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Diabetic wounds represent a significant healthcare burden and are characterized by impaired wound healing due to increased oxidative stress and persistent inflammation. We have shown that CNP-miR146a synthesized by the conjugation of cerium oxide nanoparticles (CNP) to microRNA (miR)-146a improves diabetic wound healing. CNP are divalent metal oxides that act as free radical scavenger, while miR146a inhibits the pro-inflammatory NFκB pathway, so CNP-miR146a has a synergistic role in modulating both oxidative stress and inflammation. In this study, we define the mechanism(s) by which CNP-miR146a improves diabetic wound healing by examining immunohistochemical and gene expression analysis of markers of inflammation, oxidative stress, fibrosis, and angiogenesis. We have found that intradermal injection of CNP-miR146a increases wound collagen, enhances angiogenesis, and lowers inflammation and oxidative stress, ultimately promoting faster closure of diabetic wounds.
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Cério , Diabetes Mellitus , MicroRNAs , Nanopartículas , Cério/química , Cério/farmacologia , Humanos , MicroRNAs/metabolismo , Nanopartículas/química , CicatrizaçãoRESUMO
Acute respiratory distress syndrome (ARDS) is a devastating pulmonary disease with significant in-hospital mortality and is the leading cause of death in COVID-19 patients. Excessive leukocyte recruitment, unregulated inflammation, and resultant fibrosis contribute to poor ARDS outcomes. Nanoparticle technology with cerium oxide nanoparticles (CNP) offers a mechanism by which unstable therapeutics such as the anti-inflammatory microRNA-146a can be locally delivered to the injured lung without systemic uptake. In this study, we evaluated the potential of the radical scavenging CNP conjugated to microRNA-146a (termed CNP-miR146a) in preventing acute lung injury (ALI) following exposure to bleomycin. We have found that intratracheal delivery of CNP-miR146a increases pulmonary levels of miR146a without systemic increases, and prevents ALI by altering leukocyte recruitment, reducing inflammation and oxidative stress, and decreasing collagen deposition, ultimately improving pulmonary biomechanics.
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Bleomicina/efeitos adversos , Cério , Sistemas de Liberação de Medicamentos , MicroRNAs , Síndrome do Desconforto Respiratório/tratamento farmacológico , Animais , Bleomicina/farmacologia , COVID-19/genética , COVID-19/metabolismo , Cério/química , Cério/farmacologia , Modelos Animais de Doenças , Masculino , Camundongos , MicroRNAs/química , MicroRNAs/farmacologia , Síndrome do Desconforto Respiratório/induzido quimicamente , Síndrome do Desconforto Respiratório/genética , Síndrome do Desconforto Respiratório/metabolismo , SARS-CoV-2/metabolismo , Tratamento Farmacológico da COVID-19RESUMO
The aim of this study was to develop a novel biodegradable magnesium (Mg) alloy for bone implant applications. We used scandium (Sc; 2 wt %) and strontium (Sr; 2 wt %) as alloying elements due to their high biocompatibility, antibacterial efficacy, osteogenesis, and protective effects against corrosion. In the present work, we also examined the effect of a heat treatment process on the properties of the Mg-Sc-Sr alloy. Alloys were manufactured using a metal casting process followed by heat treatment. The microstructure, corrosion, mechanical properties, antibacterial activity, and osteogenic activity of the alloy were assessed in vitro. The results showed that the incorporation of Sc and Sr elements controlled the corrosion, reduced the hydrogen generation, and enhanced mechanical properties. Furthermore, alloying with Sc and Sr demonstrated a significantly enhanced antibacterial activity and decreased biofilm formation compared to control Mg. Also, culturing Mg-Sc-Sr alloy with human bone marrow-derived mesenchymal stromal cells showed a high degree of biocompatibility (>90% live cells) and a significant increase in osteoblastic differentiation in vitro shown by Alizarin red staining and alkaline phosphatase activity. Based on these results, the Mg-Sc-Sr alloy heat-treated at 400°C displayed optimal mechanical properties, corrosion rate, antibacterial efficacy, and osteoinductivity. These characteristics make the Mg-Sc-Sr alloy a promising candidate for biodegradable orthopedic implants in the fixation of bone fractures such as bone plate-screws or intramedullary nails.
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Magnésio , Osteogênese , Humanos , Magnésio/química , Ligas/química , Corrosão , Implantes Absorvíveis , Estrôncio/química , Antibacterianos , Teste de MateriaisRESUMO
Diseases affecting the retina, such as age-related macular degeneration (AMD), diabetic retinopathy, macular edema, and retinal vein occlusions, are currently treated by the intravitreal injection of drug formulations. These disease pathologies are driven by oxidative damage due to chronic high concentrations of reactive oxygen species (ROS) in the retina. Intravitreal injections often induce retinal detachment, intraocular hemorrhage, and endophthalmitis. Furthermore, the severe eye pain associated with these injections lead to patient noncompliance and treatment discontinuation. Hence, there is a critical need for the development of a noninvasive therapy that is effective for a prolonged period for treating retinal diseases. In this study, we developed a noninvasive cerium oxide nanoparticle (CNP) delivery wafer (Cerawafer) for the modulation of ROS in the retina. We fabricated Cerawafer loaded with CNP and determined its SOD-like enzyme-mimetic activity and ability to neutralize ROS generated in vitro. We demonstrated Cerawafer's ability to deliver CNP in a noninvasive fashion to the retina in healthy mouse eyes and the CNP retention in the retina for more than a week. Our studies have demonstrated the in vivo efficacy of the Cerawafer to modulate ROS and associated down-regulation of VEGF expression in the retinas of very-low-density lipoprotein receptor knockout (vldlr-/-) mouse model. The development of a Cerawafer nanotherapeutic will fulfill a hitherto unmet need. Currently, there is no such therapeutic available, and the development of a Cerawafer nanotherapeutic will be a major advancement in the treatment of retinal diseases.
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Nanopartículas , Doenças Retinianas , Camundongos , Animais , Espécies Reativas de Oxigênio/metabolismo , Retina , Estresse Oxidativo , Nanopartículas/uso terapêutico , Doenças Retinianas/metabolismoRESUMO
Many studies have linked reactive oxygen species (ROS) to various diseases. Biomedical research has therefore sought a way to control and regulate ROS produced in biological systems. In recent years, cerium oxide nanoparticles (nanoceria, CNPs) have been pursued due to their ability to act as regenerative ROS scavengers. In particular, they are shown to have either superoxide dismutase (SOD) or catalase mimetic (CAT) potential depending on the ratio of Ce3+/Ce4+ valence states. Moreover, it has been demonstrated that SOD mimetic activity can be diminished by the presence of phosphate, which can be a problem given that many biological systems operate in a phosphate-rich environment. Herein, we report a CNP formulation with both SOD and catalase mimetic activity that is preserved in a phosphate-rich media. Characterization demonstrated a highly dispersed, stable solution of uniform-sized, spherical-elliptical shaped CNP of 12 ± 2 nm, as determined through dynamic light scattering, zeta potential, and transmission electron microscopy. Mixed valence states of Ce ions were observed via UV/Visible spectroscopy and XPS (Ce3+/Ce4+ > 1) (Ce3+â¼ 62%). X-ray diffraction and XPS confirmed the presence of oxygen-deficient cerium oxide (CeO2-x) particles. Finally, the CNP demonstrated very good biocompatibility and efficient reduction of hydrogen peroxide under in-vitro conditions.
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Antioxidantes/química , Antioxidantes/farmacologia , Cério/química , Cério/farmacologia , Nanoestruturas/química , Animais , Catalase , Linhagem Celular , Humanos , Peróxido de Hidrogênio/química , Íons , Teste de Materiais , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Fosfatos , Espécies Reativas de Oxigênio , Superóxido DismutaseRESUMO
The presence of excess fluoride (F- > 1.5 mg/L) in drinking water affects more than 260 million people globally and leads to dental and skeletal fluorosis among other health problems. This study investigated fluoride removal by graphene oxide-ceria nanohybrid (GO-CeO2) and elucidated the mechanisms involved. The nanohybrid exhibited ultra-rapid kinetics for fluoride removal and the equilibrium (85% removal, 10 mg F-/L initial concentration) was achieved within 1 min which is one of the fastest kinetics for fluoride removal reported so far. Fluoride removal by the nanohybrid followed Langmuir isotherm with a maximum adsorption capacity of 8.61 mg/g at pH 6.5 and that increased to 16.07 mg/g when the pH was lowered to 4.0. Based on the experimental results and characterization data, we have postulated that both electrostatic interaction and surface complexation participated in the fluoride removal process. The O2- ions present in the CeO2 lattice were replaced by F- ions to make a coordination compound (complex). While both Ce4+ and Ce3+ were present in ceria nanoparticles (CeO2 NPs), Ce3+ participated in fluoride complexation. During fluoride removal by GO-CeO2, the GO sheets acted as electron mediators and help to reduce Ce4+ to Ce3+ at the CeO2 NPs-GO interface, and the additional Ce3+ enhanced fluoride removal by the nanohybrid.
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Água Potável , Nanopartículas , Poluentes Químicos da Água , Purificação da Água , Adsorção , Fluoretos , Humanos , Concentração de Íons de Hidrogênio , Cinética , Poluentes Químicos da Água/análiseRESUMO
Herceptin-resistant tumor relapse remains a major clinical issue responsible for the poor prognosis of HER2+ breast cancer. Understanding the underlying mechanisms and finding a therapeutic solution are of paramount urgency to improve the patient management. Here we report that anticancer redox active cerium oxide nanoparticles (CONPs) can potently sensitize the cancer cells to the cytotoxicity of Herceptin. By comparing between Herceptin-sensitive and Herceptin-resistant human breast cancer cell lines under normoxic as well as hypoxic culture conditions, we found that in the presence of CONPs, Herceptin can kill the Herceptin-resistant cells equally effectively as it kills the Herceptin-sensitive cells under the hypoxic, but not normoxic, culture conditions by inhibiting the cell viability, survival and proliferation. Signaling analysis reveals that under the normoxic conditions, the levels of hypoxia induced factor 1α as well as vascular endothelial growth factor are higher in the Herceptin-resistant cells than that in the Herceptin-sensitive cells and are strongly induced once the culture is switched to the hypoxic conditions, which can be potently suppressed by CONPs. Treatment with CONPs plus Herceptin significantly slows down the primary tumor growth and lung metastasis of the Herceptin-resistant cells in a xenograft mouse model of orthotopic breast cancer through inhibiting the cell proliferation and survival as well as tumor angiogenesis. These results shed new lights on the mechanisms underlying the Herceptin resistance of the HER2+ breast cancer and provide insights into introducing CONPs-like agents to Herceptin-based therapy to improve treatment outcomes.
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HYPOTHESIS: Broad-spectrum antimicrobials are needed to mitigate the complicated nature of antibiotic-resistant infections. It is imperative to formulate new antimicrobials by combining agents with different mechanisms and broader microbial targets. A combined antimicrobial solution could be a highly critical step towards developing a strategy to prevent polymicrobial infections. Herein, we have investigated the interaction and antimicrobial potential of a solution that contains cerium oxide nanoparticles (CNP) and a nitric oxide (NO) donor, S-nitroso-N-acetylpenicillamine (SNAP). It is hypothesized that these two agents induce synergistic effects and would provide broad antimicrobial effects since CNP is known to be an effective antifungal agent while NO released by SNAP is known to be a potent bactericidal agent. EXPERIMENTS: Different concentrations of SNAP and CNP were combined in a solution and tested for colloidal stability, NO release, mammalian cell cytotoxicity, and antimicrobial efficacy against Staphylococcus aureus, Escherichia coli, and Candida albicans, accounting for Gram-positive bacteria, Gram-negative bacteria, and fungi, respectively. FINDINGS: SNAP and CNP combined in equimolar solution of 3 mM were found to be highly virulent for all microbes tested compared to higher amounts of the treatments required individually. These results hold a promising outlook toward the development of broad-spectrum antimicrobial coatings and films with the potential to prevent polymicrobial infections and further enhance biomedical device usage and applications.
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Anti-Infecciosos , Nanopartículas , Animais , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Cério , Testes de Sensibilidade Microbiana , Óxido Nítrico , Doadores de Óxido Nítrico/farmacologiaRESUMO
Iron (Fe)-based adsorbents have been promoted for aqueous arsenic adsorption because of their low cost and potential ease of scale-up in production. However, their field application is, so far, limited because of their low Fe use efficiency (i.e., not all available Fe is used), slow adsorption kinetics, and low adsorption capacity. In this study, we synthesized graphene oxide iron nanohybrid (GFeN) by decorating iron/iron oxide (Fe/FexOy) core-shell structured iron nanoparticles (FeNPs) on the surface of graphene oxide (GO) via a sol-gel process. The deposition of FeNPs on GO for the nanohybrid (GFeN) improves Fe use efficiency and arsenic mobility in the nanohybrid, thereby improving the arsenic removal capacity and kinetics. We achieved removal capacities of 306 mg/g for As(III) and 431 mg/g for As(V) using GFeN. Rapid reduction (>99% in <10 min) of As(III) and As(V) (initial concentration, C0 = 100 µg/L) was achieved with the nanohybrid (250 mg/L). There were no significant interferences by the coexisting anions and organic matters at environmentally relevant concentrations. Based on the experimental data, we have proposed that both electrostatic interaction and surface complexation contributed to ultra-high arsenic removal by GFeN. The GO sheets acted as the reservoirs for the electrons released during surface corrosion of the FeNPs and the electrons were transferred back to the FeNPs to rejuvenate the oxidized surface. The rejuvenated FeNP surface layer helped in additional arsenic removal.
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Arsênio/química , Poluentes Químicos da Água/química , Adsorção , Ânions , Arsênio/análise , Compostos Férricos/química , Grafite/química , Concentração de Íons de Hidrogênio , Ferro , Cinética , Nanopartículas , Oxirredução , Água , Poluentes Químicos da Água/análise , Purificação da Água/métodosRESUMO
Nanocrystalline cerium oxide (nanoceria) is a rare earth oxide with a complex surface chemistry. This material has seen substantial investigation in recent years in both fundamental and applied studies due largely to more precise characterization of the unique surface structures, which mediate its pronounced redox activity. In particular, oxygen storage/buffering capacities have been thoroughly correlated with synthesis and processing condition effects on other material features such as surface (micro-) faceting, reconstruction, and (extent of) hydration. Key material features such as these modulate nanoceria redox performance by changing the crystal microenvironment. In this review, we present nanoengineering methods, which have produced increased nanoceria performance in biomedical, energy, and catalysis applications. The impact of combined/cooperative theoretical and experimental studies are highlighted throughout.
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Exposure to ultraviolet radiation is a major contributor to premature skin aging and carcinogenesis, which is mainly driven by overproduction of reactive oxygen species (ROS). There is growing interest for research on new strategies that address photoaging prevention, such as the use of nanomaterials. Cerium oxide nanoparticles (nanoceria) show enzyme-like activity in scavenging ROS. Herein, our goal was to study whether under ultraviolet A rays (UVA)-induced oxidative redox imbalance, a low dose of nanoceria induces protective effects on cell survival, migration, and proliferation. Fibroblasts cells (L929) were pretreated with nanoceria (100 nM) and exposed to UVA radiation. Pretreatment of cells with nanoceria showed negligible cytotoxicity and protected cells from UVA-induced death. Nanoceria also inhibited ROS production immediately after irradiation and for up to 48 h and restored the superoxide dismutase (SOD) activity and GSH level. Additionally, the nanoceria pretreatment prevented apoptosis by decreasing Caspase 3/7 levels and the loss of mitochondrial membrane potential. Nanoceria significantly improved the cell survival migration and increased proliferation, over a 5 days period, as compared with UVA-irradiated cells, in wound healing assay. Furthermore, it was observed that nanoceria decreased cellular aging and ERK 1/2 phosphorylation. Our study suggests that nanoceria might be a potential ally to endogenous, antioxidant enzymes, and enhancing the redox potentials to fight against UVA-induced photodamage and consequently modulating the cells survival, migration, and proliferation.
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The Ultraviolet-B radiation (UVB) might induce cellular redox imbalance which plays an important role in the development of skin disorders. Thus, the search for photochemoprotective alternatives with antioxidant efficacy would be a safe aspect towards prevention of skin diseases. Cerium oxide nanoparticles (CNPs) have antioxidant properties, that are mostly related to CNPs catalase and superoxide dismutase (SOD)-like antioxidative mimetic activity. Considering that, we investigated whether CNPs induce photochemoprotection against UVB-induced cellular damages on L929 fibroblasts. Our results showed that CNPs prevented UVB mediated L929 cell oxidative damage by reestablishing the oxidative balance through ameliorating the reactive oxygen species (ROS) level and enhancing the antioxidant enzyme activities.
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Antioxidantes/farmacologia , Cério/farmacologia , Fibroblastos/efeitos dos fármacos , Nanopartículas/química , Substâncias Protetoras/farmacologia , Raios Ultravioleta , Antioxidantes/química , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cério/química , Humanos , Tamanho da Partícula , Processos Fotoquímicos , Substâncias Protetoras/química , Propriedades de Superfície , Cicatrização/efeitos dos fármacosRESUMO
Diabetes mellitus is a metabolic disorder associated with properties and an increased risk of chronic wounds due to sustained pro-inflammatory response. We have previously of radical scavenging cerium oxide nanoparticles (CNP) conjugated to the anti-inflammatory microRNA (miR)-146a, termed CNP-miR146a, improves diabetic wound healing by synergistically lowering oxidative stress and inflammation, and we sought to evaluate this treatment in a topical application. Silk fibroin is a biocompatible polymer that can be fabricated into nanostructures, termed nanosilk. Nanosilk is characterized by a high strength-to-density ratio and an ability to exhibit strain hardening. We therefore hypothesized that nanosilk would strengthen the biomechanical properties of diabetic skin and that nanosilk solution could effectively deliver CNP-miR146a to improve diabetic wound healing. The ability of nanosilk to deliver CNP-miR146a to murine diabetic wounds and improve healing was assessed by the rate of wound closure and inflammatory gene expression, as well as histologic analysis. The effect of nanosilk on the properties of human diabetic skin was evaluated by testing the biomechanical properties following topical application of a 7% nanosilk solution. Diabetic murine wounds treated with topical nanosilk and CNP-miR146a healed by day 14.5 compared to day 16.8 in controls (p = 0.0321). Wounds treated with CNP-miR146a had higher collagen levels than controls (p = 0.0126) with higher pro-fibrotic gene expression of TGFß-1 (p = 0.0092), Col3α1 (p = 0.0369), and Col1α2 (p = 0.0454). Treatment with CNP-miR146a lowered pro-inflammatory gene expression of IL-6 (p = 0.0488) and IL-8 (p = 0.0009). Treatment of human diabetic skin with 7% nanosilk solution resulted in significant improvement in maximum load and modulus (p < 0.05). Nanosilk solution is able to strengthen the biomechanical properties of diabetic skin and can successfully deliver CNP-miR146a to improve diabetic wound healing through inhibition of pro-inflammatory gene signaling and promotion of pro-fibrotic processes.
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Cério/administração & dosagem , Diabetes Mellitus Experimental/tratamento farmacológico , MicroRNAs/administração & dosagem , Nanopartículas/administração & dosagem , Seda/administração & dosagem , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Fenômenos Biomecânicos , Cério/química , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , MicroRNAs/química , Nanopartículas/química , Seda/química , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologiaRESUMO
Diabetics are prone to chronic wounds that have slower healing, and methods of accelerating the wound closure and to ensure protection from infections are critically needed. MicroRNA-146a gets dysregulated in diabetic wounds and injection of this microRNA combined with reactive oxygen species-scavenging cerium oxide nanoparticles (CNPs) can reduce inflammation and improve wound healing; however, a better delivery method than intradermal injections is needed. Here we demonstrate a biomaterial system of zwitterionic cryogels (gels formed below freezing temperatures) laden with CNP-miR146a that are topically applicable, injectable, self-healable, and provide sustained release of the therapeutic molecules. These cryogels are comprised of CBMA or SBMA and HEMA, and do not contain chemical crosslinkers. Properties of the gels can be manipulated by changing monomer type and ratio. These materials have demonstrated efficacy and viability in vivo with a diabetic mouse wound healing model. Overall, these materials have a high potential for application in wound treatments due to their ease of production, antifouling characteristics, durability, topical application, and sustained release mechanics. STATEMENT OF SIGNIFICANCE: This work presents the development of zwitterionic cryogels with unique physical properties including injectability and self-healing, that also offer highly sustained release of nanoparticles over time to improve wound healing in a diabetic mouse model. The nanoparticles are made of cerium oxide, which is known to scavenge reactive oxygen species and reduce oxidative stress, and these particles have been further tagged with a microRNA146a that has been shown to reduce inflammation. Zwitterionic materials are known for their superior antifouling properties and good biocompatibility and ability to incorporate bioactive factors. Given these properties, the use of these materials as wound healing dressings would be exciting, yet to date it has been difficult to prolong the release of bioactive factors from them due to their hydrophilicity. Previously we developed zwitterionic cyrogels with very sustained protein release over time, but those materials were quite brittle and difficult to handle. Here, we demonstrate for the first time that by removing the crosslinker molecule from our reaction and polymerizing gels under cryo-conditions, we are able to form zwitterionic cryogels that are injectable, self-healing, and with sustained release profiles. The sustained release of miRNA146a-tagged cerium oxide nanoparticles from these gels is demonstrated to speed up diabetic wound healing time and significantly reduce inflammation.
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Cério , Criogéis , Diabetes Mellitus Experimental , Angiopatias Diabéticas , MicroRNAs , Nanopartículas , Cicatrização/efeitos dos fármacos , Animais , Cério/química , Cério/farmacologia , Criogéis/química , Criogéis/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Angiopatias Diabéticas/tratamento farmacológico , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/patologia , Feminino , Camundongos , MicroRNAs/química , MicroRNAs/farmacologia , Nanopartículas/química , Nanopartículas/uso terapêuticoRESUMO
Wound healing is of major clinical concern and is constantly being explored for early restoration and enhanced recovery. While the etiology of the wound healing is multifactorial, high inflammation and increased oxidative stress which results in chronic inflammation, endothelial dysfunction and collagen degradation, delay the overall healing process. Thus, visual sensing of the oxidative stress would be highly informative in the successful implementation of wound healing therapies based on specific requirements. In this study, electrospinning was used to fabricate silk fibroin nanofibrous mats infused with Amplex red capable of detecting hydrogen peroxide, a reactive oxygen molecule. These mats produced a visible change in color with the limit of detection at 1 µM H2O2 concentration. In vivo studies carried out in diabetic mice with impaired wounds also displayed a visible change in color of the mats infused with Amplex red within 24 hours. These electrospun silk fibroin nanofibrous Amplex infused mats has the potential to enable a futuristic platform where decisions can be made for enhanced wound healing therapy.
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Diabetes Mellitus Experimental , Fibroínas , Nanofibras , Animais , Peróxido de Hidrogênio , Camundongos , Estresse Oxidativo , SedaRESUMO
Herein, we provide the first account of a method to control cerium oxide's mixed valence states (as Ce3+ to Ce4+ ratio) in ultra-thin films formed via atomic layer deposition (ALD). It is determined that modulation of Ce3+/Ce4+ ratio occurs with respect to film thickness and is analogous to the change in surface chemistry observed for cerium oxide nanoparticles with varying particle diameter. The influence of film thickness on enzyme-mimetic radical scavenging is also characterized. Higher film thicknesses show 9-fold increase in catalytic activity. In vitro biocompatibility (apoptosis < 4%) and electrochemical biosensing (lowest concentration: 18 ppt) studies were performed to demonstrate the potential of ALD-grown nanoceria films for biomedical applications.
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Antioxidantes/química , Antioxidantes/farmacologia , Cério/química , Cério/farmacologia , Nanopartículas/química , Nanotecnologia , Antioxidantes/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular , Cério/toxicidade , Humanos , Peróxido de Hidrogênio/análise , Tamanho da PartículaRESUMO
Correction for 'Antioxidant properties of ALD grown nanoceria films with tunable valency' by Ankur Gupta et al., Biomater. Sci., 2019, DOI: 10.1039/c9bm00397e.
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Nanoceria, typically used for "clean-air" catalytic converter technologies because of its ability to capture, store, and release oxygen, is the same material that has the potential to be used in nanomedicine. Specifically, nanoceria can be used to control oxygen content in cellular environments; as a "nanozyme", nanoceria mimics enzymes by acting as an antioxidant agent. The computational design procedures for predicting active materials for catalytic converters can therefore be used to design active ceria nanozymes. Crucially, the ceria nanomedicine is not a molecule; rather, it is a crystal and exploits its unique crystal properties. Here, we use ab initio and classical computer modeling, together with the experiment, to design structures for nanoceria that maximize its nanozymetic activity. We predict that the optimum nanoparticle shape is either a (truncated) polyhedral or a nanocube to expose (active) CeO2{100} surfaces. It should also contain oxygen vacancies and surface hydroxyl species. We also show that the surface structures strongly affect the biological activity of nanoceria. Analogous to catalyst poisoning, phosphorus "poisoning", the interaction of nanoceria with phosphate, a common bodily electrolyte, emanates from phosphate ions binding strongly to CeO2{100} surfaces, inhibiting oxygen capture and release and hence its ability to act as a nanozyme. Conversely, the phosphate interaction with {111} surfaces is weak, and therefore, these surfaces protect the nanozyme against poisoning. The atom-level understanding presented here also illuminates catalytic processes and poisoning in "clean-air" or fuel-cell technologies because the mechanism underpinning and exploited in each technology, oxygen capture, storage, and release, is identical.
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The authors investigated the role of different size and morphology of cerium oxide nanoparticles (CNPs) in cellular uptake and internalization at the nano-bio interface. Atomic force microscopy (AFM) has been utilized to record changes in the membrane elasticity as a function of ceria particle morphology and concentration. Young's Modulus was estimated in presence and absence of CNPs of different sizes by gauging the membrane elasticity of CCL30 (squamous cell carcinoma) cells. Significant change in Young's Modulus was observed for CNP treatments at higher concentrations, while minimum membrane disruption was observed at lower concentrations. Studies using blocking agents specific to energy-dependent cellular internalization pathways indicated passive cellular uptake for smaller CNPs (3-5 nm). Other observations showed that larger CNPs were unable to permeate the cell membrane, which indicates an active uptake mechanism by the cell membrane. The ability of smaller CNPs (3-5 nm) to permeate the cell membrane without energy consumption by uptake pathways suggests potential for use as nanovectors for the delivery of bioactive molecules. Specifically, the passive uptake mechanism allows for the delivery of surface-bound molecules directly to the cytoplasm, avoiding the extreme chemical conditions of endosomal pathways.
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Membrana Celular/metabolismo , Cério , Portadores de Fármacos , Nanopartículas/química , Linhagem Celular Tumoral , Cério/farmacocinética , Cério/farmacologia , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Humanos , Tamanho da PartículaRESUMO
Arsenic contamination has posed a health risk to millions of people around the world. In this study, we describe a simple and facile one-step hydrothermal synthesis of a ceria-graphene oxide (ceria-GO) composite for the efficient removal of arsenic species. The prepared ceria-GO composite materials exhibited almost complete (over 99.99%) and quick removal of both arsenic species within 0.1 mg L-1 of the initial concentration. The calculated adsorption capacities were 185 mg g-1 for As(iii) and 212 mg g-1 for As(v). It was found that Ce3+ is an active site and continuously adsorbs arsenic species; there is a concomitant change from Ce4+ to Ce3+ due to the solution redox environment. This increase in the Ce3+ concentration further facilitates the complete removal of arsenic species in solution. Thus our approach offers a promising potential for the treatment of arsenic-contaminated drinking water.