Publications by authors named "Sudipta Seal"

130 Publications

Cerium oxide nanoparticles protect against irradiation-induced cellular damage while augmenting osteogenesis.

Mater Sci Eng C Mater Biol Appl 2021 Jul 29;126:112145. Epub 2021 Apr 29.

Biionix Cluster, Department of Internal Medicine, College of Medicine, University of Central Florida, Orlando, FL, United States. Electronic address:

Increased bone loss and risk of fracture are two of the main challenges for cancer patients who undergo ionizing radiation (IR) therapy. This decline in bone quality is in part, caused by the excessive and sustained release of reactive oxygen species (ROS). Cerium oxide nanoparticles (CeONPs) have proven antioxidant and regenerative properties and the purpose of this study was to investigate the effect of CeONPs in reducing IR-induced functional damage in human bone marrow-derived mesenchymal stromal cells (hBMSCs). hBMSCs were supplemented with CeONPs at a concentration of either 1 or 10 μg/mL 24 h prior to exposure to a single 7 Gy irradiation dose. ROS levels, cellular proliferation, morphology, senescence, DNA damage, p53 expression and autophagy were evaluated as well as alkaline phosphatase, osteogenic protein gene expression and bone matrix deposition following osteogenic differentiation. Results showed that supplementation of CeONPs at a concentration of 1 μg/mL reduced cell senescence and significantly augmented cell autophagy (p = 0.01), osteogenesis and bone matrix deposition >2-fold (p = 0.0001) while under normal, non-irradiated culture conditions. Following irradiation, functional damage was attenuated and CeONPs at both 1 or 10 μg/mL significantly reduced ROS levels (p = 0.05 and 0.001 respectively), DNA damage by >4-fold (p < 0.05) while increasing autophagy >3.5-fold and bone matrix deposition 5-fold (p = 0.0001 in both groups). When supplemented with 10 μg/mL, p53 expression increased 3.5-fold (p < 0.05). We conclude that cellular uptake of CeONPs offered a significant, multifunctional and protective effect against IR-induced cellular damage while also augmenting osteogenic differentiation and subsequent new bone deposition. The use of CeONPs holds promise as a novel multifunctional therapeutic strategy for irradiation-induced bone loss.
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http://dx.doi.org/10.1016/j.msec.2021.112145DOI Listing
July 2021

Multi-functional cerium oxide nanoparticles regulate inflammation and enhance osteogenesis.

Mater Sci Eng C Mater Biol Appl 2021 May 24;124:112041. Epub 2021 Mar 24.

Biionix Cluster, Department of Internal Medicine, College of Medicine, University of Central Florida, Orlando, FL, USA. Electronic address:

Oxidative stress increases bone loss and limits repair, in part, through immunoregulation and the formation and maintenance of low-grade chronic inflammation. The aim of this study was to investigate the effect of cerium oxide nanoparticles (CeONPs) on (i) macrophage phenotype and cytokine expression under normal and simulated acute and chronic inflammatory conditions and, (ii) human mesenchymal stem cell (hBMSCs) proliferation, osteoinduction and osteogenic differentiation. Spherical particles composed of 60% Ce with a hydrodynamic size of ~35 nm and surface charge of 25.4 mV were internalized within cells. Under both acute and chronic conditions, inducible nitric oxide synthase (iNOS) activity decreased with a significant reduction seen in the 1 and 10 μg/mL groups (p < 0.001). A dose dependent and significant increase in anti-inflammatory cytokine gene expression was observed in all CeONP groups under chronic inflammatory condition. No increase in alkaline phosphatase (ALP) activity or mineral deposits were measured following hBMSCs cultured without osteogenic media in any of the CeONP groups, however, a significant increase in osteogenic-related gene expression, ALP activity and bone mineral deposits was measured when supplemented with both CeONPs and osteogenic media. CeONP activity was multifaceted and exhibited low toxicity. A therapeutic dose of 1 μg/mL delivered a disparate but protective effect when under both acute and chronic inflammatory conditions while at the same dose, potentiated osteogenesis.
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http://dx.doi.org/10.1016/j.msec.2021.112041DOI Listing
May 2021

Cerium oxide nanomaterial with dual antioxidative scavenging potential: Synthesis and characterization.

J Biomater Appl 2021 Apr 28:8853282211013451. Epub 2021 Apr 28.

University of Central Florida, Advanced Materials Processing and Analysis Center, Orlando, FL, USA.

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 Ce/Ce 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 (Ce/Ce > 1) (Ce∼ 62%). X-ray diffraction and XPS confirmed the presence of oxygen-deficient cerium oxide (CeO) particles. Finally, the CNP demonstrated very good biocompatibility and efficient reduction of hydrogen peroxide under conditions.
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http://dx.doi.org/10.1177/08853282211013451DOI Listing
April 2021

Nanosilk Increases the Strength of Diabetic Skin and Delivers CNP-miR146a to Improve Wound Healing.

Front Immunol 2020 30;11:590285. Epub 2020 Oct 30.

Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Colorado Denver School of Medicine and Children's Hospital Colorado, Aurora, CO, United States.

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 TGFβ-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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http://dx.doi.org/10.3389/fimmu.2020.590285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662112PMC
October 2020

Characterization of a nitric oxide (NO) donor molecule and cerium oxide nanoparticle (CNP) interactions and their synergistic antimicrobial potential for biomedical applications.

J Colloid Interface Sci 2021 Mar 27;586:163-177. Epub 2020 Oct 27.

School of Chemical, Materials, and Biomedical Engineering, College of Engineering, University of Georgia, Athens, GA, USA. Electronic address:

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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http://dx.doi.org/10.1016/j.jcis.2020.10.081DOI Listing
March 2021

Ceria Nanoparticles Decrease UVA-Induced Fibroblast Death Through Cell Redox Regulation Leading to Cell Survival, Migration and Proliferation.

Front Bioeng Biotechnol 2020 25;8:577557. Epub 2020 Sep 25.

Programa de Pós-Graduação em Ciências Biológicas, Universidade Estadual de Maringá, Maringá, Brazil.

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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http://dx.doi.org/10.3389/fbioe.2020.577557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546350PMC
September 2020

Exposure to nanoceria impacts larval survival, life history traits and fecundity of Aedes aegypti.

PLoS Negl Trop Dis 2020 09 25;14(9):e0008654. Epub 2020 Sep 25.

University of Central Florida College of Medicine, Department of Internal Medicine, Orlando, Florida, United States of America.

Effectively controlling vector mosquito populations while avoiding the development of resistance remains a prevalent and increasing obstacle to integrated vector management. Although, metallic nanoparticles have previously shown promise in controlling larval populations via mechanisms which are less likely to spur resistance, the impacts of such particles on life history traits and fecundity of mosquitoes are understudied. Herein, we investigate the chemically well-defined cerium oxide nanoparticles (CNPs) and silver-doped nanoceria (AgCNPs) for larvicidal potential and effects on life history traits and fecundity of Aedes (Ae.) aegypti mosquitoes. When 3rd instar larvae were exposed to nanoceria in absence of larval food, the mortality count disclosed significant activity of AgCNPs over CNPs (57.8±3.68% and 17.2±2.81% lethality, respectively) and a comparable activity to Ag+ controls (62.8±3.60% lethality). The surviving larvae showed altered life history traits (e.g., reduced egg hatch proportion and varied sex ratios), indicating activities of these nanoceria beyond just that of a larvicide. In a separate set of experiments, impacts on oocyte growth and egg generation resulting from nanoceria-laced blood meals were studied using confocal fluorescence microscopy revealing oocytes growth-arrest at 16-24h after feeding with AgCNP-blood meals in some mosquitoes, thereby significantly reducing average egg clutch. AgCNPs caused ~60% mortality in 3rd instar larvae when larval food was absent, while CNPs yielded only ~20% mortality which contrasts with a previous report on green-synthesized nanoceria and highlights the level of detail required to accurately report and interpret such studies. Additionally, AgCNPs are estimated to contain much less silver (0.22 parts per billion, ppb) than the amount of Ag+ needed to achieve comparable larvicidal activity (2.7 parts per million, ppm), potentially making these nanoceria ecofriendly. Finally, this work is the first study to demonstrate the until-now-unappreciated impacts of nanoceria on life history traits and interference with mosquito egg development.
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http://dx.doi.org/10.1371/journal.pntd.0008654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540862PMC
September 2020

Silk fibroin nanofibrous mats for visible sensing of oxidative stress in cutaneous wounds.

Biomater Sci 2020 Nov 25;8(21):5900-5910. Epub 2020 Sep 25.

Advanced Material Processing and Analysis Center, Department of Material Science and Engineering University of Central Florida, Orlando, FL 32816, USA.

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 HO 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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http://dx.doi.org/10.1039/d0bm01325kDOI Listing
November 2020

Ceria Nanoparticles Mitigate the Iron Oxidative Toxicity of Human Retinal Pigment Epithelium.

Cureus 2020 Aug 11;12(8):e9675. Epub 2020 Aug 11.

Materials Science Engineering, Advanced Materials Processing and Analysis Center, Nanoscience Technology Center, Dept. of Materials Science and Engineering, University of Central Florida, Orlando, USA.

Oxidative injury is implicated in retinal damage observed in age-related macular degeneration (AMD), as well as other degenerative conditions. Abnormally elevated levels of iron accumulation within the retinal pigment epithelium have been detected in eyes with AMD, and it is suspected to play a role in the pathogenesis through the production of reactive oxygen species (ROS). Ceria nanoparticles (CNP) have the ability to scavenge ROS. This study sought to evaluate the ability of CNP to mitigate iron-induced oxidative stress and assess cell viability in the human ARPE-19 cell line in vitro. Cell viability was measured by an MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and compared between experimental groups undergoing 48-hr exposure to a ferrous iron solution with and without 24-hr CNP pre-treatment. The CNP effect on ROS formation was evaluated additionally by H2DCFDA (2,7-dichlorodihydrofluorescein diacetate) fluorescent probe assay and superoxide dismutase assay. CNP demonstrated a three-fold increase in cell viability and a reduction in ROS generation. The results show a promising treatment modality for diseases causing oxidative damage in the eye.
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http://dx.doi.org/10.7759/cureus.9675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485992PMC
August 2020

Ultra-high arsenic adsorption by graphene oxide iron nanohybrid: Removal mechanisms and potential applications.

Chemosphere 2020 Aug 8;253:126702. Epub 2020 Apr 8.

Nanoenvirology Research Group, Department of Civil and Environmental Engineering, North Dakota State University, Fargo, ND, 58105, USA. Electronic address:

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/FeO) 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, C = 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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http://dx.doi.org/10.1016/j.chemosphere.2020.126702DOI Listing
August 2020

Engineered defects in cerium oxides: tuning chemical reactivity for biomedical, environmental, & energy applications.

Nanoscale 2020 Apr;12(13):6879-6899

Department of Materials Science & Engineering, Advanced Materials Processing and Analysis Center, University of Central Florida, Orlando, FL, USA.

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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http://dx.doi.org/10.1039/d0nr01203cDOI Listing
April 2020

Integration of amorphous ferromagnetic oxides with multiferroic materials for room temperature magnetoelectric spintronics.

Sci Rep 2020 Feb 27;10(1):3583. Epub 2020 Feb 27.

Bredesen Center, University of Tennessee, Knoxville, TN, 37996, USA.

A room temperature amorphous ferromagnetic oxide semiconductor can substantially reduce the cost and complexity associated with utilizing crystalline materials for spintronic devices. We report a new material (FeDyTb)O (FDTO), which shows semiconducting behavior with reasonable electrical conductivity (~500 mOhm-cm), an optical band-gap (2.4 eV), and a large enough magnetic moment (~200 emu/cc), all of which can be tuned by varying the oxygen content during deposition. Magnetoelectric devices were made by integrating ultrathin FDTO with multiferroic BiFeO. A strong enhancement in the magnetic coercive field of FDTO grown on BiFeO validated a large exchange coupling between them. Additionally, FDTO served as an excellent top electrode for ferroelectric switching in BiFeO with no sign of degradation after ~10 switching cycles. RT magneto-electric coupling was demonstrated by modulating the resistance states of spin-valve structures using electric fields.
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http://dx.doi.org/10.1038/s41598-020-58592-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046697PMC
February 2020

Temporal Distribution Patterns of Alexa Fluor 647-Conjugated CeNPs in the Mouse Retina After a Single Intravitreal Injection.

Adv Exp Med Biol 2019 ;1185:125-130

Department of Ophthalmology, College of Medicine, University of Oklahoma Health Sciences Center and Dean McGee Eye Institute, Oklahoma City, OK, USA.

Intravitreal (IVT) injection of ophthalmic therapeutics is the most widely used drug delivery route to the posterior segment of the eye. We employed this method to deliver our inorganic, catalytic antioxidant, cerium oxide nanoparticles (CeNPs), to rodent models of retinal degeneration. A single IVT of CeNPs delays disease progression. Even though we have shown that our synthesized CeNPs are retained in the retina for over a year, we still do not know which cell types in the retina preferentially take up these nanoparticles. In this study, we examined the temporal and spatial distribution of fluorescently labeled CeNPs in retinal sections after IVT. We detected elevated fluorescent signals in all the layers where retinal neurons and glia reside and retinal pigment epithelium (RPE) up to 90 days post injection. Additionally, we found that free fluorochrome accumulated in retinal vasculature instead of retinal cells. These data suggested that CeNP-conjugation mediated the targeting of the fluorochrome to retinal cells. We propose that CeNPs can be deployed as ophthalmic carriers to the retina.
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http://dx.doi.org/10.1007/978-3-030-27378-1_21DOI Listing
February 2020

Injectable, self-healable zwitterionic cryogels with sustained microRNA - cerium oxide nanoparticle release promote accelerated wound healing.

Acta Biomater 2020 01 11;101:262-272. Epub 2019 Nov 11.

Chemical & Biological Engineering, Colorado School of Mines, Golden, CO, United States. Electronic address:

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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http://dx.doi.org/10.1016/j.actbio.2019.11.014DOI Listing
January 2020

Correction: Antioxidant properties of ALD grown nanoceria films with tunable valency.

Biomater Sci 2019 07 19;7(7):3076. Epub 2019 Jun 19.

Department of Materials Science and Engineering, University of Central Florida, 12760 Pegasus Blvd., P.O. Box 162450, Orlando, Florida 32816, USA. and Advanced Materials Processing and Analysis Center, University of Central Florida, 4000 Central Florida Blvd., P.O. Box 162455, Orlando, Florida 32816, USA and Nanoscience Technology Center, University of Central Florida, 12424 Research Parkway Suite 400, Orlando, Florida 32816, USA and College of Medicine, University of Central Florida, Orlando, Florida 32827, USA.

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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http://dx.doi.org/10.1039/c9bm90034aDOI Listing
July 2019

Antioxidant properties of ALD grown nanoceria films with tunable valency.

Biomater Sci 2019 Jul 22;7(7):3051-3061. Epub 2019 May 22.

Department of Materials Science and Engineering, University of Central Florida, 12760 Pegasus Blvd., P.O. Box 162450, Orlando, Florida 32816, USA. and Advanced Materials Processing and Analysis Center, University of Central Florida, 4000 Central Florida Blvd., P.O. Box 162455, Orlando, Florida 32816, USA and Nanoscience Technology Center, University of Central Florida, 12424 Research Parkway Suite 400, Orlando, Florida 32816, USA and College of Medicine, University of Central Florida, Orlando, Florida 32827, USA.

Herein, we provide the first account of a method to control cerium oxide's mixed valence states (as Ce to Ce ratio) in ultra-thin films formed via atomic layer deposition (ALD). It is determined that modulation of Ce/Ce 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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http://dx.doi.org/10.1039/c9bm00397eDOI Listing
July 2019

Multiplex Viral Detection Platform Based on a Aptamers-Integrated Microfluidic Channel.

ACS Omega 2019 Jan 29;4(1):2234-2240. Epub 2019 Jan 29.

Advanced Materials Processing and Analysis Centre, Department of Materials Science and Engineering, Department of Internal Medicine, College of Medicine, and Nanoscience Technology Centre, University of Central Florida, Orlando, Florida 32827, United States.

A polydimethylsiloxane-based microfluidic device has been developed for the multiplex detection of viral envelope proteins such as Zika and chikungunya on a single platform using aptamer-analyte interactions. The channel is integrated with microsized pillars that increase the surface area allowing more aptamers to attach to the incoming envelope protein molecules, thus increasing the overall sensitivity of the system. The working of the device depends on the formation of protein-mediated sandwich morphology that is obtained using an aptamer and aptamer-functionalized gold nanoparticle (AuNP) pair. The colorimetric signal is obtained upon introduction of silver reagents into the channel, which are selectively deposited on the AuNP surface, providing a gray contrast in the testing zone. The microfluidic channel approach successfully detected clinically relevant concentrations of Zika and chikungunya envelope proteins in phosphine-buffered saline (1 pM) and calf blood (100 pM) with high specificity using gold-decorated aptamers integrated in a microfluidic channel.
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http://dx.doi.org/10.1021/acsomega.8b03277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358057PMC
January 2019

An unexpected phase transformation of ceria nanoparticles in aqueous media.

J Mater Res 2019 Feb 1;34(3):465-473. Epub 2019 Feb 1.

Environmental and Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA-99354, USA.

Cerium oxide Nanoparticles (CNPs) are of significant interest to the scientific community due to their wide spread applications in a variety of fields. It is proposed that size dependent variations in the extent of Ce3+ and Ce4+ oxidation states of cerium in CNPs determines the performance of CNPs in application environments. To obtain greater molecular and structural understanding of chemical state transformations previously reported for ceria ≈ 3 nm nanoparticles (CNPs) in response to changing ambient conditions, microXRD and Raman measurements were carried out for various solution conditions. The particles were observed to undergo a reversible transformation from a defective ceria structure to a non-ceria amorphous oxy-hydroxide/peroxide phase in response to the addition of 30% hydrogen peroxide. For CNPs made up of ~8 nm crystallites, a partial transformation was observed and no transformation was observed for CNPs made up of ~ 40 nm crystallites. This observation of differences in size dependent transition behavior may help explain the benefits of using smaller CNPs in applications requiring regenerative behavior.
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http://dx.doi.org/10.1557/jmr.2018.490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995332PMC
February 2019

Enzyme-Free Plasmonic Biosensor for Direct Detection of Neurotransmitter Dopamine from Whole Blood.

Nano Lett 2019 01 17;19(1):449-454. Epub 2018 Dec 17.

NanoScience Technology Center , University of Central Florida , Orlando , Florida 32826 , United States.

Complex biological fluids without pretreatment, separation, or purification impose stringent limitations on the practical deployment of label-free plasmonic biosensors for advanced assays needed in point of care applications. In this work, we present an enzyme-free plasmonic neurotransmitter dopamine biosensor integrated with a microfluidic plasma separator. This integrated device allows the in-line separation of plasma directly from the bloodstream and channels it to the active detection area, where inorganic cerium oxide nanoparticles function as local selective dopamine binding sites through strong surface redox reaction. A thorough understanding and engineering of the nanoparticles is carried out to maximize its dopamine sensitivity and selectivity. We obtain detection of dopamine at 100 fM concentration in simulated body fluid and 1 nM directly from blood without any prior sample preparation. The detection selectivity is found to be at least five-times higher compared to the common interfering species. This demonstration shows the feasibility of the practical implementation of the proposed plasmonic system in detection of variety of biomarkers directly from the complex biological fluids.
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http://dx.doi.org/10.1021/acs.nanolett.8b04253DOI Listing
January 2019

Use of Cerium Oxide Nanoparticles Conjugated with MicroRNA-146a to Correct the Diabetic Wound Healing Impairment.

J Am Coll Surg 2019 01 22;228(1):107-115. Epub 2018 Oct 22.

Laboratory for Fetal and Regenerative Biology, Department of Surgery, School of Medicine, University of Colorado Denver - Anschutz Medical Campus and Colorado Children's Hospital, Aurora, CO. Electronic address:

Background: Diabetic wounds have become one of the most challenging public health issues of the 21st century, yet there is no effective treatment available. We have previously shown that the diabetic wound healing impairment is associated with increased inflammation and decreased expression of the regulatory microRNA miR-146a. We have conjugated miR-146a to cerium oxide nanoparticles (CNP-miR146a) to target reactive oxygen species (ROS) and inflammation. This study aimed to evaluate the consequences of CNP-miR146a treatment of diabetic wounds.

Study Design: Eight-millimeter wounds were created on the dorsal skin of Db/Db mice and treated with PBS or differing concentrations of CNP-mir146a (1; 10; 100; or 1,000 ng) at the time of wounding. Rate of wound closure was measured until the wounds were fully healed. At 4 weeks post-healing, a dumbbell-shaped skin sample was collected, with the healed wound in the center, and an Instron 5942 testing unit was used to measure the maximum load and modulus.

Results: Our data showed that diabetic wounds treated with PBS or 1 ng CNP-miR146a took 18 days to heal. Treatment with 10, 100, or 1,000 ng of CNP+miR-146a effectively enhanced healing, and wounds were fully closed at day 14 post-wounding. The healed skin from the CNP-miR146a-treated group showed a trend of improved biomechanical properties (increased maximum load and modulus), however it did not reach significance.

Conclusions: We found that a 100-ng dose of CNP-miR146a improved diabetic wound healing and did not impair the biomechanical properties of the skin post-healing. This nanotechnology-based therapy is promising, and future studies are warranted to transfer this therapy to clinical application.
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http://dx.doi.org/10.1016/j.jamcollsurg.2018.09.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846138PMC
January 2019

Cerium oxide nanoparticles at the nano-bio interface: size-dependent cellular uptake.

Artif Cells Nanomed Biotechnol 2018 12;46(sup3):S956-S963. Epub 2018 Oct 12.

a Nanoscience Technology Center, University of Central Florida , Orlando , FL , USA.

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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http://dx.doi.org/10.1080/21691401.2018.1521818DOI Listing
June 2019

Fiber-Type Solar Cells, Nanogenerators, Batteries, and Supercapacitors for Wearable Applications.

Adv Sci (Weinh) 2018 Sep 17;5(9):1800340. Epub 2018 Jun 17.

NanoScience Technology Center University of Central Florida Orlando FL 32826 USA.

Wearable electronic devices represent a paradigm change in consumer electronics, on-body sensing, artificial skins, and wearable communication and entertainment. Because all these electronic devices require energy to operate, wearable energy systems are an integral part of wearable devices. Essentially, the electrodes and other components present in these energy devices should be mechanically strong, flexible, lightweight, and comfortable to the user. Presented here is a critical review of those materials and devices developed for energy conversion and storage applications with an objective to be used in wearable devices. The focus is mainly on the advances made in the field of solar cells, triboelectric generators, Li-ion batteries, and supercapacitors for wearable device development. As these devices need to be attached/integrated with the fabric, the discussion is limited to devices made in the form of ribbons, filaments, and fibers. Some of the important challenges and future directions to be pursued are also highlighted.
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http://dx.doi.org/10.1002/advs.201800340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145419PMC
September 2018

Engineered nanoceria cytoprotection in vivo: mitigation of reactive oxygen species and double-stranded DNA breakage due to radiation exposure.

Nanoscale 2018 Dec 18;10(45):21069-21075. Epub 2018 Sep 18.

Materials Science and Engineering, Advanced Materials Processing Center, University of Central Florida, Orlando, FL 32816, USA.

Cerium oxide nanomaterials are known to absorb ionizing radiation energy, as well as to neutralize free radicals in solution, by undergoing redox changes. We, therefore, proposed that ceria nanoparticles could be used in biomedical applications as an injectable, radio-protectant material. In this study, we examine the effectiveness of engineered nanoparticles in protecting germ cells from the damaging effects of irradiation-induced cell death, in vivo. C57BL/6J male mice were used as a model and irradiation was localized to the scrotal region at 2.5, 5, and/or 10 Gy intensities. Ceria nanoparticles were introduced as 100 μL injections at 100 nM and 100 μM via tail vein injections, weekly, for one month. Following this, the animals were sacrificed and their organs (heart, brain, kidneys) were harvested. Tissues were fixed, sectioned, and stained for instances of cell death, DNA damage (TUNEL assay), and ROS (nitro-tyrosine evolution). Tissues from mice treated with ceria nanoparticles showed significantly less (∼13% decrease; *P < 0.05) tissue damage (per immunohistochemistry) over controls at up to 5 Gy radiation. DNA damage and ROS also decrease substantially with ceria treatment, confirming ceria's capacity as an injectable, radio-protectant material. The study also highlights the ability of ceria nanoparticles to protect cells/tissues from both direct and indirect effects of ionizing radiation.
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http://dx.doi.org/10.1039/c8nr04640aDOI Listing
December 2018

Cerium Oxide Nanoparticles Sensitize Pancreatic Cancer to Radiation Therapy through Oxidative Activation of the JNK Apoptotic Pathway.

Cancers (Basel) 2018 Sep 1;10(9). Epub 2018 Sep 1.

Burnett School of Biomedical Sciences University of Central Florida College of Medicine, Orlando, FL 32827, USA.

Side effects of radiation therapy (RT) remain the most challenging issue for pancreatic cancer treatment. Cerium oxide nanoparticles (CONPs) are currently being tested in pre-clinical trials as an adjuvant to sensitize pancreatic cancer cells to RT and protect normal tissues from the harmful side effects. CONPs were not able to significantly affect RT-induced DNA damage in cancer cells, thereby ruling out sensitization through increased mitotic catastrophe. However, activation of c-Jun terminal kinase (JNK), a key driver of RT-induced apoptosis, was significantly enhanced by co-treatment with CONPs and RT in pancreatic cancer cells in vitro and human pancreatic tumors in nude mice in vivo compared to CONPs or RT treatment alone. Further, CONP-driven increase in RT-induced JNK activity was associated with a marked increase in Caspase 3/7 activation, indicative of apoptosis. We have previously shown that CONPs increase reactive oxygen species (ROS) production in cancer cells. ROS has been shown to drive the oxidation of thioredoxin 1 (TRX1) which results in the activation of apoptosis signaling kinase 1 (ASK1). The increase in ASK1 activation following the co-treatment with CONPs followed by RT suggests that the increased JNK activation is the result of increased TRX1 oxidation. The ability of CONPs to sensitize pancreatic cancer cells to RT was mitigated when the TRX1 oxidation was prevented by mutagenesis of a cysteine residue or when the JNK activation was blocked by an inhibitor. Taken together, these data demonstrate an important mechanism for CONPs in specifically killing cancer cells and provide novel insights into the utilization of CONPs as a radiosensitizer and therapeutic agent for pancreatic cancer.
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http://dx.doi.org/10.3390/cancers10090303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162528PMC
September 2018

Highly selective aptamer based organic electrochemical biosensor with pico-level detection.

Biosens Bioelectron 2018 Oct 22;117:40-46. Epub 2018 May 22.

Advanced Materials Processing and Analysis Center, Department of Materials Science and Engineering, Nanoscience Technology Center, University of Central Florida, Orlando, FL 32826, USA; College of Medicine, University of Central Florida, Orlando, FL 32826, USA. Electronic address:

An organic aptamer functionalized electrochemical transistor has been developed to detect the presence of epinephrine molecule which acts as an excitatory neurotransmitter. The abnormalities in the level of epinephrine are the direct symptoms of some diseases such as Takotsubo cardiomyopathy, myocardial infarction, arrhythmias and other heart related diseases. The present approach is based on immobilization of aptamers on the gate electrode which selectively binds to epinephrine with high affinity. The introduction of epinephrine in the system causes screening of negative charge of aptamers as well as the production of Faradaic current due to oxidation of epinephrine. The synergistic effect of these two events decreases the overall channel current which was seen in both transfer characteristics and current-time curve. Additional experiments against common interfering agents (dopamine, ascorbic acid, DOPAC etc) showed no decrease in the current which indicates high specificity of the sensor. Overall, the incorporation of aptamers in the transistor has allowed us to obtain a sensor exhibiting the lowest limit of detection for epinephrine (90 pM) till date which is comparable to normal physiological level. This approach provides a real-time detection of a large range of biomolecules and viral proteins in a time and cost-effective manner and has applications in point-of-care testing tool for several diagnostic applications.
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http://dx.doi.org/10.1016/j.bios.2018.05.031DOI Listing
October 2018

Efficacy of Different Compositions of Cerium Oxide Nanoparticles in Tumor-Stroma Interaction.

J Biomed Nanotechnol 2017 Dec;13(12):1735-1746

The biomedical application of cerium oxide nanoparticles (nanoceria) is a focal point of research for a few years. The biochemical effects of nanoceria depend on various factors including particle size, oxidation state of cerium, oxygen vacancies on the surface, use of dispersants or coatings, pH and cell type. Due to their autocatalytic redox-activity, these particles are considered to act as a specific anti-cancer tool with less side effects on healthy cells and tissues, as the particles kill tumor cells, while protecting healthy cells from oxidative damage. In the present study, four different types of nanoceria were investigated with regard to their impact on biochemical parameters in vitro, which play a pivotal role in tumor-stroma interaction. The obtained data and presented in vitro test parameters will be helpful in designing nanoceria compositions, which are ideally suited for anticancer therapy, either as a 'stand alone drug' or in combination with other chemotherapeutics.
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http://dx.doi.org/10.1166/jbn.2017.2452DOI Listing
December 2017

Atmospheric Deposition of Modified Graphene Oxide on Silicon by Evaporation-Assisted Deposition.

ACS Omega 2018 Jan 29;3(1):1154-1158. Epub 2018 Jan 29.

Department of Mechanical and Aerospace Engineering and Department of Materials Science and Engineering, University of Central Florida, 12760 Pegasus Blvd., P.O. Box 162450, Orlando, Florida 32816, United States.

We present a deposition technique termed evaporation-assisted deposition (EAD). The technique is based on a coupled evaporation-to-condensation transfer process at atmospheric conditions, where graphene oxide (GO) is transferred to a Si wafer via the vapor flux between an evaporating droplet and the Si surface. The EAD process is monitored with visible and infrared cameras. GO deposits on Si are characterized by both Raman spectroscopy and X-ray photoelectron spectroscopy. We find that a scaled energy barrier for the condensate is required for EAD, which corresponds to specific solution-substrate properties that exhibit a minimized free energy barrier at the solid-liquid-vapor interface.
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http://dx.doi.org/10.1021/acsomega.7b01816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6641421PMC
January 2018

Modulating the Catalytic Activity of Cerium Oxide Nanoparticles with the Anion of the Precursor Salt.

J Phys Chem C Nanomater Interfaces 2017 Sep 21;121(36):20039-20050. Epub 2017 Aug 21.

Advanced Materials Processing and Analysis Center (AMPAC), Materials Science and Engineering (MSE), University of Central Florida, 4000, Central Florida Boulevard, Orlando, Fl - 32816, USA.

In this work, we tested our hypothesis that surface chemistry and antioxidant properties of cerium nanoparticles (CNPs) are affected by presence of counterions. We first employed various precursor cerium (III) (Ce(III)) salts with different counterions (acetate, nitrate, chloride, sulfate) to synthesize CNPs following the same wet chemical methodology. Electron spin resonance (ESR) studies provided evidence for the formation of radicals from counterions (e.g., NO• from reduction of NO in CNPs synthesized from Ce(III) nitrate). Physicochemical properties of these CNPs, e.g., dispersion stability, hydrodynamic size, signature surface chemistry, SOD-mimetic activity, and oxidation potentials were found to be significantly affected by the anions of the precursor salts. CNPs synthesized from Ce(III) nitrate and Ce(III) chloride exhibited higher extent of SOD-mimetic activities. Therefore, these CNPs were studied extensively employing in-situ UV-Visible spectroelectrochemistry and changing the counterion concentrations affected the oxidation potentials of these CNPs. Thus, the physicochemical and antioxidant properties of CNPs can be modulated by anions of the precursor. Furthermore, our ESR studies present evidence of the formation of guanine cation radical (G•) in 5'-dGMP via UV-photoionization at 77 K in the presence of CNPs synthesized from Ce(III) nitrate and chloride and CNPs act as the scavenger of radiation-produced electrons.
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http://dx.doi.org/10.1021/acs.jpcc.7b05725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602578PMC
September 2017

Nanoparticle delivery of curcumin induces cellular hypoxia and ROS-mediated apoptosis via modulation of Bcl-2/Bax in human neuroblastoma.

Nanoscale 2017 Jul;9(29):10375-10387

Materials Science and Engineering, Advanced Materials Processing Center, University of Central Florida, Orlando, FL 32816, USA and Nanoscience Technology Center, University of Central Florida, Orlando, FL 32826, USA and College of Medicine, University of Central Florida, Orlando, FL 32816, USA.

In this study, several formulations of nanoceria and dextran-nanoceria with curcumin, each demonstrated to have anti-cancer properties, were synthesized and applied as treatment for human childhood neuroblastoma. The anti-cancer activities of these formulations were explored in neuroblastoma models of both MYCN-amplified and non-amplified cell lines. Ceria nanoparticles, coated with dextran and loaded with curcumin, were found to induce substantial cell death in neuroblastoma cells (up to a 2-fold and a 1.6-fold decrease in cell viability for MYCN-upregulated and normal expressing cell lines, respectively; *p < 0.05) while producing no or only minor toxicity in healthy cells (no toxicity at 100 μM; **p < 0.01). This formulation evokes prolonged oxidative stress, stabilizing HIF-1α, and inducing caspase-dependent apoptosis (up to a 2.4-fold increase over control; *p < 0.05). Overall, nano-therapeutic treatments showed a more pronounced effect in MYCN-amplified cells, which are traditionally more resistant to drug therapies. These results represent a very promising alternative to small molecule drug therapies for robust cancers.
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http://dx.doi.org/10.1039/c7nr02770bDOI Listing
July 2017

MicroRNA-211 Regulates Oxidative Phosphorylation and Energy Metabolism in Human Vitiligo.

J Invest Dermatol 2017 09 11;137(9):1965-1974. Epub 2017 May 11.

Sanford Burnham Prebys Medical Discovery Institute, 6400 Sanger Road, Orlando, Florida, USA. Electronic address:

Vitiligo is a common chronic skin disorder characterized by loss of epidermal melanocytes and progressive depigmentation. Vitiligo has complex immune, genetic, environmental, and biochemical causes, but the exact molecular mechanisms of vitiligo development and progression, particularly those related to metabolic control, are poorly understood. In this study we characterized the human vitiligo cell line PIG3V and the normal human melanocyte line HEM-l by RNA sequencing, targeted metabolomics, and shotgun lipidomics. Melanocyte-enriched microRNA-211, a known metabolic switch in nonpigmented melanoma cells, was severely down-regulated in vitiligo cell line PIG3V and skin biopsy samples from vitiligo patients, whereas its predicted targets PPARGC1A, RRM2, and TAOK1 were reciprocally up-regulated. microRNA-211 binds to PGC1-α 3' untranslated region locus and represses it. Although mitochondrial numbers were constant, mitochondrial complexes I, II, and IV and respiratory responses were defective in vitiligo cells. Nanoparticle-coated microRNA-211 partially augmented the oxygen consumption rate in PIG3V cells. The lower oxygen consumption rate, changes in lipid and metabolite profiles, and increased reactive oxygen species production observed in vitiligo cells appear to be partly due to abnormal regulation of microRNA-211 and its target genes. These genes represent potential biomarkers and therapeutic targets in human vitiligo.
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http://dx.doi.org/10.1016/j.jid.2017.04.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233982PMC
September 2017