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Zhiwei Sun - One of the best experts on this subject based on the ideXlab platform.

  • cardiovascular toxicity evaluation of Silica Nanoparticles in endothelial cells and zebrafish model
    Biomaterials, 2013
    Co-Authors: Junchao Duan, Zhiwei Sun
    Abstract:

    Environmental exposure to nanomaterials is inevitable as nanomaterials become part of our daily life, and as a result, nanotoxicity research is gaining attention. However, most investigators focus on the evaluation of overall toxicity instead of a certain organism system. In this regard, the evaluation of cardiovascular effects of Silica Nanoparticles was preformed in vitro and in vivo. It's worth noting that Silica Nanoparticles induced cytotoxicity as well as oxidative stress and apoptosis. ROS and apoptosis were considered as major factor to endothelial cells dysfunction, involved in several molecular mechanisms of cardiovascular diseases. In vivo study, mortality, malformation, heart rate and whole-embryo cellular death were measured in zebrafish embryos. Results showed that Silica Nanoparticles induced pericardia toxicity and caused bradycardia. We also examined the expression of cardiovascular-related proteins in embryos by western blot analysis. Silica Nanoparticles inhibited the expression of p-VEGFR2 and p-ERK1/2 as well as the downregulation of MEF2C and NKX2.5, revealed that Silica Nanoparticles could inhibit the angiogenesis and disturb the heart formation and development. In summary, our results suggest that exposure to Silica Nanoparticles is a possible risk factor to cardiovascular system.

  • toxic effect of Silica Nanoparticles on endothelial cells through dna damage response via chk1 dependent g2 m checkpoint
    PLOS ONE, 2013
    Co-Authors: Junchao Duan, Xianqing Zhou, Zhiwei Sun, Peili Huang
    Abstract:

    Silica Nanoparticles have become promising carriers for drug delivery or gene therapy. Endothelial cells could be directly exposed to Silica Nanoparticles by intravenous administration. However, the underlying toxic effect mechanisms of Silica Nanoparticles on endothelial cells are still poorly understood. In order to clarify the cytotoxicity of endothelial cells induced by Silica Nanoparticles and its mechanisms, cellular morphology, cell viability and lactate dehydrogenase (LDH) release were observed in human umbilical vein endothelial cells (HUVECs) as assessing cytotoxicity, resulted in a dose- and time- dependent manner. Silica Nanoparticles-induced reactive oxygen species (ROS) generation caused oxidative damage followed by the production of malondialdehyde (MDA) as well as the inhibition of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Both necrosis and apoptosis were increased significantly after 24 h exposure. The mitochondrial membrane potential (MMP) decreased obviously in a dose-dependent manner. The degree of DNA damage including the percentage of tail DNA, tail length and Olive tail moment (OTM) were markedly aggravated. Silica Nanoparticles also induced G2/M arrest through the upregulation of Chk1 and the downregulation of Cdc25C, cyclin B1/Cdc2. In summary, our data indicated that the toxic effect mechanisms of Silica Nanoparticles on endothelial cells was through DNA damage response (DDR) via Chk1-dependent G2/M checkpoint signaling pathway, suggesting that exposure to Silica Nanoparticles could be a potential hazards for the development of cardiovascular diseases.

  • cardiovascular toxicity of different sizes amorphous Silica Nanoparticles in rats after intratracheal instillation
    Cardiovascular Toxicology, 2013
    Co-Authors: Dali Zhao, Guanqun Cui, Li Jing, Minghua Jin, Xiaomei Liu, Ying Liu, Caixia Guo, Xianqing Zhou, Zhiwei Sun
    Abstract:

    The purpose of this work was to investigate the cardiovascular toxicity of different sizes and different dosages of Silica Nanoparticles in Wistar rats. The three Silica Nanoparticles (30, 60, and 90 nm) and one fine Silica particles (600 nm) at three doses of 2, 5, and 10 (mg/Kg bw) were used in the present experiment. After intratracheal instillation for a total of 16 times, concentration of Si in hearts and serum was measured by inductively coupled plasma optical emission spectrometer. The hematology parameters were analyzed by an automated hematology analyzer, and the inflammatory reaction, oxidative stress, endothelial dysfunction, and the myocardial enzymes in serum were measured by kits. Our results showed intratracheal-instilled Silica Nanoparticles could pass through the alveolar-capillary barrier into systemic circulation. Concentration of Si in the heart and serum depended on the particles size and dosage. The levels of reactive oxygen species (ROS) at 5, 10 mg/Kg bw of the three Silica Nanoparticles were higher than the fine Silica particles. Blood levels of inflammation-related high-sensitivity C-reactive protein and cytokines such as interleukin-1beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha were increased after exposure to three Silica Nanoparticles at 10 mg/Kg bw. Moreover, the levels of IL-1β and IL-6 at 10 mg/Kg bw of Silica Nanoparticles (30 nm) were higher than the fine Silica particles. Significant decrease in superoxide dismutase, glutathione peroxidase and significant increase in malondialdehyde were observed at 10 mg/Kg bw of the three Silica Nanoparticles. A significant decrease in nitric oxide (NO) production was induced which coincided with the reduction of nitric oxide synthase (NOS) activity and the excessive generation of ROS in rats. The levels of intercellular adhesion molecule-l and vascular cell adhesion molecule-l elevated significantly after exposure to three Silica Nanoparticles at 10 mg/Kg bw, which are considered as early steps of endothelial dysfunction. We conclude that cardiovascular toxicity of Silica Nanoparticles could be related to the particles size and dosage. Oxidative stress could be involved in inflammatory reaction and endothelial dysfunction, all of which could aggravate cardiovascular toxicology. In addition, endothelial NO/NOS system disorder caused by Nanoparticles could be one of the mechanisms for endothelial dysfunction.

Weihong Tan - One of the best experts on this subject based on the ideXlab platform.

  • surface modification of Silica Nanoparticles to reduce aggregation and nonspecific binding
    Langmuir, 2006
    Co-Authors: Rahul P Bagwe, Lisa R Hilliard, Weihong Tan
    Abstract:

    In this article, a systematic study of the design and development of surface-modification schemes for Silica Nanoparticles is presented. The nanoparticle surface design involves an optimum balance of the use of inert and active surface functional groups to achieve minimal nanoparticle aggregation and reduce nanoparticle nonspecific binding. Silica Nanoparticles were prepared in a water-in-oil microemulsion and subsequently surface modified via cohydrolysis with tetraethyl orthoSilicate (TEOS) and various organosilane reagents. Nanoparticles with different functional groups, including carboxylate, amine, amine/phosphonate, poly(ethylene glycol), octadecyl, and carboxylate/octadecyl groups, were produced. Aggregation studies using SEM, dynamic light scattering, and zeta potential analysis indicate that severe aggregation among amine-modified Silica Nanoparticles can be reduced by adding inert functional groups, such as methyl phosphonate, to the surface. To determine the effect of various surface-modificati...

  • multicolor fret Silica Nanoparticles by single wavelength excitation
    Nano Letters, 2006
    Co-Authors: Lin Wang, Weihong Tan
    Abstract:

    Fluorescent Nanoparticles with multiple emission signatures by a single wavelength excitation are needed in multiplex bioanalysis and molecular imaging. We have prepared Silica Nanoparticles encapsulated with three organic dyes using a modified Stober synthesis method. By varying the doping ratio of the three tandem dyes, fluorescence resonance energy transfer (FRET)-mediated emission signatures can be tuned to have the Nanoparticles exhibit multiple colors under one single wavelength excitation. These Nanoparticles are intensely fluorescent, highly photostable, uniform in size, and biocompatible. The acceptor emission of the FRET Nanoparticles has generated a large Stokes shift, which implicates broad applications in biological labeling and imaging. Molecular recognition moieties, such as biotin, can be covalently attached to the nanoparticle surface to allow for specific binding to target molecules. These multicolor FRET Silica Nanoparticles can be used as barcoding tags for multiplexed signaling. By us...

  • optimization of dye doped Silica Nanoparticles prepared using a reverse microemulsion method
    Langmuir, 2004
    Co-Authors: Rahul P Bagwe, Chaoyong Yang, Lisa R Hilliard, Weihong Tan
    Abstract:

    Fluorescent labeling based on Silica Nanoparticles facilitates unique applications in bioanalysis and bioseparation. Dye-doped Silica Nanoparticles have significant advantages over single-dye labeling in signal amplification, photostability and surface modification for various biological applications. We have studied the formation of tris(2,2'-bipyridyl)dichlororuthenium(II) (Ru(bpy)) dye-doped Silica Nanoparticles by ammonia-catalyzed hydrolysis of tetraethyl orthoSilicate (TEOS) in water-in-oil microemulsion. The fluorescence spectra, particle size, and size distribution of Ru(bpy) dye-doped Silica Nanoparticles were examined as a function of reactant concentrations (TEOS and ammonium hydroxide), nature of surfactant molecules, and molar ratios of water to surfactant (R) and cosurfactant to surfactant (p). The particle size and fluorescence spectra were dependent upon the type of microemulsion system chosen. The particle size was found to decrease with an increase in concentration of ammonium hydroxide and increase in water to surfactant molar ratio (R) and cosurfactant to surfactant molar ratio (p). This optimization study of the preparation of dye-doped Silica Nanoparticles provides a fundamental knowledge of the synthesis and optical properties of Ru(bpy) dye-doped Silica Nanoparticles. With this information, these Nanoparticles can be easily manipulated, with regard to particle size and size distribution, and bioconjugated as needed for bioanalysis and bioseparation applications.

  • immobilization of oligonucleotides onto Silica Nanoparticles for dna hybridization studies
    Analytica Chimica Acta, 2002
    Co-Authors: Lisa R Hilliard, Xiaojun Zhao, Weihong Tan
    Abstract:

    Abstract This paper describes the development of oligonucleotide-functionalized Nanoparticles. We used disulfide-coupling chemistry for the immobilization of oligonucleotides onto Silica Nanoparticles and subsequently demonstrated the properties of the resulting DNA Nanoparticles. Factors influencing the immobilization and hybridization processes were examined and optimized. The oligonucleotide-modified Silica Nanoparticles provide an efficient substrate for hybridization and can be used in the development of DNA biosensors and biochips.

Martin Malmsten - One of the best experts on this subject based on the ideXlab platform.

  • membrane interactions of virus like mesoporous Silica Nanoparticles
    ACS Nano, 2021
    Co-Authors: Sara Malekkhaiat Haffner, Martin Malmsten, Elisa Parraortiz, Kathryn L Browning, Elin Jorgensen, Maximilian W A Skoda, Costanza Montis, Debora Berti, Dongyuan Zhao
    Abstract:

    In the present study, we investigated lipid membrane interactions of Silica Nanoparticles as carriers for the antimicrobial peptide LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES). In doing so, smooth mesoporous Nanoparticles were compared to virus-like mesoporous Nanoparticles, characterized by a "spiky" external surface, as well as to nonporous Silica Nanoparticles. For this, we employed a combination of neutron reflectometry, ellipsometry, dynamic light scattering, and ζ-potential measurements for studies of bacteria-mimicking bilayers formed by palmitoyloleoylphosphatidylcholine/palmitoyloleoylphosphatidylglycerol. The results show that nanoparticle topography strongly influences membrane binding and destabilization. We found that virus-like particles are able to destabilize such lipid membranes, whereas the corresponding smooth Silica Nanoparticles are not. This effect of particle spikes becomes further accentuated after loading of such particles with LL-37. Thus, peptide-loaded virus-like Nanoparticles displayed more pronounced membrane disruption than either peptide-loaded smooth Nanoparticles or free LL-37. The structural basis of this was clarified by neutron reflectometry, demonstrating that the virus-like Nanoparticles induce trans-membrane defects and promote incorporation of LL-37 throughout both bilayer leaflets. The relevance of such effects of particle spikes for bacterial membrane rupture was further demonstrated by confocal microscopy and live/dead assays on Escherichia coli bacteria. Taken together, these findings demonstrate that topography influences the interaction of Nanoparticles with bacteria-mimicking lipid bilayers, both in the absence and presence of antimicrobial peptides, as well as with bacteria. The results also identify virus-like mesoporous Nanoparticles as being of interest in the design of Nanoparticles as delivery systems for antimicrobial peptides.

  • membrane interactions of mesoporous Silica Nanoparticles as carriers of antimicrobial peptides
    Journal of Colloid and Interface Science, 2016
    Co-Authors: Katharina Braun, Alexander Pochert, Mika Linden, Mina Davoudi, Artur Schmidtchen, Randi Nordstrom, Martin Malmsten
    Abstract:

    Membrane interactions are critical for the successful use of mesoporous Silica Nanoparticles as delivery systems for antimicrobial peptides (AMPs). In order to elucidate these, we here investigate effects of nanoparticle charge and porosity on AMP loading and release, as well as consequences of this for membrane interactions and antimicrobial effects. Anionic mesoporous Silica particles were found to incorporate considerable amounts of the cationic AMP LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES (LL-37), whereas loading is much lower for non-porous or positively charged Silica Nanoparticles. Due to preferential pore localization, anionic mesoporous particles, but not the other particles, protect LL-37 from degradation by infection-related proteases. For anionic mesoporous Nanoparticles, membrane disruption is mediated almost exclusively by peptide release. In contrast, non-porous Silica particles build up a resilient LL-37 surface coating due to their higher negative surface charge, and display largely particle-mediated membrane interactions and antimicrobial effects. For positively charged mesoporous Silica Nanoparticles, LL-37 incorporation promotes the membrane binding and disruption displayed by the particles in the absence of peptide, but also causes toxicity against human erythrocytes. Thus, the use of mesoporous Silica Nanoparticles as AMP delivery systems requires consideration of membrane interactions and selectivity of both free peptide and the peptide-loaded Nanoparticles, the latter critically dependent on nanoparticle properties.

Stephan Sprenger - One of the best experts on this subject based on the ideXlab platform.

  • the mechanisms and mechanics of the toughening of epoxy polymers modified with Silica Nanoparticles
    Polymer, 2010
    Co-Authors: T. H. Hsieh, Kunal Masania, Anthony J. Kinloch, A C Taylor, Stephan Sprenger
    Abstract:

    Abstract The present paper considers the mechanical and fracture properties of four different epoxy polymers containing 0, 10 and 20 wt.% of well-dispersed Silica Nanoparticles. Firstly, it was found that, for any given epoxy polymer, their Young’s modulus steadily increased as the volume fraction, v f, of the Silica Nanoparticles was increased. Modelling studies showed that the measured moduli of the different Silica-nanoparticle filled epoxy polymers lay between upper-bound values set by the Halpin–Tsai and the Nielsen ‘no-slip’ models, and lower-bound values set by the Nielsen ‘slip’ model; with the last model being the more accurate at relatively high values of v f . Secondly, the presence of Silica Nanoparticles always led to an increase in the toughness of the epoxy polymer. However, to what extent a given epoxy polymer could be so toughened was related to structure/property relationships which were governed by (a) the values of glass transition temperature, T g , and molecular weight, M c , between cross-links of the epoxy polymer, and (b) the adhesion acting at the Silica nanoparticle/epoxy-polymer interface. Thirdly, the two toughening mechanisms which were operative in all the epoxy polymers containing Silica Nanoparticles were identified to be (a) localised shear bands initiated by the stress concentrations around the periphery of the Silica Nanoparticles, and (b) debonding of the Silica Nanoparticles followed by subsequent plastic void growth of the epoxy polymer. Finally, the toughening mechanisms have been quantitatively modelled and there was good agreement between the experimentally-measured values and the predicted values of the fracture energy, G c , for all the epoxy polymers modified by the presence of Silica Nanoparticles. The modelling studies have emphasised the important roles of the stress versus strain behaviour of the epoxy polymer and the Silica nanoparticle/epoxy-polymer interfacial adhesion in influencing the extent of the two toughening mechanisms, and hence the overall fracture energy, G c , of the nanoparticle-filled polymers.

  • The toughness of epoxy polymers and fibre composites modified with rubber microparticles and Silica Nanoparticles
    Journal of Materials Science, 2010
    Co-Authors: T. H. Hsieh, Kunal Masania, Anthony J. Kinloch, A C Taylor, J. Sohn Lee, Stephan Sprenger
    Abstract:

    The present paper investigates the effect of adding Silica Nanoparticles to an anhydride-cured epoxy polymer in bulk and when used as the matrix of carbon- and glass-fibre reinforced composites. The formation of ‘hybrid’ epoxy polymers, containing both Silica Nanoparticles and carboxyl-terminated butadiene-acrylonitrile (CTBN) rubber microparticles, is also discussed. The structure/property relationships are considered, with an emphasis on the toughness and the toughening mechanisms. The fracture energy of the bulk epoxy polymer was increased from 77 to 212 J/m^2 by the presence of 20 wt% of Silica Nanoparticles. The observed toughening mechanisms that were operative were (a) plastic shear-yield bands, and (b) debonding of the matrix from the Silica Nanoparticles, followed by plastic void-growth of the epoxy. The largest increases in toughness observed were for the ‘hybrid’ materials. Here a maximum fracture energy of 965 J/m^2 was measured for a ‘hybrid’ epoxy polymer containing 9 wt% and 15 wt% of the rubber microparticles and Silica Nanoparticles, respectively. Most noteworthy was the observation that these increases in the toughness of the bulk polymers were found to be transferred to the fibre composites. Indeed, the interlaminar fracture energies for the fibre-composite materials were increased even further by a fibre-bridging toughening mechanism. The present work also extends an existing model to predict the toughening effect of the Nanoparticles in a thermoset polymer. There was excellent agreement between the predictions and the experimental data for the epoxy containing the Silica Nanoparticles, and for epoxy polymers containing micrometre-sized glass particles. The latter, relatively large, glass particles were investigated to establish whether a ‘nano-effect’, with respect to increasing the toughness of the epoxy bulk polymers, did indeed exist.

Armido Studer - One of the best experts on this subject based on the ideXlab platform.