ABSTRACT
Cerium oxide nanoparticles (nanoceria) have recyclable antioxidative activity. It has numerous potential applications in biomedical engineering, such as mitigating damage from burns, radiation, and bacterial infection. This mitigating activity is analogous to that property of metabolic enzymes such as superoxide dismutase (SOD) and catalase - scavengers of reactive oxygen species (ROS). Therefore, nanoceria can protect cells from environmental oxidative stress. This therapeutic effect prompted studies of nanoceria and metabolic enzymes as a combination therapy. The activity and structure of SOD, catalase, and lysozyme were examined in the presence of nanoceria. A complementary relationship between SOD and nanoceria motivated the present work, in which we explored a method for simultaneous delivery of SOD and nanoceria. The biocompatibility and tunable degradation of poly(lactic-co-glycolic acid) (PLGA) made it a candidate material for encapsulating both nanoceria and SOD. Cellular uptake studies were conducted along with a cytotoxicity assay. The antioxidative properties of PLGA-nanoceria-SOD particles were verified by adding H2O2 to cell culture and imaging with fluorescent markers of oxidative stress. Our results suggest that PLGA is a suitable encapsulating carrier for simultaneous delivering nanoceria and SOD together, and that this combination effectively reduces oxidative stress in vitro.
Subject(s)
Cerium , Nanoparticles , Antioxidants , Catalase , Hydrogen Peroxide , Oxidative Stress , Reactive Oxygen Species , Superoxide Dismutase/metabolismABSTRACT
Photochromic tungsten oxide (WO3) nanoparticles stabilized by polyvinylpyrrolidone (PVP) were synthesized to evaluate their potential for biomedical applications. PVP-stabilized tungsten oxide nanoparticles demonstrated a highly selective cytotoxic effect on normal and cancer cells in vitro. WO3 nanoparticles were found to induce substantial cell death in osteosarcoma cells (MNNG/HOS cell line) with a half-maximal inhibitory concentration (IC50) of 5 mg/mL, while producing no, or only minor, toxicity in healthy human mesenchymal stem cells (hMSc). WO3 nanoparticles induced intracellular oxidative stress, which led to apoptosis type cell death. The selective anti-cancer effects of WO3 nanoparticles are due to the pH sensitivity of tungsten oxide and its capability of reactive oxygen species (ROS) generation, which is expressed in the modulation of genes involved in reactive oxygen species metabolism, mitochondrial dysfunction, and apoptosis.
Subject(s)
Antineoplastic Agents/pharmacology , Metal Nanoparticles/chemistry , Neoplasms/drug therapy , Oxides/chemistry , Povidone/pharmacology , Tungsten/chemistry , Apoptosis/drug effects , Biocompatible Materials/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Cytoskeleton/metabolism , Drug Screening Assays, Antitumor , Humans , Hydrogen-Ion Concentration , Inhibitory Concentration 50 , Mesenchymal Stem Cells/drug effects , Microscopy, Electron, Transmission , Mitochondria/pathology , Nanoparticles/chemistry , Osteosarcoma/drug therapy , Oxidative Stress , Reactive Oxygen SpeciesABSTRACT
The electrorheological (ER) effect was experimentally observed in dielectric suspensions containing tungsten oxide (WO3) modified with surfactant molecules (sodium dodecyl sulfate (SDS) and dodecylamine (DDA)) in electric fields up to several kilovolts per millimeter. The dielectric properties of WO3 suspensions in silicone oil were analyzed, depending on the frequency of the electric field, in the range from 25 to 106 Hz. Unmodified WO3 suspensions, as well as suspensions modified with sodium dodecyl sulfate, were shown to exhibit a positive electrorheological effect, whereas suspensions modified with dodecylamine demonstrated a negative electrorheological effect. The quantitative characteristics of the negative electrorheological effect in the strain-compression and shear regimes were obtained for the first time. Visualization experiments were performed to see the chain structures formed by WO3 particles modified with sodium dodecyl sulfate, as well as for dynamic electroconvection in electrorheological fluids containing WO3 modified with dodecylamine. The negative electrorheological effect was shown to be associated with the processes of phase separation in the electric field, which led to a multiplicative effect and a strong electroconvection of the suspension at field strengths above 1 kV/mm.
Subject(s)
Amines/chemistry , Electrochemical Techniques , Oxides/chemistry , Rheology , Sodium Dodecyl Sulfate/chemistry , Surface-Active Agents/chemistry , Tungsten/chemistry , SuspensionsABSTRACT
We report the first experimental evidence for the mitogenic action of cerium(IV) oxide and cerium(III) fluoride nanoparticles (CONs and CFNs) on the regeneration of a whole organism - freshwater flatworms Schmidtea mediterranea (planarian). Both types of cerium-containing nanoparticles are shown to be a highly potent mitogen for planaria. Both CONs and CFNs, in micro- and nanomolar concentrations, markedly accelerate planarian blastema growth, due to the enhancement of cellular proliferation, causing an increase in the mitotic index and in the quantity of blastema cells in regenerating planaria. CONs provided maximum activity at concentrations which were two orders of magnitude lower than those for CeF3. The valence state of cerium in cerium-containing nanoparticles plays a significant role in the planarian regeneration mechanism: CeO2 nanoparticles containing predominantly Ce4+ species presumably scavenge wound induced reactive oxygen species and moderately activate gene expression processes, while the regenerative action of CeF3 nanoparticles containing only Ce3+ species is manifested in the pronounced expression of the genes involved in cell division, differentiation and migration. This is the first report on the effect of cerium-containing nanoparticles on tissue regeneration in vivo, further revealing the mechanisms of their biological action, which enhances the possibility of their use in cellular technologies.
