoceria has both oxidase‐like and phosphatase‐like activities. The differences reflect the different dephosphorylation catalytic activities of nanoceria to the NTP used. Furthermore, based on the NTP‐promoted oxidase‐like activity of nanoceria and the differences among the different types of NTPs, series effective and high‐throughput colorimetric assays for single‐nucleotide polymorphism (SNP) typing are developed.