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1

Antibacterial titanium plate deposited by silver nanoparticles exhibits cell compatibility  

PubMed Central

Microbial colonization and biofilm formation on the surface of implant devices may cause peri-implantitis and lead to bone loss. The aim of this study was to develop a novel antibacterial titanium implant surface and to test its biological performance. In a previous study, we demonstrated that titanium plates deposited by nanosilver acquired antibacterial activity to Staphylococcus aureus and Escherichia coli. While antibacterial activity is important, biomaterial surfaces should be modified to achieve excellent cell compatibility as well. In the present study, using the MTT assay, fluorescence microscopy, and scanning electron microscopy, we assessed cell viability, cytoskeletal architecture and cell attachment, respectively, on our silver nanoparticle-modified titanium (Ti-nAg) plate. The results demonstrate that the Ti-nAg do not show any cytotoxicity to the human gingival fibroblasts. Our data indicate that Ti-nAg is a novel material with both good antibacterial properties and uncompromised cytocompatibility, which can be used as an implanted biomaterial.

Liao, Juan; Anchun, Mo; Zhu, Zhimin; Quan, Yuan

2010-01-01

2

Kinetically Assembled Nanoparticles of Bioactive Macromolecules Exhibit Enhanced Stability and Cell-Targeted Biological Efficacy  

PubMed Central

Kinetically assembled nanoparticles are fabricated from an advanced class of bioactive macromolecules that have potential utility in counteracting atherosclerotic plaque development via receptor-level blockage of inflammatory cells. In contrast to micellar analogs that exhibit poor potency and structural integrity under physiologic conditions, these kinetic nanoparticle assemblies maintain structural stability and demonstrate superior bioactivity in mediating oxidized low-density lipoprotein (oxLDL) uptake in inflammatory cells.

York, Adam W.; Zablocki, Kyle R.; Lewis, Daniel R.; Gu, Li; Uhrich, Kathryn E.; Prud'homme, Robert K.

2012-01-01

3

TRAIL conjugated to nanoparticles exhibits increased anti-tumor activities in glioma cells and glioma stem cells in vitro and in vivo.  

PubMed

Glioblastomas (GBM) are characterized by resistance to chemotherapy and radiotherapy, and therefore, alternative therapeutic approaches are needed. TRAIL induces apoptosis in cancer but not in normal cells and is considered to be a promising anti-tumor agent. However, its short in vivo half-life and lack of efficient administration modes are serious impediments to its therapeutic efficacy. Nanoparticles (NP) have been used as effective delivery tools for various anticancer drugs. TRAIL was conjugated to magnetic ferric oxide NP by binding the TRAIL primary amino groups to activated double bonds on the surface of the NP. The effect of NP-TRAIL was examined on the apoptosis of glioma cells and self-renewal of glioma stem cells (GSCs). In addition, the ability of the NP-TRAIL to track U251 cell-derived glioma xenografts and to affect cell apoptosis, tumor volume, and survival among xenografted rats was also examined. Conjugation of TRAIL to NP increased its apoptotic activity against different human glioma cells and GSCs, as compared with free recombinant TRAIL. Combined treatment with NP-TRAIL and ?-radiation or bortezomib sensitized TRAIL-resistant GSCs to NP-TRAIL. Using rhodamine-labeled NP and U251 glioma cell-derived xenografts, we demonstrated that the NP-TRAIL were found in the tumor site and induced a significant increase in glioma cell apoptosis, a decrease in tumor volume, and increased animal survival. In summary, conjugation of TRAIL to NP increased its apoptotic activity both in vitro and in vivo. Therefore, NP-TRAIL represents a targeted anticancer agent with more efficient action for the treatment of GBM and the eradication of GSCs. PMID:23144078

Perlstein, Benny; Finniss, Susan A; Miller, Cathie; Okhrimenko, Hana; Kazimirsky, Gila; Cazacu, Simona; Lee, Hae Kyung; Lemke, Nancy; Brodie, Shlomit; Umansky, Felix; Rempel, Sandra A; Rosenblum, Mark; Mikklesen, Tom; Margel, Shlomo; Brodie, Chaya

2012-11-08

4

Boron Polylactide Nanoparticles Exhibiting Fluorescence and Phosphorescence in Aqueous Medium  

PubMed Central

Difluoroboron dibenzoylmethane-polylactide, BF2dbmPLA, a biocompatible polymerluminophore conjugate was fabricated as nanoparticles. Spherical particles <100 nm in size were generated via nanoprecipitation. Intense blue fluorescence, two-photon absorption, and long-lived room temperature phosphorescence (RTP) are retained in aqueous suspension. The nanoparticles were internalized by cells and visualized by fluorescence microscopy. Luminescent boron biomaterials show potential for imaging and sensing.

Pfister, Anne; Zhang, Guoqing; Zareno, Jessica; Horwitz, Alan F.; Fraser, Cassandra L.

2008-01-01

5

Cell tracking using nanoparticles.  

PubMed

Tracking cells in regenerative medicine is becoming increasingly important for basic cell therapy science, for cell delivery optimization and for accurate biodistribution studies. This report describes nanoparticles that utilize stable-isotope metal labels for multiple detection technologies in preclinical studies. Cells labeled with nanoparticles can be imaged by electron microscopy, fluorescence, and magnetic resonance. The nanoparticle-labeled cells can be quantified by neutron activation, thereby allowing, with the use of standard curves, the determination of the number of labeled cells in tissue samples from in vivo sources. This report describes the characteristics of these nanoparticles and methods for using these nanoparticles to label and track cells. PMID:20559922

Vaccaro, Dennis E; Yang, Meiheng; Weinberg, James S; Reinhardt, Christopher P; Groman, Ernest V

2008-07-08

6

Nanoparticle–polymer photovoltaic cells  

Microsoft Academic Search

The need to develop and deploy large-scale, cost-effective, renewable energy is becoming increasingly important. In recent years photovoltaic (PV) cells based on nanoparticles blended with semiconducting polymers have achieved good power conversion efficiencies (PCE). All the nanoparticle types used in these PV cells can be considered as colloids. These include spherical, rod-like or branched organic or inorganic nanoparticles. Nanoparticle–polymer PV

Brian R. Saunders; Michael L. Turner

2008-01-01

7

Surface functionalization of gold nanoparticles with red blood cell membranes.  

PubMed

Gold nanoparticles are enclosed in cellular membranes derived from natural red blood cells (RBCs) by a top-down approach. The gold nanoparticles exhibit a complete membrane surface layer and biological characteristics of the source cells. The combination of inorganic gold nanoparticles with biological membranes is a compelling way to develop biomimetic gold nanostructures for future applications, such as those requiring evasion of the immune system. PMID:23712782

Gao, Weiwei; Hu, Che-Ming J; Fang, Ronnie H; Luk, Brian T; Su, Jing; Zhang, Liangfang

2013-05-27

8

CuS Nanoparticles for Photothermal Ablation of Tumor Cells  

NASA Astrophysics Data System (ADS)

Here, we report the photothermal ablation effects of 3-nm CuS nanoparticles. CuS nanoparticles exhibited strong absorption in the near infrared (NIR) region. Irradiation by a laser beam at 808 nm elevated the temperature of aqueous solutions of CuS nanoparticles as a function of exposure time and nanoparticle concentration. CuS nanoparticles mediated photothermal destruction of HeLa cells in a laser dose- and nanoparticle concentration-dependent manner, and displayed minimal cytotoxic effects with a profile similar to that of gold nanoparticles. Owing to their unique optical property, small size, low cost of production, and low cytotoxicity, CuS nanoparticles are promising new nanomaterials for cancer photothermal ablation therapy.

Chen, Wei; Li, Yuebin; Li, Chun; Lu, Wei; Huang, Qian; Huang, Miao

2011-03-01

9

Polyelectrolyte-assisted formation of molecular nanoparticles exhibiting strongly enhanced fluorescence.  

PubMed

A polyelectrolyte-assisted reprecipitation method is developed to fabricate nanoparticles of highly soluble molecules. The approach is demonstrated by using a zwitterionic diaminodicyanoquinodimethane molecule bearing remote ammonium functionalities with high solubility in water as well as organic solvents. Nanoparticles are prepared by injecting aqueous solutions of this compound containing an optimum concentration of sodium poly(styrenesulfonate) into methanol. The strong fluorescence exhibited by the compound in the aggregated state is reflected in the enhanced fluorescence of the polyelectrolyte complex in water. The nanoparticles formed in the colloidal state manifest even stronger fluorescence, which leads to an overall enhancement by about 90 times relative to aqueous solutions of the pure compound. The conditions for achieving the emission enhancement are optimized and a model for the molecular-level interactions and aggregation effects is developed through a range of spectroscopy, microscopy, and calorimetry investigations and control experiments. PMID:20575120

Chandaluri, Ch G; Patra, A; Radhakrishnan, T P

2010-08-01

10

Preferential killing of cancer cells and activated human T cells using ZnO nanoparticles  

PubMed Central

Nanoparticles are increasingly being recognized for their potential utility in biological applications including nanomedicine. Here we examine the response of normal human cells to ZnO nanoparticles under different signaling environments and compare it to the response of cancerous cells. ZnO nanoparticles exhibit a strong preferential ability to kill cancerous T cells (?28–35×) compared to normal cells. Interestingly, the activation state of the cell contributes toward nanoparticle toxicity, as resting T cells display a relative resistance while cells stimulated through the T cell receptor and CD28 costimulatory pathway show greater toxicity in direct relation to the level of activation. Mechanisms of toxicity appear to involve the generation of reactive oxygen species, with cancerous T cells producing higher inducible levels than normal T cells. In addition, nanoparticles were found to induce apoptosis and the inhibition of reactive oxygen species was found to be protective against nanoparticle induced cell death. The novel findings of cell selective toxicity, towards potential disease causing cells, indicate a potential utility of ZnO nanoparticles in the treatment of cancer and/or autoimmunity.

Hanley, Cory; Layne, Janet; Punnoose, Alex; Reddy, K M; Coombs, Isaac; Coombs, Andrew; Feris, Kevin; Wingett, Denise

2008-01-01

11

Simulation of transport and extravasation of nanoparticles in tumors which exhibit enhanced permeability and retention effect.  

PubMed

Determining the factors that influence the delivery of sub-micron particles to tumors and understanding the relative importance of each of these factors is fundamental to the optimization of the particle delivery process. In this paper, a model that combines random walk with the pressure driven movement of nanoparticles in a tumor vasculature is presented. Nanoparticle movement in a cylindrical tube with dimensions similar to the tumor's blood capillary with a single pore is simulated. Nanoparticle velocities are calculated as a pressure driven flow over imposed to Brownian motion. The number and percentage of nanoparticles leaving the blood vessel through a single pore is obtained as a function of pore size, nanoparticle size and concentration, interstitial pressure, and blood pressure. The model presented here is able to determine the importance of these controllable parameters and thus it can be used to understand the process and predict the best conditions for nanoparticle-based treatment. The results indicate that the nanoparticle delivery gradually increases with pore size and decreases with nanoparticle size for tumors with high interstitial fluid pressure (in this work we found this behavior for head and neck carcinoma and for metastatic melanoma with interstitial pressures of 18mmHg and 19mmHg, respectively). For tumors with lower interstitial fluid pressure (rectal carcinoma with 15.3mmHg) however, delivery is observed to have little sensitivity to particle size for almost the entire nanoparticle size range. Though an increase in nanoparticle concentration increases the number of nanoparticles being delivered, the efficiency of the delivery (percentage of nanoparticles delivered) is found to remain closely unaffected. PMID:23871689

Podduturi, Vishwa Priya; Magaña, Isidro B; O'Neal, D Patrick; Derosa, Pedro A

2013-07-18

12

Transferrin-modified Doxorubicin-loaded biodegradable nanoparticles exhibit enhanced efficacy in treating brain glioma-bearing rats.  

PubMed

Abstract Doxorubicin (Dox) is widely used for the treatment of solid tumors but its clinical utility on glioma is limited. In this study, we developed a novel nano-scale drug delivery system employing biodegradable nanoparticle (NP) as carriers to load Dox. Transferrin (Tf) was conjugated to the surface of NP to specifically target the NP to glioma. Tf-NP-Dox was prepared via emulsification-solvent evaporation method, and characterized for the size, Drug loading capacity (DLC), entrapment efficiency, and Tf number on the surface. The antitumor efficiency in vitro was evaluated via CCK-8 assay. The transmembrane transportation was evaluated via HPLC assay. The antitumor efficiency in vivo was assessed in C6 glioma intracranial implant rat model. The average diameter of Tf-NP-Dox was 100?nm with ?32 Tf molecules on the surface. DLC was 4.4%. CCK-8 assay demonstrated much stronger cytotoxicity of Tf-NP-Dox to C6 glioma cells compared to NP-Dox or Dox. HPLC assay showed that Tf-NP-Dox transported Dox into C6 cells with high efficiency. In vivo, Tf-NP-Dox could transport Dox into tumors compare to contralateral part, with tumor inhibitory ratio and survival higher than NP-Dox or Dox. Taken together, our results suggest that Tf-NP-Dox exhibits better therapeutic effects against glioma both in vitro and in vivo, and is a potential nano-scale drug delivery system for glioma chemotherapy. PMID:23786401

Liu, Guodong; Mao, Jinning; Jiang, Zirong; Sun, Tao; Hu, Yunfeng; Jiang, Zhen; Zhang, Caiyuan; Dong, Jun; Huang, Qiang; Lan, Qing

2013-06-20

13

Levetiracetam exhibits protective properties on rat Schwann cells in vitro.  

PubMed

Oxidative stress and inflammation represent pathways causing substantial damage to the peripheral nervous system. Levetiracetam (LEV) is a commonly used antiepileptic drug targeting high-voltage activated N-type calcium channels. Recent evidence suggests that LEV may also act as a histone deacetylase inhibitor, suggesting that this drug exhibits both anti-inflammatory and anti-oxidative effects, and as such may represent an interesting candidate for treating inflammatory diseases affecting the peripheral nerve. Therefore, we analysed the influence of LEV ex vivo on purified Schwann cells from neonatal P3 rats as well as on dorsal root ganglia prepared from E15 rat embryos. LEV diminished a lipopolysaccharide (LPS)-induced increase of the pro-inflammatory signature molecules tumour necrosis factor alpha, matrix metalloproteinase 9 (MMP-9), and caspase 6. Furthermore, LEV decreased LPS-induced cell death and protected cells against oxidative stress in a glutamate-based oxidative stress model. MMP-2 activity, usually elevated during myelination and repair, was also found to be up-regulated following LEV, while LEV exhibited no negative effects on myelination. Intracellular sodium or calcium concentrations were unaltered by LEV. Thus, LEV may be a promising, well-tolerated drug that - besides its antiepileptic potential - mediates anti-inflammatory, anti-oxidative, and anti-apoptotic properties that may potentially be useful in treating diseases of the peripheral nerve. PMID:22003940

Stettner, Mark; Dehmel, Thomas; Mausberg, Anne K; Köhne, Angelika; Rose, Christine R; Kieseier, Bernd C

2011-09-01

14

Ion mediated targeting of cells with nanoparticles  

NASA Astrophysics Data System (ADS)

In eukaryotic cells, Ca^2+ ions are necessary for intracellular signaling, in activity of mitochondria and a variety of other cellular process that have been linked to cell apoptosis, proteins synthesis and cell-cycle regulation. Here we show that Ca^2+ ions, serving as the bio-compatible interface can be used to target Saccharomyces cerevisiae (SaC, baker's yeast), a model eukaryotic cell, with Au nanoparticles (10 nm). The Ca^2+ ions bind to the carboxylic acid groups in the citrate functionalized Au nanoparticles. This transforms the nanoparticles into micron long 1-D branched chain assemblies due to inter-particle dipole-dipole interaction and inter-particle bonding due to the divalent nature of the Ca^2+ ion. A similar transformation is observed with the use of divalent ions Mg^2+, Cd^2+ and Fe^2+. The 1-D assembly aids the interfacing of ion-nanoparticles on the cell by providing multiple contact points. Further monovalent ions such as Na^+ are also effective for the targeting of the cell with nanoparticles. However Na-Au nanoparticles are limited in their deposition as they exist in solution as single particles. The cells remain alive after the deposition process and their vitality is unaffected by the interfacing with ion-nanoparticles.

Maheshwari, Vivek; Fu, Jinlong

2010-03-01

15

Modeling of interactions between nanoparticles and cell membranes  

NASA Astrophysics Data System (ADS)

Rapid development of nanotechnology and ability to manufacture materials and devices with nanometer feature size leads to exciting innovations in many areas including the medical and electronic fields. However, the possible health and environmental impacts of manufactured nanomaterials are not fully known. Recent experimental reports suggest that some of the manufactured nanomaterials, such as fullerenes and carbon nanotubes, are highly toxic even in small concentrations. The goal of the current work is to understand the mechanisms responsible for the toxicity of nanomaterials. In the current study coarse-grained molecular dynamics simulations are employed to investigate the interactions between NPs and cellular membranes at a molecular level. One of the possible toxicity mechanisms of the nanomaterials is membrane disruption. Possibility of membrane disruption exposed to the manufactured nanomaterials are examined by considering chemical reactions and non-reactive physical interactions as chemical as well as physical mechanisms. Mechanisms of transport of carbon-based nanoparticles (fullerene and its derivative) across a phospholipid bilayer are investigated. The free energy profile is obtained using constrained simulations. It is shown that the considered nanoparticles are hydrophobic and therefore they tend to reside in the interior of the lipid bilayer. In addition, the dynamics of the membrane fluctuations is significantly affected by the nanoparticles at the bilayer-water interface. The hydrophobic interaction between the particles and membrane core induces the strong coupling between the nanoparticle motion and membrane deformation. It is observed that the considered nanoparticles affect several physical properties of the membrane. The nanoparticles embedded into the membrane interior lead to the membrane softening, which becomes more significant with increase in CNT length and concentration. The lateral pressure profile and membrane energy in the membrane containing the nanoparticles exhibit localized perturbation around the nanoparticle. The nanoparticles are not likely to affect membrane protein function by the weak perturbation of the internal stress in the membrane. Due to the short-ranged interactions between the nanoparticles, the nanoparticles would not form aggregates inside membranes. The effect of lipid peroxidation on cell membrane deformation is assessed. The peroxidized lipids introduce a perturbation to the internal structure of the membrane leading to higher amplitude of the membrane fluctuations. Higher concentration of the peroxidized lipids induces more significant perturbation. Cumulative effects of lipid peroxidation caused by nanoparticles are examined for the first time. The considered amphiphilic particle appears to reduce the perturbation of the membrane structure at its equilibrium position inside the peroxidized membrane. This suggests a possibility of antioxidant effect of the nanoparticle.

Ban, Young-Min

16

Encapsulation of plasmid DNA in calcium phosphate nanoparticles: stem cell uptake and gene transfer efficiency  

PubMed Central

Background The purpose of this study was to develop calcium phosphate nanocomposite particles encapsulating plasmid DNA (CP-pDNA) nanoparticles as a nonviral vector for gene delivery. Methods CP-pDNA nanoparticles employing plasmid transforming growth factor beta 1 (TGF-?1) were prepared and characterized. The transfection efficiency and cell viability of the CP-pDNA nanoparticles were evaluated in mesenchymal stem cells, which were identified by immunofluorescence staining. Cytotoxicity of plasmid TGF-?1 and calcium phosphate to mesenchymal stem cells were evaluated by MTT assay. Results The integrity of TGF-?1 encapsulated in the CP-pDNA nanoparticles was maintained. The well dispersed CP-pDNA nanoparticles exhibited an ultralow particle size (20–50 nm) and significantly lower cytotoxicity than Lipofectamine™ 2000. Immunofluorescence staining revealed that the cultured cells in this study were probably mesenchymal stem cells. The cellular uptake and transfection efficiency of the CP-pDNA nanoparticles into the mesenchymal stem cells were higher than that of needle-like calcium phosphate nanoparticles and a standard calcium phosphate transfection kit. Furthermore, live cell imaging and confocal laser microscopy vividly showed the transportation process of the CP-pDNA nanoparticles in mesenchymal stem cells. The results of a cytotoxicity assay found that both plasmid TGF-?1 and calcium phosphate were not toxic to mesenchymal stem cells. Conclusion CP-pDNA nanoparticles can be developed into an effective alternative as a nonviral gene delivery system that is highly efficient and has low cytotoxicity.

Cao, Xia; Deng, Wenwen; Wei, Yuan; Su, Weiyan; Yang, Yan; Wei, Yawei; Yu, Jiangnan; Xu, Ximing

2011-01-01

17

Enhancement of cell radiation sensitivity by pegylated gold nanoparticles.  

PubMed

Biocompatible Au nanoparticles with surfaces modified by PEG (polyethylene glycol) were developed in view of possible applications for the enhancement of radiotherapy. Such nanoparticles exhibit preferential deposition at tumor sites due to the enhanced permeation and retention (EPR) effect. Here, we systematically studied their effects on EMT-6 and CT26 cell survival rates during irradiation for a dose up to 10 Gy with a commercial biological irradiator (E(average) = 73 keV), a Cu-Kalpha(1) x-ray source (8.048 keV), a monochromatized synchrotron source (6.5 keV), a radio-oncology linear accelerator (6 MeV) and a proton source (3 MeV). The percentage of surviving cells after irradiation was found to decrease by approximately 2-45% in the presence of PEG-Au nanoparticles ([Au] = 400, 500 or 1000 microM). The cell survival rates decreased as a function of the dose for all sources and nanoparticle concentrations. These results could open the way to more effective cancer irradiation therapies by using nanoparticles with optimized surface treatment. Difficulties in applying MTT assays were also brought to light, showing that this approach is not suitable for radiobiology. PMID:20090183

Liu, Chi-Jen; Wang, Chang-Hai; Chen, Shin-Tai; Chen, Hsiang-Hsin; Leng, Wei-Hua; Chien, Chia-Chi; Wang, Cheng-Liang; Kempson, Ivan M; Hwu, Y; Lai, Tsung-Ching; Hsiao, Michael; Yang, Chung-Shi; Chen, Yu-Jen; Margaritondo, G

2010-01-20

18

Enhancement of cell radiation sensitivity by pegylated gold nanoparticles  

NASA Astrophysics Data System (ADS)

Biocompatible Au nanoparticles with surfaces modified by PEG (polyethylene glycol) were developed in view of possible applications for the enhancement of radiotherapy. Such nanoparticles exhibit preferential deposition at tumor sites due to the enhanced permeation and retention (EPR) effect. Here, we systematically studied their effects on EMT-6 and CT26 cell survival rates during irradiation for a dose up to 10 Gy with a commercial biological irradiator (Eaverage = 73 keV), a Cu-K?1 x-ray source (8.048 keV), a monochromatized synchrotron source (6.5 keV), a radio-oncology linear accelerator (6 MeV) and a proton source (3 MeV). The percentage of surviving cells after irradiation was found to decrease by ~2-45% in the presence of PEG-Au nanoparticles ([Au] = 400, 500 or 1000 µM). The cell survival rates decreased as a function of the dose for all sources and nanoparticle concentrations. These results could open the way to more effective cancer irradiation therapies by using nanoparticles with optimized surface treatment. Difficulties in applying MTT assays were also brought to light, showing that this approach is not suitable for radiobiology.

Liu, Chi-Jen; Wang, Chang-Hai; Chen, Shin-Tai; Chen, Hsiang-Hsin; Leng, Wei-Hua; Chien, Chia-Chi; Wang, Cheng-Liang; Kempson, Ivan M.; Hwu, Y.; Lai, Tsung-Ching; Hsiao, Michael; Yang, Chung-Shi; Chen, Yu-Jen; Margaritondo, G.

2010-02-01

19

Nitric oxide-releasing silica nanoparticle inhibition of ovarian cancer cell growth  

PubMed Central

Although the potent anti-tumor activity of nitric oxide (NO) supports its promise as an anti-neoplastic agent, effective and selective delivery and action on tumor and not normal cells remains a limiting factor. Nanoparticle-based delivery of NO has been considered as one approach to overcome these limitations. Therefore, we determined the utility of NO delivery using silica nanoparticles and evaluated their anti-tumor efficacy against human ovarian tumor and nontumor cells. The NO-releasing nanoparticles exhibited enhanced growth inhibition of ovarian tumor cells when compared to both control nanoparticles and a previously reported small molecule NO donor, PYRRO/NO. In addition, the NO-releasing nanoparticles showed greater inhibition of the anchorage-independent growth of tumor-derived and Ras-transformed ovarian cells. Confocal microscopy analysis revealed that fluorescently-labeled NO-releasing nanoparticles entered the cytosol of the cell and localized to late endosomes and lysosomes. Furthermore, we observed a nanoparticle size dependency on efficacy against normal versus transformed ovarian cells. Our study provides the first application of nanoparticle-derived NO as an antitumor therapy and supports the merit for future studies examining nanoparticle formulation for in vivo applications.

Stevens, Ellen V.; Wells, Alexis; Shin, Jae Ho; Liu, Jinsong; Der, Channing J.; Schoenfisch, Mark H.

2013-01-01

20

Nanotemplate Engineering of Cell Specific Nanoparticles  

Microsoft Academic Search

Through nanotechnology, it is now possible to cost?effectively and reproducibly create and develop useful small particles for applications in the pharmaceutical, medical, chemical, and engineering fields. In the pharmaceutical field, cost?effective, reproducible, and scalable processes to engineer cell? or tissue?targeted nanoparticles are sought to deliver potent drugs as new therapies. A natural and spontaneous method to engineer nanoparticles has been

Russell J. Mumper; Zhengrong Cui; Moses O. Oyewumi

2003-01-01

21

Tracking stem cells using magnetic nanoparticles  

PubMed Central

Stem cell therapies offer great promise for many diseases, especially those without current effective treatments. It is believed that noninvasive imaging techniques, which offer the ability to track the status of cells after transplantation, will expedite progress in this field and help to achieve maximized therapeutic effect. Today’s biomedical imaging technology allows for real-time, noninvasive monitoring of grafted stem cells including their biodistribution, migration, survival, and differentiation, with magnetic resonance imaging (MRI) of nanoparticle-labeled cells being one of the most commonly used techniques. Among the advantages of MR cell tracking are its high spatial resolution, no exposure to ionizing radiation, and clinical applicability. In order to track cells by MRI, the cells need to be labeled with magnetic nanoparticles, for which many types exist. There are several cellular labeling techniques available, including simple incubation, use of transfection agents, magnetoelectroporation, and magnetosonoporation. In this overview article, we will review the use of different magnetic nanoparticles and discuss how these particles can be used to track the distribution of transplanted cells in different organ systems. Caveats and limitations inherent to the tracking of nanoparticle-labeled stem cells are also discussed.

Cromer Berman, Stacey M.; Walczak, Piotr; Bulte, Jeff W.M.

2011-01-01

22

Imaging nanoparticles in cells by nanomechanical holography  

SciTech Connect

Nanomaterials have potential medical applications, for example in the area of drug delivery, and their possible adverse effects and cytotoxicity are curently receiving attention1,2. Inhalation of nanoparticles is of great concern, because nanoparticles can be easily aerosolized. Imaging techniques that can visualize local populations of nanoparticles at nanometre resolution within the structures of cells are therefore important3. Here we show that cells obtained from mice exposed to single-walled carbon nanohorns can be probed using a scanning probe microscopy technique called scanning near field ultrasonic holography. The nanohorns were observed inside the cells, and this was further confirmed using micro Raman spectroscopy. Scanning near field ultrasonic holography is a useful technique for probing the interactions of engineered nanomaterials in biological systems, which will greatly benefit areas in drug delivery and nanotoxicology.

Tetard, Laurene [ORNL; Passian, Ali [ORNL; Venmar, Katherine T [ORNL; Lynch, Rachel M [ORNL; Voy, Brynn H [ORNL; Shekhawat, Gajendra [Northwestern University, Evanston; Dravid, Vinayak [Northwestern University, Evanston; Thundat, Thomas George [ORNL

2008-06-01

23

ZnO nanoparticles induces cell death in malignant human T98G gliomas, KB and non-malignant HEK cells.  

PubMed

This paper reports the synthesis and characterization of ZnO nanoparticles prepared by soft chemical process. The nanoparticles of ZnO possess wurtzite hexagonal phase and were used for the induction of cell death in malignant human T98G gliomas, KB epithermoids and HEK normal non-malignant kidney cells. By applying ZnO nanoparticles, the cells exhibit that the nanoparticles are more efficacious on T98G cancer cells, moderately effective on KB cells and least toxic on normal human HEK cells. The results demonstrated that the treatment with ZnO nanoparticles sensitize T98G cells by increasing both the mitotic (linked to cytogenetic damage) and interphase (apoptosis) death. The ZnO nanoparticles behave as genotoxic drugs, since they induce a micronucleus formation in cells. The present study could be helpful in designing more potent anticancer agents for the therapeutic uses. PMID:23909132

Wahab, Rizwan; Kaushik, Nagendra Kumar; Kaushik, Neha; Choi, Eun Ha; Umar, Ahmad; Dwivedi, Sourabh; Musarrat, Javed; Al-Khedhairy, Abdulaziz A

2013-07-01

24

Evaluating cell specific cytotoxicity of differentially charged silver nanoparticles.  

PubMed

Silver nanoparticles (AgNPs) are one of the most commercially viable nanotechnological products, nevertheless; safety issues are raised regarding the use of such nanoparticles due to unintentional health and environmental impacts. In the present study, AgNPs were synthesized by chemically reducing silver nitrate alternatively with sodium borohydride, tannic acid, ascorbic acid and sodium citrate. AgNPs synthesized by reduction with tannic acid (TSNPs) and sodium borohydride (BSNPs) exhibited highest and lowest surface potential respectively. Therefore these two types of AgNPs were selected for their toxicity assessment in cellular environment. We treated skin epithelial A431, lung epithelial A549 and murine macrophages RAW264.7 cells with AgNPs over a range of doses (5-100?g/ml). Toxicity was evaluated by measuring changes in cellular morphology, ROS generation, metabolic activity and expression of various stress markers. Interestingly, TSNPs exhibited a higher negative zeta-potential and also higher toxicity. Higher toxicity of TSNPs was attested by dose-dependent increase in cellular disruption and ROS generation. BSNPs showed cytotoxic effect up to the concentration of 50?g/ml and thereafter the cytotoxic effect attenuated. TSNPs induced a dose dependent increase in the expression of stress markers pp38, TNF-? and HSP-70. Our report proposes that cytotoxicity of AgNPs changes with surface potential of nanoparticles and cells type. PMID:22975145

Kaur, Jasmine; Tikoo, Kulbhushan

2012-08-30

25

?? T cells exhibit multifunctional and protective memory in intestinal tissues.  

PubMed

The study of T cell memory and the target of vaccine design have focused on memory subsumed by T cells bearing the ?? T cell receptor. Alternatively, ?? T cells are thought to provide rapid immunity, particularly at mucosal borders. Here, we have shown that a distinct subset of mucosal ?? T cells mounts an immune response to oral Listeria monocytogenes (Lm) infection and leads to the development of multifunctional memory T cells capable of simultaneously producing interferon-? and interleukin-17A in the murine intestinal mucosa. Challenge infection with oral Lm, but not oral Salmonella or intravenous Lm, induced rapid expansion of memory ?? T cells, suggesting contextual specificity to the priming pathogen. Importantly, memory ?? T cells were able to provide enhanced protection against infection. These findings illustrate that ?? T cells play a role with hallmarks of adaptive immunity in the intestinal mucosa. PMID:23890071

Sheridan, Brian S; Romagnoli, Pablo A; Pham, Quynh-Mai; Fu, Han-Hsuan; Alonzo, Francis; Schubert, Wolf-Dieter; Freitag, Nancy E; Lefrançois, Leo

2013-07-25

26

Cell selective response to gold nanoparticles  

Microsoft Academic Search

Gold nanoparticles (GNPs) are considered a potential probe to detect cancer. The present article investigates whether GNPs, even in the absence of any specific functionalization, induce any cell-specific response. We report GNP-induced death response in human carcinoma lung cell line A549. In contrast, the two other cell lines tested, BHK21 (baby hamster kidney) and HepG2 (human hepatocellular liver carcinoma), remained

Hirak K. Patra; Shuvojit Banerjee; Utpal Chaudhuri; Prabir Lahiri; Anjan Kr. Dasgupta

2007-01-01

27

CNS microvascular pericytes exhibit multipotential stem cell activity  

Microsoft Academic Search

It has been suggested that a vascular-like cell has multipotent regenerative and mesenchymal lineage relationships. The identity of this stem\\/progenitor cell has remained elusive. We report here that adult central nervous system (CNS) capillaries contain a distinct population of microvascular cells, the pericyte that are nestin\\/NG2 positive and in response to basic fibroblast growth factor (bFGF) differentiate into cells of

Paula Dore-Duffy; Andre Katychev; Xueqian Wang; Eric Van Buren

2006-01-01

28

Functionalized magnetic-fluorescent hybrid nanoparticles for cell labelling  

NASA Astrophysics Data System (ADS)

A facile method of synthesizing 60 nm magnetic-fluorescent core-shell bifunctional nanocomposites with the ability to label cells is presented. Hydrophobic trioctylphosphine oxide (TOPO)-capped CdSe@ZnS quantum dots (QDs) were assembled on polyethyleneimine (PEI)-coated Fe3O4 nanoparticles (MNP). Polyethyleneimine was utilized for the realization of multifunction, including attaching 4 nm TOPO capped CdSe@ZnS quantum dots onto magnetite particles, altering the surface properties of quantum dots from hydrophobic to hydrophilic as well as preventing the formation of large aggregates. Results show that these water-soluble hybrid nanocomposites exhibit good colloidal stability and retain good magnetic and fluorescent properties. Because TOPO-capped QDs are assembled instead of their water-soluble equivalents, the nanocomposites are still highly luminescent with no shift in the PL peak position and present long-term fluorescence stability. Moreover, TAT peptide (GRKKRRQRRRPQ) functionalized hybrid nanoparticles were also studied due to their combined magnetic enrichment and optical detection for cell separation and rapid cell labelling. A cell viability assay revealed good biocompatibility of these hybrid nanoparticles. The potential application of the new magnetic-fluorescent nanocomposites in biological and medicine is demonstrated.

Lou, Lei; Yu, Ke; Zhang, Zhengli; Li, Bo; Zhu, Jianzhong; Wang, Yiting; Huang, Rong; Zhu, Ziqiang

2011-05-01

29

In vitro effects of nanoparticles on renal cells  

PubMed Central

Background The ability of nanoparticles to cross the lung-blood barrier suggests that they may translocate to blood and to targets distant from their portal of entry. Nevertheless, nanotoxicity in organs has received little attention. The purpose of this study was to evaluate nanotoxicity in renal cells using in vitro models. Various carbon black (CB) (FW2–13 nm, Printex60-21 nm and LB101-95 nm) and titanium dioxide (TiO2-15 and TiO2-50 nm) nanoparticles were characterized on size by electron microscopy. We evaluated theirs effects on glomerular mesangial (IP15) and epithelial proximal tubular (LLC-PK1) renal cells, using light microscopy, WST-1 assay, immunofluorescence labeling and DCFH-DA for reactive oxygen species (ROS) assay. Results Nanoparticles induced a variety of cell responses. On both IP15 and LLC-PK1 cells, the smallest FW2 NP was found to be the most cytotoxic with classic dose-behavior. For the other NPs tested, different cytotoxic profiles were found, with LLC-PK1 cells being more sensitive than IP15 cells. Exposure to FW2 NPs, evidenced in our experiments as the most cytotoxic particle type, significantly enhanced production of ROS in both IP15 and LLC-PK1 cells. Immunofluorescence microscopy using latex beads indicated that depending on their size, the cells internalized particles, which accumulated in the cell cytoplasm. Additionally using transmission electronic microscope micrographs show nanoparticles inside the cells and trapped in vesicles. Conclusion The present data constitute the first step towards determining in vitro dose effect of manufactured CB and TiO2 NPs in renal cells. Cytotoxicological assays using epithelial tubular and glomerular mesangial cell lines rapidly provide information and demonstrated that NP materials exhibit varying degrees of cytotoxicity. It seems clear that in vitro cellular systems will need to be further developed, standardized and validated (relative to in vivo effects) in order to provide useful screening data about the relative toxicity of nanoparticles.

L'Azou, Beatrice; Jorly, Joana; On, Dinhill; Sellier, Elisabeth; Moisan, Frederic; Fleury-Feith, Jocelyne; Cambar, Jean; Brochard, Patrick; Ohayon-Courtes, Celine

2008-01-01

30

Nanoparticle Solar Cell Final Technical Report  

SciTech Connect

The purpose of this work was to demonstrate all-inorganic nanoparticle-based solar cells with photovoltaic performance extending into the near-IR region of the solar spectrum as a pathway towards improving power conversion efficiencies. The field of all-inorganic nanoparticle-based solar cells is very new, with only one literature publication in the prior to our project. Very little is understood regarding how these devices function. Inorganic solar cells with IR performance have previously been fabricated using traditional methods such as physical vapor deposition and sputtering, and solution-processed devices utilizing IR-absorbing organic polymers have been investigated. The solution-based deposition of nanoparticles offers the potential of a low-cost manufacturing process combined with the ability to tune the chemical synthesis and material properties to control the device properties. This work, in collaboration with the Sue Carter research group at the University of California, Santa Cruz, has greatly expanded the knowledge base in this field, exploring multiple material systems and several key areas of device physics including temperature, bandgap and electrode device behavior dependence, material morphological behavior, and the role of buffer layers. One publication has been accepted to Solar Energy Materials and Solar Cells pending minor revision and another two papers are being written now. While device performance in the near-IR did not reach the level anticipated at the beginning of this grant, we did observe one of the highest near-IR efficiencies for a nanoparticle-based solar cell device to date. We also identified several key parameters of importance for improving both near-IR performance and nanoparticle solar cells in general, and demonstrated multiple pathways which showed promise for future commercialization with further research.

Breeze, Alison, J; Sahoo, Yudhisthira; Reddy, Damoder; Sholin, Veronica; Carter, Sue

2008-06-17

31

Inhibition of Tumor Cell Invasion with Chlorotoxin-Bound Superparamagnetic Nanoparticles  

PubMed Central

Nanoparticles have been investigated as drug delivery vehicles, contrast agents, and multifunctional devices for patient care. Current nanoparticle-based therapeutic strategies for cancer treatment have been mainly based on delivery of chemotherapeutic agents to induce apoptosis or DNA/siRNA to regulate oncogene expression. Here, we present a nanoparticle system that demonstrates an alternative approach to the treatment of cancers, through the inhibition of cell invasion, while serving as a magnetic resonance and optical imaging contrast agent. The nanoparticle is comprised of an iron oxide nanoparticle core, conjugated with an amine-functionalized PEG silane and a small peptide, chlorotoxin (CTX), which enables the tumor cell-specific binding of the nanoparticle. We show that the nanoparticle exhibits substantially enhanced cellular uptake and an invasion inhibition rate of ~98% compared to unbound CTX (~45%). Significantly, our investigation from flow cytometry analysis, transmission electron microscopy and fluorescent imaging revealed that the CTX-enabled nanoparticles deactivated the membrane-bound matrix metalloproteinase 2 (MMP-2) and induced increased internalization of lipid rafts that contain surface-expressed MMP-2 and volume-regulating ion channels through receptor-mediated endocytosis, leading to enhanced prohibitory effects. Since upregulation and activity of MMP-2 have been observed in tumors of neuroectodermal origin, and in cancers of the breast, colon, skin, lung, prostate, ovaries and a host of others, this nanoparticle system can be potentially used for non-invasive diagnosis and treatment of a variety of cancer types.

Veiseh, Omid; Gunn, Jonathan W.; Kievit, Forrest; Sun, Conroy; Fang, Chen; Lee, Jerry S.H.; Zhang, Miqin

2009-01-01

32

Histone H1 null vertebrate cells exhibit altered nucleosome architecture  

PubMed Central

In eukaryotic nuclei, DNA is wrapped around an octamer of core histones to form nucleosomes, and chromatin fibers are thought to be stabilized by linker histones of the H1 type. Higher eukaryotes express multiple variants of histone H1; chickens possess six H1 variants. Here, we generated and analyzed the phenotype of a complete deletion of histone H1 genes in chicken cells. The H1-null cells showed decreased global nucleosome spacing, expanded nuclear volumes, and increased chromosome aberration rates, although proper mitotic chromatin structure appeared to be maintained. Expression array analysis revealed that the transcription of multiple genes was affected and was mostly downregulated in histone H1-deficient cells. This report describes the first histone H1 complete knockout cells in vertebrates and suggests that linker histone H1, while not required for mitotic chromatin condensation, plays important roles in nucleosome spacing and interphase chromatin compaction and acts as a global transcription regulator.

Hashimoto, Hideharu; Takami, Yasunari; Sonoda, Eiichiro; Iwasaki, Tomohito; Iwano, Hidetomo; Tachibana, Makoto; Takeda, Shunichi; Nakayama, Tatsuo; Kimura, Hiroshi; Shinkai, Yoichi

2010-01-01

33

Nanoparticle adhesion to the cell membrane and its effect on nanoparticle uptake efficiency.  

PubMed

The interactions between nanosized particles and living systems are commonly mediated by what adsorbs to the nanoparticle in the biological environment, its biomolecular corona, rather than the pristine surface. Here, we characterize the adhesion toward the cell membrane of nanoparticles of different material and size and study how this is modulated by the presence or absence of a corona on the nanoparticle surface. The results are corroborated with adsorption to simple model supported lipid bilayers using a quartz crystal microbalance. We conclude that the adsorption of proteins on the nanoparticle surface strongly reduces nanoparticle adhesion in comparison to what is observed for the bare material. Nanoparticle uptake is described as a two-step process, where the nanoparticles initially adhere to the cell membrane and subsequently are internalized by the cells via energy-dependent pathways. The lowered adhesion in the presence of proteins thereby causes a concomitant decrease in nanoparticle uptake efficiency. The presence of a biomolecular corona may confer specific interactions between the nanoparticle-corona complex and the cell surface including triggering of regulated cell uptake. An important effect of the corona is, however, a reduction in the purely unspecific interactions between the bare material and the cell membrane, which in itself disregarding specific interactions, causes a decrease in cellular uptake. We suggest that future nanoparticle-cell studies include, together with characterization of size, charge, and dispersion stability, an evaluation of the adhesion properties of the material to relevant membranes. PMID:23301582

Lesniak, Anna; Salvati, Anna; Santos-Martinez, Maria J; Radomski, Marek W; Dawson, Kenneth A; Åberg, Christoffer

2013-01-22

34

Capillary Sprout Endothelial Cells Exhibit a CD36low Phenotype  

PubMed Central

Endothelial cells acquire distinctive molecular signatures in their transformation to an angiogenic phenotype that are indicative of changes in cell behavior and function. Using a rat mesentery model of inflammation-induced angiogenesis and a panel of known endothelial markers (CD31, VE-cadherin, BS-I lectin), we identified a capillary sprout-specific endothelial phenotype that is characterized by the marked down-regulation of CD36, a receptor for the anti-angiogenic molecule thrombospondin-1 (TSP-1). TSP-1/CD36 interactions were shown to regulate angiogenesis in this model as application of TSP-1 inhibited angiogenesis and blockade of both TSP-1 and CD36 accelerated angiogenesis. Vascular endothelial growth factor, which was up-regulated in the in vivo model, elicited a dose- and time-dependent down-regulation of CD36 (ie, to a CD36low phenotype) in cultured human umbilical vein endothelial cells. Human umbilical vein endothelial cells that had been conditioned to a CD36low phenotype with VEGF were found to be refractory to anti-proliferative TSP-1 signaling via a CD36-dependent mechanism. The loss of exposure to wall shear stress, which occurs in vivo when previously quiescent cells begin to sprout, also generated a CD36low phenotype. Ultimately, our results identified the regulation of endothelial cell CD36 expression as a novel mechanism through which VEGF stimulates and sustains capillary sprouting in the presence of TSP-1. Additionally, CD36 was shown to function as a potential molecular linkage through which wall shear stress may regulate both microvessel sprouting and quiescence.

Anderson, Christopher R.; Hastings, Nicole E.; Blackman, Brett R.; Price, Richard J.

2008-01-01

35

Lithium-inorganic electrolyte cells exhibiting improved low temperature performance  

SciTech Connect

The capacity/rate performance of Li/SOCl/sub 2/ cells decreases significantly at low temperatures. One of the factors which contribute to this decrease appears to be increased stability of the solvates formed between Li/sup +/ and the solvent. This lowers the mobility of Li/sup +/, thereby worsening the Li/sup +/ mass transport properties. Despite several attempts to modify the Li/sulfur oxyhalide cells by incorporating various additives, there have been surprisingly no reports of investigations aimed specifically at improving the low temperature performance of these systems, especially in the -20 to -50/sup 0/C temperature range. One possible route to improve the low temperature discharge behavior of these cells is to employ mixed solvent/depolarizer systems. Mixed solvents may lead to the formation of structurally disordered complexes between the solvent molecules and Li/sup +/ which, in turn, facilitate Li/sup +/ mass transport properties. The authors report here on studies to improve the low temperature discharge behavior of the Li/sulfur oxychloride cells by employing a binary mixture composed of SOCl/sub 2/ and SO/sub 2/Cl/sub 2/.

Abraham, K.M.; Alamgir, M.

1987-01-01

36

Lipid Nanoparticles Containing siRNA Synthesized by Microfluidic Mixing Exhibit an Electron-Dense Nanostructured Core.  

PubMed

Lipid nanoparticles (LNP) containing ionizable cationic lipids are the leading systems for enabling therapeutic applications of siRNA; however, the structure of these systems has not been defined. Here we examine the structure of LNP siRNA systems containing DLinKC2-DMA(an ionizable cationic lipid), phospholipid, cholesterol and a polyethylene glycol (PEG) lipid formed using a rapid microfluidic mixing process. Techniques employed include cryo-transmission electron microscopy, (31)P NMR, membrane fusion assays, density measurements, and molecular modeling. The experimental results indicate that these LNP siRNA systems have an interior lipid core containing siRNA duplexes complexed to cationic lipid and that the interior core also contains phospholipid and cholesterol. Consistent with experimental observations, molecular modeling calculations indicate that the interior of LNP siRNA systems exhibits a periodic structure of aqueous compartments, where some compartments contain siRNA. It is concluded that LNP siRNA systems formulated by rapid mixing of an ethanol solution of lipid with an aqueous medium containing siRNA exhibit a nanostructured core. The results give insight into the mechanism whereby LNP siRNA systems are formed, providing an understanding of the high encapsulation efficiencies that can be achieved and information on methods of constructing more sophisticated LNP systems. PMID:22962627

Leung, Alex K K; Hafez, Ismail M; Baoukina, Svetlana; Belliveau, Nathan M; Zhigaltsev, Igor V; Afshinmanesh, Elham; Tieleman, D Peter; Hansen, Carl L; Hope, Michael J; Cullis, Pieter R

2012-07-18

37

Lipid Nanoparticles Containing siRNA Synthesized by Microfluidic Mixing Exhibit an Electron-Dense Nanostructured Core  

PubMed Central

Lipid nanoparticles (LNP) containing ionizable cationic lipids are the leading systems for enabling therapeutic applications of siRNA; however, the structure of these systems has not been defined. Here we examine the structure of LNP siRNA systems containing DLinKC2-DMA(an ionizable cationic lipid), phospholipid, cholesterol and a polyethylene glycol (PEG) lipid formed using a rapid microfluidic mixing process. Techniques employed include cryo-transmission electron microscopy, 31P NMR, membrane fusion assays, density measurements, and molecular modeling. The experimental results indicate that these LNP siRNA systems have an interior lipid core containing siRNA duplexes complexed to cationic lipid and that the interior core also contains phospholipid and cholesterol. Consistent with experimental observations, molecular modeling calculations indicate that the interior of LNP siRNA systems exhibits a periodic structure of aqueous compartments, where some compartments contain siRNA. It is concluded that LNP siRNA systems formulated by rapid mixing of an ethanol solution of lipid with an aqueous medium containing siRNA exhibit a nanostructured core. The results give insight into the mechanism whereby LNP siRNA systems are formed, providing an understanding of the high encapsulation efficiencies that can be achieved and information on methods of constructing more sophisticated LNP systems.

2012-01-01

38

Nanoparticle-based monitoring of cell therapy  

PubMed Central

Exogenous cell therapy aims to replace/repair diseased or dysfunctional cells and promises to revolutionize medicine by restoring tissue and organ function. To develop effective cell therapy, the location, distribution and long-term persistence of transplanted cells must be evaluated. Nanoparticle (NP) based imaging technologies have the potential to track transplanted cells non-invasively. Here we summarize the most recent advances in NP-based cell tracking with emphasis on (1) the design criteria for cell tracking NPs, (2) protocols for cell labeling, (3) a comparison of available imaging modalities and their corresponding contrast agents, (4) a summary of preclinical studies on NP-based cell tracking and finally (5) perspectives and future directions.

Xu, Chenjie; Mu, Luye; Roes, Isaac; Miranda-Nieves, David; Nahrendorf, Matthias; Ankrum, James A; Zhao, Weian; Karp, Jeffrey M

2012-01-01

39

Nanoparticle-based monitoring of cell therapy  

NASA Astrophysics Data System (ADS)

Exogenous cell therapy aims to replace/repair diseased or dysfunctional cells and promises to revolutionize medicine by restoring tissue and organ function. To develop effective cell therapy, the location, distribution and long-term persistence of transplanted cells must be evaluated. Nanoparticle (NP) based imaging technologies have the potential to track transplanted cells non-invasively. Here we summarize the most recent advances in NP-based cell tracking with emphasis on (1) the design criteria for cell tracking NPs, (2) protocols for cell labeling, (3) a comparison of available imaging modalities and their corresponding contrast agents, (4) a summary of preclinical studies on NP-based cell tracking and finally (5) perspectives and future directions.

Xu, Chenjie; Mu, Luye; Roes, Isaac; Miranda-Nieves, David; Nahrendorf, Matthias; Ankrum, James A.; Zhao, Weian; Karp, Jeffrey M.

2011-12-01

40

Improvement of the separation of tumour cells from peripheral blood cells using magnetic nanoparticles  

NASA Astrophysics Data System (ADS)

Circulating tumour cells are a key challenge in tumour therapy. Numerous approaches are on the way to achieving the elimination of these potential sources of metastasis formation. Antibody-directed magnetic cell sorting is supposed to enrich tumour cells with high selectivity, but low efficiency. The short term application of carboxymethyl dextran (CMD) coated magnetit/maghemit nanoparticles allows the discrimination of tumour cells from leukocytes. In the present work we show that the interaction of CMD nanoparticles is cell-type specific and time dependent. The breast cancer cell line MCF-7 and the CML cell line K-562 are characterized by a rapid and high interaction rate, whereas leukocytes exhibit a decelerated behaviour. The addition of carboxymethyl dextran or glucose stimulated the magnetic labelling of leukocytes. The variation of the degree of substitution of dextran with carboxymethyl groups did not affect the labelling profile of leukocytes and MCF-7 cells. In order to verify the in vitro results, whole blood samples from 13 cancer patients were analysed ex vivo. Incubation of the purified leukocyte fraction with CMD nanoparticles in the presence of low amounts of plasma reduced the overall cell content in the positive fraction. In contrast, the absolute number of residual tumour cells in the positive fraction was 90% of the initial amount.

Schwalbe, M.; Pachmann, K.; Höffken, K.; Clement, J. H.

2006-09-01

41

[Gd@C82(OH)22]n nanoparticles inhibit the migration and adhesion of glioblastoma cells  

PubMed Central

In our previous study, [Gd@C82(OH)22]n, a fullerene-based nanoparticle, exhibited potent anti-tumor effects in mouse tumor-bearing models without detectable toxicity. The mechanism involved in the anti-tumor effect exerted by [Gd@C82(OH)22]n remains to be elucidated. This study found that glioblastoma cells treated with [Gd@C82(OH)22]n nanoparticles showed a significant impairment in migration and adhesion by cell chemotaxis, scratch and adhesion assays in vitro. Furthermore, our data showed that the key proteins, CD40 and ICAM-1, were involved in the inhibition of adhesion in the [Gd@C82(OH)22]n nanoparticle-treated glioblastoma cells. Thus, our study suggests that the [Gd@C82(OH)22]n nanoparticle is a new potential anti-tumor effector and a therapeutic component for malignant glioblastoma infiltration.

WANG, JING; GU, FENG; DING, TING; LIU, XIAOLI; XING, GENGMEI; ZHAO, YULIANG; ZHANG, NING; MA, YONGJIE

2010-01-01

42

Single-Chromophore-Based Photoswitchable Nanoparticles Enable Dual-Alternating-Color Fluorescence for Unambiguous Live Cell Imaging  

PubMed Central

We have developed a class of spiropyran dyes and their fluorescence colors can be reversibly photoswitched from red color to green, blue, or nearly dark, thus alternating between two colors. Such individual dyes emit either one color or the other, but not both simultaneously. These photoswitchable dyes-enabled nanoparticles, however, emit either one pure color or a combination of both colors because the nanoparticle fluorescence originates from multiple dyes therein. As a result, the nanoparticle shines >30 times brighter than the state-of-the-art organic dyes such as fluorescein. Interestingly, these copolymer nanoparticles exhibit tunable non-specific interactions with live cells and nanoparticles containing properly balanced butyl acrylate and acrylamide monomers render essentially very little non-specific binding to live cells. Decorated with HMGA1 protein, these optically switchable dual-color nanoparticles undergo endocytosis and unambiguously identify themselves from fluorescence interference including autofluorescence, thus enabling a new tool for live cell imaging.

Tian, Zhiyuan; Wu, Wuwei; Wan, Wei; Li, Alexander D. Q.

2009-01-01

43

Ginger phytochemicals exhibit synergy to inhibit prostate cancer cell proliferation.  

PubMed

Dietary phytochemicals offer nontoxic therapeutic management as well as chemopreventive intervention for slow-growing prostate cancers. However, the limited success of several single-agent clinical trials suggest a paradigm shift that the health benefits of fruits and vegetables are not ascribable to individual phytochemicals, rather may be ascribed to synergistic interactions among them. We recently reported growth-inhibiting and apoptosis-inducing properties of ginger extract (GE) in in vitro and in vivo prostate cancer models. Nevertheless, the nature of interactions among the constituent ginger biophenolics, viz. 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogoal, remains elusive. Here we show antiproliferative efficacy of the most-active GE biophenolics as single-agents and in binary combinations, and investigate the nature of their interactions using the Chou-Talalay combination index (CI) method. Our data demonstrate that binary combinations of ginger phytochemicals synergistically inhibit proliferation of PC-3 cells with CI values ranging from 0.03 to 0.88. To appreciate synergy among phytochemicals present in GE, the natural abundance of ginger biophenolics was quantitated using LC-UV/MS. Interestingly, combining GE with its constituents (in particular, 6-gingerol) resulted in significant augmentation of GE's antiproliferative activity. These data generate compelling grounds for further preclinical evaluation of GE alone and in combination with individual ginger biophenols for prostate cancer management. PMID:23441614

Brahmbhatt, Meera; Gundala, Sushma R; Asif, Ghazia; Shamsi, Shahab A; Aneja, Ritu

2013-01-01

44

Nanoparticles: molecular targets and cell signalling  

Microsoft Academic Search

Increasing evidence linking nanoparticles (NPs) with different cellular outcomes necessitate an urgent need for the better\\u000a understanding of cellular signalling pathways triggered by NPs. Oxidative stress has largely been reported to be implicated\\u000a in NP-induced toxicity. It could activate a wide variety of cellular events such as cell cycle arrest, apoptosis, inflammation\\u000a and induction of antioxidant enzymes. These responses occur

Francelyne Marano; Salik Hussain; Fernando Rodrigues-Lima; Armelle Baeza-Squiban; Sonja Boland

2011-01-01

45

Mercury bioaccumulation and simultaneous nanoparticle synthesis by Enterobacter sp. cells  

Microsoft Academic Search

A mercury resistant strain of Enterobacter sp. is reported. The strain exhibited a novel property of mercury bioaccumulation with simultaneous synthesis of mercury nanoparticles. The culture conditions viz. pH 8.0 and lower concentration of mercury promotes synthesis of uniform sized 2–5nm, spherical and monodispersed intracellular mercury nanoparticles. The remediated mercury trapped in the form of nanoparticles is unable to vaporize

Arvind Sinha; Sunil K. Khare

2011-01-01

46

Cellular Uptake of Gold Nanoparticles into Normal and Cancer Cells  

Microsoft Academic Search

Gold nanoparticles intracellular uptake was investigated using both normal and cancer human cells. Cell uptake was analyzed\\u000a using Atomic Absorption Spectrometry (AAS). It was found that combining 20nm gold nanoparticles with longer incubation time\\u000a and lower concentration can optimize the uptake of gold nanoparticles by cancer cell. The findings of this study will help\\u000a in the design and optimization of

Jade Trono; Kazue Mizuno; Noritaka Yusa; Takehisa Matsukawa; Mitsuru Uesaka

47

Simple monitoring of cancer cells using nanoparticles.  

PubMed

Here we present a new strategy for a simple and fast detection of cancer circulating cells (CTCs) using nanoparticles. The human colon adenocarcinoma cell line (Caco2) was chosen as a model CTC. Similarly to other adenocarcinomas, colon adenocarcinoma cells have a strong expression of EpCAM, and for this reason this glycoprotein was used as the capture target. We combine the capturing capability of anti-EpCAM functionalized magnetic beads (MBs) and the specific labeling through antibody-modified gold nanoparticles (AuNPs), with the sensitivity of the AuNPs-electrocatalyzed hydrogen evolution reaction (HER) detection technique. The fully optimized process was used for the electrochemical detection of Caco2 cells in the presence of monocytes (THP-1), other circulating cells that could interfere in real blood samples. Therefore we obtained a novel and simple in situ-like sensing format that we applied for the rapid quantification of AuNPs-labeled CTCs in the presence of other human cells. PMID:22817451

Maltez-da Costa, Marisa; de la Escosura-Muñiz, Alfredo; Nogués, Carme; Barrios, Lleonard; Ibáñez, Elena; Merkoçi, Arben

2012-07-24

48

Single-cell nanotoxicity assays of superparamagnetic iron oxide nanoparticles.  

PubMed

Properly evaluating the nanotoxicity of nanoparticles involves much more than bulk-cell assays of cell death by necrosis. Cells exposed to nanoparticles may undergo repairable oxidative stress and DNA damage or be induced into apoptosis. Exposure to nanoparticles may cause the cells to alter their proliferation or differentiation or their cell-cell signaling with neighboring cells in a tissue. Nanoparticles are usually more toxic to some cell subpopulations than others, and toxicity often varies with cell cycle. All of these facts dictate that any nanotoxicity assay must be at the single-cell level and must try whenever feasible and reasonable to include many of these other factors. Focusing on one type of quantitative measure of nanotoxicity, we describe flow and scanning image cytometry approaches to measuring nanotoxicity at the single-cell level by using a commonly used assay for distinguishing between necrotic and apoptotic causes of cell death by one type of nanoparticle. Flow cytometry is fast and quantitative, provided that the cells can be prepared into a single-cell suspension for analysis. But when cells cannot be put into suspension without altering nanotoxicity results, or if morphology, attachment, and stain location are important, a scanning image cytometry approach must be used. Both methods are described with application to a particular type of nanoparticle, a superparamagnetic iron oxide nanoparticle (SPION), as an example of how these assays may be applied to the more general problem of determining the effects of nanomaterial exposure to living cells. PMID:22975957

Eustaquio, Trisha; Leary, James F

2012-01-01

49

Ocular surface epithelia contain ABCG2-dependent side population cells exhibiting features associated with stem cells  

PubMed Central

Summary When cell populations are incubated with the DNA-binding dye Hoechst 33342 and subjected to flow cytometry analysis for Hoechst 33342 emissions, active efflux of the dye by the ABCG2/BCRP1 transporter causes certain cells to appear as a segregated cohort, known as a side population (SP). Stem cells from several tissues have been shown to possess the SP phenotype. As the lack of specific surface markers has hindered the isolation and subsequent biochemical characterization of epithelial stem cells this study sought to determine the existence of SP cells and expression of ABCG2 in the epithelia of the ocular surface and evaluate whether such SP cells had features associated with epithelial stem cells. Human and rabbit limbal-corneal and conjunctival epithelial cells were incubated with Hoechst 33342, and analyzed and sorted by flow cytometry. Sorted cells were subjected to several tests to determine whether the isolated SP cells displayed features consistent with the stem cell phenotype. Side populations amounting to <1% of total cells, which were sensitive to the ABCG2-inhibitor fumitremorgin C, were found in the conjunctival and limbal epithelia, but were absent from the stem cell-free corneal epithelium. Immunohistochemistry was used to establish the spatial expression pattern of ABCG2. The antigen was detected in clusters of conjunctival and limbal epithelia basal cells but was not present in the corneal epithelium. SP cells were characterized by extremely low light side scattering and contained a high percentage of cells that: showed slow-cycling prior to tissue collection; exhibited an initial delay in proliferation after culturing; and displayed clonogenic capacity and resistance to phorbol-induced differentiation; all features that are consistent with a stem cell phenotype.

Budak, Murat T.; Alpdogan, Onder S.; Zhou, Mingyuan; Lavker, Robert M.; Akinci, M.A. Murat; Wolosin, J. Mario

2005-01-01

50

Enhanced cell uptake of superparamagnetic iron oxide nanoparticles functionalized with dendritic guanidines.  

PubMed

Magnetic resonance imaging (MRI) is a powerful tool for the diagnosis of disease and the study of biological processes such as cancer metastasis and inflammation. Superparamagnetic iron oxide (SPIO) nanoparticles have been shown to be effective contrast agents for labeling cells to provide high sensitivity in MRI, but this sensitivity depends on the ability to label cells with sufficient quantities of SPIO, which can be challenging for nonphagocytic cells such as cancer cells. To address this issue, a novel cell-penetrating polyester dendron with peripheral guanidines was developed and conjugated to the surface of SPIO. The functionalized nanoparticles were characterized by transmission electron microscopy, infrared spectroscopy, and dynamic light scattering, and it was found that the surface functionalization reaction proceeded to completion and did not have any adverse effects on the SPIO. In GL261 mouse glioma cells, the dendritic guanidine exhibited remarkably similar cell-penetrating capabilities to the HIV-Tat(47-57) peptide for the transport of fluorescein, and when conjugated to SPIO, it provided significantly enhanced uptake in comparison with nanoparticles having no dendron or dendrons with hydroxyl or amine peripheries. This uptake led to substantial decreases in the transverse relaxation time (T(2)) of labeled cells relative to control cells. While the nanoparticles functionalized with dendritic guanidines exhibited somewhat greater toxicity than those functionalized with dendrons having hydroxyl or amine peripheries, they were still relatively nontoxic at the low concentrations required for labeling. PMID:19053308

Martin, Amanda L; Bernas, Lisa M; Rutt, Brian K; Foster, Paula J; Gillies, Elizabeth R

2008-12-01

51

The effect of silica nanoparticle-modified surfaces on cell morphology, cytoskeletal organization and function  

PubMed Central

Chemical and morphological characteristics of a biomaterial surface are thought to play an important role in determining cellular differentiation and apoptosis. In this report, we investigate the effect of nanoparticle (NP) assemblies arranged on a flat substrate on cytoskeletal organization, proliferation and metabolic activity on two cell types, Bovine aortic endothelial cells (BAECs) and mouse calvarial preosteoblasts (MC3T3-E1). To vary roughness without altering chemistry, glass substrates were coated with monodispersed silica nanoparticles of 50, 100 and 300 nm in diameter. The impact of surface roughness at the nanoscale on cell morphology was studied by quantifying cell spreading, shape, cytoskeletal F-actin alignment, and recruitment of focal adhesion complexes (FAC) using image analysis. Metabolic activity was followed using a thiazolyl blue tetrazolium bromide assay. In the two cell types tested, surface roughness introduced by nanoparticles had cell type specific effects on cell morphology and metabolism. While BAEC on NP-modified substrates exhibited smaller cell areas and fewer focal adhesion complexes compared to BAEC grown on glass, MC3T3-E1 cells in contrast exhibited larger cell areas on NP-modified surfaces and an increased number of FACs, in comparison to unmodified glass. However, both cell types on 50 nm NP had the highest proliferation rates (comparable to glass control) whereas cells grown on 300 nm NP exhibited inhibited proliferation. Interestingly, for both cell types surface roughness promoted the formation of long, thick F-actin fibers, which aligned with the long axis of each cell. These findings are consistent with our earlier result that osteogenic differentiation of human mesenchymal progenitor cells is enhanced on NP-modified surfaces. Our finding that nanoroughness, as imparted by nanoparticle assemblies, effects cellular processes in a cell specific manner, can have far reaching consequences on the development of “smart” biomaterials especially for directing stem cell differentiation.

Lipski, Anna M.; Pino, Christopher J.; Haselton, Frederick R.; Chen, I.-Wei; Shastri, V. Prasad

2010-01-01

52

Simple method for preparing superhydrophobic paper: spray-deposited hydrophobic silica nanoparticle coatings exhibit high water-repellency and transparency.  

PubMed

Superhydrophobic and transparent coatings are deposited onto paper by spraying alcohol suspensions of SiO(2) nanoparticles. Superhydrophobicity depends on the aggregation states of nanoparticles, which are determined by the type of alcohol used in the suspensions. The superhydrophobicity of the paper is maintained after touching the paper with a bare finger. PMID:22369269

Ogihara, Hitoshi; Xie, Jing; Okagaki, Jun; Saji, Tetsuo

2012-02-29

53

Modeling magnetic nanoparticle dipole-dipole interactions inside living cells  

NASA Astrophysics Data System (ADS)

Biomedical applications based on superparamagnetic nanoparticles injected in vivo may be affected by the cellular uptake of these nanoparticles. Living cells indeed capture and internalize nanoparticles, concentrating them into intracellular vesicles called lysosomes. As a consequence, nanoparticles interact magnetically with each other, modifying their magnetic properties. The effects of cellular uptake can be observed on the temperature dependence of zero-field cooled (ZFC) magnetization, which is known to be sensitive to magnetic interactions. In this paper, a theoretical model is proposed to account for weak magnetic interactions between nanoparticles aggregated into spherical compartments. This model suggests a new interpretation of the maximum of the ZFC curve, uncorrelated with the nanoparticle relaxation time but with the extent of interaction effects. It focuses on the local field felt by each nanoparticle, which is the sum of the applied magnetic field and the field created by all the other nanoparticles. For the considered organization of nanoparticles, only the field created by touching neighbors has to be taken into account, setting up the local nanoparticle volume fraction as the unique parameter of the model. This parameter relates the global magnetization measurements to the local distribution of nanoparticles in cells and tissues or in other complex media with aggregated organization.

Lévy, Michael; Gazeau, Florence; Bacri, Jean-Claude; Wilhelm, Claire; Devaud, Martin

2011-08-01

54

BaSnO3 perovskite nanoparticles for high efficiency dye-sensitized solar cells.  

PubMed

The synthesis of highly crystalline perovskite BaSnO3 nanoparticles for use as photoanode materials in dye-sensitized solar cells (DSSCs) is reported, and the photovoltaic properties of DSSCs based on BaSnO3 nanoparticles (BaSnO3 cells) are demonstrated. The resulting DSSCs exhibit remarkably rapid charge collection and a DSSC fabricated with a BaSnO3 film thickness of 43?µm leads to a high energy conversion efficiency of 5.2?%, which is one of the highest reported for ternary oxide-based DSSCs. More importantly, the BaSnO3 cells show superior charge collection in nanoparticle films compared to TiO2 cells and could offer a breakthrough in the efficiencies of DSSCs. PMID:23417972

Kim, Dong Wook; Shin, Seong Sik; Lee, Sangwook; Cho, In Sun; Kim, Dong Hoe; Lee, Chan Woo; Jung, Hyun Suk; Hong, Kug Sun

2013-02-18

55

Magnetic nanoparticles: Internal probes and heaters within living cells  

Microsoft Academic Search

Tagging living cells with magnetic nanoparticles raised increasing interest in the fields of magnetic resonance imaging, magnetic hyperthermia, cell sorting or tissue engineering. Here, we demonstrate that the confinement of magnetic nanoparticles at the intracellular level, inside endosomes vesicles, allows developing original magnetic manipulations in response to different magnetic field solicitations. These manipulations are used to deform cellular internal membrane,

Claire Wilhelm; Florence Gazeau

2009-01-01

56

Noninvasive assessment of magnetic nanoparticle-cancer cell interactions  

PubMed Central

The success of magnetic nanoparticle (mNP)-based diagnostic and therapeutic techniques is dependent upon how the mNP are distributed in vivo. The potential efficacy and timing of a given magnetic nanoparticle treatment or diagnostic test is largely determined by the number of nanoparticles in each tissue and microscopic compartment: e.g., in the intravascular and extravascular spaces, in the interstitial space, cell surface and in cell cytoplasm. Techniques for monitoring these cell-level interactions generally require the harvesting and destruction of tissues or cells at each time point of interest. We present a method (magnetic spectroscopy of Brownian motion, MSB) for longitudinally monitoring nanoparticle binding to cell surface proteins and uptake by cancer cells in vitro using the harmonics of the magnetization produced by the nanoparticles. These harmonics can be measured rapidly and noninvasively without the need for nanoparticle modifications and without damaging the cells. We demonstrate sensitivity of this harmonic signal to the nanoparticles’ microenvironment and use this technique to monitor the nanoparticle binding activities of different cell lines.

Giustini, Andrew J.; Perreard, Irina; Rauwerdink, Adam M.; Hoopes, P. Jack; Weaver, John B.

2012-01-01

57

Metal nanoparticles in a photovoltaic cell: Effect of metallic loss  

Microsoft Academic Search

We examined numerically the contribution of contrasting characteristics of metal nanoparticles, strong polarization and metallic loss, to the total efficiency of photovoltaic cells. A layer of nanoparticle array was chosen as a model. We found that depending on the location of the layer in the cell, the metallic loss offsets the enhanced photoabsorption due to the strong near field. A

Ryosuke Watanabe; Kenjiro Miyano

2011-01-01

58

Survival differences exhibited by normal and transformed rat liver epithelial cell lines in the aggregate form.  

PubMed

Normal and transformed rat liver epithelial cell lines exhibited differences in the ability to survive in the aggregate form. Normal rat liver epithelial cells in the aggregate form underwent a rapid decline in the number of viable cells, while counterpart transformed epithelial cells exhibited an ability to survive and proliferate in the aggregate form. This survival ability was found to correlate with colony formation in soft agar and tumorigenicity in nude mice. Cell survival in the aggregate form could possibly serve as a criterion for in vitro transformation of epithelial cells derived from rat liver. PMID:870190

Steuer, A F; Hentosh, P M; Diamond, L; Ting, R C

1977-06-01

59

Effect of ZnO nanoparticle properties on dye-sensitized solar cell performance.  

PubMed

We have investigated the effect of ZnO nanoparticle properties on the dye-sensitized solar cell performance. Nanoparticles with different sizes and optical properties were considered. We found that there is a complex relationship between native defects, dye adsorption, charge transport and solar cell performance. The presence of a high concentration of nonradiative defects was found to be detrimental to photovoltaic performance, whereas for radiative defects, samples displaying orange-red defect emission exhibited better performance compared to samples with green defect emission (when the samples had similar emission intensities). Detailed discussion of the nanoparticle properties and their relationship with dye adsorption, electron injection, electron lifetime, electron transport time, and solar cell performance is given. PMID:22321170

Wong, Ka Kan; Ng, Annie; Chen, Xin Yi; Ng, Yip Hang; Leung, Yu Hang; Ho, Kam Hong; Djuriši?, Aleksandra B; Ng, Alan Man Ching; Chan, Wai Kin; Yu, Lihong; Phillips, David Lee

2012-02-22

60

Induction of Functional Changes of Dendritic Cells by Silica Nanoparticles  

PubMed Central

Silica is one of the most abundant compounds found in nature. Immoderate exposure to crystalline silica has been linked to pulmonary disease and crystalline silica has been classified as a Group I carcinogen. Ultrafine (diameter <100 nm) silica particles may have different toxicological properties compared to larger particles. We evaluated the effect of ultrafine silica nanoparticles on mouse bone marrow-derived dendritic cells (BMDC) and murine dendritic cell line, DC2.4. The exposure of dendritic cells (DCs) to ultrafine silica nanoparticles showed a decrease in cell viability and an induction of cell death in size- and concentration-dependent manners. In addition, in order to examine the phenotypic changes of DCs following co-culture with silica nanoparticles, we added each sized-silica nanoparticle along with GM-CSF and IL-4 during and after DC differentiation. Expression of CD11c, a typical DC marker, and multiple surface molecules such as CD54, CD80, CD86, MHC class II, was changed by silica nanoparticles in a size-dependent manner. We also found that silica nanoparticles affect inflammatory response in DCs in vitro and in vivo. Finally, we found that p38 and NF-?B activation may be critical for the inflammatory response by silica nanoparticles. Our data demonstrate that ultrafine silica nanoparticles have cytotoxic effects on dendritic cells and immune modulation effects in vitro and in vivo.

Kang, Kyeongah

2012-01-01

61

Nanosize and surface charge effects of hydroxyapatite nanoparticles on red blood cell suspensions.  

PubMed

In this paper, the effects of size and surface charge of hydroxyapatite (HAP) particles on a red blood cell (RBC) suspension were studied. Results showed that the HAP particles exhibited nanosize and surface charge effects on the RBC suspension. Differing from HAP microparticles, HAP nanoparticles induced some aggregation of the RBCs in the unstructured agglutinates. HAP nanoparticles were adhered to the surface membrane of the RBCs due to their remarkably higher adsorption capacity than the HAP microparticles, resulting in the formation of a sunken appearance ("caves") on the surface membrane of the RBCs without rupturing the lipid bilayer. In the case of high negatively charged HAP nanoparticles after heparin modification, the aggregation of the RBCs induced by the HAP nanoparticles was inhibited. Such HAP nanoparticle-induced aggregation of the RBCs could be attributed to the bridging force via the electrostatic interaction between the positively charged binding sites on the HAP surface and the negatively charged groups on the surface of the RBCs. The surface charge of the HAP nanoparticles is thus a crucial factor influencing the interaction between the HAP nanoparticles and the RBCs. PMID:22860897

Han, Yingchao; Wang, Xinyu; Dai, Honglian; Li, Shipu

2012-08-14

62

Establishment and characterization of a mutagenized cell line exhibiting the 'cell-in-cell' phenotype at a high frequency.  

PubMed

Cell-in-cell structures represent live cell events in which one cell internalizes another. Because formation of cell-in-cell structures is a rare event in most cell types and the event is associated with cell death, there has been limited clarification of this phenomenon, and its physiological role and molecular mechanism are yet to be precisely elucidated. In this study, we established a mutagenized cell line that exhibited cell-in-cell structures at a more than 10-fold higher frequency as compared to the parent cells. Interestingly, both engulfment and invasion were increased in the mutagenized cell line as compared with that in the parent cell line in the suspension culture condition. This finding indicates that this mutagenized cell line showed an interchangeable status in terms of its ability to form cell-in-cell structures, and the system described here could be useful for elucidation of the mechanisms regulating the formation of cell-in-cell structures, including engulfment and invasion, in a given cellular environment. Further studies using this cell line are warranted to understand the mechanism of formation and biological significance of the cell-in-cell formation. PMID:24165024

Kahyo, Tomoaki; Sugimura, Haruhiko

2013-09-24

63

Heparin immobilized gold nanoparticles for targeted detection and apoptotic death of metastatic cancer cells  

Microsoft Academic Search

In the present study, heparin immobilized, multifunctional gold nanoparticles (AuNPs) were developed as a new class of theragnostic nanomaterials for metastatic cancer cell imaging and apoptosis. AuNPs were surface modified with fluorescent dye labeled heparin molecules to detect a metastatic stage of cancer cells that over-express heparin-degrading enzymes. The heparin immobilized AuNPs exhibited enhanced fluorescence signals by specific cleavage of

Kyuri Lee; Hyukjin Lee; Ki Hyun Bae; Tae Gwan Park

2010-01-01

64

Biological cell positioning and spatially selective destruction via magnetic nanoparticles  

NASA Astrophysics Data System (ADS)

We report a procedure on biological cells (erythrocytes) where magnetite (Fe3O4) nanoparticles have been used for micro-scale blood cell positioning and space selective destruction. The experiment was accomplished on the top of the microelectromagnet serving as a source of magnetic field and as a local heater at the same time. We observed the controlled motion and focusing of the blood cells dragged by the flow of magnetic nanoparticles. Furthermore, we found that the increase of the electric current through the microelectromagnet leads to the local cell haemolysis. The haemolysis is observed only in the vicinity (5-10 microns) of the current-carrying wires. The whole procedure takes less than 3 seconds. The obtained results provide a rich resource showing the dynamics of cell dragging by the magnetic nanoparticles and demonstrate the feasibility of using magnetic nanoparticles for cell positioning and surgery on the cellular level with micrometer-scale precision.

Gertz, Frederick; Azimov, Rustam; Khitun, Alexander

2012-07-01

65

Aptamer-Conjugated Nanoparticles for Cancer Cell Detection  

PubMed Central

Aptamer-conjugated nanoparticles (ACNPs) have been used for a variety of applications, particularly dual nanoparticles for magnetic extraction and fluorescent labeling. In this type of assay, silica-coated magnetic and fluorophore-doped silica nanoparticles are conjugated to highly selective aptamers to detect and extract targeted cells in a variety of matrices. However, considerable improvements are required in order to increase the selectivity and sensitivity of this two-particle assay to be useful in a clinical setting. To accomplish this, several parameters were investigated, including nanoparticle size, conjugation chemistry, use of multiple aptamer sequences on the nanoparticles, and use of multiple nanoparticles with different aptamer sequences. After identifying the best-performing elements, the improvements made to this assay’s conditional parameters were combined to illustrate the overall enhanced sensitivity and selectivity of the two particle assay using an innovative multiple aptamer approach, signifying a critical feature in the advancement of this technique.

Medley, Colin D.; Bamrungsap, Suwussa; Tan, Weihong; Smith, Joshua E.

2011-01-01

66

Bacteria-mediated delivery of nanoparticles and cargo into cells  

Microsoft Academic Search

Nanoparticles and bacteria can be used, independently, to deliver genes and proteins into mammalian cells for monitoring or altering gene expression and protein production. Here, we show the simultaneous use of nanoparticles and bacteria to deliver DNA-based model drug molecules in vivo and in vitro. In our approach, cargo (in this case, a fluorescent or a bioluminescent gene) is loaded

Demir Akin; Jennifer Sturgis; Kathy Ragheb; Debby Sherman; Kristin Burkholder; J. Paul. Robinson; Arun K. Bhunia; Sulma Mohammed; Rashid Bashir

2007-01-01

67

Dual-responsive magnetic core-shell nanoparticles for nonviral gene delivery and cell separation.  

PubMed

We present the synthesis of dual-responsive (pH and temperature) magnetic core-shell nanoparticles utilizing the grafting-from approach. First, oleic acid stabilized superparamagnetic maghemite (?-Fe(2)O(3)) nanoparticles (NPs), prepared by thermal decomposition of iron pentacarbonyl, were surface-functionalized with ATRP initiating sites bearing a dopamine anchor group via ligand exchange. Subsequently, 2-(dimethylamino)ethyl methacrylate (DMAEMA) was polymerized from the surface by ATRP, yielding dual-responsive magnetic core-shell NPs (?-Fe(2)O(3)@PDMAEMA). The attachment of the dopamine anchor group on the nanoparticle's surface is shown to be reversible to a certain extent, resulting in a grafting density of 0.15 chains per nm(2) after purification. Nevertheless, the grafted NPs show excellent long-term stability in water over a wide pH range and exhibit a pH- and temperature-dependent reversible agglomeration, as revealed by turbidimetry. The efficiency of ?-Fe(2)O(3)@PDMAEMA hybrid nanoparticles as a potential transfection agent was explored under standard conditions in CHO-K1 cells. Remarkably, ?-Fe(2)O(3)@PDMAEMA led to a 2-fold increase in the transfection efficiency without increasing the cytotoxicity, as compared to polyethyleneimine (PEI), and yielded on average more than 50% transfected cells. Moreover, after transfection with the hybrid nanoparticles, the cells acquired magnetic properties that could be used for selective isolation of transfected cells. PMID:22296556

Majewski, Alexander P; Schallon, Anja; Jérôme, Valérie; Freitag, Ruth; Müller, Axel H E; Schmalz, Holger

2012-02-22

68

Detecting and Tracking Nonfluorescent Nanoparticles Probes in Live Cells  

SciTech Connect

Precisely imaging and tracking dynamic biological processes in live cells are crucial for both fundamental research in life sciences and biomedical applications. Nonfluorescent nanoparticles are emerging as important optical probes in live-cell imaging because of their excellent photostability, large optical cross sections, and low cytotoxicity. Here, we provide a review of recent development in optical imaging of nonfluorescent nanoparticle probes and their applications in dynamic tracking and biosensing in live cells. A brief discussion on cytotoxicity of nanoparticle probes is also provided.

Wang, Gufeng; Fang, Ning

2012-01-17

69

Comparison of stem morphology and anatomy of two alfalfa clonal lines exhibiting divergent cell wall composition  

Technology Transfer Automated Retrieval System (TEKTRAN)

In previous research, two alfalfa clonal lines (252, 1283) were identified that exhibited environmentally stable differences in stem cell walls. Compared to stems of 1283, stems of 252 have a higher cell wall concentration and greater amounts of lignin and cellulose but reduced levels of pectic suga...

70

Bacteria-mediated delivery of nanoparticles and cargo into cells  

NASA Astrophysics Data System (ADS)

Nanoparticles and bacteria can be used, independently, to deliver genes and proteins into mammalian cells for monitoring or altering gene expression and protein production. Here, we show the simultaneous use of nanoparticles and bacteria to deliver DNA-based model drug molecules in vivo and in vitro. In our approach, cargo (in this case, a fluorescent or a bioluminescent gene) is loaded onto the nanoparticles, which are carried on the bacteria surface. When incubated with cells, the cargo-carrying bacteria (`microbots') were internalized by the cells, and the genes released from the nanoparticles were expressed in the cells. Mice injected with microbots also successfully expressed the genes as seen by the luminescence in different organs. This new approach may be used to deliver different types of cargo into live animals and a variety of cells in culture without the need for complicated genetic manipulations.

Akin, Demir; Sturgis, Jennifer; Ragheb, Kathy; Sherman, Debby; Burkholder, Kristin; Robinson, J. Paul.; Bhunia, Arun K.; Mohammed, Sulma; Bashir, Rashid

2007-07-01

71

Nanoparticle accumulation and transcytosis in brain endothelial cell layers.  

PubMed

The blood-brain barrier (BBB) is a selective barrier, which controls and limits access to the central nervous system (CNS). The selectivity of the BBB relies on specialized characteristics of the endothelial cells that line the microvasculature, including the expression of intercellular tight junctions, which limit paracellular permeability. Several reports suggest that nanoparticles have a unique capacity to cross the BBB. However, direct evidence of nanoparticle transcytosis is difficult to obtain, and we found that typical transport studies present several limitations when applied to nanoparticles. In order to investigate the capacity of nanoparticles to access and transport across the BBB, several different nanomaterials, including silica, titania and albumin- or transferrin-conjugated gold nanoparticles of different sizes, were exposed to a human in vitro BBB model of endothelial hCMEC/D3 cells. Extensive transmission electron microscopy imaging was applied in order to describe nanoparticle endocytosis and typical intracellular localisation, as well as to look for evidence of eventual transcytosis. Our results show that all of the nanoparticles were internalised, to different extents, by the BBB model and accumulated along the endo-lysosomal pathway. Rare events suggestive of nanoparticle transcytosis were also observed for several of the tested materials. PMID:24077327

Ye, Dong; Raghnaill, Michelle Nic; Bramini, Mattia; Mahon, Eugene; Aberg, Christoffer; Salvati, Anna; Dawson, Kenneth A

2013-09-27

72

A pretargeted nanoparticle system for tumor cell labeling  

PubMed Central

Nanoparticle-based cancer diagnostics and therapeutics can be significantly enhanced by selective tissue localization, but the strategy can be complicated by the requirement of a targeting ligand conjugated on nanoparticles, that is specific to only one or a limited few types of neoplastic cells, necessitating the development of multiple nanoparticle systems for different diseases. Here, we present a new nanoparticle system that capitalizes on a targeting pretreatment strategy, where a circulating fusion protein (FP) selectively prelabels the targeted cellular epitope, and a biotinylated iron oxide nanoparticle serves as a secondary label that binds to the FP on the target cell. This approach enables a single nanoparticle formulation to be used with any one of existing fusion proteins to bind a variety of target cells. We demonstrated this approach with two fusion proteins against two model cancer cell lines: lymphoma (Ramos) and leukemia (Jurkat), which showed 72.2% and 91.1% positive labeling, respectively. Notably, TEM analysis showed that a large nanoparticle population was endocytosed via attachment to the non-internalizing CD20 epitope.

Gunn, Jonathan; Park, Steven I.; Veiseh, Omid; Press, Oliver W.; Zhang, Miqin

2011-01-01

73

A pretargeted nanoparticle system for tumor cell labeling.  

PubMed

Nanoparticle-based cancer diagnostics and therapeutics can be significantly enhanced by selective tissue localization, but the strategy can be complicated by the requirement of a targeting ligand conjugated on nanoparticles, that is specific to only one or a limited few types of neoplastic cells, necessitating the development of multiple nanoparticle systems for different diseases. Here, we present a new nanoparticle system that capitalizes on a targeting pretreatment strategy, where a circulating fusion protein (FP) selectively prelabels the targeted cellular epitope, and a biotinylated iron oxide nanoparticle serves as a secondary label that binds to the FP on the target cell. This approach enables a single nanoparticle formulation to be used with any one of existing fusion proteins to bind a variety of target cells. We demonstrated this approach with two fusion proteins against two model cancer cell lines: lymphoma (Ramos) and leukemia (Jurkat), which showed 72.2% and 91.1% positive labeling, respectively. Notably, TEM analysis showed that a large nanoparticle population was endocytosed via attachment to the non-internalizing CD20 epitope. PMID:21107453

Gunn, Jonathan; Park, Steven I; Veiseh, Omid; Press, Oliver W; Zhang, Miqin

2010-11-24

74

Tracking nanoparticles optically to study their interaction with cells  

Microsoft Academic Search

\\u000a Nanoparticles are by definition too small to be visible in an optical microscope and devices such as scanning electron microscopes\\u000a must be used to resolve them. However electron beams quickly lead to cell death and so it is difficult to study the interaction\\u000a of nanoparticles with living cells in order to establish whether such interactions could be damaging to the

Jean-Michel Gineste; Peter Macko; Eann Patterson; Maurice Whelan

75

Selective entrance of gold nanoparticles into cancer cells  

Microsoft Academic Search

We report that Au(0) nanoparticles, stabilized by 5-aminovaleric acid, selectively penetrate into K562 cancer cells in a short\\u000a time. These experiments were carried out in order to verify the specific recognition of gold sol by abnormal cells. The observed\\u000a selectivity towards gold nanoparticles by K562 makes the metallic system attractive for cancer therapy.

Z. Krpetic; F. Porta; G. Scarì

2006-01-01

76

Intracellular Uptake and Trafficking of Difluoroboron Dibenzoylmethane-Poly(lactic acid) Nanoparticles in HeLa Cells  

PubMed Central

In this study, nanoparticles based on difluoroboron dibenzoylmethane-poly(lactic acid) (BF2dbmPLA) are prepared. Polylactic acid or polylactide is a commonly used degradable polymer, while the boron dye possesses a large extinction coefficient, high emission quantum yield, 2-photon absorption, and sensitivity to the surrounding environment. BF2dbmPLA exhibits molecular weight-dependent emission properties, and can be formulated as stable nanoparticles, suggesting that its unique optical properties may be useful in multiple contexts for probing intracellular environments. Here we show that BF2dbmPLA nanoparticles are internalized into cultured HeLa cells by endocytosis, and that within the cellular milieu they retain their fluorescence properties. BF2dbmPLA nanoparticles are photostable, resisting laser-induced photobleaching under conditions that destroy the fluorescence of a common photostable probe, LysoTracker™ blue. Their endocytosis is also lipid raft-dependent, as evidenced by their significant co-localization with cholera toxin B subunit in membrane compartments after uptake, and their sensitivity of uptake to methyl-?-cyclodextrin. Additionally, BF2dbmPLA nanoparticle endocytosis utilizes microtubules and actin filaments. Internalized BF2dbmPLA nanoparticles do not accumulate in acidic late endosomes and lysosomes, but within a perinuclear non-lysosomal compartment. These findings demonstrate the feasibility of using novel BF2dbmPLA nanoparticles exhibiting diverse emission properties for in situ, live cell imaging, and suggest that their endogenous uptake occurs through a lipid-raft dependent endocytosis mechanism.

Contreras, Janette; Xie, Jiansong; Chen, Yin Jie; Pei, Hua; Zhang, Guoqing; Fraser, Cassandra L.; Hamm-Alvarez, Sarah F.

2010-01-01

77

Drosophila piwi mutants exhibit germline stem cell tumors that are sustained by elevated Dpp signaling.  

PubMed

Drosophila Piwi is the founding member of a gonadal clade of Argonaute proteins that serve as silencing effectors for ?26-32 nt Piwi-interacting RNAs (piRNAs) [1], and piwi mutants exhibit dramatically rudimentary ovaries [2]. It was proposed that somatic Piwi maintains germline stem cells (GSCs) by promoting Dpp signaling, presumably via cap cells that form the somatic niche for GSCs [3-5]. However, we unexpectedly observed that piwi mutants exhibit high-frequency GSC-like tumors that persist throughout adult life. Multiple readouts demonstrated hyperactive Dpp signaling in piwi mutants, including the failure to express the germline differentiation factor bag-of-marbles (bam), and restoration of bam expression relieved piwi GSC-like tumors. Tissue-specific rescue and knockdown experiments indicate that Piwi is not required in cap cells, the source of niche Dpp, but instead is required in gonadal intermingled cells (ICs, the progenitor cells of escort cells). Adult-specific knockdown of dpp in escort cells substantially rescued piwi tumors, demonstrating that they are driven by excess Dpp signaling. However, the temporal requirement for piwi to restrict GSC numbers was much earlier, during the wandering third-instar larval stage. Indeed, piwi mutant larval gonads exhibited defective morphology and loss of Bam. Our data indicate that loss of Piwi causes defects in ICs and escort cells, leading to ectopic Dpp signaling and consequent blockage of GSC differentiation. PMID:23891114

Jin, Zhigang; Flynt, Alex S; Lai, Eric C

2013-07-25

78

Single Walled Carbon Nanotubes Exhibit Dual-Phase Regulation to Exposed Arabidopsis Mesophyll Cells  

PubMed Central

Herein we are the first to report that single-walled carbon nanotubes (SWCNTs) exhibit dual-phase regulation to Arabidopsis mesophyll cells exposed to different concentration of SWCNTs. The mesophyll protoplasts were prepared by enzyme digestion, and incubated with 15, 25, 50, 100 ?g/ml SWCNTs for 48 h, and then were observed by optical microscopy and transmission electron microscopy, the reactive oxygen species (ROS) generation was measured. Partial protoplasts were stained with propidium iodide and 4'-6- diamidino-2-phenylindole, partial protoplasts were incubated with fluorescein isothiocyanate-labeled SWCNTs, and observed by fluorescence microscopy. Results showed that SWCNTs could traverse both the plant cell wall and cell membrane, with less than or equal to 50 ?g/ml in the culture medium, SWCNTs stimulated plant cells to grow out trichome clusters on their surface, with more than 50 ?g/ml SWCNTs in the culture medium, SWCNTs exhibited obvious toxic effects to the protoplasts such as increasing generation of ROS, inducing changes of protoplast morphology, changing green leaves into yellow, and inducing protoplast cells' necrosis and apoptosis. In conclusion, single walled carbon nanotubes can get through Arabidopsis mesophyll cell wall and membrane, and exhibit dose-dependent dual-phase regulation to Arabidopsis mesophyll protoplasts such as low dose stimulating cell growth, and high dose inducing cells' ROS generation, necrosis or apoptosis.

2011-01-01

79

Single Walled Carbon Nanotubes Exhibit Dual-Phase Regulation to Exposed Arabidopsis Mesophyll Cells  

NASA Astrophysics Data System (ADS)

Herein we are the first to report that single-walled carbon nanotubes (SWCNTs) exhibit dual-phase regulation to Arabidopsis mesophyll cells exposed to different concentration of SWCNTs. The mesophyll protoplasts were prepared by enzyme digestion, and incubated with 15, 25, 50, 100 ?g/ml SWCNTs for 48 h, and then were observed by optical microscopy and transmission electron microscopy, the reactive oxygen species (ROS) generation was measured. Partial protoplasts were stained with propidium iodide and 4'-6- diamidino-2-phenylindole, partial protoplasts were incubated with fluorescein isothiocyanate-labeled SWCNTs, and observed by fluorescence microscopy. Results showed that SWCNTs could traverse both the plant cell wall and cell membrane, with less than or equal to 50 ?g/ml in the culture medium, SWCNTs stimulated plant cells to grow out trichome clusters on their surface, with more than 50 ?g/ml SWCNTs in the culture medium, SWCNTs exhibited obvious toxic effects to the protoplasts such as increasing generation of ROS, inducing changes of protoplast morphology, changing green leaves into yellow, and inducing protoplast cells' necrosis and apoptosis. In conclusion, single walled carbon nanotubes can get through Arabidopsis mesophyll cell wall and membrane, and exhibit dose-dependent dual-phase regulation to Arabidopsis mesophyll protoplasts such as low dose stimulating cell growth, and high dose inducing cells' ROS generation, necrosis or apoptosis.

Yuan, Hengguang; Hu, Shanglian; Huang, Peng; Song, Hua; Wang, Kan; Ruan, Jing; He, Rong; Cui, Daxiang

2010-12-01

80

Nanoparticle-labeled stem cells: a novel therapeutic vehicle  

PubMed Central

Nanotechnology has been described as a general purpose technology. It has already generated a range of inventions and innovations. Development of nanotechnology will provide clinical medicine with a range of new diagnostic and therapeutic opportunities such as medical imaging, medical diagnosis, drug delivery, and cancer detection and management. Nanoparticles such as manganese, polystyrene, silica, titanium oxide, gold, silver, carbon, quantum dots, and iron oxide have received enormous attention in the creation of new types of analytical tools for biotechnology and life sciences. Labeling of stem cells with nanoparticles overcame the problems in homing and fixing stem cells to their desired site and guiding extension of stem cells to specific directions. Although the biologic effects of some nanoparticles have already been assessed, information on toxicity and possible mechanisms of various particle types remains inadequate. The aim of this review is to give an overview of the mechanisms of internalization and distribution of nanoparticles inside stem cells, as well as the influence of different types of nanoparticles on stem cell viability, proliferation, differentiation, and cytotoxicity, and to assess the role of nanoparticles in tracking the fate of stem cells used in tissue regeneration.

El-Sadik, Abir O; El-Ansary, Afaf; Sabry, Sherif M

2010-01-01

81

Polystyrene nanoparticles activate ion transport in human airway epithelial cells  

PubMed Central

Background Over the last decade, nanotechnology has provided researchers with new nanometer materials, such as nanoparticles, which have the potential to provide new therapies for many lung diseases. In this study, we investigated the acute effects of polystyrene nanoparticles on epithelial ion channel function. Methods Human submucosal Calu-3 cells that express cystic fibrosis transmembrane conductance regulator (CFTR) and baby hamster kidney cells engineered to express the wild-type CFTR gene were used to investigate the actions of negatively charged 20 nm polystyrene nanoparticles on short-circuit current in Calu-3 cells by Ussing chamber and single CFTR Clchannels alone and in the presence of known CFTR channel activators by using baby hamster kidney cell patches. Results Polystyrene nanoparticles caused sustained, repeatable, and concentration-dependent increases in short-circuit current. In turn, these short-circuit current responses were found to be biphasic in nature, ie, an initial peak followed by a plateau. EC50 values for peak and plateau short-circuit current responses were 1457 and 315.5 ng/mL, respectively. Short-circuit current was inhibited by diphenylamine-2-carboxylate, a CFTR Cl? channel blocker. Polystyrene nanoparticles activated basolateral K+ channels and affected Cl? and HCO3 ? secretion. The mechanism of short-circuit current activation by polystyrene nanoparticles was found to be largely dependent on calcium-dependent and cyclic nucleotide-dependent phosphorylation of CFTR Cl? channels. Recordings from isolated inside-out patches using baby hamster kidney cells confirmed the direct activation of CFTR Cl? channels by the nanoparticles. Conclusion This is the first study to identify the activation of ion channels in airway cells after exposure to polystyrene-based nanomaterials. Thus, polystyrene nanoparticles cannot be considered as a simple neutral vehicle for drug delivery for the treatment of lung diseases, due to the fact that they may have the ability to affect epithelial cell function and physiological processes on their own.

McCarthy, J; Gong, X; Nahirney, D; Duszyk, M; Radomski, MW

2011-01-01

82

Functional nanoparticles translocation into cell and adhesion force curve analysis.  

PubMed

The aim of this research is to investigate the cell translocation of two functional nanoparticles (barium sulfate (BaSO4NPs), europium (III) doped gadolinium oxide nanoparticles (Gd2O3@EuNPs)) into A549 cells by Bio-Atomic Force Microscopy (Bio-AFM). Successful cell translocation of these two nanoparticles are ensured from the measurement of changes in the cell surface roughness and interaction (extension), retraction forces from the vertical deflection of tip towards substrate surfaces through force-distance curve slope analysis. Measurement of typical adhesion forces (i.e., extension and retraction) between the tip-substrate (0.0963 and 1.155 nN), tip-A549 cell substrate (0.1177 and 2.468 nN), tip-Gd2O3@EuNPs/A549 substrate (0.0785 and 0.4276 nN) and tip-BaSO4NPs/A549 substrate (0.518 and 6.838 nN) confirms the successful cell translocation of functional nanoparticles into A549 cells. Further the nanoscale resolution of topographical height and 3D images evinces the surface characteristics of normal A549 cells and nanoparticles translocated A549 cells. PMID:23421137

Lee, Haisung; Veerapandian, Murugan; Kim, Byung Tae; Yun, Kyusik; Seo, Soo-Won

2012-10-01

83

Meayamycin Inhibits pre-mRNA Splicing and Exhibits Picomolar Activity Against Multidrug Resistant Cells  

PubMed Central

FR901464 is a potent antitumor natural product that binds to the SF3b complex and inhibits pre-mRNA splicing. Its analogue, meayamycin, is two orders of magnitude more potent as an antiproliferative agent against human breast cancer MCF-7 cells. Here, we report the picomolar antiproliferative activity of meayamycin against various cancer cell lines and multidrug resistant cells. Time-dependence studies implied that meayamycin may form a covalent bond with its target protein(s). Meayamycin inhibited pre-mRNA splicing in HEK-293 cells but not alternative splicing in a neuronal system. Meayamycin exhibited specificity toward human lung cancer cells compared to non-tumorigenic human lung fibroblasts and retained picomolar growth inhibitory activity against multi-drug resistant cells. These data suggest that meayamycin is a useful chemical probe to study pre-mRNA splicing in live cells and is a promising lead as an anticancer agent.

Albert, Brian J.; McPherson, Peter A.; O'Brien, Kristine; Czaicki, Nancy L.; DeStefino, Vincent; Osman, Sami; Li, Miaosheng; Day, Billy W.; Grabowski, Paula J.; Moore, Melissa J.; Vogt, Andreas; Koide, Kazunori

2009-01-01

84

Facile synthesis of Cu2CoSnS4 nanoparticles exhibiting red-edge-effect: Application in hybrid photonic devices  

NASA Astrophysics Data System (ADS)

Cu2CoSnS4 (CCTS) quaternary semiconducting nanoparticles with size distribution from 20 nm to 60 nm were synthesized by one-pot low temperature time and surfactant dependent hydrothermal route. Nanoparticles were characterized structurally and optically. Excitation dependent fluorescence exhibited a dynamic stoke shift referring to the Red-Edge-Effect with peak shifting by a greater magnitude (>100 nm) towards red side, in all the samples. Hybrid devices, fabricated from CCTS nanoparticle inorganic counterparts benefitting from the conjugation of organic P3HT polymer matrix, were demonstrated for photodetection under infra-red and A.M 1.5 solar light illuminations. Faster rise and decay constants of 37 ms and 166 ms, with one order photocurrent amplification from 1.6 × 10-6 A in the dark to 6.55 × 10-5 A, upon the 18.50 mW cm-2 IR lamp illumination, make CCTS a potential candidate for photodetector and photovoltaic applications.

Murali, Banavoth; Krupanidhi, S. B.

2013-10-01

85

Nanoparticle-GFP "chemical nose" sensor for cancer cell identification.  

PubMed

Nanoparticle-based sensor arrays have been used to distinguish a wide range of bio-related molecules through pattern recognition. This "chemical nose" approach uses nanoparticles as receptors to selectively identify the analytes, while a transducer reports the binding through a readable signal (fluorescence). Here we describe a procedure that uses functionalized gold nanoparticles as receptors and green fluorescent protein (GFP) as the transducer to identify and differentiate cell state (normal, cancerous, and metastatic), an important tool in early diagnosis and treatment of tumors. PMID:23546653

Moyano, Daniel F; Rotello, Vincent M

2013-01-01

86

Uptake of functionalized mesoporous silica nanoparticles by human cancer cells.  

PubMed

Mesoporous silica nanoparticles (MSN) were functionalised by aminofluorescein (AMF) with diethylenetriaminepentaacetic acid spacer molecules which provide free carboxylic groups for binding cell-specific ligands such as folate. AMF allowed the exploration of cellular uptake by HeLa cells using confocal microscopy and flow cytometry. The functionalized nanoparticles (MSN-AMF) penetrated efficiently into HeLa cell cytoplasm through a clathrin dependent endocytosis mechanism. The number of endocytosed MSN-AMF was enhanced when using folate as a targeting molecule. Uptake kinetics revealed that most of MSN-AMF were internalized within 4 h of incubation. Moreover, we found that MSN-AMF were capable of escaping the acidic endolysosomal vesicles of HeLa cells. Cytotoxicity studies suggested that these nanoparticles are non-toxic to HeLa cells up to a dose level of 50 microg/ml. PMID:20355428

Fisichella, Matthieu; Dabboue, Hinda; Bhattacharyya, Sanjib; Lelong, Gérald; Saboungi, Marie-Louise; Warmont, Fabienne; Midoux, Patrick; Pichon, Chantal; Guérin, Martine; Hevor, Tobias; Salvetat, Jean-Paul

2010-04-01

87

Nanoparticle distribution in polymer solar cells  

NASA Astrophysics Data System (ADS)

Polymer based solar cells (PSC) hold the promise of cheap, versatile devices for harnessing solar energy. A widely studied PSC is poly-3-hexylthiophene (P3HT) blended with [6,6] - phenyl-C61 - butyric acid methyl ester (PCBM) nanoparticles. The acceptor PCBM is needed to inhibit exciton recombination, thus, proper PCBM distribution is critical for photovoltaic performance. However, determining this distribution is challenging, as PCBM is extremely difficult to distinguish from P3HT via standard techniques like microscopy or x-ray diffraction. Neutron scattering presents a solution, as the scattering potential for PCBM is ˜5 x that of P3HT. Thus, we have studied PCBM:P3HT thin film samples using neutron reflectometry, which is sensitive to the compositional depth profile.[1] Measurements were conducted both with a weak scatterer (air) and then with a strong scatterer (D2O) backing the sample, such that the depth profile could be calculated from the reflectometry data with no fitting parameters, and/or model fitted with virtually no ambiguity. We find that PCBM aggregates near the substrate and surface interfaces of the P3HT film, implying that the PCBM is not optimally distributed for best photovoltaic performance. In general, this work demonstrates the extreme utility of neutron reflectometry for studying this class of materials. [1] Kiel, et al. Soft Matter, DOI:10.1039/B920979D (2009).

Kirby, B. J.; Kiel, J. W.; Maranville, B. B.; Majkrzak, C. F.; Mackay, M. E.

2010-03-01

88

Human cancer cells exhibit in vitro individual receptiveness towards different mistletoe extracts.  

PubMed

In vitro cytotoxic effects of three aqueous mistletoe extracts on cell physiology against different human tumor cell lines and primary cancer cells were investigated in order to compare the receptiveness of different cancer cells against different mistletoe products. Therefore cell proliferation (BrdU-incorporation assay), mitochondrial activity (MTT-testing) and necrotic cell toxicity (LDH assay) were assayed over serial dilutions of the test products. Data obtained with HELA-S3, MOLT-4, MFM-223, COR-L51, KPL-1 and VM-CUB1 tumor cell lines and Iscador M (20 mg/ml), Iscador Q (20 mg/ml) and Abnobaviscum Fraxini -2 (20 mg/ml) indicated significant growth-inhibition of all cell lines, but also different cell susceptibilities against the different extracts. These variations were not only monitored on established cell lines but also on primary mamma carcinoma cells from surgical resectates. Concerning cell proliferation and mitochondrial activity Abnobaviscum Fraxini exhibits stronger inhibitory effects compared to products from the Iscador series. In case the evaluation was standardized on the active contents of VAA-I within the different products, the Iscador extracts possess higher cytotoxic activity. Pure viscotoxins and mistletoe lectins exhibited less effects than the extracts. The simultaneous presence of pure mistletoe lectins and mistletoe polysaccharides diminished the VAA-mediated cytotoxic effects. The presence of fetal calf serum (FCS) in cultivation media during in vitro testing diminished the cytotoxic effects of mistletoe extracts. It was shown that in vivo application of mistletoe preparations led to the formation of antibodies against unknown compounds of the extracts, diminishing the cytotoxic effect. PMID:15997835

Knöpfl-Sidler, F; Viviani, A; Rist, L; Hensel, A

2005-06-01

89

Preparation of iron oxide-entrapped chitosan nanoparticles for stem cell labeling.  

PubMed

This study intended to prepare iron oxide nanoparticle-entrapped chitosan (CS) nanoparticles for stem cell labeling. The nanoparticles were synthesized by polymerizing iron oxide nanoparticle-associated methacrylic acid monomer in the presence of CS. TEM revealed that the well-defined iron oxide nanoparticles were successfully encapsulated inside the CS nanoparticles. The effect of CS at different [NH(2)]/[COOH] molar ratios on particle size, surface charge, thermal stability and magnetic properties was determined systematically. Internalization and localization of the coated nanoparticles were evaluated by atomic absorption spectrometry and confocal laser scanning microscopy. The Kusa O cell line was chosen as a stem cell model. Interestingly, the uptake of iron oxide-entrapped CS nanoparticles was remarkably enhanced under magnetization and the nanoparticles were mostly located inside cellular compartments. It can be concluded that the iron oxide-entrapped CS nanoparticles have a strong potential for stem cell labeling. PMID:20537238

Chaleawlert-Umpon, Saowaluk; Mayen, Varissaporn; Manotham, Krissanapong; Pimpha, Nuttaporn

2010-06-09

90

Ultrastructural characterization of CD133+ stem cells bound to superparamagnetic nanoparticles: possible biotechnological applications.  

PubMed

CD133 antigen is an integral membrane glycoprotein that can bind with different cells. Originally, however, this cellular surface antigen was expressed in human stem cells and in various cellular progenitors of the haematopoietic system. Human cord blood has been described as an excellent source of CD133(+) haematopoietic progenitor cells with a large application potential. One of the main objectives of the present study is to describe for the first time the ultrastructural characteristics of CD133(+) stem cells using transmission electronic microscopy. Another objective of the manuscript is to demonstrate through transmission electronic microscopy the molecular image of magnetic nanoparticles connected to the stem cells of great biotechnological importance, as well as demonstrating the value of this finding for electronic paramagnetic resonance and its related nanobioscientific value. Ultrastructural results showed the monoclonal antibody anti-CD133 bound to the superparamagnetic nanoparticles by the presence of electrondense granules in cell membrane, as well as in the cytoplasm, revealing the ultrastructural characteristics of CD133(+) cells, exhibiting a round morphology with discrete cytoplasmic projections, having an active nucleus that follows this morphology. The cellular cytoplasm was filled up with mitochondrias, as well as microtubules and vesicles pinocitic, characterizing the process as being related to internalization of the magnetic nanoparticles that were endocyted by the cells in question. Electronic paramagnetic resonance analysis of the CD133(+) stem cells detected that the signal (spectrum) generated by the labelled cells comes from the superparamagnetic nanoparticles that are bound to them. These results strongly suggest that these CD133(+) cells can be used in nanobiotechnology applications, with benefits in different biomedical areas. PMID:18754992

Pavon, L F; Gamarra, L F; Marti, L C; Amaro Junior, E; Moreira-Filho, C A; Camargo-Mathias, M I; Okamoto, O K

2008-09-01

91

Nanoparticle-aptamer conjugates for cancer cell targeting and detection.  

PubMed

Aptamers are DNA or RNA oligonucleotide sequences that selectively bind to their target with high affinity and specificity. They are obtained using an iterative selection protocol called SELEX. Several small molecules and proteins have been used as targets. Recently, a variant of this methodology, known as cell-SELEX, has been developed for a new generation of aptamers, which are capable of recognizing whole living cells. We have used this methodology for the selection of aptamers, which show high affinity and specificity for several cancer cells. In this chapter, we describe (1) the process followed for the generation of aptamers capable of recognizing acute leukemia cells (CCRF-CEM cells) and (2) the method of enhancing the selectivity and sensitivity of these aptamers by conjugation with a dual-nanoparticle system, which combines magnetic nanoparticles (MNP) and fluorescent silica nanoparticles (FNP). Specifically, the selected aptamers, which showed dissociation constants in the nanomolar range, have been coupled to MNPs in order to selectively collect and enrich cells from complex matrices, including blood samples. The additional coupling of the aptamer to FNPs offers an excellent and highly sensitive method for detecting cancer cells. In order to prove the potential of this rapid and low-cost method for diagnostic purposes, confocal microscopy was used to confirm the specific collection and detection of target cells in concentrations as low as 250 cells. The final fluorescence of the cells labeled with the nanoparticles was quantified using a fluorescence microplate reader. PMID:20217600

Estévez, M Carmen; Huang, Yu-Fen; Kang, Huaizhi; O'Donoghue, Meghan B; Bamrungsap, Suwussa; Yan, Jilin; Chen, Xiaolan; Tan, Weihong

2010-01-01

92

Antibiotic-induced bacterial cell death exhibits physiological and biochemical hallmarks of apoptosis  

PubMed Central

Summary Programmed cell death is a gene-directed process involved in the development and homeostasis of multicellular organisms. The most common mode of programmed cell death is apoptosis, which is characterized by a stereotypical set of biochemical and morphological hallmarks. Here we report that Escherichia coli also exhibit characteristic markers of apoptosis – including phosphatidylserine exposure, chromosome condensation and DNA fragmentation – when faced with cell death-triggering stress, namely bactericidal antibiotic treatment. Notably, we also provide proteomic and genetic evidence for the ability of multifunctional RecA to bind peptide sequences that serve as substrates for eukaryotic caspases, and regulation of this phenotype by the protease, ClpXP, under conditions of cell death. Our findings illustrate that prokaryotic organisms possess mechanisms to dismantle and mark dying cells in response to diverse noxious stimuli, and suggest that elaborate, multilayered proteolytic regulation of these features may have evolved in eukaryotes to harness and exploit their deadly potential.

Dwyer, Daniel J; Camacho, Diogo M; Kohanski, Michael A; Callura, Jarred M; Collins, James J

2013-01-01

93

Toxicity of Cerium Oxide Nanoparticles in Human Lung Cancer Cells  

SciTech Connect

With the fast development of nanotechnology, the nanomaterials start to cause people's attention for potential toxic effect. In this paper, the cytotoxicity and oxidative stress caused by 20-nm cerium oxide (CeO2) nanoparticles in cultured human lung cancer cells was investigated. The sulforhodamine B method was employed to assess cell viability after exposure to 3.5, 10.5, and 23.3 ?g/ml of CeO2 nanoparticles for 24, 48, and 72 h. Cell viability decreased significantly as a function of nanoparticle dose and exposure time. Indicators of oxidative stress and cytotoxicity, including total reactive oxygen species, glutathione, malondialdehyde, ?-tocopherol, and lactate dehydrogenase, were quantitatively assessed. It is concluded from the results that free radicals generated by exposure to 3.5 to 23.3 ?g/ml CeO2 nanoparticles produce significant oxidative stress in the cells, as reflected by reduced glutathione and ?-tocopherol levels; the toxic effects of CeO2 nanoparticles are dose dependent and time dependent; elevated oxidative stress increases the production of malondialdehyde and lactate dehydrogenase, which are indicators of lipid peroxidation and cell membrane damage, respectively.

Weisheng, Lin; Huang, Yue-wern; Zhou, Xiao Dong; Ma, Yinfa

2006-12-31

94

Dendritic cells exposed to estrogen in vitro exhibit therapeutic effects in ongoing experimental allergic encephalomyelitis.  

PubMed

Immunomodulatory effects of estrogen have been demonstrated by clinical and experimental observations, but the mechanisms by which estrogen exhibits the effects remain to be defined. One possible mechanism by which estrogen inhibits the development of experimental allergic encephalomyelitis (EAE), a commonly used model of multiple sclerosis (MS) in humans, is over the functions of dendritic cells (DC). Here, we describe that splenic DC from Lewis rats obtained on day 12 post-immunization (p.i.) with myelin basic protein (MBP) encephalitogenic peptide 68-86+Freund's complete adjuvant (FCA), after being exposed in vitro 17beta-estradiol, exhibited therapeutic effects on acute EAE when injected subcutaneously on day 5 p.i. Blood mononuclear cells (MNC) were isolated from thus treated rats on day 12 p.i. Administration of estrogen-exposed DC prevented the expansion of CD4+ T cells and increased proportions of regulatory T cells producing IL-10 and CD4+CD28- suppressor T cells, accompanied with increased IL-10 and IFN-gamma, and reduced TNF-alpha production. Infiltrates of CD68+ macrophages within the central nervous system and MBP 68-86-induced T cell proliferation were inhibited in rats injected with estrogen-exposed DC compared to rats injected with naive DC. Estrogen up-regulated the expression of indoleamine 2,3-dioxygenase, which promotes tolerogenic properties of DC. The results suggest that in vitro exposure of DC to estrogen modulates DC functions and results in a therapeutic effect of DC. PMID:15465596

Pettersson, Asa; Ciumas, Carolina; Chirsky, Vadim; Link, Hans; Huang, Yu-Min; Xiao, Bao-Guo

2004-11-01

95

Single cells from human primary colorectal tumors exhibit polyfunctional heterogeneity in secretions of ELR+ CXC chemokines.  

PubMed

Cancer is an inflammatory disease of tissue that is largely influenced by the interactions between multiple cell types, secreted factors, and signal transduction pathways. While single-cell sequencing continues to refine our understanding of the clonotypic heterogeneity within tumors, the complex interplay between genetic variations and non-genetic factors ultimately affects therapeutic outcome. Much has been learned through bulk studies of secreted factors in the tumor microenvironment, but the secretory behavior of single cells has been largely uncharacterized. Here we directly profiled the secretions of ELR+ CXC chemokines from thousands of single colorectal tumor and stromal cells, using an array of subnanoliter wells and a technique called microengraving to characterize both the rates of secretion of several factors at once and the numbers of cells secreting each chemokine. The ELR+ CXC chemokines are highly redundant, pro-angiogenic cytokines that signal via the CXCR1 and CXCR2 receptors, influencing tumor growth and progression. We find that human primary colorectal tumor and stromal cells exhibit polyfunctional heterogeneity in the combinations and magnitudes of secretions for these chemokines. In cell lines, we observe similar variance: phenotypes observed in bulk can be largely absent among the majority of single cells, and discordances exist between secretory states measured and gene expression for these chemokines among single cells. Together, these measures suggest secretory states among tumor cells are complex and can evolve dynamically. Most importantly, this study reveals new insight into the intratumoral phenotypic heterogeneity of human primary tumors. PMID:23995780

Adalsteinsson, Viktor A; Tahirova, Narmin; Tallapragada, Naren; Yao, Xiaosai; Campion, Liam; Angelini, Alessandro; Douce, Thomas B; Huang, Cindy; Bowman, Brittany; Williamson, Christina A; Kwon, Douglas S; Wittrup, K Dane; Love, J Christopher

2013-09-23

96

Remnant living cells that escape cell loss in late-stage tumors exhibit cancer stem cell-like characteristics.  

PubMed

A balance between cell proliferation and cell loss is essential for tumor progression. Although up to 90% of cells are lost in late-stage carcinomas, the progression and characteristics of remnant living cells in tumor mass are unclear. Here we used molecular imaging to track the progression of living cells in a syngeneic tumor model, and ex vivo investigated the properties of this population at late-stage tumor. The piggyBac transposon system was used to stably introduce the dual reporter genes, including monomeric red fluorescent protein (mRFP) and herpes simplex virus type-1 thymidine kinase (HSV1-tk) genes for fluorescence-based and radionuclide-based imaging of tumor growth in small animals, respectively. Iodine-123-labeled 5-iodo-2'-fluoro-1-beta-D-arabinofuranosyluracil was used as a radiotracer for HSV1-tk gene expression in tumors. The fluorescence- and radionuclide-based imaging using the single-photon emission computed tomography/computed tomography revealed that the number of living cells reached the maximum at 1 week after implantation of 4T1 tumors, and gradually decreased and clustered near the side of the body until 4 weeks accompanied by enlargement of tumor mass. The remnant living cells at late-stage tumor were isolated and investigated ex vivo. The results showed that these living cells could form mammospheres and express cancer stem cell (CSC)-related biomarkers, including octamer-binding transcription factor 4, SRY (sex-determining region Y)-box 2, and CD133 genes compared with those cultured in vitro. Furthermore, this HSV1-tk-expressing CSC-like population was sensitive to ganciclovir applied for the suicide therapy. Taken together, the current data suggested that cells escaping from cell loss in late-stage tumors exhibit CSC-like characteristics, and HSV1-tk may be considered a theranostic agent for targeting this population in vivo. PMID:23034334

Chen, Y L; Wang, S Y; Liu, R S; Wang, H E; Chen, J C; Chiou, S H; Chang, C A; Lin, L T; Tan, D T W; Lee, Y J

2012-10-04

97

Intracellular Confinement of Magnetic Nanoparticles by Living Cells: Impact for Imaging and Therapeutic Applications  

Microsoft Academic Search

Superparamagnetic properties of iron-oxide nanoparticles paved the way for various biomedical applications, such as magnetic resonance imaging (MRI), magnetic targeting of drug vectors or magnetically-induced therapeutic hyperthermia. Living cells interact with nanoparticles by internalizing them within intracellular compartments, called lysosomes. In the course of cellular uptake, the spatial distribution of magnetic nanoparticles changes from dilute isolated nanoparticles to a highly

Florence Gazeau; Michael Lévy; Claire Wilhelm

2011-01-01

98

Tumor Cells Exhibit Deregulation of the Cell Cycle Histone Gene Promoter Factor HiNF-D  

Microsoft Academic Search

Cell cycle-regulated gene expression is essential for normal cell growth and development and loss of stringent growth control is associated with the acquisition of the transformed phenotype. The selective synthesis of histone proteins during the S phase of the cell cycle is required to render cells competent for the ordered packaging of replicating DNA into chromatin. Regulation of H4 histone

Joost Holthuis; Thomas A. Owen; Andre J. van Wijnen; Kenneth L. Wright; Anna Ramsey-Ewing; Mary Beth Kennedy; Ruth Carter; Stephen C. Cosenza; Kenneth J. Soprano; Jane B. Lian; Janet L. Stein; Gary S. Stein

1990-01-01

99

Ex vivo expansion of canine cytotoxic large granular lymphocytes exhibiting characteristics of natural killer cells.  

PubMed

Canine NK cells still are not well-characterized due to the lack of information concerning specific NK cell markers and the fact that NK cells are not an abundant cell population. In this study, we selectively expanded the canine cytotoxic large granular lymphocytes (CLGLs) that exhibit morphologic, genetic, and functional characteristics of NK cells from normal donor PBMCs. The cultured CLGLs were characterized by a high proportion of CD5(dim) expressing cells, of which the majority of cells co-expressed CD3 and CD8, but did not express TCR?? and TCR??. The phenotype of the majority of the CLGLs was CD5(dim)CD3(+)CD8(+) TCR??(-)TCR??(-)CD4(-)CD21(-)CD11c(+/-)CD11d(+/-)CD44(+). The expression of mRNAs for NK cell-associated receptors (NKG2D, NKp30, NKp44, Ly49, perforin, and granzyme B) were highly upregulated in cultured CLGLs. Specifically, NKp46 was remarkably upregulated in the cultured CLGLs compared to PBMCs. The mRNAs for the NKT-associated iTCR? gene in CLGLs was present at a basal level. The cytotoxic activity of the CLGLs against canine NK cell-sensitive CTAC cells was remarkably elevated in a dose-dependent manner, and the CLGLs produced large amounts of IFN-?. The antitumor activity of CLGLs extended to different types of canine tumor cells (CF41.Mg and K9TCC-pu-AXC) without specific antigen recognition. These results are consistent with prior reports, and strongly suggest that the selectively expanded CLGLs represent a population of canine NK cells. The results of this study will contribute to future research on canine NK cells as well as NK cell-based immunotherapy. PMID:23548866

Shin, Dong-Jun; Park, Ji-Yun; Jang, Youn-Young; Lee, Je-Jung; Lee, Youn-Kyung; Shin, Myung-Geun; Jung, Ji-Youn; Carson, William E; Cho, Duck; Kim, Sang-Ki

2013-03-21

100

Selective Cell Targeting with Light-Absorbing Microparticles and Nanoparticles  

Microsoft Academic Search

We describe a new method for selective cell targeting based on the use of light-absorbing microparticles and nanoparticles that are heated by short laser pulses to create highly localized cell damage. The method is closely related to chromophore-assisted laser inactivation and photodynamic therapy, but is driven solely by light absorption, without the need for photochemical intermediates (particularly singlet oxygen). The

Costas M. Pitsillides; Edwin K. Joe; Xunbin Wei; R. Rox Anderson; Charles P. Lin

2003-01-01

101

Cells surviving fractional killing by TRAIL exhibit transient but sustainable resistance and inflammatory phenotypes  

PubMed Central

When clonal populations of human cells are exposed to apoptosis-inducing agents, some cells die and others survive. This fractional killing arises not from mutation but from preexisting, stochastic differences in the levels and activities of proteins regulating apoptosis. Here we examine the properties of cells that survive treatment with agonists of two distinct death receptors, tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) and anti-FasR antibodies. We find that “survivor” cells are highly resistant to a second ligand dose applied 1 d later. Resistance is reversible, resetting after several days of culture in the absence of death ligand. “Reset” cells appear identical to drug-naive cells with respect to death ligand sensitivity and gene expression profiles. TRAIL survivors are cross-resistant to activators of FasR and vice versa and exhibit an NF-?B–dependent inflammatory phenotype. Remarkably, reversible resistance is induced in the absence of cell death when caspase inhibitors are present and can be sustained for 1 wk or more, also without cell death, by periodic ligand exposure. Thus stochastic differences in cell state can have sustained consequences for sen­sitivity to prodeath ligands and acquisition of proinflammatory phenotypes. The important role played by periodicity in TRAIL exposure for induction of opposing apoptosis and survival mechanisms has implications for the design of optimal therapeutic agents and protocols.

Flusberg, Deborah A.; Roux, Jeremie; Spencer, Sabrina L.; Sorger, Peter K.

2013-01-01

102

Chick hair cells do not exhibit voltage-dependent somatic motility  

PubMed Central

It is generally believed that mechanical amplification by cochlear hair cells is necessary to enhance the sensitivity and frequency selectivity of hearing. In the mammalian ear, the basis of cochlear amplification is believed to be the voltage-dependent electromotility of outer hair cells (OHCs). The avian basilar papilla contains tall and short hair cells, with the former being comparable to inner hair cells, and the latter comparable to OHCs, based on their innervation patterns. In this study, we sought evidence for somatic electromotility by direct measurements of voltage-dependent length changes in both tall and short hair cells at nanometre resolution. Microchamber and whole-cell voltage-clamp techniques were used. Motility was measured with a photodiode-based measurement system. Non-linear capacitance, an electrical signature of somatic motility, was also measured to complement motility measurement. Significantly, chick hair cells did not exhibit somatic motility nor express non-linear capacitance. The lack of somatic motility suggests that in avian hair cells the active process resides elsewhere, most likely in the hair cell stereocilia.

He, David Z Z; Beisel, Kirk W; Chen, Lin; Ding, Da-Lian; Jia, Shuping; Fritzsch, Bernd; Salvi, Richard

2003-01-01

103

Decreased astroglial cell adhesion and proliferation on zinc oxide nanoparticle polyurethane composites  

PubMed Central

Nanomaterials offer a number of properties that are of interest to the field of neural tissue engineering. Specifically, materials that exhibit nanoscale surface dimensions have been shown to promote neuron function while simultaneously minimizing the activity of cells such as astrocytes that inhibit central nervous system regeneration. Studies demonstrating enhanced neural tissue regeneration in electrical fields through the use of conductive materials have led to interest in piezoelectric materials (or those materials which generate a transient electrical potential when mechanically deformed) such as zinc oxide (ZnO). It has been speculated that ZnO nanoparticles possess increased piezoelectric properties over ZnO micron particles. Due to this promise in neural applications, the objective of the present in vitro study was, for the first time, to assess the activity of astroglial cells on ZnO nanoparticle polymer composites. ZnO nanoparticles embedded in polyurethane were analyzed via scanning electron microscopy to evaluate nanoscale surface features of the composites. The surface chemistry was characterized via X-ray photoelectron spectroscopy. Astroglial cell response was evaluated based on cell adhesion and proliferation. Astrocyte adhesion was significantly reduced on ZnO nanoparticle/polyurethane (PU) composites with a weight ratio of 50:50 (PU:ZnO) wt.%, 75:25 (PU:ZnO) wt.%, and 90:10 (PU:ZnO) wt.% in comparison to pure PU. The successful production of ZnO nanoparticle composite scaffolds suitable for decreasing astroglial cell density demonstrates their potential as a nerve guidance channel material with greater efficiency than what may be available today.

Seil, Justin T; Webster, Thomas J

2008-01-01

104

Cell cycle-arrested tumor cells exhibit increased sensitivity towards TRAIL-induced apoptosis.  

PubMed

Resting tumor cells represent a huge challenge during anticancer therapy due to their increased treatment resistance. TNF-related apoptosis-inducing ligand (TRAIL) is a putative future anticancer drug, currently in phases I and II clinical studies. We recently showed that TRAIL is able to target leukemia stem cell surrogates. Here, we tested the ability of TRAIL to target cell cycle-arrested tumor cells. Cell cycle arrest was induced in tumor cell lines and xenografted tumor cells in G0, G1 or G2 using cytotoxic drugs, phase-specific inhibitors or RNA interference against cyclinB and E. Biochemical or molecular arrest at any point of the cell cycle increased TRAIL-induced apoptosis. Accordingly, when cell cycle arrest was disabled by addition of caffeine, the antitumor activity of TRAIL was reduced. Most important for clinical translation, tumor cells from three children with B precursor or T cell acute lymphoblastic leukemia showed increased TRAIL-induced apoptosis upon knockdown of either cyclinB or cyclinE, arresting the cell cycle in G2 or G1, respectively. Taken together and in contrast to most conventional cytotoxic drugs, TRAIL exerts enhanced antitumor activity against cell cycle-arrested tumor cells. Therefore, TRAIL might represent an interesting drug to treat static-tumor disease, for example, during minimal residual disease. PMID:23744361

Ehrhardt, H; Wachter, F; Grunert, M; Jeremias, I

2013-06-06

105

Cell uptake enhancement of folate targeted polymer coated magnetic nanoparticles.  

PubMed

Dual targeted drug delivery systems represent a potential platform for developing efficient vector to tumor sites. In this study we evaluated a folate- and magnetic-targeted nanocarriers based on 10 nm iron oxide nanodomais coated with the properly synthesized and characterized folic acid (FA)-functionalized amphiphilic copolymer PHEA-PLA-PEG-FA. FA was chemically conjugated to one end of diamino-polyethylene glycol of 2000 Da, in order to ensure its exposition on the polymer coated magnetic nanoparticles (MNPs-FA). The prepared nanoparticles have been exhaustively characterized by different methods, including DLS, SEM, FT-IR and magnetic measurements. Magnetic nanoparticles showed dimension of about 37 nm with a narrow size distribution and a characteristic superparamagnetic behaviour. The lack of cytotoxicity of MNPs-FA and MNPs was assessed both on MCF7 cells, used as a model tumor cell line, and on 16HBE, used as normal human cell model, by evaluating cell viability using MTS assay, while the preferential internalization of MNPs-FA into tumor cells rather that into normal cells was confirmed by the quantization of internalized iron oxide. Uptake studies were also performed in the presence of a permanent magnet in order to verify the synergistic effect of magnetic field in enhancing the internalization of magnetic nanoparticles. Finally, real-time confocal microscopy experiments were carried out to further confirmed that FA ligand enhances the MNPs-FA accumulation into cancer cell cytoplasm. PMID:23858959

Licciardi, Mariano; Scialabba, Cinzia; Cavallaro, Gennara; Sangregorio, Claudio; Fantechi, Elvira; Giammona, Gaetano

2013-06-01

106

Polymeric microfluidic devices exhibiting sufficient capture of cancer cell line for isolation of circulating tumor cells.  

PubMed

Here, we developed polymeric microfluidic devices for the isolation of circulating tumor cells. The devices, with more than 30,000 microposts in the channel, were produced successfully by a UV light-curing process lasting 3 min. The device surface was coated with anti-epithelial cell adhesion molecule antibody by just contacting the antibody solution, and a flow system including the device was established to send a cell suspension through it. We carried out flow tests for evaluation of the device's ability to capture tumor cells using an esophageal cancer cell line, KYSE220, dispersed in phosphate-buffered saline or mononuclear cell separation from whole blood. After the suspension flowed through the chip, many cells were seen to be captured on the microposts coated with the antibody, whereas there were few cells in the device without the antibody. Owing to the transparency of the device, we could observe the intact and the stained cells captured on the microposts by transmitted light microscopy and phase contrast microscopy, in addition to fluorescent microscopy, which required fluorescence labeling. Cell capture efficiencies (i.e., recovery rates of the flowing cancer cells by capture with the microfluidic device) were measured. The resulting values were 0.88 and 0.95 for cell suspension in phosphate-buffered saline, and 0.85 for the suspension in the mononuclear cell separation, suggesting the sufficiency of this device for the isolation of circulating tumor cells. Therefore, our device may be useful for research and treatments that rely on investigation of circulating tumor cells in the blood of cancer patients. PMID:23666489

Ohnaga, Takashi; Shimada, Yutaka; Moriyama, Makoto; Kishi, Hiroyuki; Obata, Tsutomu; Takata, Koji; Okumura, Tomoyuki; Nagata, Takuya; Muraguchi, Atsushi; Tsukada, Kazuhiro

2013-08-01

107

Enhancement of the optical Kerr effect exhibited by an integrated configuration of silicon quantum dots and silver nanoparticles  

NASA Astrophysics Data System (ADS)

We present nonlinear refractive results for three different systems produced by ion implantation: high purity silica substrates with silicon quantum dots (Si-QDs), silver nanoparticles (Ag-NPs), and one sample containing both. We used a femtosecond optical Kerr gate (OKG) with 80 fs pulses at 830 nm to investigate the magnitude and response time of their nonlinear response. The Ag-NPs samples were prepared implanting 2 MeV Ag2+ ions at different fluencies. A sample with 1×1017 ions/cm2 showed no discernible Kerr signal, while for one with 2.4×1017 ions/cm2 we measured |?(3)|1111 = 5.1×10-11 esu. The Si-QDs sample required irradiation with 1.5 MeV Si2+ ions, at a 2.5×1017 ions/cm2 fluence in order that the OKG results for this sample yielded a similar |?(3)|1111 value. The sample containing the Si-QDs was then irradiated by 1 MeV Ag2+ ions at a 4.44 × 1016 ions/cm2 fluence and thermally treated, for which afterward we measured |?(3)|1111 = 1.7×10-10 esu. In all cases the response time was quasi-instantaneous. These results imply that the inclusion of Ag-NPs at low fluence, enhances the nonlinearity of the composite by a factor of around three, and that this is purely electronic in nature. Pump-probe results show that there is not any nonlinear absorption present. We estimate that the confinement effect of the Si-QDs in the sample plays an important role for the excitation of the Surface Plasmon Resonance (SPR) related to the Ag-NPs. A theoretical model that describes the modification of the third order nonlinearity is also presented.

López-Suárez, A.; R, Rangel-Rojo; Torres-Torres, C.; Benami, A.; L, Tamayo-Rivera; Reyes-Esqueda, J. A.; Cheang-Wong, J. C.; Rodríguez-Fernández, L.; Crespo-Sosa, A.; Oliver, A.

2011-01-01

108

Monitoring lysosomal activity in nanoparticle-treated cells.  

PubMed

Certain nanoparticles have been shown to accumulate within lysosome and hence may cause lysosomal pathologies such as phospholipidosis, lysosomal overload, and autophagy. This chapter describes a method for evaluation of lysosomal activity in porcine kidney cells (LLC-PK1) after exposure to nanoparticles. This method uses the accumulation of a cationic fluorescent dye (LysoTracker Red) in acidic cellular compartments as an indicator of total lysosome content. The lysotracker signal is normalized to the signal from a thiol-reactive dye which is proportional to the total number of viable cells. PMID:21116970

Neun, Barry W; Stern, Stephan T

2011-01-01

109

Gold nanoparticles delivery in mammalian live cells: a critical review  

PubMed Central

Functional nanomaterials have recently attracted strong interest from the biology community, not only as potential drug delivery vehicles or diagnostic tools, but also as optical nanomaterials. This is illustrated by the explosion of publications in the field with more than 2,000 publications in the last 2 years (4,000 papers since 2000; from ISI Web of Knowledge, ‘nanoparticle and cell’ hit). Such a publication boom in this novel interdisciplinary field has resulted in papers of unequal standard, partly because it is challenging to assemble the required expertise in chemistry, physics, and biology in a single team. As an extreme example, several papers published in physical chemistry journals claim intracellular delivery of nanoparticles, but show pictures of cells that are, to the expert biologist, evidently dead (and therefore permeable). To attain proper cellular applications using nanomaterials, it is critical not only to achieve efficient delivery in healthy cells, but also to control the intracellular availability and the fate of the nanomaterial. This is still an open challenge that will only be met by innovative delivery methods combined with rigorous and quantitative characterization of the uptake and the fate of the nanoparticles. This review mainly focuses on gold nanoparticles and discusses the various approaches to nanoparticle delivery, including surface chemical modifications and several methods used to facilitate cellular uptake and endosomal escape. We will also review the main detection methods and how their optimum use can inform about intracellular localization, efficiency of delivery, and integrity of the surface capping.

Levy, Raphael; Shaheen, Umbreen; Cesbron, Yann; See, Violaine

2010-01-01

110

Antimicrobial efficacy and ocular cell toxicity from silver nanoparticles  

PubMed Central

Silver in various forms has long been recognized for antimicrobial properties, both in biomedical devices and in eyes. However, soluble drugs used on the ocular surface are rapidly cleared through tear ducts and eventually ingested, resulting in decreased efficacy of the drug on its target tissue and potential concern for systemic side effects. Silver nanoparticles were studied as a source of anti-microbial silver for possible controlled-release contact lens controlled delivery formulations. Silver ion release over a period of several weeks from nanoparticle sources of various sizes and doses in vitro was evaluated in vitro against Pseudomonas aeruginosa strain PA01. Mammalian cell viability and cytokine expression in response to silver nanoparticle exposure is evaluated using corneal epithelial cells and eye-associated macrophages cultured in vitro in serum-free media. Minimal microcidal and cell toxic effects were observed for several silver nanoparticle suspensions and aqueous extraction times for bulk total silver concentrations commensurate with comparative silver ion (e.g., Ag+(aq)) toxicity. This indicates that (1) silver particles themselves are not microcidal under conditions tested, and (2) insufficient silver ion is generated from these particles at these loadings to produce observable biological effects in these in vitro assays. If dosing allows substantially increased silver particle loading in the lens, the bactericidal efficacy of silver nanoparticles in vitro is one possible approach to limiting bacterial colonization problems associated with extended-wear contact lenses.

Santoro, Colleen M.; Duchsherer, Nicole L.

2009-01-01

111

Skeletal muscle neural progenitor cells exhibit properties of NG2-glia.  

PubMed

Reversing brain degeneration and trauma lesions will depend on cell therapy. Our previous work identified neural precursor cells derived from the skeletal muscle of Nestin-GFP transgenic mice, but their identity, origin, and potential survival in the brain are only vaguely understood. In this work, we show that Nestin-GFP+ progenitor cells share morphological and molecular markers with NG2-glia, including NG2, PDGFR?, O4, NGF receptor (p75), glutamate receptor-1(AMPA), and A2B5 expression. Although these cells exhibit NG2, they do not express other pericyte markers, such as ?-SMA or connexin-43, and do not differentiate into the muscle lineage. Patch-clamp studies displayed outward potassium currents, probably carried through Kir6.1 channels. Given their potential therapeutic application, we compared their abundance in tissues and concluded that skeletal muscle is the richest source of predifferentiated neural precursor cells. We found that these cells migrate toward the neurogenic subventricular zone displaying their typical morphology and nestin-GFP expression two weeks after brain injection. For translational purposes, we sought to identify these neural progenitor cells in wild-type species by developing a DsRed expression vector under Nestin-Intron II control. This approach revealed them in nonhuman primates and aging rodents throughout the lifespan. PMID:22999866

Birbrair, Alexander; Zhang, Tan; Wang, Zhong-Min; Messi, María Laura; Enikolopov, Grigori N; Mintz, Akiva; Delbono, Osvaldo

2012-09-20

112

Induced pluripotent stem cells derived from rabbits exhibit some characteristics of na?ve pluripotency  

PubMed Central

Summary Not much is known about the molecular and functional features of pluripotent stem cells (PSCs) in rabbits. To address this, we derived and characterized 2 types of rabbit PSCs from the same breed of New Zealand White rabbits: 4 lines of embryonic stem cells (rbESCs), and 3 lines of induced PSCs (rbiPSCs) that were obtained by reprogramming adult skin fibroblasts. All cell lines required fibroblast growth factor 2 for their growth and proliferation. All rbESC lines showed molecular and functional properties typically associated with primed pluripotency. The cell cycle of rbESCs had a prolonged G1 phase and a DNA damage checkpoint before entry into the S phase, which are the 2 features typically associated with the somatic cell cycle. In contrast, the rbiPSC lines exhibited some characteristics of naïve pluripotency, including resistance to single-cell dissociation by trypsin, robust activity of the distal enhancer of the mouse Oct4 gene, and expression of naïve pluripotency-specific genes, as defined in rodents. According to gene expression profiles, rbiPSCs were closer to the rabbit inner cell mass (ICM) than rbESCs. Furthermore, rbiPSCs were capable of colonizing the ICM after aggregation with morulas. Therefore, we propose that rbiPSCs self-renew in an intermediate state between naïve and primed pluripotency, which represents a key step toward the generation of bona fide naïve PSC lines in rabbits.

Osteil, Pierre; Tapponnier, Yann; Markossian, Suzy; Godet, Murielle; Schmaltz-Panneau, Barbara; Jouneau, Luc; Cabau, Cedric; Joly, Thierry; Blachere, Thierry; Gocza, Elen; Bernat, Agnieszka; Yerle, Martine; Acloque, Herve; Hidot, Sullivan; Bosze, Zsuzsanna; Duranthon, Veronique; Savatier, Pierre; Afanassieff, Marielle

2013-01-01

113

Kaempferol nanoparticles achieve strong and selective inhibition of ovarian cancer cell viability  

PubMed Central

Ovarian cancer is one of the leading causes of cancer death for women throughout the Western world. Kaempferol, a natural flavonoid, has shown promise in the chemoprevention of ovarian cancer. A common concern about using dietary supplements for chemoprevention is their bioavailability. Nanoparticles have shown promise in increasing the bioavailability of some chemicals. Here we developed five different types of nanoparticles incorporating kaempferol and tested their efficacy in the inhibition of viability of cancerous and normal ovarian cells. We found that positively charged nanoparticle formulations did not lead to a significant reduction in cancer cell viability, whereas nonionic polymeric nanoparticles resulted in enhanced reduction of cancer cell viability. Among the nonionic polymeric nanoparticles, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) nanoparticles incorporating kaempferol led to significant reduction in cell viability of both cancerous and normal cells. Poly(DL-lactic acid-co-glycolic acid) (PLGA) nanoparticles incorporating kaempferol resulted in enhanced reduction of cancer cell viability together with no significant reduction in cell viability of normal cells compared with kaempferol alone. Therefore, both PEO-PPO-PEO and PLGA nanoparticle formulations were effective in reducing cancer cell viability, while PLGA nanoparticles incorporating kaempferol had selective toxicity against cancer cells and normal cells. A PLGA nanoparticle formulation could be advantageous in the prevention and treatment of ovarian cancers. On the other hand, PEO-PPO-PEO nanoparticles incorporating kaempferol were more effective inhibitors of cancer cells, but they also significantly reduced the viability of normal cells. PEO-PPO-PEO nanoparticles incorporating kaempferol may be suitable as a cancer-targeting strategy, which could limit the effects of the nanoparticles on normal cells while retaining their potency against cancer cells. We have identified two nanoparticle formulations incorporating kaempferol that may lead to breakthroughs in cancer treatment. Both PEO-PPO-PEO and PLGA nanoparticle formulations had superior effects compared with kaempferol alone in reducing cancer cell viability.

Luo, Haitao; Jiang, Bingbing; Li, Bingyun; Li, Zhaoliang; Jiang, Bing-Hua; Chen, Yi Charlie

2012-01-01

114

Arbovirus-Derived piRNAs Exhibit a Ping-Pong Signature in Mosquito Cells  

PubMed Central

The siRNA pathway is an essential antiviral mechanism in insects. Whether other RNA interference pathways are involved in antiviral defense remains unclear. Here, we report in cells derived from the two main vectors for arboviruses, Aedes albopictus and Aedes aegypti, the production of viral small RNAs that exhibit the hallmarks of ping-pong derived piwi-associated RNAs (piRNAs) after infection with positive or negative sense RNA viruses. Furthermore, these cells produce endogenous piRNAs that mapped to transposable elements. Our results show that these mosquito cells can initiate de novo piRNA production and recapitulate the ping-pong dependent piRNA pathway upon viral infection. The mechanism of viral-piRNA production is discussed.

Vodovar, Nicolas; Bronkhorst, Alfred W.; van Cleef, Koen W. R.; Miesen, Pascal; Blanc, Herve; van Rij, Ronald P.; Saleh, Maria-Carla

2012-01-01

115

Hybrid plasmonic magnetic nanoparticles as molecular specific agents for MRI/optical imaging and photothermal therapy of cancer cells  

NASA Astrophysics Data System (ADS)

Nanoparticles which consist of a plasmonic layer and an iron oxide moiety could provide a promising platform for development of multimodal imaging and therapy approaches in future medicine. However, the feasibility of this platform has yet to be fully explored. In this study we demonstrated the use of gold-coated iron oxide hybrid nanoparticles for combined molecular specific MRI/optical imaging and photothermal therapy of cancer cells. The gold layer exhibits a surface plasmon resonance that provides optical contrast due to light scattering in the visible region and also presents a convenient surface for conjugating targeting moieties, while the iron oxide cores give strong T2 (spin-spin relaxation time) contrast. The strong optical absorption of the plasmonic gold layer also makes these nanoparticles a promising agent for photothermal therapy. We synthesized hybrid nanoparticles which specifically target epidermal growth factor receptor (EGFR), a common biomarker for many epithelial cancers. We demonstrated molecular specific MRI and optical imaging in MDA-MB-468 breast cancer cells. Furthermore, we showed that receptor-mediated aggregation of anti-EGFR hybrid nanoparticles allows selective destruction of highly proliferative cancer cells using a nanosecond pulsed laser at 700 nm wavelength, a significant shift from the peak absorbance of isolated hybrid nanoparticles at 532 nm.

Larson, Timothy A.; Bankson, James; Aaron, Jesse; Sokolov, Konstantin

2007-08-01

116

Cytarabine and paclitaxel exhibit different cell-cycle specificities in different cell growing status  

Microsoft Academic Search

Objective  To investigate the cell-cycle specificites of cytarabine and paclitaxel in different growing status of target cell.\\u000a \\u000a \\u000a \\u000a Methods  Using flow cytometry, we tested the cell-cycle specificities of cytarabine and paclitaxel on acute lymphocte leukemia cell\\u000a line Molt-4 in different growing status and on clinical acute lymphocyte leukemia specimens in vitro as well as in leukemia patients in vivo.\\u000a \\u000a \\u000a \\u000a Results  Cytarabine induced S phase

Peng Zhang; Yi Zhou; Deding Tao; Jianfeng Zhou; Jianping Gong

2006-01-01

117

Microenvironments and different nanoparticle dynamics in living cells revealed by a standard nanoparticle.  

PubMed

For quantitative analysis of nanoparticle diffusions and submicro-environments in living cells, use of newly synthesized silica-based fluorescent nanoparticle (Si-FNP) as a standard nanoprobe is successfully demonstrated. The appropriate characteristics of a standard probe were fully analyzed in vitro by single molecule detection, transmission electron microscopy, and dynamic light scattering. Using fluorescence correlation analysis in single living cells, we quantitatively compared the diffusional properties of the standard Si-FNP with a diameter of 50 nm, peptide coated Si-FNP, streptavidin coated Qdot, and GFP molecule which have different sizes and surface properties. The result demonstrates that the standard Si-FNP without coat is minimally trapped in the vesicles in the process of cellular endocytosis. Interestingly, a large proportion of Si-FNP introduced into the cells by electroporation diffuses freely in the cells during a cell cycle suggesting free diffusing NPs are hardly trapped in the vesicles. The simple but highly sensitive method will provide insight into strategies to understanding the hydrodynamic process of nanoparticle delivery into living cells as well as the cellular microenvironment in the view of submicro-size. PMID:22922061

Pack, Chan Gi; Song, Mi Ryoung; Tae, Eunju Lee; Hiroshima, Michio; Byun, Kyung Hee; Kim, Jun Sung; Sako, Yasushi

2012-08-16

118

Internalization of Nanoparticles into Spiral Ganglion Cells  

Microsoft Academic Search

The delivery of drugs or genes to the inner ear in a controlled and biocompatible manner could lead to new treat- ments for conditions such as Ménière's disease, tinnitus, schwannomas of the ear, and for improving hearing. The concept of multifunctional nanoparticles, which are targetable, biodegradable, and traceable, has led to new approaches to controlled drug release and localized delivery

Malin Anderson; A. H. Johnston; T. A. Newman; P. D. Dalton; Helge Rask-Andersen

2008-01-01

119

The role of surface charge on the uptake and biocompatibility of hydroxyapatite nanoparticles with osteoblast cells.  

PubMed

The objective of this study is to evaluate the effect of hydroxyapatite (HAP) nanoparticles with different surface charges on the cellular uptake behavior and in vitro cell viability and proliferation of MC3T3-E1 cell lines (osteoblast). The nanoparticles' surface charge was varied by surface modification with two carboxylic acids: 12-aminododecanoic acid (positive) and dodecanedioic acid (negative). The untreated HAP nanoparticles and dodecanoic acid modified HAP nanoparticles (neutral) were used as the control. X-ray diffraction (XRD) revealed that surface modifications by the three carboxylic acids did not change the crystal structure of HAP nanoparticles; Fourier transform infrared spectroscopy (FT-IR) confirmed the adsorption and binding of the carboxylic acids on the HAP nanoparticles' surfaces; and zeta potential measurement confirmed that the chemicals successfully modified the surface charge of HAP nanoparticles in water based solution. Transmission electron microscopy (TEM) images showed that positively charged, negatively charged and untreated HAP nanoparticles, with similar size and shape, all penetrated into the cells and cells had more uptake of HAP nanoparticles with positive charge compared to those with negative charge, which might be attributed to the attractive or repulsive interaction between the negatively charged cell membrane and positively/negatively charged HAP nanoparticles. The neutral HAP nanoparticles could not penetrate the cell membrane due to their larger size. MTT assay and LDH assay results indicated that as compared with the polystyrene control, greater cell viability and cell proliferation were measured on MC3T3-E1 cells treated with the three kinds of HAP nanoparticles (neutral, positive, and untreated), among which positively charged HAP nanoparticles showed the strongest improvement for cell viability and cell proliferation. In summary, the surface charge of HAP nanoparticles can be modified to influence the cellular uptake of HAP nanoparticles and the different uptake also influences the behavior of cells. These in vitro results may also provide useful information for investigations of HAP nanoparticle applications in gene delivery and intracellular drug delivery. PMID:21289408

Chen, Liang; Mccrate, Joseph M; Lee, James C-M; Li, Hao

2011-02-02

120

The role of surface charge on the uptake and biocompatibility of hydroxyapatite nanoparticles with osteoblast cells  

NASA Astrophysics Data System (ADS)

The objective of this study is to evaluate the effect of hydroxyapatite (HAP) nanoparticles with different surface charges on the cellular uptake behavior and in vitro cell viability and proliferation of MC3T3-E1 cell lines (osteoblast). The nanoparticles' surface charge was varied by surface modification with two carboxylic acids: 12-aminododecanoic acid (positive) and dodecanedioic acid (negative). The untreated HAP nanoparticles and dodecanoic acid modified HAP nanoparticles (neutral) were used as the control. X-ray diffraction (XRD) revealed that surface modifications by the three carboxylic acids did not change the crystal structure of HAP nanoparticles; Fourier transform infrared spectroscopy (FT-IR) confirmed the adsorption and binding of the carboxylic acids on the HAP nanoparticles' surfaces; and zeta potential measurement confirmed that the chemicals successfully modified the surface charge of HAP nanoparticles in water based solution. Transmission electron microscopy (TEM) images showed that positively charged, negatively charged and untreated HAP nanoparticles, with similar size and shape, all penetrated into the cells and cells had more uptake of HAP nanoparticles with positive charge compared to those with negative charge, which might be attributed to the attractive or repulsive interaction between the negatively charged cell membrane and positively/negatively charged HAP nanoparticles. The neutral HAP nanoparticles could not penetrate the cell membrane due to their larger size. MTT assay and LDH assay results indicated that as compared with the polystyrene control, greater cell viability and cell proliferation were measured on MC3T3-E1 cells treated with the three kinds of HAP nanoparticles (neutral, positive, and untreated), among which positively charged HAP nanoparticles showed the strongest improvement for cell viability and cell proliferation. In summary, the surface charge of HAP nanoparticles can be modified to influence the cellular uptake of HAP nanoparticles and the different uptake also influences the behavior of cells. These in vitro results may also provide useful information for investigations of HAP nanoparticle applications in gene delivery and intracellular drug delivery.

Chen, Liang; Mccrate, Joseph M.; C-M Lee, James; Li, Hao

2011-03-01

121

The role of surface charge on the uptake and biocompatibility of hydroxyapatite nanoparticles with osteoblast cells  

PubMed Central

The objective of this study is to evaluate the effect of hydroxyapatite (HAP) nanoparticles with different surface charges on the cellular uptake behavior and in vitro cell viability and proliferation of MC3T3-E1 cell lines (osteoblast). The nanoparticles surface charge was varied by the surface modification with two carboxylic acids: 12-aminododecanoic acid (positive) and dodecanedioic acid (negative). The untreated HAP nanoparticles and dodecanoic acid modified HAP nanoparticles (neutral) were used as the control. X-ray diffraction (XRD) revealed that surface modifications by the three carboxylic acids did not change the crystal structure of HAP nanoparticles; Fourier transform infrared spectroscopy (FTIR) confirmed the adsorption and binding of the carboxylic acids on HAP nanoparticle surface; and zeta potential measurement confirmed that the chemicals successfully modified the surface charge of HAP nanoparticles in water based solution. Transmission electron microscopy (TEM) images showed that positively charged, negatively charged and untreated HAP nanoparticles, with similar size and shape, all penetrated into the cells and cells had more uptake of HAP nanoparticles with positive charge compared to those with negative charge, which might be attributed to the attractive or repulsive interaction between the negatively charged cell membrane and positively/negatively charged HAP nanoparticles. The neutral HAP nanoparticles could not penetrate cell membrane due to the larger size. MTT assay and LDH assay results indicated that as compared with the polystyrene control, greater cell viability and cell proliferation were measured on MC3T3-E1 cells treated with the three kinds of the HAP nanoparticles (neutral, positive, and untreated), among which positively charged HAP nanoparticles shows strongest improvement for cell viability and cell proliferation. In summary, the surface charge of HAP nanoparticles can be modified to influence the cellular uptake of HAP nanoparticles and the different uptake also influence the behavior of cells. These in-vitro results may also provide useful information for investigations of HAP nanoparticles applications in the gene delivery and intracellular drug delivery.

Chen, Liang; Mccrate, Joseph M.; Lee, James C-M.; Li, Hao

2011-01-01

122

Nanoparticle PEBBLE sensors in live cells and in vivo  

PubMed Central

Nanoparticle sensors have been developed for imaging and dynamic monitoring, in live cells and in vivo, of the molecular or ionic components, constructs, forces and dynamics, all in real time, during biological/chemical/physical processes. With their biocompatible small size and inert matrix, nanoparticle sensors have been successfully applied for non-invasive real-time measurements of analytes and fields in cells and rodents, with spatial, temporal, physical and chemical resolution. This review describes the diverse designs of nanoparticle sensors for ions and small molecules, physical fields and biological features, as well as the characterization, properties, and applications of these nanosensors to in vitro and in vivo measurements. Their floating as well as localization ability in biological media is captured by the acronym PEBBLE: photonic explorer for bioanalysis with biologically localized embedding.

Smith, Ron

2009-01-01

123

Monocyte cytokine synthesis in response to extracellular cell stress proteins suggests these proteins exhibit network behaviour.  

PubMed

Human peripheral blood monocytes were exposed to single or pairs of cell stress proteins (CSPs), specifically Hsp10, Hsp27, Hsp60 and Hsp70-the former two having anti-inflammatory actions while the latter pair being assumed to be pro-inflammatory in activity. This study was to test if these proteins exhibited any network behaviour. To control for possible lipopolysaccharide contamination, polymyxin B was used. Surprisingly, at concentrations higher than 1 ?g/ml, polymyxin B itself could induce cytokine synthesis. A number of commercial sources of the molecular chaperones were tested, and marked variations in monocyte cytokine synthesis were found. All four CSPs stimulated the same profile of IL-1/IL-6 synthesis and IL-10/TNF-? synthesis although the kinetics of production of these two pairs of cytokines were very different. A key question was whether extracellular molecular chaperones exhibited network behaviour. To test this, monocytes were cultured with suboptimal concentrations of single CSP and pairs of CSP to look for additive, synergistic or antagonistic cell responses. The major finding was that pairs of molecular chaperones, including chaperones thought to stimulate monocyte cytokine synthesis, could produce significant antagonistic cellular responses. This demonstrates that extracellular CSPs constitute an additional potent layer within the complex cytokine network and furthermore suggests that monocytes have evolved to dampen their immune responses upon exposure to extracellular networks of CSPs-perhaps as a mechanism for protecting cells against detrimental cellular stress responses. PMID:23775284

Kaiser, Frank; Steptoe, Andrew; Thompson, Stephen; Henderson, Brian

2013-06-18

124

Enhancement of TiO2 nanoparticle properties and efficiency of dye-sensitized solar cells using modifiers  

NASA Astrophysics Data System (ADS)

A low-temperature hydrothermal process developed to synthesizes titania nanoparticles with controlled size. We investigate the effects of modifier substances, urea, on surface chemistry of titania (TiO2) nanopowder and its applications in dye-sensitized solar cells (DSSCs). Treating the nanoparticles with a modifier solution changes its morphology, which allows the TiO2 nanoparticles to exhibit properties that differ from untreated TiO2 nanoparticles. The obtained TiO2 nanoparticle electrodes characterized by XRD, SEM, TEM/HRTEM, UV-VIS Spectroscopy and FTIR. Experimental results indicate that the effect of bulk traps and the surface states within the TiO2 nanoparticle films using modifiers enhances the efficiency in DSSCs. Under 100-mW cm-2 simulated sunlight, the titania nanoparticles DSSC showed solar energy conversion efficiency = 4.6 %, with V oc = 0.74 V, J sc = 9.7324 mA cm-2, and fill factor = 71.35.

Rashad, M. M.; Shalan, A. E.; Lira-Cantú, Mónica; Abdel-Mottaleb, M. S. A.

2013-04-01

125

Transitional B cells Exhibit a BCR-specific Nuclear Defect In Gene Transcription  

PubMed Central

The signaling programs that enforce negative selection in early transitional (T1) B cells in response to B cell receptor (BCR) engagement remain poorly defined. We carried out a comprehensive comparison of BCR signaling in T1 vs. follicular mature (FM) splenic B cells. T1, in contrast to FM B cells, failed to express key NF-?B target genes in response to BCR engagement; and exhibited a striking defect in assembly of an active transcriptional complex at the promoter of the survival and proliferative genes, A1 and c-Myc. Surprisingly, and contrary to previous models, classical PKC and IKK activation, NF-?B nuclear translocation and DNA binding were intact in T1 B cells. Further, despite a marked reduction in NFAT1 expression, differential NFAT or AP-1 activation cannot explain this transcriptional defect. Our combined findings demonstrate that T1 B cells are programmed for signal- and stage-specific ‘nuclear non-responsiveness’ upon encounter with self-antigens.

Andrews, Sarah F; Rawlings, David J

2009-01-01

126

Nucleotide excision repair-deficient human cells in culture exhibit decreased survival after 2-chlorodeoxyadenosine treatment.  

PubMed

2-Chloro-2'-deoxyadenosine (CldAdo, cladribine) is a clinically important nucleoside analog for adult and pediatric leukemias. We previously described an activity in HeLa cell nuclear extracts that specifically recognized CldAMP-substituted oligomers. The factor was present in extracts prepared from repair-deficient xeroderma pigmentosum (XP) complementation group A cells, but not from group E--which are defective in damaged DNA-binding (DDB) protein--suggesting a possible repair process for incorporated analogs. Here we examined XP lymphoblast survival after CldAdo treatment using a cell proliferation assay. Control CEM leukemia cells and immortalized normal human lymphoblasts exhibited similar cytotoxicity profiles at each concentration tested. However, a 2.1-fold increase in sensitivity to CldAdo was detected in XP-E (5) cells lacking a functional DDB subunit. XP-A, XP-D and XP-G cell lines also had increased sensitivity to CldAdo, ranging from 1.61- to 1.91-fold greater compared to normal lymphoblasts. Our findings suggest that the clinical efficacy of CldAdo may be attenuated by repair mechanisms that target and remove such altered nucleic acids from cellular DNA. PMID:12926046

Lawrenzi, James; Bunnell, Amy; Hentosh, Patricia

127

Cellular Nanomedicine Cell selective response to gold nanoparticles  

Microsoft Academic Search

Gold nanoparticles (GNPs) are considered a potential probe to detect cancer. The present article investigates whether GNPs, even in the absence of any specific functionalization, induce any cell- specific response. We report GNP-induced death response in human carcinoma lung cell line A549. In contrast, the two other cell lines tested, BHK21 (baby hamster kidney) and HepG2 (human hepatocellular liver carcinoma),

Hirak K. Patra; Utpal Chaudhuri; Prabir Lahiri

128

Aronia melanocarpa fruit extract exhibits anti-inflammatory activity in human aortic endothelial cells  

Microsoft Academic Search

Background  Altered expression of cell adhesion molecules (CAMs) has been implicated in a variety of chronic inflammatory conditions,\\u000a including atherosclerosis. Regulation of adhesion molecule expression by specific redox-sensitive mechanisms has been reported.\\u000a Additionally, it has been observed that the extract of Aronia melanocarpa (A. Melanocarpa) fruits, rich in polyphenols, exhibits potent anti-oxidant properties and displays cardioprotective activity.\\u000a \\u000a \\u000a \\u000a \\u000a Methods and results  Human aortic

D. Zapolska-DownarD; D. Bryk; M. Ma?ecki; K. Hajdukiewicz; D. Sitkiewicz

129

Geminin-Deficient Neural Stem Cells Exhibit Normal Cell Division and Normal Neurogenesis  

PubMed Central

Neural stem cells (NSCs) are the progenitors of neurons and glial cells during both embryonic development and adult life. The unstable regulatory protein Geminin (Gmnn) is thought to maintain neural stem cells in an undifferentiated state while they proliferate. Geminin inhibits neuronal differentiation in cultured cells by antagonizing interactions between the chromatin remodeling protein Brg1 and the neural-specific transcription factors Neurogenin and NeuroD. Geminin is widely expressed in the CNS during throughout embryonic development, and Geminin expression is down-regulated when neuronal precursor cells undergo terminal differentiation. Over-expression of Geminin in gastrula-stage Xenopus embryos can expand the size of the neural plate. The role of Geminin in regulating vertebrate neurogenesis in vivo has not been rigorously examined. To address this question, we created a strain of Nestin-Cre/Gmnnfl/fl mice in which the Geminin gene was specifically deleted from NSCs. Interestingly, we found no major defects in the development or function of the central nervous system. Neural-specific Gmnn?/? mice are viable and fertile and display no obvious neurological or neuroanatomical abnormalities. They have normal numbers of BrdU+ NSCs in the subgranular zone of the dentate gyrus, and Gmnn?/? NSCs give rise to normal numbers of mature neurons in pulse-chase experiments. Gmnn?/? neurosphere cells differentiate normally into both neurons and glial cells when grown in growth factor-deficient medium. Both the growth rate and the cell cycle distribution of cultured Gmnn?/? neurosphere cells are indistinguishable from controls. We conclude that Geminin is largely dispensable for most of embryonic and adult mammalian neurogenesis.

Schultz, Kathryn M.; McGuire, Tammy; Kessler, John A.; Miller, Richard J.; McGarry, Thomas J.

2011-01-01

130

Cell adhesion and proliferation on polyethylene grafted with Au nanoparticles  

NASA Astrophysics Data System (ADS)

Plasma treatment and subsequent Au nano-particles grafting of polyethylene (PE) lead to changes in surface morphology, roughness and wettability, significantly increasing the attractiveness of the material for cells. The PE samples were exposed to argon plasma. Plasma modified PE was chemically grafted by immersion to biphenyldithiol and consequently into solution of Au nano-particles. Changes in chemical structure of the modified PE were studied using X-ray Photoelectron Spectroscopy (XPS) and electrokinetic analysis (?-potential). The surface wettability of the modified PE samples was examined by measurement of the contact angle by standard goniometry. The surface morphology of the plasma modified PE and that grafted with Au nano-particles was studied by Atomic Force Microscopy (AFM). The modified PE samples were seeded with rat vascular smooth muscle cells (VSMCs) and their adhesion and proliferation were studied. Chemically bounded biphenyldithiol increases the number of the incorporated gold nano-particles and changes sample surface properties. The presence of the biphenyldithiol and the gold nano-particles on the PE surface influences dramatically adhesion and proliferation of VSMCs.

Kasálková, N. Slepi?ková; Slepi?ka, P.; Kolská, Z.; Sajdl, P.; Ba?áková, L.; Rimpelová, S.; Švor?ík, V.

2012-02-01

131

Mechanisms of nanoparticle-mediated photomechanical cell damage  

PubMed Central

Laser-assisted killing of gold nanoparticle targeted macrophages was investigated. Using pressure transient detection, flash photography and transmission electron microscopy (TEM) imaging, we studied the mechanism of single cell damage by vapor bubble formation around gold nanospheres induced by nanosecond laser pulses. The influence of the number of irradiating laser pulses and of particle size and concentration on the threshold for acute cell damage was determined. While the single pulse damage threshold is independent of the particle size, the threshold decreases with increasing particle size when using trains of pulses. The dependence of the cell damage threshold on the nanoparticle concentration during incubation reveals that particle accumulation and distribution inside the cell plays a key role in tissue imaging or cell damaging.

Peeters, Sara; Kitz, Michael; Preisser, Stefan; Wetterwald, Antoinette; Rothen-Rutishauser, Barbara; Thalmann, George N.; Brandenberger, Christina; Bailey, Arthur; Frenz, Martin

2012-01-01

132

Psoriasis patients exhibit impairment of the high potency CCR5(+) T regulatory cell subset.  

PubMed

CCR5 expression on CD4(+)CD25(high)Foxp3(+) regulatory T cells (Tregs) has been reported to be crucial for limiting Th1 inflammation associated with autoimmunity and bacterial infections. We inquired whether abnormalities in chemokine receptors expressed on Tregs might be involved in the psoriatic pathogenesis. Indeed, the proportion of CCR5(+) Treg was 58.8% in healthy individuals (n=9), whereas only half as many CCR5(+) Treg cells were found in psoriatic individuals (29.1%, n=8, p<0.01). The flow-enriched control CCR5(+) Tregs consistently exceeded the suppressive capacity of unsorted Tregs in autologous MLR assays (n=5, p<0.05) showing that CCR5(+) Treg subset is a high potency regulatory T cell population. Interestingly, psoriatic CCR5(+) Treg cells exhibited significantly less migratory capacity toward CCR5 ligands MIP-1? and RANTES in vitro compared to CCR5(+) Treg controls (n=3, p<0.05). Our data demonstrate that psoriatic CCR5(+) Tregs cells are numerically-, functionally- and chemotactically-deficient compared to controls and may pose a triple impairment on the ability of psoriatic Tregs to restrain inflammation. PMID:23954573

Soler, David C; Sugiyama, Hideaki; Young, Andrew B; Massari, Jessica V; McCormick, Thomas S; Cooper, Kevin D

2013-07-06

133

Magnetic nanoparticle effects on the red blood cells  

Microsoft Academic Search

In vitro tests on magnetite colloidal nanoparticles effects upon animal red blood cells were carried out. Magnetite cores were stabilized with citric acid in the form of biocompatible magnetic fluid administrated in different dilutions in the whole blood samples. The hemolysis extent was found increased up to 2.75 in horse blood and respectively up to 2.81 in the dog blood.

D. E. Creanga; M. Culea; C. Nadejde; S. Oancea; L. Curecheriu; M. Racuciu

2009-01-01

134

Lanthanide-doped upconverting nanoparticles: harvesting light for solar cells.  

PubMed

Nanoharvest on a big scale: The capacity to harvest near-infrared photons from the sun can greatly improve the efficiency of solar cells. Near-infrared excitation of upconverting nanoparticles results in the generation of visible emission and increasing the electrical output of a photovoltaic device. PMID:23868815

Naccache, Rafik; Vetrone, Fiorenzo; Capobianco, John A

2013-07-19

135

Epirubicin loaded to pre-polymerized poly(butyl cyanoacrylate) nanoparticles: preparation and in vitro evaluation in human lung adenocarcinoma cells.  

PubMed

This article describes the preparation of epirubicin-loaded nanoparticles, prepared by loading of the drug in pre-polymerized poly(butyl cyanoacrylate) nanoparticles, their physicochemical characterization and in vitro evaluation on human lung adenocarcinoma (A549) cells. Nanoparticles were also coated in aqueous dispersions with two different non-ionic surfactants (Pluronic F68 and Polysorbate 80). All particles were spherical in shape, with monomodal size distributions. The zeta-potentials at pH 7.4 increased with augmentation of the particle drug content. The increased drug content was found to correlate with the initial concentration of the drug, used for the particle preparation. In vitro studies on A549 cells showed that the drug-loaded nanoparticles, as well as the combinations of free drug and empty nanoparticles, exhibited higher cytotoxicity than the free drug alone. The presence of surfactants also resulted in increased cytotoxicity. Fluorescent imaging of epirubicin internalization by the adenocarcinoma cells revealed that the free drug was predominantly localized in the cell nucleus, while a cytoplasmic localization was observed for the nanoparticle-bound drug formulations, suggesting the probability of nanoparticle endocytosis. Thus the hereby presented results could be useful for development of nanoparticle-based anthracycline formulations for treatment of lung adenocarcinoma. PMID:23466549

Yordanov, Georgi; Evangelatov, Alexander; Skrobanska, Ralica

2013-02-11

136

Monitoring the endocytosis of magnetic nanoparticles by cells using permanent micro-flux sources.  

PubMed

Trapping of cells is essential to perform basic handling operations in cell-based microsystems, such as media exchange, concentration, cell isolation and cell sorting. Cell trapping by magnetophoresis typically requires cell labeling with magnetic nanoparticles. Here we report on endocytotic uptake of 100 nm magnetic nanoparticles by Human Embryonic Kidney 293 cells. The attraction of labeled cells by micro-magnet arrays characterised by very high magnetic field gradients (?10? T/m) was studied as a function of labeling conditions (nanoparticle concentration in the extracellular medium, incubation time). The threshold incubation conditions for effective magnetophoretic trapping were established. This simple technique may be exploited to minimise the quantity of magnetic nanoparticles needed for efficient cell trapping, thus reducing stress or nanoparticle-mediated toxicity. Nanoparticle internalization into cells was confirmed using both confocal and Transmission Electron Microscopy (TEM). PMID:22773161

Osman, O; Zanini, L F; Frénéa-Robin, M; Dumas-Bouchiat, F; Dempsey, N M; Reyne, G; Buret, F; Haddour, N

2012-10-01

137

Controlling the hydrophilicity and contact resistance of fuel cell bipolar plate surfaces using layered nanoparticle assembly  

NASA Astrophysics Data System (ADS)

Hybrid nanostructured coatings exhibiting the combined properties of electrical conductivity and surface hydrophilicity were obtained by using Layer-by-Layer (LBL) assembly of cationic polymer, silica nanospheres, and carbon nanoplatelets. This work demonstrates that by controlling the nanoparticle zeta (zeta) potential through the suspension parameters (pH, organic solvent type and amount, and ionic content) as well as the assembly sequence, the nanostructure and composition of the coatings may be adjusted to optimize the desired properties. Two types of silica nanospheres were evaluated as the hydrophilic component: X-TecRTM 3408 from Nano-X Corporation, with a diameter of about 20 nm, and polishing silica from Electron Microscopy Supply, with diameter of about 65 nm. Graphite nanoplatelets with a thickness of 5~10nm (Aquadag RTM E from Acheson Industries) were used as electrically conductive filler. A cationic copolymer of acrylamide and a quaternary ammonium salt (SuperflocRTM C442 from Cytec Corporation) was used as the binder for the negatively charged nanoparticles. Coatings were applied to gold-coated stainless steel substrates presently used a bipolar plate material for proton exchange membrane (PEM) fuel cells. Coating thickness was found to vary nearly linearly with the number of polymer-nanoparticle layers deposited while a monotonic increase in coating contact resistance was observed for all heterogeneous and pure silica coatings. Thickness increased if the difference in the oppositely charged zeta potentials of the adsorbing components was enhanced through alcohol addition. Interestingly, an opposite effect was observed if the zeta potential difference was increased through pH variation. This previously undocumented difference in adsorption behavior is herein related to changes to the surface chemical heterogeneity of the nanoparticles. Coating contact resistance and surface wettability were found to have a more subtle dependence on the assembly sequence and coating composition. Various LBL assembly sequences were investigated to control heterogeneous coating nanostructure and tune their hydrophilic and electrically conductive properties. Assembly from mixed nanoparticle suspensions yielded competitive nanoparticle adsorption and is denoted as cLBL assembly. The absence of intervening polymer binder during sequential deposition from first carbon then silica nanoparticle suspensions directed the assembly process with each applied layer and is denoted as dLBL assembly. Use of intervening polymer binder as in standard LBL deposition is denoted as sLBL assembly. The cLBL assembly sequence was found to yield nanoparticle competition for available surface sites between the heterogeneous nanoparticles and result in phase separation within each layer, producing coatings with high electrical contact resistance but poor hydrophilicity. Coatings prepared using dLBL assembly exhibited improved contact resistance due to improved alignment of a carbon phase perpendicular to the substrate surface but continued poor hydrophilicity. The sLBL assembly scheme produced optimum coating performance due to the adsorption of highly dispersed silica layers directly onto the graphite platelets, while maintaining through-plane platelet to platelet contact. The wetting behavior of the prepared coatings was satisfactorily described by Johnson-Dettre model while exhibiting little response to changes in surface morphology (in contrast to Wenzel's equation). Hydrophilicity of the cLBL assembled coatings could be enhanced by altering the silica nanoparticle zeta potential in mixed suspensions. Coating durability was demonstrated through LBL assembly onto industrial-size bipolar plate materials and testing under PEM fuel cell operating conditions.

Wang, Feng

138

T cells enhance gold nanoparticle delivery to tumors in vivo  

PubMed Central

Gold nanoparticle-mediated photothermal therapy (PTT) has shown great potential for the treatment of cancer in mouse studies and is now being evaluated in clinical trials. For this therapy, gold nanoparticles (AuNPs) are injected intravenously and are allowed to accumulate within the tumor via the enhanced permeability and retention (EPR) effect. The tumor is then irradiated with a near infrared laser, whose energy is absorbed by the AuNPs and translated into heat. While reliance on the EPR effect for tumor targeting has proven adequate for vascularized tumors in small animal models, the efficiency and specificity of tumor delivery in vivo, particularly in tumors with poor blood supply, has proven challenging. In this study, we examine whether human T cells can be used as cellular delivery vehicles for AuNP transport into tumors. We first demonstrate that T cells can be efficiently loaded with 45 nm gold colloid nanoparticles without affecting viability or function (e.g. migration and cytokine production). Using a human tumor xenograft mouse model, we next demonstrate that AuNP-loaded T cells retain their capacity to migrate to tumor sites in vivo. In addition, the efficiency of AuNP delivery to tumors in vivo is increased by more than four-fold compared to injection of free PEGylated AuNPs and the use of the T cell delivery system also dramatically alters the overall nanoparticle biodistribution. Thus, the use of T cell chaperones for AuNP delivery could enhance the efficacy of nanoparticle-based therapies and imaging applications by increasing AuNP tumor accumulation.

2011-01-01

139

Magnetic CoPt nanoparticles as MRI contrast agent for transplanted neural stem cells detection.  

PubMed

Neural stem cells (NSCs) exhibit features that make them suitable candidates for stem cell replacement therapy and spinal cord reconstruction. Magnetic resonance imaging (MRI) offers the potential to track cells in vivo using innovative approaches to cell labeling and image acquisition. In this study, experiments were carried out to optimize the loading condition of magnetic CoPt hollow nanoparticles (CoPt NPs) into neural stem cells and to define appropriate MRI parameters. Both cell viability and multipotency analysis showed that CoPt NPs at a concentration of 16 µg ml(-1) reduced T2 relaxation times in labeled rat NSCs, producing greater contrast on spin echo acquisitions at 4.7 T, yet did not affect cell viability and in vitro differentiation potential compared to controls. After optimizing nanoparticle loading concentrations and labeled cell numbers for MRI detection, CoPt-loaded NSCs were transplanted into organotypic spinal cord slices. The results showed that MRI could efficiently detect low numbers of CoPt-labeled NSCs with the enhanced image contrast. Our study demonstrated that MRI of grafted NSCs labeled with CoPt NPs is a useful tool to evaluate organotypic spinal cord slice models and has potential applications in other biological systems. PMID:21293831

Meng, Xiaoting; Seton, Hugh C; Lu, Le T; Prior, Ian A; Thanh, Nguyen T K; Song, Bing

2011-02-04

140

Magnetic CoPt nanoparticles as MRI contrast agent for transplanted neural stem cells detection  

NASA Astrophysics Data System (ADS)

Neural stem cells (NSCs) exhibit features that make them suitable candidates for stem cell replacement therapy and spinal cord reconstruction. Magnetic resonance imaging (MRI) offers the potential to track cells in vivo using innovative approaches to cell labeling and image acquisition. In this study, experiments were carried out to optimize the loading condition of magnetic CoPt hollow nanoparticles (CoPt NPs) into neural stem cells and to define appropriate MRI parameters. Both cell viability and multipotency analysis showed that CoPt NPs at a concentration of 16 µg ml-1 reduced T2 relaxation times in labeled rat NSCs, producing greater contrast on spin echo acquisitions at 4.7 T, yet did not affect cell viability and in vitro differentiation potential compared to controls. After optimizing nanoparticle loading concentrations and labeled cell numbers for MRI detection, CoPt-loaded NSCs were transplanted into organotypic spinal cord slices. The results showed that MRI could efficiently detect low numbers of CoPt-labeled NSCs with the enhanced image contrast. Our study demonstrated that MRI of grafted NSCs labeled with CoPt NPs is a useful tool to evaluate organotypic spinal cord slice models and has potential applications in other biological systems.

Meng, Xiaoting; Seton, Hugh C.; Lu, Le T.; Prior, Ian A.; Thanh, Nguyen T. K.; Song, Bing

2011-03-01

141

BDNF+/- mice exhibit deficits in oligodendrocyte lineage cells of the basal forebrain.  

PubMed

Previous work indicated that brain-derived neurotrophic factor (BDNF), through the trkB receptor, increases DNA synthesis in oligodendrocyte (OLG) progenitor cells (OPCs) and differentiation of postmitotic OLGs of the basal forebrain (BF). In the present studies, BDNF knockout animals were used to investigate BDNF's effects on OLG lineage cells (OLCs) in vivo. OLCs of the BF were found to express the trkB receptor, suggesting they are responsive to BDNF. Immunohistochemistry using NG2 and CC1 antibodies was utilized to examine the numbers of NG2+ OPCs and CC1+ postmitotic BF OLGs. At embryonic day 17 (E17), BDNF-/- animals display reduced NG2+ cells. This reduction was also observed in BDNF+/- mice at E17 and at postnatal day 1 (P1), P14, and adult stage, suggesting that BDNF plays a role in OPC development. BDNF+/- mice do not exhibit deficits in numbers of CC1+ OLGs. However, myelin basic protein, myelin associated glycoprotein, and proteolipid protein are reduced in BDNF+/- mice, suggesting that BDNF plays a role in differentiation. These data indicate that progenitor cells and myelin proteins may be affected in vivo by a decrease in BDNF. PMID:20091777

Vondran, Melissa W; Clinton-Luke, Patricia; Honeywell, Jean Z; Dreyfus, Cheryl F

2010-05-01

142

Bulbispermine: A Crinine-Type Amaryllidaceae Alkaloid Exhibiting Cytostatic Activity towards Apoptosis-Resistant Glioma Cells  

PubMed Central

The Amaryllidaceae alkaloid bulbispermine was derivatized to produce a small group of synthetic analogues. These, together with bulbispermine’s natural crinine-type congeners, were evaluated in vitro against a panel of cancer cell lines with various levels of resistance to proapoptotic stimuli. Bulbispermine, haemanthamine and haemanthidine showed the most potent antiproliferative activities as determined by the MTT colorimetric assay. Among the synthetic bulbispermine analogues, only the C1,C2-dicarbamate derivative exhibited noteworthy growth inhibitory properties. All active compounds were found not to discriminate between the cancer cell lines based on the apoptosis sensitivity criterion and displayed comparable potencies in both cell types, indicating that apoptosis induction is not the primary mechanism responsible for antiproliferative activity in this series of compounds. It was also found that bulbispermine inhibits the proliferation of glioblastoma cells through cytostatic effects, possibly arising from the rigidification of the actin cytoskeleton. These findings lead us to argue that crinine-type alkaloids are potentially useful drug leads for the treatment of apoptosis resistant cancers and glioblastoma in particular.

Luchetti, Giovanni; Johnston, Robert; Mathieu, Veronique; Lefranc, Florence; Hayden, Kathryn; Andolfi, Anna; Lamoral-Theys, Delphine; Reisenauer, Mary R.; Champion, Cody; Pelly, Stephen C.; van Otterlo, Willem A. L.; Magedov, Igor V.; Kiss, Robert; Evidente, Antonio; Rogelj, Snezna; Kornienko, Alexander

2012-01-01

143

Multidentate zwitterionic chitosan oligosaccharide modified gold nanoparticles: stability, biocompatibility and cell interactions.  

PubMed

Surface engineering of nanoparticles plays an essential role in their colloidal stability, biocompatibility and interaction with biosystems. In this study, a novel multidentate zwitterionic biopolymer derivative is obtained from conjugating dithiolane lipoic acid and zwitterionic acryloyloxyethyl phosphorylcholine to the chitosan oligosaccharide backbone. Gold nanoparticles (AuNPs) modified by this polymer exhibit remarkable colloidal stabilities under extreme conditions including high salt conditions, wide pH range and serum or plasma containing media. The AuNPs also show strong resistance to competition from dithiothreitol (as high as 1.5 M). Moreover, the modified AuNPs demonstrate low cytotoxicity investigated by both MTT and LDH assays, and good hemocompatibility evaluated by hemolysis of human red blood cells. In addition, the intracellular fate of AuNPs was investigated by ICP-MS and TEM. It showed that the AuNPs are uptaken by cells in a concentration dependent manner, and they can escape from endosomes/lysosomes to cytosol and tend to accumulate around the nucleus after 24 h incubation but few of them are excreted out of the cells. Gold nanorods are also stabilized by this ligand, which demonstrates robust dispersion stability and excellent hemocompatibility. This kind of multidentate zwitterionic chitosan derivative could be widely used for stabilizing other inorganic nanoparticles, which will greatly improve their performance in a variety of bio-related applications. PMID:23546384

Liu, Xiangsheng; Huang, Haoyuan; Liu, Gongyan; Zhou, Wenbo; Chen, Yangjun; Jin, Qiao; Ji, Jian

2013-04-02

144

Nonviral cell labeling and differentiation agent for induced pluripotent stem cells based on mesoporous silica nanoparticles.  

PubMed

The generation of induced pluripotent stem cells (iPSCs) is an innovative personalized-regenerative technology, which can transform own-self somatic cells into embryonic stem (ES)-like cells, which have the potential to differentiate into all cell types of three dermal lineages. However, how to quickly, efficiently, and safely produce specific-lineage differentiation from pluripotent-state cells and iPSCs is still an open question. The objective of the present study was to develop a platform of a nonviral gene delivery system of mesoporous silica nanoparticles (MSNs) to rapidly generate iPSC-derived definitive-lineage cells, including endodermal-differentiated cells. We also evaluated the feasibility and efficiency of FITC-conjugated MSNs (FMSNs) for labeling of iPSCs and utilized the multifunctional properties of FMSNs for a suitable carrier for biomolecule delivery. We showed that FMSNs of various surface charges could be efficiently internalized by iPSCs without causing cytotoxicity. The levels of reactive oxygen species and pluripotent status, including in vitro stemness signatures and in vivo teratoma formation, remained unaltered. Notably, positive-charged FMSN enhanced cellular uptake efficiency and retention time. Moreover, when using positive-charged FMSN to deliver hepatocyte nuclear factor 3? (HNF3?) plasmid DNA (pDNA), the treated iPSCs exhibited significantly improved definitive endoderm formation and further quickly differentiated into hepatocyte-like cells with mature functions (low-density lipoprotein uptake and glycogen storage) within 2 weeks in vitro. Double delivery of pHNF3? further improved mRNA expression levels of liver-specific genes. These findings reveal the multiple advantages of FMSNs to serve as ideal vectors not only for stem cell labeling but also for safe gene delivery to promote the production of hepatocyte-like cells from iPSCs. PMID:24063246

Chen, Wei; Tsai, Ping-Hsing; Hung, Yann; Chiou, Shih-Hwa; Mou, Chung-Yuan

2013-09-30

145

Toxicity of Cerium Oxide Nanoparticles in Human Lung Cancer Cells  

Microsoft Academic Search

With the fast development of nanotechnology, the nanomate-rials start to cause people's attention for potential toxic effect. In this paper, the cytotoxicity and oxidative stress caused by 20-nm cerium oxide (CeO2) nanoparticles in cultured human lung cancer cells was investigated. The sulforhodamine B method was employed to assess cell viability after exposure to 3.5, 10.5, and 23.3 µg\\/ml of CeO2

Weisheng Lin; Yue-wern Huang; Xiao-Dong Zhou; Yinfa Ma

2006-01-01

146

Tumor-targeted Chlorotoxin-coupled Nanoparticles for Nucleic Acid Delivery to Glioblastoma Cells: A Promising System for Glioblastoma Treatment.  

PubMed

The present work aimed at the development and application of a lipid-based nanocarrier for targeted delivery of nucleic acids to glioblastoma (GBM). For this purpose, chlorotoxin (CTX), a peptide reported to bind selectively to glioma cells while showing no affinity for non-neoplastic cells, was covalently coupled to liposomes encapsulating antisense oligonucleotides (asOs) or small interfering RNAs (siRNAs). The resulting targeted nanoparticles, designated CTX-coupled stable nucleic acid lipid particles (SNALPs), exhibited excellent features for in vivo application, namely small size (<180?nm) and neutral surface charge. Cellular association and internalization studies revealed that attachment of CTX onto the liposomal surface enhanced particle internalization into glioma cells, whereas no significant internalization was observed in noncancer cells. Moreover, nanoparticle-mediated miR-21 silencing in U87 human GBM and GL261 mouse glioma cells resulted in increased levels of the tumor suppressors PTEN and PDCD4, caspase 3/7 activation and decreased tumor cell proliferation. Preliminary in vivo studies revealed that CTX enhances particle internalization into established intracranial tumors. Overall, our results indicate that the developed targeted nanoparticles represent a valuable tool for targeted nucleic acid delivery to cancer cells. Combined with a drug-based therapy, nanoparticle-mediated miR-21 silencing constitutes a promising multimodal therapeutic approach towards GBM.Molecular Therapy-Nucleic Acids (2013) 2, e100; doi:10.1038/mtna.2013.30; published online 18 June 2013. PMID:23778499

Costa, Pedro M; Cardoso, Ana L; Mendonça, Liliana S; Serani, Angelo; Custódia, Carlos; Conceição, Mariana; Simões, Sérgio; Moreira, João N; Pereira de Almeida, Luís; Pedroso de Lima, Maria C

2013-06-18

147

PEG-templated mesoporous silica nanoparticles exclusively target cancer cells  

NASA Astrophysics Data System (ADS)

Mesoporous silica nanoparticles (MSNs) have been proposed as DNA and drug delivery carriers, as well as efficient tools for fluorescent cell tracking. The major limitation is that MSNs enter cells regardless of a target-specific functionalization. Here we show that non functionalized MSNs, synthesized using a PEG surfactant-based interfacial synthesis procedure, do not enter cells, while a highly specific, receptor mediated, cellular internalization of folic acid (FOL) grafted MSNs (MSN-FOL), occurs exclusively in folate receptor (FR) expressing cells. Neither the classical clathrin pathway nor macropinocytosis is involved in the MSN endocytic process, while fluorescent MSNs (MSN-FITC) enter cells through aspecific, caveolae-mediated, endocytosis. Moreover, internalized particles seem to be mostly exocytosed from cells within 96 h. Finally, cisplatin (Cp) loaded MSN-FOL were tested on cancerous FR-positive (HeLa) or normal FR-negative (HEK293) cells. A strong growth arrest was observed only in HeLa cells treated with MSN-FOL-Cp. The results presented here show that our mesoporous nanoparticles do not enter cells unless opportunely functionalized, suggesting that they could represent a promising vehicle for drug targeting applications.Mesoporous silica nanoparticles (MSNs) have been proposed as DNA and drug delivery carriers, as well as efficient tools for fluorescent cell tracking. The major limitation is that MSNs enter cells regardless of a target-specific functionalization. Here we show that non functionalized MSNs, synthesized using a PEG surfactant-based interfacial synthesis procedure, do not enter cells, while a highly specific, receptor mediated, cellular internalization of folic acid (FOL) grafted MSNs (MSN-FOL), occurs exclusively in folate receptor (FR) expressing cells. Neither the classical clathrin pathway nor macropinocytosis is involved in the MSN endocytic process, while fluorescent MSNs (MSN-FITC) enter cells through aspecific, caveolae-mediated, endocytosis. Moreover, internalized particles seem to be mostly exocytosed from cells within 96 h. Finally, cisplatin (Cp) loaded MSN-FOL were tested on cancerous FR-positive (HeLa) or normal FR-negative (HEK293) cells. A strong growth arrest was observed only in HeLa cells treated with MSN-FOL-Cp. The results presented here show that our mesoporous nanoparticles do not enter cells unless opportunely functionalized, suggesting that they could represent a promising vehicle for drug targeting applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c1nr10253b

Morelli, Catia; Maris, Pamela; Sisci, Diego; Perrotta, Enrico; Brunelli, Elvira; Perrotta, Ida; Panno, Maria Luisa; Tagarelli, Antonio; Versace, Carlo; Casula, Maria Francesca; Testa, Flaviano; Andò, Sebastiano; Nagy, Janos B.; Pasqua, Luigi

2011-08-01

148

Cerium oxide and platinum nanoparticles protect cells from oxidant-mediated apoptosis  

PubMed Central

Catalytic nanoparticles represent a potential clinical approach to replace or correct aberrant enzymatic activities in patients. Several diseases, including many blinding eye diseases, are promoted by excessive oxidant stress due to reactive oxygen species (ROS). Cerium oxide and platinum nanoparticles represent two potentially therapeutic nanoparticles that de-toxify ROS. In the present study we directly compare these two classes of catalytic nanoparticles. Cerium oxide and platinum nanoparticles were found to be 16±2.4 nm and 1.9±0.2 nm in diameter, respectively. Using surface plasmon enhanced microscopy, we find that these nanoparticles associate with cells. Furthermore, cerium oxide and platinum nanoparticles demonstrated superoxide dismutase catalytic activity, but did not promote hemolytic or cytolytic pathways in living cells. Importantly, both cerium oxide and platinum nanoparticles reduce oxidant-mediated apoptosis in target cells as judged by the activation of caspase 3. The ability to diminish apoptosis may contribute to maintaining healthy tissues.

Clark, Andrea; Zhu, Aiping; Sun, Kai; Petty, Howard R.

2011-01-01

149

Damnacanthal, a noni component, exhibits antitumorigenic activity in human colorectal cancer cells.  

PubMed

Damnacanthal, an anthraquinone compound, is isolated from the roots of Morinda citrifolia L. (noni), which has been used for traditional therapy in several chronic diseases including cancer. Although noni has been consumed for a long time in Asian and Polynesian countries, the molecular mechanisms by which it exerts several benefits are starting to emerge. In this report, we examined systematic approaches on the cancer-suppressing capability of damnacanthal in colorectal tumorigenesis. Damnacanthal exhibits cell growth arrest as well as caspase activity induction in colorectal cancer cells. We also examined several potential target proteins and found that the proapoptotic protein nonsteroidal anti-inflammatory activated gene-1 (NAG-1) is highly induced. Subsequently, we have found that damnacanthal also enhances transcription factor CCAAT/enhancer binding protein ? (C/EBP?), which controls NAG-1 transcriptional activity. Blocking of C/EBP? by shRNA results in the reduction of NAG-1 expression as well as caspase activity in the presence of damnacanthal. Taken together, these results indicate that damnacanthal increases antitumorigenic activity in human colorectal cancer cells and that C/EBP? plays a role in damnacanthal-induced NAG-1 expression. PMID:21852088

Nualsanit, Thararat; Rojanapanthu, Pleumchitt; Gritsanapan, Wandee; Lee, Seong-Ho; Lawson, Darunee; Baek, Seung Joon

2011-08-17

150

Damnacanthal, a Noni component, exhibits anti-tumorigenic activity in human colorectal cancer cells  

PubMed Central

Damnacanthal, an anthraquinone compound, is isolated from the roots of Morinda citrifolia L. (noni), which has been used for traditional therapy in several chronic diseases including cancer. Although noni has been consumed for a long time in Asian and Polynesian countries, the molecular mechanisms by which it exerts several benefits are starting to emerge. In this report, we examined systematic approaches on the cancer suppressing capability of damnacanthal in colorectal tumorigenesis. Damnacanthal exhibits cell growth arrest as well as caspase activity induction in colorectal cancer cells. We also examined several potential target proteins and found that the pro-apoptotic protein Nonsteroidal anti-inflammatory activated gene-1 (NAG-1) is highly induced. Subsequently, we have found that damnacanthal also enhances transcription factor C/EBP?, which controls NAG-1 transcriptional activity. Blocking of C/EBP? by shRNA results in the reduction of NAG-1 expression as well as caspase activity in the presence of damnacanthal. Taken together, these results indicate that damnacanthal increases anti-tumorigenic activity in human colorectal cancer cells, and C/EBP? plays a role in damnacanthal-induced NAG-1 expression.

Nualsanit, Thararat; Rojanapanthu, Pleumchitt; Gritsanapan, Wandee; Lee, Seong-Ho; Lawson, Darunee; Baek, Seung Joon

2011-01-01

151

Human induced pluripotent stem cell-derived endothelial cells exhibit functional heterogeneity.  

PubMed

Human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs) are promising for treatment of vascular diseases. However, hiPSC-ECs purified based on CD31 expression are comprised of arterial, venous, and lymphatic subtypes. It is unclear whether hiPSC-ECs are heterogeneous in nature, and whether there may be functional benefits of enriching for specific subtypes. Therefore, we sought to characterize the hiPSC-ECs and enrich for each subtype, and demonstrate whether such enrichment would have functional significance. The hiPSC-ECs were generated from differentiation of hiPSCs using vascular endothelial growth factor (VEGF)-A and bone morphogenetic protein-4. The hiPSC-ECs were purified based on positive expression of CD31. Subsequently, we sought to enrich for each subtype. Arterial hiPSC-ECs were induced using higher concentrations of VEGF-A and 8-bromoadenosine-3':5'-cyclic monophosphate in the media, whereas lower concentrations of VEGF-A favored venous subtype. VEGF-C and angiopoietin-1 promoted the expression of lymphatic phenotype. Upon FACS purification based on CD31+ expression, the hiPSC-EC population was observed to display typical endothelial surface markers and functions. However, the hiPSC-EC population was heterogeneous in that they displayed arterial, venous, and to a lesser degree, lymphatic lineage markers. Upon comparing vascular formation in matrigel plugs in vivo, we observed that arterial enriched hiPSC-ECs formed a more extensive capillary network in this model, by comparison to a heterogeneous population of hiPSC-ECs. This study demonstrates that FACS purification of CD31+ hiPSC-ECs produces a diverse population of ECs. Refining the differentiation methods can enrich for subtype-specific hiPSC-ECs with functional benefits of enhancing neovascularization. PMID:23390563

Rufaihah, Abdul Jalil; Huang, Ngan F; Kim, Jeanna; Herold, Joerg; Volz, Katharina S; Park, Tea Soon; Lee, Jerry C; Zambidis, Elias T; Reijo-Pera, Renee; Cooke, John P

2013-01-21

152

Distinct Xp11.2 breakpoints in two renal cell carcinomas exhibiting X;autosome translocations.  

PubMed

Several human renal cell carcinomas with X;autosome translocations have been reported in recent years. The t(X;1)(p11.2;q21) appears to be a specific primary anomaly, suggesting that tumors with this translocation form a distinct subgroup of RCC. Here we report two new cases, one with a t(X;10)(p11.2;q23), the other with a t(X;1)(p11.2;p34). The common breakpoint in Xp11.2 suggests that they belong to the above-mentioned subset of RCC. Using FISH in conjunction with X-specific YAC clones, we demonstrate that the two new cases exhibited distinct breakpoints within Xp11.2. PMID:8527383

Dijkhuizen, T; van den Berg, E; Wilbrink, M; Weterman, M; Geurts van Kessel, A; Störkel, S; Folkers, R P; Braam, A; de Jong, B

1995-09-01

153

Nanoparticles isolated from blood: a reflection of vesiculability of blood cells during the isolation process  

PubMed Central

Background Shedding of nanoparticles from the cell membrane is a common process in all cells. These nanoparticles are present in body fluids and can be harvested by isolation. To collect circulating nanoparticles from blood, a standard procedure consisting of repeated centrifugation and washing is applied to the blood samples. Nanoparticles can also be shed from blood cells during the isolation process, so it is unclear whether nanoparticles found in the isolated material are present in blood at sampling or if are they created from the blood cells during the isolation process. We addressed this question by determination of the morphology and identity of nanoparticles harvested from blood. Methods The isolates were visualized by scanning electron microscopy, analyzed by flow cytometry, and nanoparticle shapes were determined theoretically. Results The average size of nanoparticles was about 300 nm, and numerous residual blood cells were found in the isolates. The shapes of nanoparticles corresponded to the theoretical shapes obtained by minimization of the membrane free energy, indicating that these nanoparticles can be identified as vesicles. The concentration and size of nanoparticles in blood isolates was sensitive to the temperature during isolation. We demonstrated that at lower temperatures, the nanoparticle concentration was higher, while the nanoparticles were on average smaller. Conclusion These results indicate that a large pool of nanoparticles is produced after blood sampling. The shapes of deformed blood cells found in the isolates indicate how fragmentation of blood cells may take place. The results show that the contents of isolates reflect the properties of blood cells and their interaction with the surrounding solution (rather than representing only nanoparticles present in blood at sampling) which differ in different diseases and may therefore present a relevant clinical parameter.

Sustar, Vid; Bedina-Zavec, Apolonija; Stukelj, Roman; Frank, Mojca; Bobojevic, Goran; Jansa, Rado; Ogorevc, Eva; Kruljc, Peter; Mam, Keriya; Simunic, Bostjan; Mancek-Keber, Mateja; Jerala, Roman; Rozman, Blaz; Veranic, Peter; Hagerstrand, Henry; Kralj-Iglic, Veronika

2011-01-01

154

Air-pollutant chemicals and oxidized lipids exhibit genome-wide synergistic effects on endothelial cells  

PubMed Central

Background Ambient air pollution is associated with increased cardiovascular morbidity and mortality. We have found that exposure to ambient ultrafine particulate matter, highly enriched in redox cycling organic chemicals, promotes atherosclerosis in mice. We hypothesize that these pro-oxidative chemicals could synergize with oxidized lipid components generated in low-density lipoprotein particles to enhance vascular inflammation and atherosclerosis. Results We have used human microvascular endothelial cells (HMEC) to study the combined effects of a model air pollutant, diesel exhaust particles (DEP), and oxidized 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (ox-PAPC) on genome-wide gene expression. We treated the cells in triplicate wells with an organic DEP extract, ox-PAPC at various concentrations, or combinations of both for 4 hours. Gene-expression profiling showed that both the DEP extract and ox-PAPC co-regulated a large number of genes. Using network analysis to identify coexpressed gene modules, we found three modules that were most highly enriched in genes that were differentially regulated by the stimuli. These modules were also enriched in synergistically co-regulated genes and pathways relevant to vascular inflammation. We validated this synergy in vivo by demonstrating that hypercholesterolemic mice exposed to ambient ultrafine particles exhibited significant upregulation of the module genes in the liver. Conclusion Diesel exhaust particles and oxidized phospholipids synergistically affect the expression profile of several gene modules that correspond to pathways relevant to vascular inflammatory processes such as atherosclerosis.

Gong, Ke Wei; Zhao, Wei; Li, Ning; Barajas, Berenice; Kleinman, Michael; Sioutas, Constantinos; Horvath, Steve; Lusis, Aldons J; Nel, Andre; Araujo, Jesus A

2007-01-01

155

Effect of carbon nanoparticles on renal epithelial cell structure, barrier function, and protein expression  

PubMed Central

To assess effects of carbon nanoparticle (CNP) exposure on renal epithelial cells, fullerenes (C60), single-walled carbon nanotubes (SWNT), and multi-walled carbon nanotubes (MWNT) were incubated with a confluent renal epithelial line for 48 h. At low concentrations, CNP-treated cells exhibited significant decreases in transepithelial electrical resistance (TEER) but no changes in hormone-stimulated ion transport or CNP-induced toxicity or stress responses as measured by lactate dehydrogenase or cytokine release. The changes in TEER, manifested as an inverse relationship with CNP concentration, were mirrored by an inverse correlation between dose and changes in protein expression. Lower, more physiologically relevant, concentrations of CNP have the most profound effects on barrier cell function and protein expression. These results indicate an impact of CNPs on renal epithelial cells at concentrations lower than have been previously studied and suggest caution with regard to increasing CNP levels entering the food chain due to increasing environmental pollution.

BLAZER-YOST, BONNIE L.; BANGA, AMIRAJ; AMOS, ADAM; CHERNOFF, ELLEN; LAI, XIANYIN; LI, CHENG; MITRA, SOMENATH; WITZMANN, FRANK A.

2011-01-01

156

Effect of carbon nanoparticles on renal epithelial cell structure, barrier function, and protein expression.  

PubMed

To assess effects of carbon nanoparticle (CNP) exposure on renal epithelial cells, fullerenes (C(60)), single-walled carbon nanotubes (SWNT), and multi-walled carbon nanotubes (MWNT) were incubated with a confluent renal epithelial line for 48 h. At low concentrations, CNP-treated cells exhibited significant decreases in transepithelial electrical resistance (TEER) but no changes in hormone-stimulated ion transport or CNP-induced toxicity or stress responses as measured by lactate dehydrogenase or cytokine release. The changes in TEER, manifested as an inverse relationship with CNP concentration, were mirrored by an inverse correlation between dose and changes in protein expression. Lower, more physiologically relevant, concentrations of CNP have the most profound effects on barrier cell function and protein expression. These results indicate an impact of CNPs on renal epithelial cells at concentrations lower than have been previously studied and suggest caution with regard to increasing CNP levels entering the food chain due to increasing environmental pollution. PMID:21067278

Blazer-Yost, Bonnie L; Banga, Amiraj; Amos, Adam; Chernoff, Ellen; Lai, Xianyin; Li, Cheng; Mitra, Somenath; Witzmann, Frank A

2010-11-10

157

PLGA-based gene delivering nanoparticle enhance suppression effect of miRNA in HePG2 cells  

NASA Astrophysics Data System (ADS)

The biggest challenge in the field of gene therapy is how to effectively deliver target genes to special cells. This study aimed to develop a new type of poly( D, L-lactide-co-glycolide) (PLGA)-based nanoparticles for gene delivery, which are capable of overcoming the disadvantages of polyethylenimine (PEI)- or cationic liposome-based gene carrier, such as the cytotoxicity induced by excess positive charge, as well as the aggregation on the cell surface. The PLGA-based nanoparticles presented in this study were synthesized by emulsion evaporation method and characterized by transmission electron microscopy, dynamic light scattering, and energy dispersive spectroscopy. The size of PLGA/PEI nanoparticles in phosphate-buffered saline (PBS) was about 60 nm at the optimal charge ratio. Without observable aggregation, the nanoparticles showed a better monodispersity. The PLGA-based nanoparticles were used as vector carrier for miRNA transfection in HepG2 cells. It exhibited a higher transfection efficiency and lower cytotoxicity in HepG2 cells compared to the PEI/DNA complex. The N/P ratio (ratio of the polymer nitrogen to the DNA phosphate) 6 of the PLGA/PEI/DNA nanocomplex displays the best property among various N/P proportions, yielding similar transfection efficiency when compared to Lipofectamine/DNA lipoplexes. Moreover, nanocomplex shows better serum compatibility than commercial liposome. PLGA nanocomplexes obviously accumulate in tumor cells after transfection, which indicate that the complexes contribute to cellular uptake of pDNA and pronouncedly enhance the treatment effect of miR-26a by inducing cell cycle arrest. Therefore, these results demonstrate that PLGA/PEI nanoparticles are promising non-viral vectors for gene delivery.

Feng Liang, Gao; Zhu, Yan Liang; Sun, Bo; Hu, Fei Hu; Tian, Tian; Li, Shu Chun; Xiao, Zhong Dang

2011-07-01

158

Interactions of silica nanoparticles with lung epithelial cells and the association to flotillins.  

PubMed

Amorphous silica nanoparticles (aSNPs) gain increasing popularity for industrial and therapeutic claims. The lung with its surface area of 100-140 m(2) displays an ideal target for therapeutic approaches, but it represents also a serious area of attack for harmful nanomaterials. The exact nature of the cytotoxic effects of NPs is still unknown. Furthermore, cellular pathways and the destiny of internalized NPs are still poorly understood. Therefore, we examined the cytotoxicity (MTS, LDH) and inflammatory responses (IL-8) for different-sized aSNPs (30, 70, 300 nm) on our lung epithelial cells line NCI H441 and endothelial cell line ISO-HAS-1. Additionally, colocalization studies have been conducted via immunofluorescence staining for flotillin-1- and flotillin-2-bearing endocytic vesicles. Subsequently, the relevance of flotillins concerning the viability of aSNP-exposed epithelial cells has been evaluated using flotillin-1/2 depleted cells (siRNA). This study reveals the relevance of the nanoparticle size regarding cytotoxicity (MTS, LDH) and inflammatory responses (IL-8), whereat the smaller the size of the nanoparticle is, the more harmful are the effects. All different aSNP sizes have been incorporated in flotillin-1- and flotillin-2-labelled vesicles in lung epithelial and endothelial cells, which display a marker for late endosomal or lysosomal structures and appear to exhibit a clathrin- or caveolae-independent mode of endocytosis. Flotillin-depleted H441 showed a clearly decreased uptake of aSNPs. Additionally, the viability of aSNP-exposed cells was reduced in these cells. These findings indicate a contribution of flotillins in as yet unknown (clathrin or caveolae-independent) endocytosis mechanisms and (or) endosomal storage. PMID:22669515

Kasper, Jennifer; Hermanns, Maria I; Bantz, Christoph; Koshkina, Olga; Lang, Thomas; Maskos, Michael; Pohl, Christine; Unger, Ronald E; Kirkpatrick, C James

2012-06-06

159

Long Circulating Nanoparticles via Adhesion on Red Blood Cells: Mechanism and Extended Circulation  

Microsoft Academic Search

Polymeric nanoparticles have long been sought after as carriers for systemic and targeted drug delivery. However, applications of nanoparticles are limited by their short in vivo circulation lifetimes. We report that by attaching polymeric nanoparticles to the surface of red blood cells, it is possible to dramatically improve their in vivo circulation lifetime. The particles remain in circulation as long

ELIZABETH CHAMBERS; SAMIR MITRAGOTRI

2007-01-01

160

Intracellular Confinement of Magnetic Nanoparticles by Living Cells: Impact for Imaging and Therapeutic Applications  

NASA Astrophysics Data System (ADS)

Superparamagnetic properties of iron-oxide nanoparticles paved the way for various biomedical applications, such as magnetic resonance imaging (MRI), magnetic targeting of drug vectors or magnetically-induced therapeutic hyperthermia. Living cells interact with nanoparticles by internalizing them within intracellular compartments, called lysosomes. In the course of cellular uptake, the spatial distribution of magnetic nanoparticles changes from dilute isolated nanoparticles to a highly concentrated assembly of nanoparticles confined in micrometric lysosomes. This local organization of nanoparticles, which is induced by the intracellular environment, may have important consequences for their superparamagnetic behaviour. In particular, it may deeply affect their magnetic properties used for biomedical purposes and therefore must be considered when optimizing the properties of nanoparticles for a peculiar application. In this paper, we review the role of intracellular confinement of nanoparticles for their three main biomedical uses: MR cellular imaging, magnetic targeting of cells and magnetically induced hyperthermia.

Gazeau, Florence; Lévy, Michael; Wilhelm, Claire

2011-03-01

161

Enhanced detection of circulating melanoma cells using gold nanoparticles as photoacoustic contrasting agents  

Microsoft Academic Search

Nanotechnology and the various properties of gold nanoparticles (AuNPs) are quickly changing the field of cancer detection and treatment. Photoacoustic detection methods show an increase in sensitivity using gold nanoparticle antibody conjugation, which selectively targets melanoma cancer cells. Instead of targeting melanoma tumors, we tag single cells, analogous to circulating metastatic melanoma cells. Using an in vitro, stationary cell system

Devin R. McCormack; Kiran Bhattacharyya; Raghuraman Kannan; Kattesh Katti; John A. Viator

2010-01-01

162

Nanoparticle injection to single animal cells using femtosecond laser-induced impulsive force  

NASA Astrophysics Data System (ADS)

An impulsive force, which was generated by focusing tightly a femtosecond laser into a cell culture medium, was applied to inject nanoparticles into local areas of a single mouse fibroblast NIH3T3 cell. When the impulsive force was induced near the cell, the nanoparticles adhering on the cell membrane were introduced, which was directly confirmed by confocal fluorescence microscopy.

Yamaguchi, Atsushi; Hosokawa, Yoichiroh; Louit, Guillaume; Asahi, Tsuyoshi; Shukunami, Chisa; Hiraki, Yuji; Masuhara, Hiroshi

2008-10-01

163

Solid Lipid Nanoparticles Enhance the Delivery of the HIV Protease Inhibitor, Atazanavir, by a Human Brain Endothelial Cell Line  

Microsoft Academic Search

Purpose  Protease inhibitors (PIs) exhibit low brain permeability. As a result, unchallenged HIV viral replication can lead to HIV-encephalitis\\u000a and antiretroviral drug resistance. The objective of this study was to develop and evaluate a lipid nanoparticle system for\\u000a enhanced brain delivery of the potent and frequently used HIV PI, atazanavir, using a well characterized human brain microvessel\\u000a endothelial cell line (hCMEC\\/D3)

Niladri Chattopadhyay; Jason Zastre; Ho-Lun Wong; Xiao Yu Wu; Reina Bendayan

2008-01-01

164

Electrical and optical interconnection for mechanically stacked multi-junction solar cells mediated by metal nanoparticle arrays  

NASA Astrophysics Data System (ADS)

An interconnection approach for mechanical stacking of solar cells is described. In this approach, block copolymer-templated fabrication of metal nanoparticle arrays and van der Waals bonding were integrated to design interfaces which permit both high interfacial conductivities and minimal transmission losses upon interconnections of solar cells. A series of electrical and optical characterizations verified that the approach potentially provides resistances of as low as 3.7 ?-cm2 with transmission losses of less than 2%. The demonstrative two-junction solar cell exhibited promising open-circuit voltage and fill factor, suggesting the possibility of achieving high-efficiency multi-junction solar cells based on this unique strategy.

Mizuno, Hidenori; Makita, Kikuo; Matsubara, Koji

2012-11-01

165

Genotoxic responses to titanium dioxide nanoparticles and fullerene in gpt delta transgenic MEF cells  

Microsoft Academic Search

BACKGROUND: Titanium dioxide (TiO2) nanoparticles and fullerene (C60) are two attractive manufactured nanoparticles with great promise in industrial and medical applications. However, little is known about the genotoxic response of TiO2 nanoparticles and C60 in mammalian cells. In the present study, we determined the mutation fractions induced by either TiO2 nanoparticles or C60 in gpt delta transgenic mouse primary embryo

An Xu; Yunfei Chai; Takehiko Nohmi; Tom K Hei

2009-01-01

166

Hydrazinocurcumin Encapsuled nanoparticles "re-educate" tumor-associated macrophages and exhibit anti-tumor effects on breast cancer following STAT3 suppression.  

PubMed

Tumor-associated macrophages (TAMs) are essential cellular components within tumor microenvironment (TME). TAMs are educated by TME to transform to M2 polarized population, showing a M2-like phenotype, IL-10(high), IL-12(low), TGF-?(high). STAT3 signaling triggers crosstalk between tumor cells and TAMs, and is crucial for the regulation of malignant progression. In our study, legumain-targeting liposomal nanoparticles (NPs) encapsulating HC were employed to suppress STAT3 activity and "re-educate" TAMs, and to investigate the effects of suppression of tumor progression in vivo. The results showed that TAMs treated by HC encapsuled NPs could switch to M1-like phenotype, IL-10(low), IL-12(high), TGF-?(low), and the "re-educated" macrophages (M1-like macrophages) considerably demonstrated opposite effect of M2-like macrophages, especially the induction of 4T1 cells migration and invasion in vitro, and suppression of tumor growth, angiogenesis and metastasis in vivo. These data indicated that inhibition of STAT3 activity of TAMs by HC-NPs was able to reverse their phenotype and could regulate their crosstalk between tumor cells and TAMs in order to suppress tumor progression. PMID:23825527

Zhang, Xiwen; Tian, Wenxia; Cai, Xiaozhong; Wang, Xiaofei; Dang, Weiqi; Tang, Hao; Cao, Hong; Wang, Lin; Chen, Tingmei

2013-06-25

167

Visualizing DNA Nanoparticle Motion under Graphene Liquid Cell TEM  

NASA Astrophysics Data System (ADS)

We think of a simple colloidal nanocrystal as one type of artificial atoms. They mutually interact, cluster into artificial molecules, and further arrange into macroscopically functional artificial solids. The ``atomic'' resolution dynamics of this bottom-up strategy in materials design is studied here in a system of artificial molecules composed of DNA and nanoparticle. The observation of dynamics in their liquid environment is recently enabled by graphene liquid cell transmission electron microscopy (TEM). In comparison to conventional TEM, wherein the assembled 3D artificial structures are dried out during sample preparation and thus are collapsed, this graphene liquid cell introduces a special local liquid structure that retains the conformations as well as the dynamics of the assemblies. In situ imaging of correlated motions of DNA and nanoparticle provides insights into the design principles of artificial nanocrystal molecules and solids linked by DNA.

Chen, Qian; Smith, Jessica; Park, Jungwon; Lee, Somin; Zettl, Alex; Alivisatos, Paul

2013-03-01

168

Gold Nanoparticle Enhancement for Polymer Electrolyte Membrane (PEM) Fuel Cell  

NASA Astrophysics Data System (ADS)

PEM fuel cell is one of the most promising future alternative energy sources. However, its relatively low power output has prevented it from many practical applications. Marvrikakis et al have predicted that gold nanoparticles that are platelet shaped andhave direct contact to the substrate to be the perfect catalysts. In our experiment, hydrophobic, thiol-functionalized gold nanoparticles were synthesized through two-phase method developed by Brust et al. When particle solution is spread at the air water interface, EXAFS spectroscopy indicate that some of the gold atoms are removed, as the water displaces the hydrophobic thiol chains from the particle surface, resulting in platelet shaped particles. Furthermore, after these nanoparticles are spread on the surface of water in a Langmuir-Blodgett trough where surface pressure can be applied to compress them, they form LB film consisting of one or more monolayers. This LB film can then be deposited onto a solid surface, such as the Nafion membrane where the particle surface can make direct contact with electrodes and take effect. We also find that there is an optimal surface pressure for forming gold nanoparticles monolayer to achieve the highest enhancement of output power.

Pan, Cheng; Qin, Sisi; Rafailovich, Miriam

2013-03-01

169

A dose-controlled system for air-liquid interface cell exposure and application to zinc oxide nanoparticles  

Microsoft Academic Search

BACKGROUND: Engineered nanoparticles are becoming increasingly ubiquitous and their toxicological effects on human health, as well as on the ecosystem, have become a concern. Since initial contact with nanoparticles occurs at the epithelium in the lungs (or skin, or eyes), in vitro cell studies with nanoparticles require dose-controlled systems for delivery of nanoparticles to epithelial cells cultured at the air-liquid

Anke Gabriele Lenz; Erwin Karg; Bernd Lentner; Vlad Dittrich; Christina Brandenberger; Barbara Rothen-Rutishauser; Holger Schulz; George A Ferron; Otmar Schmid

2009-01-01

170

Dietary Phenolic Acids Act as Effective Antioxidants in Membrane Models and in Cultured Cells, Exhibiting Proapoptotic Effects in Leukaemia Cells  

PubMed Central

Caffeic, syringic, and protocatechuic acids are phenolic acids derived directly from food intake or come from the gut metabolism of polyphenols. In this study, the antioxidant activity of these compounds was at first evaluated in membrane models, where caffeic acid behaved as a very effective chain-breaking antioxidant, whereas syringic and protocatechuic acids were only retardants of lipid peroxidation. However, all three compounds acted as good scavengers of reactive species in cultured cells subjected to exogenous oxidative stress produced by low level of H2O2. Many tumour cells are characterised by increased ROS levels compared with their noncancerous counterparts. Therefore, we investigated whether phenolic acids, at low concentrations, comparable to those present in human plasma, were able to decrease basal reactive species. Results show that phenolic acids reduced ROS in a leukaemia cell line (HEL), whereas no effect was observed in normal cells, such as HUVEC. The compounds exhibited no toxicity to normal cells while they decreased proliferation in leukaemia cells, inducing apoptosis. In the debate on optimal ROS-manipulating strategies in cancer therapy, our work in leukaemia cells supports the antioxidant ROS-depleting approach.

Zambonin, Laura; Caliceti, Cristiana; Vieceli Dalla Sega, Francesco; Fiorentini, Diana; Hrelia, Silvana; Landi, Laura; Prata, Cecilia

2012-01-01

171

Self-renewing epiblast stem cells exhibit continual delineation of germ cells with epigenetic reprogramming in vitro.  

PubMed

Pluripotent epiblast stem cells (EpiSCs) derived from postimplantation embryos exhibit properties that are characteristically different when compared with pluripotent embryonic stem cells (ESCs) derived from mouse blastocysts. However, EpiSCs are relatively less well characterised compared with ESCs. In particular, the relationship between EpiSCs and primordial germ cells (PGCs) is unknown, and is worthy of investigation because PGCs originate from postimplantation epiblast cells in vivo. We show that EpiSCs have an infinite capacity for generating PGCs, under conditions that sustain their pluripotency and self-renewal. These PGCs generated in vitro show appropriate transcriptional and epigenetic reprogramming events and are able to develop further into late germ cells. Notably, the PGCs can, in turn, be induced to undergo dedifferentiation into pluripotent embryonic germ cells (EGCs), which resemble ESCs and not the EpiSC from which they are derived. Our observations demonstrate intrinsic reprogramming during specification of PGCs that results in the erasure of epigenetic memory of EpiSCs following reactivation of the X-chromosome, DNA demethylation and re-expression of key pluripotency genes. This study provides novel insights into the nature and properties of EpiSCs, and introduces an in vitro model system that will be useful for investigations on PGC specification and on mechanisms regulating epigenetic reprogramming in germ cells. PMID:19793888

Hayashi, Katsuhiko; Surani, M Azim

2009-09-30

172

Biomedical Applications of Magnetic Nanoparticles: Delivering Genes and Remote Control of Cells  

NASA Astrophysics Data System (ADS)

The use of magnetic micro- and nanoparticles for biomedical applications was first proposed in the 1920s as a way to measure the rehological properties of the cell's cytoplasm. Since that time, magnetic micro- and nanoparticle synthesis, coating and bio-functionalization have advanced significantly, as have the applications for these particles. Magnetic micro- and nanoparticles are now used in a variety of biomedical techniques such as targeted drug delivery, MRI contrast enhancement, gene transfection, immno-assay and cell sorting. More recently, magnetic micro- and nanoparticles have been used to investigate and manipulate cellular processes both in vitro and in vivo. This talk will focus on magnetic nanoparticle targeting to and actuation of cell surface receptors to control cell signaling cascades to control cell behavior. This technology has applications in disease therapy, cell engineering and regenerative medicine. The use of magnetic nanoparticles and oscillating magnet arrays for enhanced gene delivery will also be discussed.

Dobson, Jon

2013-03-01

173

Cyto and genotoxicity of gold nanoparticles in human hepatocellular carcinoma and peripheral blood mononuclear cells.  

PubMed

Engineered nanomaterials have been extensively applied as active materials for technological applications. Since the impact of these nanomaterials on health and environment remains undefined, research on their possible toxic effects has attracted considerable attention. It is known that in humans, for example, the primary site of gold nanoparticles (AuNps) accumulation is the liver. The latter has motivated research regarding the use of AuNps for cancer therapy, since specific organs can be target upon appropriate functionalization of specific nanoparticles. In this study, we investigate the geno and cytotoxicity of two types of AuNps against human hepatocellular carcinoma cells (HepG2) and peripheral blood mononuclear cells (PBMC) from healthy human volunteers. The cells were incubated in the presence of different concentrations of AuNps capped with either sodium citrate or polyamidoamine dendrimers (PAMAM). Our results suggest that both types of AuNps interact with HepG2 cells and PBMC and may exhibit in vitro geno and cytotoxicity even at very low concentrations. In addition, the PBMC were less sensitive to DNA damage toxicity effects than cancer HepG2 cells upon exposure to AuNps. PMID:23046612

Paino, Iêda Maria Martinez; Marangoni, Valéria Spolon; de Oliveira, Rita de Cássia Silva; Antunes, Lusânia Maria Greggi; Zucolotto, Valtencir

2012-10-06

174

Intracellular drug release from curcumin-loaded PLGA nanoparticles induces G2/M block in breast cancer cells.  

PubMed

PLGA nanoparticles are among the most studied polymer nanoformulations for several drugs against different kinds of malignant diseases, thanks to their in vivo stability and tumor localization exploiting the well-documented "enhanced permeation and retention" (EPR) effect. In this paper, we have developed uniform curcumin-bearing PLGA nanoparticles by a single-emulsion process, which exhibited a curcumin release following a Fickian-law diffusion over 10 days in vitro. PLGA nanoparticles were about 120 nm in size, as determined by dynamic light scattering, with a surface negative charge of -30 mV. The loading ratio of encapsulated drug in our PLGA nanoformulation was 8 wt%. PLGA encapsulation provided efficient protection of curcumin from environment, as determined by fluorescence emission experiments. Next, we have investigated the possibility to study the intracellular degradation of nanoparticles associated with a specific G2/M blocking effect on MCF7 breast cancer cells caused by curcumin release in the cytoplasm, which provided direct evidence on the mechanism of action of our nanocomplex. This study was carried out using Annexin V-based cell death analysis, MTT assessment of proliferation, flow cytometry, and confocal laser scanning microscopy. PLGA nanoparticles proved to be completely safe, suggesting a potential utilization of this nanocomplex to improve the intrinsically poor bioavailability of curcumin for the treatment of severe malignant breast cancer. PMID:23350530

Verderio, Paolo; Bonetti, Paolo; Colombo, Miriam; Pandolfi, Laura; Prosperi, Davide

2013-02-15

175

Ion mediated targeting of cells with nanoparticles  

Microsoft Academic Search

In eukaryotic cells, Ca^2+ ions are necessary for intracellular signaling, in activity of mitochondria and a variety of other cellular process that have been linked to cell apoptosis, proteins synthesis and cell-cycle regulation. Here we show that Ca^2+ ions, serving as the bio-compatible interface can be used to target Saccharomyces cerevisiae (SaC, baker's yeast), a model eukaryotic cell, with Au

Vivek Maheshwari; Jinlong Fu

2010-01-01

176

New mechanisms for non-porative ultrasound stimulation of cargo delivery to cell cytosol with targeted perfluorocarbon nanoparticles  

PubMed Central

The cell membrane constitutes a major barrier for non-endocytotic intracellular delivery of therapeutic molecules from drug delivery vehicles. Existing approaches to breaching the cell membrane include cavitational ultrasound (with microbubbles), electroporation and cell-penetrating peptides. We report the use of diagnostic ultrasound for intracellular delivery of therapeutic bulky cargo with the use of molecularly targeted liquid perfluorocarbon (PFC) nanoparticles. To demonstrate the concept, we used a lipid with a surrogate polar head group, nanogold-DPPE, incorporated into the nanoparticle lipid monolayer. Melanoma cells were incubated with nanogold particles and this was followed by insonication with continuous wave ultrasound (2.25 MHz, 5 min, 0.6 MPa). Cells not exposed to ultrasound showed gold particles partitioned only in the outer bilayer of the cell membrane with no evidence of the intracellular transit of nanogold. However, the cells exposed to ultrasound exhibited numerous nanogold-DPPE components inside the cell that appeared polarized inside intracellular vesicles demonstrating cellular uptake and trafficking. Further, ultrasound-exposed cells manifested no incorporation of calcein or the release of lactate dehydrogenase. These observations are consistent with a mechanism that suggests that ultrasound is capable of stimulating the intracellular delivery of therapeutic molecules via non-porative mechanisms. Therefore, non-cavitational adjunctive ultrasound offers a novel paradigm in intracellular cargo delivery from PFC nanoparticles.

Soman, NR; Marsh, JN; Lanza, GM; Wickline, SA

2009-01-01

177

New mechanisms for non-porative ultrasound stimulation of cargo delivery to cell cytosol with targeted perfluorocarbon nanoparticles  

NASA Astrophysics Data System (ADS)

The cell membrane constitutes a major barrier for non-endocytotic intracellular delivery of therapeutic molecules from drug delivery vehicles. Existing approaches to breaching the cell membrane include cavitational ultrasound (with microbubbles), electroporation and cell-penetrating peptides. We report the use of diagnostic ultrasound for intracellular delivery of therapeutic bulky cargo with the use of molecularly targeted liquid perfluorocarbon (PFC) nanoparticles. To demonstrate the concept, we used a lipid with a surrogate polar head group, nanogold-DPPE, incorporated into the nanoparticle lipid monolayer. Melanoma cells were incubated with nanogold particles and this was followed by insonication with continuous wave ultrasound (2.25 MHz, 5 min, 0.6 MPa). Cells not exposed to ultrasound showed gold particles partitioned only in the outer bilayer of the cell membrane with no evidence of the intracellular transit of nanogold. However, the cells exposed to ultrasound exhibited numerous nanogold-DPPE components inside the cell that appeared polarized inside intracellular vesicles demonstrating cellular uptake and trafficking. Further, ultrasound-exposed cells manifested no incorporation of calcein or the release of lactate dehydrogenase. These observations are consistent with a mechanism that suggests that ultrasound is capable of stimulating the intracellular delivery of therapeutic molecules via non-porative mechanisms. Therefore, non-cavitational adjunctive ultrasound offers a novel paradigm in intracellular cargo delivery from PFC nanoparticles.

Soman, N. R.; Marsh, J. N.; Lanza, G. M.; Wickline, S. A.

2008-05-01

178

A lubricious formulation exhibiting reduced thrombogenicity, cell proliferation, and protein adsorption.  

PubMed

The adhesion of human platelets, erythrocytes, and leukocytes, the adsorption of protein, and the proliferation of human umbilical vein endothelial cells (HUVEC) on the surface of electropolished stainless steel and the lumen of polyurethane tubing coated with Hydromer's lubricious Duality T8B formulation was evaluated. Following exposure to a platelet-enriched suspension from citrated human whole blood, stainless steel coated with this formulation exhibited significantly reduced adhesion of platelets, erythrocytes, and granulocytes. This reduction in adhesion was confirmed using an immunohistochemical method utilizing antibodies to CD41, CD235, and CD15, respectively. The proliferation of HUVEC cells were significantly reduced when cultured on coated stainless steel. This formulation was also able to significantly reduce the adsorption of plasma proteins and the major protein in tear fluid (lysozyme) to the surface of stainless steel. The nonthrombogenic properties of Duality T8B after application to the lumen of polyurethane tubing were also examined. Following a short-term (3 h) static exposure to citrated human whole blood, microscopic examination revealed that the adhesion of platelets and erythrocytes was reduced significantly, a finding confirmed using anti-CD41 and anti-CD235 antibodies in the immunohistochemical method. A long-term (12 day) study yielded essentially identical results indicating a significant reduction in the adhesion of blood components on the luminal surface of coated polyurethane tubing. In summary, these data indicate that the application of Duality T8B onto surfaces of medical devices, such as catheters, extracorporeal circuitry, and coronary stents, could aid in reducing or preventing not only thrombus formation but also the process of restenosis. PMID:19130614

Vicario, Pasquale P; Lu, Zichun J; Grigorian, Irina A; Schottman, Tom

2009-07-01

179

Human-induced pluripotent stem cell-derived cardiomyocytes exhibit temporal changes in phenotype.  

PubMed

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) have been recently derived and are used for basic research, cardiotoxicity assessment, and phenotypic screening. However, the hiPS-CM phenotype is dependent on their derivation, age, and culture conditions, and there is disagreement as to what constitutes a functional hiPS-CM. The aim of the present study is to characterize the temporal changes in hiPS-CM phenotype by examining five determinants of cardiomyocyte function: gene expression, ion channel functionality, calcium cycling, metabolic activity, and responsiveness to cardioactive compounds. Based on both gene expression and electrophysiological properties, at day 30 of differentiation, hiPS-CMs are immature cells that, with time in culture, progressively develop a more mature phenotype without signs of dedifferentiation. This phenotype is characterized by adult-like gene expression patterns, action potentials exhibiting ventricular atrial and nodal properties, coordinated calcium cycling and beating, suggesting the formation of a functional syncytium. Pharmacological responses to pathological (endothelin-1), physiological (IGF-1), and autonomic (isoproterenol) stimuli similar to those characteristic of isolated adult cardiac myocytes are present in maturing hiPS-CMs. In addition, thyroid hormone treatment of hiPS-CMs attenuated the fetal gene expression in favor of a more adult-like pattern. Overall, hiPS-CMs progressively acquire functionality when maintained in culture for a prolonged period of time. The description of this evolving phenotype helps to identify optimal use of hiPS-CMs for a range of research applications. PMID:23832699

Ivashchenko, Christine Y; Pipes, Gordon C; Lozinskaya, Irina M; Lin, Zuojun; Xiaoping, Xu; Needle, Saul; Grygielko, Eugene T; Hu, Erding; Toomey, John R; Lepore, John J; Willette, Robert N

2013-07-05

180

A Humidity-Sensitive Arabidopsis Copine Mutant Exhibits Precocious Cell Death and Increased Disease Resistance  

PubMed Central

The copines are a newly identified class of calcium-dependent, phospholipid binding proteins that are present in a wide range of organisms, including Paramecium, plants, Caenorhabditis elegans, mouse, and human. However, the biological functions of the copines are unknown. Here, we describe a humidity-sensitive copine mutant in Arabidopsis. Under nonpermissive, low-humidity conditions, the cpn1-1 mutant displayed aberrant regulation of cell death that included a lesion mimic phenotype and an accelerated hypersensitive response (HR). However, the HR in cpn1-1 showed no increase in sensitivity to low pathogen titers. Low-humidity-grown cpn1-1 mutants also exhibited morphological abnormalities, increased resistance to virulent strains of Pseudomonas syringae and Peronospora parasitica, and constitutive expression of pathogenesis-related (PR) genes. Growth of cpn1-1 under permissive, high-humidity conditions abolished the increased disease resistance, lesion mimic, and morphological mutant phenotypes but only partially alleviated the accelerated HR and constitutive PR gene expression phenotypes. The disease resistance phenotype of cpn1-1 suggests that the CPN1 gene regulates defense responses. Alternatively, the primary function of CPN1 may be the regulation of plant responses to low humidity, and the effect of the cpn1-1 mutation on disease resistance may be indirect.

Jambunathan, Niranjani; Siani, Jennifer M.; McNellis, Timothy W.

2001-01-01

181

A humidity-sensitive Arabidopsis copine mutant exhibits precocious cell death and increased disease resistance.  

PubMed

The copines are a newly identified class of calcium-dependent, phospholipid binding proteins that are present in a wide range of organisms, including Paramecium, plants, Caenorhabditis elegans, mouse, and human. However, the biological functions of the copines are unknown. Here, we describe a humidity-sensitive copine mutant in Arabidopsis. Under nonpermissive, low-humidity conditions, the cpn1-1 mutant displayed aberrant regulation of cell death that included a lesion mimic phenotype and an accelerated hypersensitive response (HR). However, the HR in cpn1-1 showed no increase in sensitivity to low pathogen titers. Low-humidity-grown cpn1-1 mutants also exhibited morphological abnormalities, increased resistance to virulent strains of Pseudomonas syringae and Peronospora parasitica, and constitutive expression of pathogenesis-related (PR) genes. Growth of cpn1-1 under permissive, high-humidity conditions abolished the increased disease resistance, lesion mimic, and morphological mutant phenotypes but only partially alleviated the accelerated HR and constitutive PR gene expression phenotypes. The disease resistance phenotype of cpn1-1 suggests that the CPN1 gene regulates defense responses. Alternatively, the primary function of CPN1 may be the regulation of plant responses to low humidity, and the effect of the cpn1-1 mutation on disease resistance may be indirect. PMID:11595798

Jambunathan, N; Siani, J M; McNellis, T W

2001-10-01

182

Toxicity of gold nanoparticles on somatic and reproductive cells.  

PubMed

Along with the number of potential applications for gold nanoparticles (AuNP) especially for medical and scientific purposes, the interest in possible toxic effects of such particles is rising. The general perception views nanosized gold colloids as relatively inert towards biological systems. However, a closer analysis of pertinent studies reveals a more complex picture. While the chemical compound of which the nanoparticles consists plays an important role, further biocompatibility determining aspects have been made out. The vast majority of trials concerning AuNP-toxicity were performed using somatic cell culture lines. The results show a considerable dependency of toxic effects on size, zeta potential and surface functionalisation. In vivo studies on this subject are still rare. Based on the existing data it can be assumed, that a dosage of under <400 µg Au/kg showed no untoward effects. If higher amounts were applied toxicity depended on route of administration and particle size. Since nanoparticles have been shown to cross reproduction-relevant biological barriers such as the blood-testicle and the placental barrier the question of their reprotoxicity arises. Yet data concerning this subject is far from adequate. Regarding gametes, recent experiments showed a dose-dependent sensitivity of spermatozoa towards AuNP. Oocytes have not yet been tested in that respect. Interestingly, so far no effects were detected on embryos after gold nanoparticle exposure. In conclusion, the biocompatibility of gold nanoparticles depends on a range of particle specific aspects as well as the choice of target tissue. Further clarification of such matters are subject to ongoing research. PMID:22101718

Taylor, U; Barchanski, A; Garrels, W; Klein, S; Kues, W; Barcikowski, S; Rath, D

2012-01-01

183

Soy protein extract (SPE) exhibits differential in vitro cell proliferation effects in oral cancer and normal cell lines.  

PubMed

Prior research has demonstrated that specific isoflavones derived from soy may exhibit antitumor effects against many cancers, including oral cancer. Most of this prior research involved isolation and testing of individual soy components, such as genistein, daidzein, and glycitein, which exhibit cytotoxicity against cancerous cells but may also have residual cytotoxic effects on normal cells. Few studies have evaluated whole soy extract, containing a combination of these isoflavones, and other bioreactive compounds, which may function synergistically and more effectively against oral cancers. This study compared the antiproliferative effects of whole soy protein extract (SPE) on CAL 27 and SCC25 oral cancer cell lines in vitro. Administration of SPE significantly inhibited oral cancer growth and exerted these effects at lower concentrations compared with another class of flavonoids (proanthocyanidins) that were previously tested on these cell lines. This SPE-induced growth inhibition correlated with down-regulated mRNA expression in the oral cancer cell-cycle promoter ornithine decarboxylase (ODC), as well as upregulation of caspase-2 and caspase-8, initiators and effectors of apoptosis. These results suggest that SPE may represent a potential chemopreventive or chemotherapeutic option for oral cancer. Moreover, SPE may be more effective than other flavonoids currently used and may be effective at lower concentrations that approximate physiologic serum levels (0-2 ?mol/l). This study may help to explain why diets rich in fruits, vegetables, and soy protein are associated with protection against development and progression of oral cancers, although further study is needed to develop specific public health recommendations for oral cancer treatment and prevention. PMID:22432688

Kingsley, Karl; Truong, Khanh; Low, Erik; Hill, Charles K; Chokshi, Shruti B; Phipps, Don; West, M Abigail; Keiserman, Mark A; Bergman, Christine J

2011-06-01

184

Biocompatible fluorescent nanoparticles for in vivo stem cell tracking.  

PubMed

Efficient application of stem cells to the treatment of neurodegenerative diseases requires safe cell tracking to follow stem cell fate over time in the host environment after transplantation. In this work, for the first time, fluorescent and biocompatible methyl methacrylate (MMA)-based nanoparticles (fluoNPs) were synthesized through a free-radical co-polymerization process with a fluorescent macromonomer obtained by linking Rhodamine B and hydroxyethyl methacrylate. We demonstrate that the fluoNPs produced by polymerization of MMA-Rhodamine complexes (1) were efficient for the labeling and tracking of multipotent human amniotic fluid cells (hAFCs); (2) did not alter the main biological features of hAFCs (such as viability, cell growth and metabolic activity); (3) enabled us to determine the longitudinal bio-distribution of hAFCs in different brain areas after graft in the brain ventricles of healthy mice by a direct fluorescence-based technique. The reliability of our approach was furthermore confirmed by magnetic resonance imaging analyses, carried out by incubating hAFCs with both superparamagnetic iron oxide nanoparticles and fluoNPs. Our data suggest that these finely tunable and biocompatible fluoNPs can be exploited for the longitudinal tracking of stem cells. PMID:23690139

Cova, Lidia; Bigini, Paolo; Diana, Valentina; Sitia, Leopoldo; Ferrari, Raffaele; Pesce, Ruggiero Maria; Khalaf, Rushd; Bossolasco, Patrizia; Ubezio, Paolo; Lupi, Monica; Tortarolo, Massimo; Colombo, Laura; Giardino, Daniela; Silani, Vincenzo; Morbidelli, Massimo; Salmona, Mario; Moscatelli, Davide

2013-05-20

185

Biocompatible fluorescent nanoparticles for in vivo stem cell tracking  

NASA Astrophysics Data System (ADS)

Efficient application of stem cells to the treatment of neurodegenerative diseases requires safe cell tracking to follow stem cell fate over time in the host environment after transplantation. In this work, for the first time, fluorescent and biocompatible methyl methacrylate (MMA)-based nanoparticles (fluoNPs) were synthesized through a free-radical co-polymerization process with a fluorescent macromonomer obtained by linking Rhodamine B and hydroxyethyl methacrylate. We demonstrate that the fluoNPs produced by polymerization of MMA-Rhodamine complexes (1) were efficient for the labeling and tracking of multipotent human amniotic fluid cells (hAFCs); (2) did not alter the main biological features of hAFCs (such as viability, cell growth and metabolic activity); (3) enabled us to determine the longitudinal bio-distribution of hAFCs in different brain areas after graft in the brain ventricles of healthy mice by a direct fluorescence-based technique. The reliability of our approach was furthermore confirmed by magnetic resonance imaging analyses, carried out by incubating hAFCs with both superparamagnetic iron oxide nanoparticles and fluoNPs. Our data suggest that these finely tunable and biocompatible fluoNPs can be exploited for the longitudinal tracking of stem cells.

Cova, Lidia; Bigini, Paolo; Diana, Valentina; Sitia, Leopoldo; Ferrari, Raffaele; Pesce, Ruggiero Maria; Khalaf, Rushd; Bossolasco, Patrizia; Ubezio, Paolo; Lupi, Monica; Tortarolo, Massimo; Colombo, Laura; Giardino, Daniela; Silani, Vincenzo; Morbidelli, Massimo; Salmona, Mario; Moscatelli, Davide

2013-06-01

186

Monocyte-Derived Dendritic Cells Exhibit Increased Levels of Lysosomal Proteolysis as Compared to Other Human Dendritic Cell Populations  

PubMed Central

Background Fine control of lysosomal degradation for limited processing of internalized antigens is a hallmark of professional antigen presenting cells. Previous work in mice has shown that dendritic cells (DCs) contain lysosomes with remarkably low protease content. Combined with the ability to modulate lysosomal pH during phagocytosis and maturation, murine DCs enhance their production of class II MHC-peptide complexes for presentation to T cells. Methodology/Principal Findings In this study we extend these findings to human DCs and distinguish between different subsets of DCs based on their ability to preserve internalized antigen. Whereas DCs derived in vitro from CD34+ hematopoietic progenitor cells or isolated from peripheral blood of healthy donors are protease poor, DCs derived in vitro from monocytes (MDDCs) are more similar to macrophages (M?s) in protease content. Unlike other DCs, MDDCs also fail to reduce their intralysosomal pH in response to maturation stimuli. Indeed, functional characterization of lysosomal proteolysis indicates that MDDCs are comparable to M?s in the rapid degradation of antigen while other human DC subtypes are attenuated in this capacity. Conclusions/Significance Human DCs are comparable to murine DCs in exhibiting a markedly reduced level of lysosomal proteolysis. However, as an important exception to this, human MDDCs stand apart from all other DCs by a heightened capacity for proteolysis that resembles that of M?s. Thus, caution should be exercised when using human MDDCs as a model for DC function and cell biology.

McCurley, Nathanael; Mellman, Ira

2010-01-01

187

Titanium dioxide nanoparticles cause genotoxicity in human lung epithelial cells  

EPA Science Inventory

The use of engineered nanoparticles in consumer products is steadily increasing. However, the health effects of exposure to these nanoparticles are not thoroughly understood. This study investigated the genotoxicity of six titanium dioxide and two cerium oxide nanoparticles of va...

188

Mast cells contribute to altered vascular reactivity and ischemia-reperfusion injury following cerium oxide nanoparticle instillation  

PubMed Central

Cerium oxide (CeO2) represents an important nanomaterial with wide ranging applications. However, little is known regarding how CeO2 exposure may influence pulmonary or systemic inflammation. Furthermore, how mast cells would influence inflammatory responses to a nanoparticle exposure is unknown. We thus compared pulmonary and cardiovascular responses between C57BL/6 and B6.Cg-KitW-sh mast cell deficient mice following CeO2 nanoparticle instillation. C57BL/6 mice instilled with CeO2 exhibited mild pulmonary inflammation. However, B6.Cg-KitW-sh mice did not display a similar degree of inflammation following CeO2 instillation. Moreover, C57BL/6 mice instilled with CeO2 exhibited altered aortic vascular responses to adenosine and an increase in myocardial ischemia/reperfusion injury which was absent in B6.Cg-KitW-sh mice. In vitro CeO2 exposure resulted in increased production of PGD2, TNF-?, IL-6 and osteopontin by cultured mast cells. These findings demonstrate that CeO2 nanoparticles activate mast cells contributing to pulmonary inflammation, impairment of vascular relaxation and exacerbation of myocardial ischemia/reperfusion injury.

WINGARD, CHRISTOPHER J.; WALTERS, DIANNE M.; CATHEY, BROOK L.; HILDERBRAND, SUSANA C.; KATWA, PRANITA; LIN, SIJIE; KE, PU CHUN; PODILA, RAMAKRISHNA; RAO, APPARAO; LUST, ROBERT M.; BROWN, JARED M.

2011-01-01

189

cIBR effectively targets nanoparticles to LFA-1 on acute lymphoblastic T cells  

PubMed Central

Leukocyte function associated antigen-1 (LFA-1) is a primary cell adhesion molecule of leukocytes required for mediating cellular transmigration into sites of inflammation via the vascular endothelium. A cyclic peptide, cIBR, possesses high affinity for LFA-1 and conjugation to the surface of poly(dl-lactic-co-glycolic acid) nanoparticles can specifically target and deliver the encapsulated agents to T cells expressing LFA-1. The kinetics of targeted nanoparticle uptake by acute lymphoblastic leukemia T cells was investigated by flow cytometry and microscopy and compared to untargeted nanoparticles. The specificity of targeted nanoparticles binding to the LFA-1 integrin was demonstrated by competitive inhibition using free cIBR peptide or using the I domain of LFA-1 to inhibit the binding of targeted nanoparticles. The uptake of targeted nanoparticles was concentration and energy dependent. The cIBR-conjugated nanoparticles did not appear to localize with lysosomes whereas untargeted nanoparticles were detected in lysosomes in 6 hrs and steadily accumulated in lysosomes for 24 hrs. Finally, T-cell adhesion to epithelial cells was inhibited by cIBR-nanoparticles. Thus, nanoparticles displaying the cIBR ligand may offer a useful targeted drug delivery system as an alternative treatment of inflammatory diseases involving transmigration of leukocytes.

Chittasupho, Chuda; Manikwar, Prakash; Krise, Jeffrey P.; Siahaan, Teruna J.; Berkland, Cory

2009-01-01

190

Drug loading and release on tumor cells using silk fibroin-albumin nanoparticles as carriers  

NASA Astrophysics Data System (ADS)

Polymeric and biodegradable nanoparticles are frequently used in drug delivery systems. In this study silk fibroin-albumin blended nanoparticles were prepared using the desolvation method without any surfactant. These nanoparticles are easily internalized by the cells, reside within perinuclear spaces and act as carriers for delivery of the model drug methotrexate. Methotrexate loaded nanoparticles have better encapsulation efficiency, drug loading ability and less toxicity. The in vitro release behavior of methotrexate from the nanoparticles suggests that about 85% of the drug gets released after 12 days. The encapsulation and loading of a drug would depend on factors such as size, charge and hydrophobicity, which affect drug release. MTT assay and conjugation of particles with FITC demonstrate that the silk fibroin-albumin nanoparticles do not affect the viability and biocompatibility of cells. This blended nanoparticle, therefore, could be a promising nanocarrier for the delivery of drugs and other bioactive molecules.

Subia, B.; Kundu, S. C.

2013-01-01

191

Endothelial Cells from Diverse Tissues Exhibit Differences in Growth and Morphology  

Microsoft Academic Search

An increased recognition of the role of endothelial cells in disease and the development of methods for endothelial cell culture has led to an upsurge inin vitrostudies of endothelial cell function. However, the cells most often used for these studies do not reflect thein vivoheterogeneity of endothelial cells. To assess intrinsic differences between large and small vessel endothelial cells from

Linden E. Craig; Jeffrey P. Spelman; John D. Strandberg; M. Christine Zink

1998-01-01

192

Commercial Nanoparticles for Stem Cell Labeling and Tracking  

PubMed Central

Stem cell therapy provides promising solutions for diseases and injuries that conventional medicines and therapies cannot effectively treat. To achieve its full therapeutic potentials, the homing process, survival, differentiation, and engraftment of stem cells post transplantation must be clearly understood. To address this need, non-invasive imaging technologies based on nanoparticles (NPs) have been developed to track transplanted stem cells. Here we summarize existing commercial NPs which can act as contrast agents of three commonly used imaging modalities, including fluorescence imaging, magnetic resonance imaging and photoacoustic imaging, for stem cell labeling and tracking. Specifically, we go through their technologies, industry distributors, applications and existing concerns in stem cell research. Finally, we provide an industry perspective on the potential challenges and future for the development of new NP products.

Wang, Yaqi; Xu, Chenjie; Ow, Hooisweng

2013-01-01

193

Programming stem cells for therapeutic angiogenesis using biodegradable polymeric nanoparticles.  

PubMed

Controlled vascular growth is critical for successful tissue regeneration and wound healing, as well as for treating ischemic diseases such as stroke, heart attack or peripheral arterial diseases. Direct delivery of angiogenic growth factors has the potential to stimulate new blood vessel growth, but is often associated with limitations such as lack of targeting and short half-life in vivo. Gene therapy offers an alternative approach by delivering genes encoding angiogenic factors, but often requires using virus, and is limited by safety concerns. Here we describe a recently developed strategy for stimulating vascular growth by programming stem cells to overexpress angiogenic factors in situ using biodegradable polymeric nanoparticles. Specifically our strategy utilized stem cells as delivery vehicles by taking advantage of their ability to migrate toward ischemic tissues in vivo. Using the optimized polymeric vectors, adipose-derived stem cells were modified to overexpress an angiogenic gene encoding vascular endothelial growth factor (VEGF). We described the processes for polymer synthesis, nanoparticle formation, transfecting stem cells in vitro, as well as methods for validating the efficacy of VEGF-expressing stem cells for promoting angiogenesis in a murine hindlimb ischemia model. PMID:24121540

Keeney, Michael; Deveza, Lorenzo; Yang, Fan

2013-09-27

194

Performance enhancement of solar cells based on single-walled carbon nanotubes by Au nanoparticles  

NASA Astrophysics Data System (ADS)

The efficiency enhancement of solar cells based on a single-walled carbon nanotubes (SWNTs) and Silicon (Si) heterojunction by gold (Au) nanoparticles has been studied. Our experimental results confirm that the density of Au nanoparticles plays a critical role in improving the performance of solar cell. With the optimum amount of Au nanoparticles on SWNTs, the obvious enhanced photocurrent is observed compared with the case without Au decoration due to the decrease of series resistance. However, the high density of Au nanoparticles will decrease the shunt resistance between Si and SWNTs, which leads to the performance degradation of solar cell.

Li, Yongfeng; Kodama, Soichiro; Kaneko, Toshiro; Hatakeyama, Rikizo

2012-08-01

195

Receptor-mediated cell modulator delivery to hepatocyte using nanoparticles coated with carbohydrate-carrying polymers  

Microsoft Academic Search

Cell modulators such as colchicine (CO), cytochalasin B (CY) and taxol (TX) loaded nanoparticles coated with carbohydrate-carrying polymers, as hepatocyte-specific targeting material using galactose ligands as recognition signals to asialoglycoprotein receptors were prepared by the diafiltration method. Effects of cell modulators from their loaded nanoparticles on morphology of hepatocytes were studied. Receptor-mediated endocytosis of the nanoparticles were examined by fluorescence

Chong-Su Cho; Akira Kobayashi; Ryotaro Takei; Tsutomu Ishihara; Atsushi Maruyama; Toshihiro Akaike

2000-01-01

196

Morphological studies of living cells using gold nanoparticles and dark-field optical section microscopy  

Microsoft Academic Search

The morphologic changes of living cells under drug interactions were studied by using 80-nm gold nanoparticles and dark-field optical section microscopy. The gold nanoparticles were coated with poly (L-lysine), which attached to the membranes of various cells by way of electrostatic attractive force. A three-dimensional (3-D) morphological image was obtained by measuring the peak scattering intensities of gold nanoparticles at

Chia-Wei Lee; Miin Jang Chen; Ji-Yen Cheng; Pei-Kuen Wei

2009-01-01

197

Measuring and modelling cell-to-cell variation in uptake of gold nanoparticles.  

PubMed

The cell-to-cell variation of gold nanoparticle (GNP) uptake is important for therapeutic applications. We directly counted the GNPs in hundreds of individual cells, and showed that the large variation from cell-to-cell could be directly modelled by assuming log-normal distributions of both cell mass and GNP rate of uptake. This was true for GNPs non-specifically bound to fetal bovine serum or conjugated to a cell penetrating peptide. Within a population of cells, GNP content varied naturally by a factor greater than 10 between individual cells. PMID:24102065

Jeynes, J Charles G; Jeynes, Christopher; Merchant, Michael J; Kirkby, Karen J

2013-10-08

198

Enhanced penetration into 3D cell culture using two and three layered gold nanoparticles.  

PubMed

Nano-scale particles sized 10-400 nm administered systemically preferentially extravasate from tumor vasculature due to the enhanced permeability and retention effect. Therapeutic success remains elusive, however, because of inhomogeneous particle distribution within tumor tissue. Insufficient tumor vascularization limits particle transport and also results in avascular hypoxic regions with non-proliferating cells, which can regenerate tissue after nanoparticle-delivered cytotoxicity or thermal ablation. Nanoparticle surface modifications provide for increasing tumor targeting and uptake while decreasing immunogenicity and toxicity. Herein, we created novel two layer gold-nanoshell particles coated with alkanethiol and phosphatidylcholine, and three layer nanoshells additionally coated with high-density-lipoprotein. We hypothesize that these particles have enhanced penetration into 3-dimensional cell cultures modeling avascular tissue when compared to standard poly(ethylene glycol) (PEG)-coated nanoshells. Particle uptake and distribution in liver, lung, and pancreatic tumor cell cultures were evaluated using silver-enhancement staining and hyperspectral imaging with dark field microscopy. Two layer nanoshells exhibited significantly higher uptake compared to PEGylated nanoshells. This multilayer formulation may help overcome transport barriers presented by tumor vasculature, and could be further investigated in vivo as a platform for targeted cancer therapies. PMID:24124360

England, Christopher G; Priest, Thomas; Zhang, Guandong; Sun, Xinghua; Patel, Dhruvinkumar N; McNally, Lacey R; van Berkel, Victor; Gobin, André M; Frieboes, Hermann B

2013-10-01

199

Enhanced penetration into 3D cell culture using two and three layered gold nanoparticles  

PubMed Central

Nano-scale particles sized 10–400 nm administered systemically preferentially extravasate from tumor vasculature due to the enhanced permeability and retention effect. Therapeutic success remains elusive, however, because of inhomogeneous particle distribution within tumor tissue. Insufficient tumor vascularization limits particle transport and also results in avascular hypoxic regions with non-proliferating cells, which can regenerate tissue after nanoparticle-delivered cytotoxicity or thermal ablation. Nanoparticle surface modifications provide for increasing tumor targeting and uptake while decreasing immunogenicity and toxicity. Herein, we created novel two layer gold-nanoshell particles coated with alkanethiol and phosphatidylcholine, and three layer nanoshells additionally coated with high-density-lipoprotein. We hypothesize that these particles have enhanced penetration into 3-dimensional cell cultures modeling avascular tissue when compared to standard poly(ethylene glycol) (PEG)-coated nanoshells. Particle uptake and distribution in liver, lung, and pancreatic tumor cell cultures were evaluated using silver-enhancement staining and hyperspectral imaging with dark field microscopy. Two layer nanoshells exhibited significantly higher uptake compared to PEGylated nanoshells. This multilayer formulation may help overcome transport barriers presented by tumor vasculature, and could be further investigated in vivo as a platform for targeted cancer therapies.

England, Christopher G; Priest, Thomas; Zhang, Guandong; Sun, Xinghua; Patel, Dhruvinkumar N; McNally, Lacey R; van Berkel, Victor; Gobin, Andre M; Frieboes, Hermann B

2013-01-01

200

Transformed and Tumor-derived Human Cells Exhibit Preferential Sensitivity to the Thiol Antioxidants, N-Acetyl Cysteine and Penicillamine  

Microsoft Academic Search

Thiol antioxidants, typified by N-acetyl cysteine, are known to induce p53-dependent apoptosis in transformed mouse embryo fibroblasts but not in normal mouse embryo fibroblasts. We now report that this is also the case for human cells. First, we used an isogenic fibroblast cell lineage exhibiting progressive stages of transformation, from primary derived cells to v-MYC immortalized to tumorigenic. At the

Pamela A. Havre; Sandra O'Reilly; J. Justin McCormick; Douglas E. Brash

2002-01-01

201

Delivery of a transforming growth factor ?-1 plasmid to mesenchymal stem cells via cationized Pleurotus eryngii polysaccharide nanoparticles  

PubMed Central

The objective of this study was to investigate the use of cationized Pleurotus eryngii polysaccharide (CPEPS) as a nonviral gene delivery vehicle to transfer plasmid DNA encoding transforming growth factor beta-1 (pTGF-?1) into mesenchymal stem cells (MSCs) in vitro. Crude P. eryngii polysaccharide was purified, and then cationized by grafting spermine onto the backbone of the polysaccharide. Agarose gel electrophoresis, transmission electron microscopy, and a Nano Sense Zetasizer (Malvern Instruments, Malvern, UK) were used to characterize the CPEPS-pTGF-?1 nanoparticles. The findings of cytotoxicity analysis showed that when the nanoparticles were formulated with a CPEPS/pTGF-?1 weight ratio ? 10:1, a greater gel retardation effect was observed during agarose gel electrophoresis. The CPEPS-pTGF-?1 nanoparticles with a weight ratio of 20:1, respectively, possessed an average particle size of 80.8 nm in diameter and a zeta potential of +17.4 ± 0.1 mV. Significantly, these CPEPS-pTGF-?1 nanoparticles showed lower cytotoxicity and higher transfection efficiency than both polyethylenimine (25 kDa) (P = 0.006, Student’s t-test) and LipofectamineTM 2000 (P = 0.002, Student’s t-test). Additionally, the messenger RNA expression level of TGF-?1 in MSCs transfected with CPEPS-pTGF-?1 nanoparticles was significantly higher than that of free plasmid DNA-transfected MSCs and slightly elevated compared with that of Lipofectamine 2000-transfected MSCs. Flow cytometry analysis demonstrated that 92.38% of MSCs were arrested in the G1 phase after being transfected with CPEPS-pTGF-?1 nanoparticles, indicating a tendency toward differentiation. In summary, the findings of this study suggest that the CPEPS-pTGF-?1 nanoparticles prepared in this work exhibited excellent transfection efficiency and low toxicity. Therefore, they could be developed into a promising nonviral vector for gene delivery in vitro.

Deng, Wen Wen; Cao, Xia; Wang, Miao; Qu, Rui; Su, Wei Yan; Yang, Yan; Wei, Ya Wei; Xu, Xi Ming; Yu, Jiang Nan

2012-01-01

202

Optoacoustic imaging of gold nanoparticles targeted to breast cancer cells  

NASA Astrophysics Data System (ADS)

Optoacoustic Tomography (OAT) is a rapidly growing technology that enables noninvasive deep imaging of biological tissues based on their light absorption. In OAT, the interaction of a pulsed laser with tissue increases the temperature of the absorbing components in a confined volume of tissue. Rapid perturbation of the temperature (<1°C) deep within tissue produces weak acoustic waves that easily travel to the surface of the tissue with minor attenuation. Abnormal angiogenesis in a malignant tumor, that increases its blood content, makes a native contrast for optoacoustic imaging; however, the application of OAT for early detection of malignant tumors requires the enhancement of optoacoustic signals originated from tumor by using an exogenous contrast agent. Due to their strong absorption, we have used gold nanoparticles (NP) as a contrast agent. 40nm spherical gold nanoparticles were attached to monoclonal antibody to target cell surface of breast cancer cells. The targeted cancer cells were implanted at depth of 5-6cm within a gelatinous object that optically resembles human breast. Experimental sensitivity measurements along with theoretical analysis showed that our optoacoustic imaging system is capable of detecting a phantom breast tumor with the volume of 0.15ml, which is composed of 25 million NP-targeted cancer cells, at a depth of 5 centimeters in vitro.

Eghtedari, Mohammad; Motamedi, Massoud; Popov, Vsevolod L.; Kotov, Nicholas A.; Oraevsky, Alexander A.

2004-07-01

203

Multidentate zwitterionic chitosan oligosaccharide modified gold nanoparticles: stability, biocompatibility and cell interactions  

NASA Astrophysics Data System (ADS)

Surface engineering of nanoparticles plays an essential role in their colloidal stability, biocompatibility and interaction with biosystems. In this study, a novel multidentate zwitterionic biopolymer derivative is obtained from conjugating dithiolane lipoic acid and zwitterionic acryloyloxyethyl phosphorylcholine to the chitosan oligosaccharide backbone. Gold nanoparticles (AuNPs) modified by this polymer exhibit remarkable colloidal stabilities under extreme conditions including high salt conditions, wide pH range and serum or plasma containing media. The AuNPs also show strong resistance to competition from dithiothreitol (as high as 1.5 M). Moreover, the modified AuNPs demonstrate low cytotoxicity investigated by both MTT and LDH assays, and good hemocompatibility evaluated by hemolysis of human red blood cells. In addition, the intracellular fate of AuNPs was investigated by ICP-MS and TEM. It showed that the AuNPs are uptaken by cells in a concentration dependent manner, and they can escape from endosomes/lysosomes to cytosol and tend to accumulate around the nucleus after 24 h incubation but few of them are excreted out of the cells. Gold nanorods are also stabilized by this ligand, which demonstrates robust dispersion stability and excellent hemocompatibility. This kind of multidentate zwitterionic chitosan derivative could be widely used for stabilizing other inorganic nanoparticles, which will greatly improve their performance in a variety of bio-related applications.Surface engineering of nanoparticles plays an essential role in their colloidal stability, biocompatibility and interaction with biosystems. In this study, a novel multidentate zwitterionic biopolymer derivative is obtained from conjugating dithiolane lipoic acid and zwitterionic acryloyloxyethyl phosphorylcholine to the chitosan oligosaccharide backbone. Gold nanoparticles (AuNPs) modified by this polymer exhibit remarkable colloidal stabilities under extreme conditions including high salt conditions, wide pH range and serum or plasma containing media. The AuNPs also show strong resistance to competition from dithiothreitol (as high as 1.5 M). Moreover, the modified AuNPs demonstrate low cytotoxicity investigated by both MTT and LDH assays, and good hemocompatibility evaluated by hemolysis of human red blood cells. In addition, the intracellular fate of AuNPs was investigated by ICP-MS and TEM. It showed that the AuNPs are uptaken by cells in a concentration dependent manner, and they can escape from endosomes/lysosomes to cytosol and tend to accumulate around the nucleus after 24 h incubation but few of them are excreted out of the cells. Gold nanorods are also stabilized by this ligand, which demonstrates robust dispersion stability and excellent hemocompatibility. This kind of multidentate zwitterionic chitosan derivative could be widely used for stabilizing other inorganic nanoparticles, which will greatly improve their performance in a variety of bio-related applications. Electronic supplementary information (ESI) available: More experimental details for the synthesis of AuNPs and AuNRs. Fig. S1, 1H NMR spectrum of LA-CSO-PC and Fig. S2, FT-IR spectrum of AuNP-LA-CSO-PC. See DOI: 10.1039/c3nr00284e

Liu, Xiangsheng; Huang, Haoyuan; Liu, Gongyan; Zhou, Wenbo; Chen, Yangjun; Jin, Qiao; Ji, Jian

2013-04-01

204

Luminescent solar concentrators and all-inorganic nanoparticle solar cells for solar energy harvesting  

NASA Astrophysics Data System (ADS)

Increasing energy demand and the parallel increase of greenhouse gas emissions are challenging researchers to find new and cleaner energy sources. Solar energy harvesting is arguably the most promising candidate for replacing fossil-fuel power generation. Photovoltaics are the most direct way of collecting solar energy; cost continues to hinder large-scale implementation of photovoltaics, however. Therefore, alternative technologies that will allow the extraction of solar power, while maintaining the overall costs of fabrication, installation, collection, and distribution low, must be explored. This thesis focuses on the fabrication and testing of two types of devices that step up to this challenge: the luminescent solar concentrator (LSC) and all-inorganic nanoparticle solar cells. In these devices I make use of novel materials, semiconducting polymers and inorganic nanoparticles, both of which have lower costs than the crystalline materials used in the fabrication of traditional photovoltaics. Furthermore, the cost of manufacturing LSCs and the nanoparticle solar cells is lower than the manufacturing cost of traditional optics-based concentrators and crystalline solar cells. An LSC is essentially a slab of luminescent material that acts as a planar light pipe. The LSC absorbs incoming photons and channels fluoresced photons toward appropriately located solar cells, which perform the photovoltaic conversion. By covering large areas with relatively inexpensive fluorescing organic dyes or semiconducting polymers, the area of solar cell needed is greatly reduced. Because semiconducting polymers and quantum dots may have small absorption/emission band overlaps, tunable absorption, and longer lifetimes, they are good candidates for LSC fabrication, promising improvement with respect to laser dyes traditionally used to fabricate LSCs. Here the efficiency of LSCs consisting of liquid solutions of semiconducting polymers encased in glass was measured and compared to the efficiency of LSCs based on small molecule laser dyes and on quantum dots. Factors affecting the optical efficiency of the system such as the luminescing properties of the fluorophors were examined. The experimental results were compared to Monte-Carlo simulations. Our results suggest that commercially available quantum dots cannot serve as viable LSC dyes because of large absorption/emission band overlap and relatively low quantum yield. Materials such as Red F demonstrate that semi-conducting polymers with high quantum yield and small absorption/emission band overlap are good candidates for LSCs. Recently, a solar cell system based purely on CdSe and Cite nanoparticles as the absorbing materials was proposed ans it was suggested that its operational mechanism was that of polymer donor/acceptor systems. Here we present solar cells consisting of a sintered active bilayer of CdSe and PbSe nanoparticles in the structure ITO/CdSe/interlayer/PbSe/Al, where an interlayer of LiF or Al2O3 was found necessary to prevent low shunt resistance from suppressing the photovoltaic behavior. We fabricated unoptimized solar cells with a short-circuit current of 6 mA/cm2, an open-circuit voltage of 0.18 V, and a fill factor of 41%. External quantum efficiency spectra revealed that photons from the infrared portion of the spectrum were not collected, suggesting that the low bandgap PbSe film did not contribute to the photocurrent of the structure despite exhibiting photoconductivity. Other measurements, however, showed that the PbSe film was indeed necessary to produce a photovoltage and transport electrons. Through sintering, the nanoparticle films acquired bandgaps similar to those of the corresponding bulk materials and became more conductive. Because the PbSe films were found to be considerably more conductive than the CdSe ones, we suggest that the PbSe layer is effectively behaving like a low conductivity electrical contact. Therefore, in contrast to the photovoltaics presented in the seminal research on CdSe/Cite solar cells, the CdSe/PbSe solar cell system presented here d

Sholin, Veronica

205

Proper design of silica nanoparticles combines high brightness, lack of cytotoxicity and efficient cell endocytosis.  

PubMed

Silica-based luminescent nanoparticles (SiNPs) show promising prospects in nanomedicine in light of their chemical properties and versatility. In this study, we have characterized silica core-PEG shell SiNPs derivatized with PEG moieties (NP-PEG), with external amino- (NP-PEG-amino) or carboxy-groups (NP-PEG-carbo), both in cell cultures as well as in animal models. By using different techniques, we could demonstrate that these SiNPs were safe and did not exhibit appreciable cytotoxicity in different relevant cell models, of normal or cancer cell types, growing either in suspension (JVM-2 leukemic cell line and primary normal peripheral blood mononuclear cells) or in adherence (human hepatocarcinoma Huh7 and umbilical vein endothelial cells). Moreover, by multiparametric flow cytometry, we could demonstrate that the highest efficiency of cell uptake and entry was observed with NP-PEG-amino, with a stable persistence of the fluorescence signal associated with SiNPs in the loaded cell populations both in vitro and in vivo settings suggesting this as an innovative method for cell traceability and detection in whole organisms. Finally, experiments performed with the endocytosis inhibitor Genistein clearly suggested the involvement of a caveolae-mediated pathway in SiNP endocytosis. Overall, these data support the safe use of these SiNPs for diagnostic and therapeutic applications. PMID:23851463

Rampazzo, Enrico; Voltan, Rebecca; Petrizza, Luca; Zaccheroni, Nelsi; Prodi, Luca; Casciano, Fabio; Zauli, Giorgio; Secchiero, Paola

2013-09-01

206

Ultrafine titanium dioxide nanoparticles induce cell death in human bronchial epithelial cells  

Microsoft Academic Search

Titanium dioxide (TiO2) nanoparticles (TNPs), once perceived as harmless, have been shown to induce cytotoxicity on various cell types under UV radiation. However, whether TNPs elicit cell death in the absence of UV has not been thoroughly studied. This study aims to investigate the TNPs-induced cell death mechanism in UV-absent condition by examining the reduction of cell viability and apoptotic

Eric Chen; Miguel Ruvalcaba; Lindsey Araujo; Ryan Chapman; Wei-Chun Chin

2008-01-01

207

Human Natural Killer Cells Exhibit Direct Activity Against Aspergillus fumigatus Hyphae, But Not Against Resting Conidia  

PubMed Central

Because natural killer (NK) cells kill tumor cells and combat infections, there is growing interest in adoptively transferring NK cells to hematopoietic stem cell recipients. Unfortunately, in humans, the activity of NK cells against Aspergillus species, the major cause of invasive fungal infection in stem cell recipients, are poorly characterized. Our results show that unstimulated and interleukin-2 prestimulated human NK cells kill Aspergillus fumigatus hyphae but do not affect resting conidia. Killing is also induced by the supernatant of prestimulated NK cells and human perforin. The high levels of interferon-? and granulocyte macrophage colony-stimulating factor produced by prestimulated NK cells are significantly reduced by Aspergillus, indicating an immunosuppressive effect of the fungus. Whereas Aspergillus hyphae activate NK cells, resting, and germinating, conidia and conidia of ?rodA mutants lacking the hydrophobic surface layer do not. Our results suggest that adoptively transferred human NK cells may be a potential antifungal tool in the transplantation context.

Schmidt, Stanislaw; Tramsen, Lars; Hanisch, Mitra; Latge, Jean-Paul; Huenecke, Sabine; Koehl, Ulrike

2011-01-01

208

Comparison of intracellular accumulation and cytotoxicity of free mTHPC and mTHPC-loaded PLGA nanoparticles in human colon carcinoma cells  

NASA Astrophysics Data System (ADS)

The second generation photosensitizer mTHPC was approved by the European Medicines Agency (EMA) for the palliative treatment of advanced head and neck cancer in October 2001. It is known that mTHPC possesses a significant phototoxicity against a variety of human cancer cells in vitro but also exhibits dark toxicity and can cause adverse effects (especially skin photosensitization). Due to its poor water solubility, the administration of hydrophobic photosensitizer still presents several difficulties. To overcome the administration problems, the use of nanoparticles as drug carrier systems is much investigated. Nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) have been extensively studied as delivery systems into tumours due to their biocompatibility and biodegradability. The goal of this study was the comparison of free mTHPC and mTHPC-loaded PLGA nanoparticles concerning cytotoxicity and intracellular accumulation in human colon carcinoma cells (HT29). The nanoparticles delivered the photosensitizer to the colon carcinoma cells and enabled drug release without losing its activity. The cytotoxicity assays showed a time- and concentration-dependent decrease in cell proliferation and viability after illumination. However, first and foremost mTHPC lost its dark toxic effects using the PLGA nanoparticles as a drug carrier system. Therefore, PLGA nanoparticles are a promising drug carrier system for the hydrophobic photosensitizer mTHPC.

Löw, Karin; Knobloch, Thomas; Wagner, Sylvia; Wiehe, Arno; Engel, Andrea; Langer, Klaus; von Briesen, Hagen

2011-06-01

209

Casein-coated iron oxide nanoparticles for high MRI contrast enhancement and efficient cell targeting.  

PubMed

Surface properties, as well as inherent physicochemical properties, of the engineered nanomaterials play important roles in their interactions with the biological systems, which eventually affect their efficiency in diagnostic and therapeutic applications. Here we report a new class of MRI contrast agent based on milk casein protein-coated iron oxide nanoparticles (CNIOs) with a core size of 15 nm and hydrodynamic diameter ~30 nm. These CNIOs exhibited excellent water-solubility, colloidal stability, and biocompatibility. Importantly, CNIOs exhibited prominent T2 enhancing capability with a transverse relaxivity r2 of 273 mM(-1) s(-1) at 3 tesla. The transverse relaxivity is ~2.5-fold higher than that of iron oxide nanoparticles with the same core but an amphiphilic polymer coating. CNIOs showed pH-responsive properties, formed loose and soluble aggregates near the pI (pH ~4.0). The aggregates could be dissociated reversibly when the solution pH was adjusted away from the pI. The transverse relaxation property and MRI contrast enhancing effect of CNIOs remained unchanged in the pH range of 2.0-8.0. Further functionalization of CNIOs can be achieved via surface modification of the protein coating. Bioaffinitive ligands, such as a single chain fragment from the antibody of epidermal growth factor receptor (ScFvEGFR), could be readily conjugated onto the protein coating, enabling specific targeting to MDA-MB-231 breast cancer cells overexpressing EGFR. T2-weighted MRI of mice intravenously administered with CNIOs demonstrated strong contrast enhancement in the liver and spleen. These favorable properties suggest CNIOs as a class of biomarker targeted magnetic nanoparticles for MRI contrast enhancement and related biomedical applications. PMID:23633522

Huang, Jing; Wang, Liya; Lin, Run; Wang, Andrew Y; Yang, Lily; Kuang, Min; Qian, Weiping; Mao, Hui

2013-05-14

210

EGFR-Targeted Hybrid Plasmonic Magnetic Nanoparticles Synergistically Induce Autophagy and Apoptosis in Non-Small Cell Lung Cancer Cells  

PubMed Central

Background The epidermal growth factor receptor (EGFR) is overexpressed in 80% of non-small cell lung cancer (NSCLC) and is associated with poor survival. In recent years, EGFR-targeted inhibitors have been tested in the clinic for NSCLC. Despite the emergence of novel therapeutics and their application in cancer therapy, the overall survival rate of lung cancer patients remains 15%. To develop more effective therapies for lung cancer we have combined the anti-EGFR antibody (Clone 225) as a molecular therapeutic with hybrid plasmonic magnetic nanoparticles (NP) and tested on non-small cell lung cancer (NSCLC) cells. Methodology/Principal Findings Cell viability was determined by trypan-blue assay. Cellular protein expression was determined by Western blotting. C225-NPs were detected by electron microscopy and confocal microscopy, and EGFR expression using immunocytochemistry. C225-NP exhibited a strong and selective antitumor effect on EGFR-expressing NSCLC cells by inhibiting EGFR-mediated signal transduction and induced autophagy and apoptosis in tumor cells. Optical images showed specificity of interactions between C225-NP and EGFR-expressing NSCLC cells. No binding of C225-NP was observed for EGFR-null NSCLC cells. C225-NP exhibited higher efficiency in induction of cell killing in comparison with the same amount of free C225 antibody in tumor cells with different levels of EGFR expression. Furthermore, in contrast to C225-NP, free C225 antibody did not induce autophagy in cells. However, the therapeutic efficacy of C225-NP gradually approached the level of free antibodies as the amount of C225 antibody conjugated per nanoparticle was decreased. Finally, attaching C225 to NP was important for producing the enhanced tumor cell killing as addition of mixture of free C225 and NP did not demonstrate the same degree of cell killing activity. Conclusions/Significance We demonstrated for the first time the molecular mechanism of C225-NP induced cytotoxic effects in lung cancer cells that are not characteristic for free molecular therapeutics thus increasing efficacy of therapy against NSCLC.

Kuroda, Shinji; Scott, Ailing W.; Aaron, Jesse; Larson, Tim; Shanker, Manish; Correa, Arlene M.; Kondo, Seiji; Roth, Jack A.; Sokolov, Konstantin; Ramesh, Rajagopal

2011-01-01

211

Toxicity of Tungsten Carbide and Cobalt-Doped Tungsten Carbide Nanoparticles in Mammalian Cells in Vitro  

PubMed Central

Background Tungsten carbide nanoparticles are being explored for their use in the manufacture of hard metals. To develop nanoparticles for broad applications, potential risks to human health and the environment should be evaluated and taken into consideration. Objective We aimed to assess the toxicity of well-characterized tungsten carbide (WC) and cobaltdoped tungsten carbide (WC-Co) nanoparticle suspensions in an array of mammalian cells. Methods We examined acute toxicity of WC and of WC-Co (10% weight content Co) nanoparticles in different human cell lines (lung, skin, and colon) as well as in rat neuronal and glial cells (i.e., primary neuronal and astroglial cultures and the oligodendro cyte precursor cell line OLN-93). Furthermore, using electron microscopy, we assessed whether nanoparticles can be taken up by living cells. We chose these in vitro systems in order to evaluate for potential toxicity of the nanoparticles in different mammalian organs (i.e., lung, skin, intestine, and brain). Results Chemical–physical characterization confirmed that WC as well as WC-Co nanoparticles with a mean particle size of 145 nm form stable suspensions in serum-containing cell culture media. WC nanoparticles were not acutely toxic to the studied cell lines. However, cytotoxicity became apparent when particles were doped with Co. The most sensitive were astrocytes and colon epithelial cells. Cytotoxicity of WC-Co nanoparticles was higher than expected based on the ionic Co content of the particles. Analysis by electron microscopy demonstrated presence of WC nanoparticles within mammalian cells. Conclusions Our findings demonstrate that doping of WC nanoparticles with Co markedly increases their cytotoxic effect and that the presence of WC-Co in particulate form is essential to elicit this combinatorial effect.

Bastian, Susanne; Busch, Wibke; Kuhnel, Dana; Springer, Armin; Meissner, Tobias; Holke, Roland; Scholz, Stefan; Iwe, Maria; Pompe, Wolfgang; Gelinsky, Michael; Potthoff, Annegret; Richter, Volkmar; Ikonomidou, Chrysanthy; Schirmer, Kristin

2009-01-01

212

Fabrication of curcumin encapsulated PLGA nanoparticles for improved therapeutic effects in metastatic cancer cells.  

PubMed

Curcumin, a natural polyphenolic compound, has shown promising chemopreventive and chemotherapeutic activities in cancer. Although phase I clinical trials have shown curcumin as a safe drug even at high doses, poor bioavailability and suboptimal pharmacokinetics largely moderated its anti-cancer activity in pre-clinical and clinical models. To improve its applicability in cancer therapy, we encapsulated curcumin in poly(lactic-co-glycolide) (PLGA) (biodegradable polymer) nanoparticles, in the presence of poly(vinyl alcohol) and poly(L-lysine) stabilizers, using a nano-precipitation technique. These curcumin nano-formulations were characterized for particle size, zeta potential, drug encapsulation, drug compatibility and drug release. Encapsulated curcumin existed in a highly dispersed state in the PLGA core of the nanoparticles and exhibited good solid-solid compatibility. An optimized curcumin nano-formulation (nano-CUR6) has demonstrated two and sixfold increases in the cellular uptake performed in cisplatin resistant A2780CP ovarian and metastatic MDA-MB-231 breast cancer cells, respectively, compared to free curcumin. In these cells, nano-CUR6 has shown an improved anti-cancer potential in cell proliferation and clonogenic assays compared to free curcumin. This effect was correlated with enhanced apoptosis induced by the nano-CUR6 formulation. Herein, we have also shown antibody conjugation compatibility of our PLGA-NP formulation. Results of this study suggest that therapeutic efficacy of curcumin may be enhanced by such PLGA nanoparticle formulations, and furthermore tumor specific targeted delivery of curcumin is made feasible by coupling of anti-cancer antibody to the NPs. PMID:20627257

Yallapu, Murali Mohan; Gupta, Brij K; Jaggi, Meena; Chauhan, Subhash C

2010-05-12

213

Novel lines of Pax6-\\/- embryonic stem cells exhibit reduced neurogenic capacity without loss of viability  

Microsoft Academic Search

BACKGROUND: Embryonic stem (ES) cells can differentiate into all cell types and have been used extensively to study factors affecting neuronal differentiation. ES cells containing mutations in known genes have the potential to provide useful in vitro models for the study of gene function during neuronal differentiation. Recently, mouse ES cell lines lacking the neurogenic transcription factor Pax6 were reported;

Jane C Quinn; Michael Molinek; Tomasz J Nowakowski; John O Mason; David J Price

2010-01-01

214

An amphiphilic-like fluoroalkyl modified SiO2 nanoparticle@Nafion proton exchange membrane with excellent fuel cell performance.  

PubMed

A new route to enhance the cell performance of a Nafion proton exchange membrane is provided by incorporating fluoroalkyl modified SiO2 nanoparticles. In favor of the achieved amphiphilic-like surface characteristics of SiO2 nanoparticles, the so-formed nanocomposite membrane exhibited great enhancement of single cell performance at 80 °C: ?34% increase in output power relative to the Nafion reference and a superior maximum output power as high as 579.6 mW cm(-2). PMID:24022594

Yuan, Du; Liu, Zhaolin; Tay, Siok Wei; Fan, Xiaoshan; Zhang, Xiwen; He, Chaobin

2013-09-24

215

Incidental MALT Type Lymphoma Exhibiting Prominent Plasma Cell Differentiation Associated with Hashimoto's Thyroiditis. A Two Case Report  

PubMed Central

We present here two cases of incidental extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) showing prominent plasma cell differentiation associated with Hashimoto’s thyroiditis (HT). Histological examination demonstrated that both lesions exhibited HT including lymphoplasmacytic infiltration with the formation of germinal centers, destruction of the normal thyroid follicular architecture, Hürthle cell changes, and squamous metaplasia. The dominant tumor nodules of both cases contained large, well-circumscribed but unencapsulated aggregation of mature plasma cells and scattered centrocyte-like cells (CCL-cells). Both lesions contained a few lymphoepithelial lesions. Moreover, immunohistochemical study demonstrated that plasma cells and CCL-cells of these two lesions contained monotypic intracytoplasmic kappa light chain. Other small B-cell lymphomas, plasmacytoma and plasmablastic lymphoma were excluded using stains for CD5, CD10, CD23, CD43, CD56. Cyclin D1, human herpes virus type-8.

Shimizu, Ken; Shimizu, Kazuhiko; Masawa, Nobuhide

2008-01-01

216

Microbubbles-overlapping mode for laser killing of cancer cells with absorbing nanoparticle clusters  

Microsoft Academic Search

Laser-induced bubble formation around nanoparticles may play a crucial role in selective laser nanophotothermolysis of cancer cells targeted with nanoparticles. In this paper, we propose theoretically, and confirm experimentally, a new dynamic mode for selective cancer treatment that involves the overlapping of bubbles inside the cell volume. This bubbles-overlapping mode (BOM) can dramatically increase the efficiency of cancer treatment by

V P Zharov; R R Letfullin; E N Galitovskaya

2005-01-01

217

Enhanced charge separation in chlorophyll a solar cell by gold nanoparticles  

Microsoft Academic Search

An efficient organic photoelectrochemical cell based on chlorophyll a (Chla) and gold nanoparticles is constructed. The enhanced performance of this cell is due to the beneficial role of gold nanoparticles in accepting and shuttling the photogenerated electrons in Chla to the collecting electrode. This produces a long-distance charge-separated state, resulting into an enhancement in charge separation efficiency.

Saïd Barazzouk; Surat Hotchandani

2004-01-01

218

Carbon black nanoparticles induce type II epithelial cells to release chemotaxins for alveolar macrophages  

Microsoft Academic Search

BACKGROUND: Alveolar macrophages are a key cell in dealing with particles deposited in the lungs and in determining the subsequent response to that particle exposure. Nanoparticles are considered a potential threat to the lungs and the mechanism of pulmonary response to nanoparticles is currently under intense scrutiny. The type II alveolar epithelial cell has previously been shown to release chemoattractants

Peter G Barlow; Anna Clouter-Baker; Ken Donaldson; Janis MacCallum; Vicki Stone

2005-01-01

219

Investigation on Zinc Sulphide Nanoparticles in Dye Sensitized Solar Cell  

NASA Astrophysics Data System (ADS)

Nanoparticles of zinc sulphide in cubic sphalerite phase are synthesized by aqueous chemical method. UV-Vis absorption spectrum of nano ZnS is blue shifted from the bulk by 50 nm and methyl blue sensitized nano ZnS shows a strong visible absorption at 600 nm. PL spectrum of methyl blue sensitized ZnS shows two broad emission at 402 nm and 510 nm which are compared with earlier investigations and discussed. The solar conversion efficiency (?) of this dye sensitized solar cell (DSSC) was found to have enhanced due to charge transfer from dye molecules.

Ragam, M.; Sankar, N.; Ramachandran, K.

2011-07-01

220

Engineering of Targeted Nanoparticles for Cancer Therapy Using Internalizing Aptamers Isolated by Cell-Uptake Selection  

PubMed Central

One of the major challenges in the development of targeted nanoparticles (NPs) for cancer therapy is to discover targeting ligands that allow for differential binding and uptake by the target cancer cells. Using prostate cancer (PCa) as a model disease, we developed a cell-uptake selection strategy to isolate PCa-specific internalizing 2'-Omethyl RNA aptamers (Apts) for NP incorporation. Twelve cycles of selection and counter-selection were done to obtain a panel of internalizing Apts, which can distinguish PCa cells from non-prostate and normal prostate cells. After Apt characterization, size minimization, and conjugation of the Apts with fluorescently-labeled polymeric NPs, the NP-Apt bioconjugates exhibit PCa specificity and enhancement in cellular uptake when compared to non-targeted NPs lacking the internalizing Apts. Furthermore, when docetaxel, a chemotherapeutic agent used for the treatment of PCa, was encapsulated within the NP-Apt, a significant improvement in cytotoxicity was achieved in targeted PCa cells. Rather than isolating high-affinity Apts as reported in previous selection processes, our selection strategy was designed to enrich cancer-cell specific internalizing Apts. A similar cell-uptake selection strategy may be used to develop specific internalizing ligands for a myriad of other diseases and can potentially facilitate delivering various molecules, including drugs and siRNAs, into cells.

Xiao, Zeyu; Levy-Nissenbaum, Etgar; Alexis, Frank; Luptak, Andrej; Teply, Benjamin A.; Chan, Juliana M.; Shi, Jinjun; Digga, Elise; Cheng, Judy; Langer, Robert; Farokhzad, Omid C.

2012-01-01

221

Multipositional silica-coated silver nanoparticles for high-performance polymer solar cells.  

PubMed

We demonstrate high-performance polymer solar cells using the plasmonic effect of multipositional silica-coated silver nanoparticles. The location of the nanoparticles is critical for increasing light absorption and scattering via enhanced electric field distribution. The device incorporating nanoparticles between the hole transport layer and the active layer achieves a power conversion efficiency of 8.92% with an external quantum efficiency of 81.5%. These device efficiencies are the highest values reported to date for plasmonic polymer solar cells using metal nanoparticles. PMID:23611150

Choi, Hyosung; Lee, Jung-Pil; Ko, Seo-Jin; Jung, Jae-Woo; Park, Hyungmin; Yoo, Seungmin; Park, Okji; Jeong, Jong-Ryul; Park, Soojin; Kim, Jin Young

2013-04-23

222

Scaffold-independent Patterning of Cells using Magnetic Nanoparticles  

NASA Astrophysics Data System (ADS)

Spatial patterning of cells in vitro relies on direct contact of cells on to solid surfaces. Scaffold independent patterning of cells has never been achieved so far. Patterning of cells has wide applications including stem cell biology, tissue architecture and regenerative medicine besides fundamental biology. Magnetized cells in a suspension can be manipulated using an externally applied magnetic field enabling directed patterning. We magnetized mammalian cells by internalization of superparamagnetic nanoparticles coated with bovine serum albumin (BSA). A magnetic field is then used to arrange cells in a desired pattern on a substrate or in suspension. The control strategy is derived from the self-assembly of magnetic colloids in a liquid considering magnetostatic interactions. The range of achievable structural features promise novel experimental methods investigating the influence of tissue shape and size on cell population dynamics wherein Fickian diffusion of autocrine growth signals are known to play a significant role. By eliminating the need for a scaffold, intercellular adhesion mechanics and the effects of temporally regulated signals can be investigated. The findings can be applied to novel tissue engineering methods.

Ghosh, Suvojit; Biswas, Moanaro; Elankumaran, Subbiah; Puri, Ishwar

2013-03-01

223

CD58 and CD59 molecules exhibit potentializing effects in T cell adhesion and activation.  

PubMed

We have generated stable Chinese hamster ovary (CHO) cell transfectants expressing either CD58 or CD59 or both molecules to compare their respective parts played in T cell adhesion and activation. Using a rosetting assay, we have shown the following: 1) The CD59 molecule was directly responsible for adhesive interaction between human T cells and CD59+ CHO transfectants. CD59-mediated adhesion induced 12 +/- 2% (mean +/- SEM, n = 25) of rosettes. 2) The CD58 molecule expressed on CD58+ CHO transfectants induced 29 +/- 6% (mean +/- SEM, n = 8) of rosettes. 3) Double transfected CD58+CD59+ CHO cells formed up to 80% of rosettes, largely exceeding the sum of rosettes formed by single transfectants, thus disclosing at least an additive and possibly a synergic action of both molecules in mediating adhesion to T cells. Culturing purified human T cells in the presence of fixed CHO transfectants and submitogenic doses of PHA + rIL-1 alpha showed that: 1) CD59+ CHO transfectants induced sevenfold T cell proliferation enhancement, demonstrating the direct involvement of the CD59 molecule in T cell activation; 2) CD58+ CHO transfectants induced 20-fold T cell proliferation increase; and 3) the enhancement induced by CD58+CD59+ CHO cells was more than 40-fold. These results suggest that CD58 and CD59 molecules present on the surface of accessory cells might exert synergic function in T cell adhesive interactions and in the stimulation of T cell activation. PMID:1370512

Deckert, M; Kubar, J; Bernard, A

1992-02-01

224

Embryonic germ cells from mice and rats exhibit properties consistent with a generic pluripotent ground state.  

PubMed

Mouse and rat embryonic stem cells can be sustained in defined medium by dual inhibition (2i) of the mitogen-activated protein kinase (Erk1/2) cascade and of glycogen synthase kinase 3. The inhibitors suppress differentiation and enable self-renewal of pluripotent cells that are ex vivo counterparts of naïve epiblast cells in the mature blastocyst. Pluripotent stem cell lines can also be derived from unipotent primordial germ cells via a poorly understood process of epigenetic reprogramming. These are termed embryonic germ (EG) cells to denote their distinct origin. Here we investigate whether EG cell self-renewal and derivation are supported by 2i. We report that mouse EG cells can be established with high efficiency using 2i in combination with the cytokine leukaemia inhibitory factor (LIF). Furthermore, addition of fibroblast growth factor or stem cell factor is unnecessary using 2i-LIF. The derived EG cells contribute extensively to healthy chimaeric mice, including to the germline. Using the same conditions, we describe the first derivations of EG cells from the rat. Rat EG cells express a similar marker profile to rat and mouse ES cells. They have a diploid karyotype, can be clonally expanded and genetically manipulated, and are competent for multilineage colonisation of chimaeras. These findings lend support to the postulate of a conserved molecular ground state in pluripotent rodent cells. Future research will determine the extent to which this is maintained in other mammals and whether, in some species, primordial germ cells might be a more tractable source than epiblast for the capture of naïve pluripotent stem cells. PMID:20519324

Leitch, Harry G; Blair, Kate; Mansfield, William; Ayetey, Harold; Humphreys, Peter; Nichols, Jennifer; Surani, M Azim; Smith, Austin

2010-06-02

225

Rationally engineered nanoparticles target multiple myeloma cells, overcome cell-adhesion-mediated drug resistance, and show enhanced efficacy in vivo.  

PubMed

In the continuing search for effective cancer treatments, we report the rational engineering of a multifunctional nanoparticle that combines traditional chemotherapy with cell targeting and anti-adhesion functionalities. Very late antigen-4 (VLA-4) mediated adhesion of multiple myeloma (MM) cells to bone marrow stroma confers MM cells with cell-adhesion-mediated drug resistance (CAM-DR). In our design, we used micellar nanoparticles as dynamic self-assembling scaffolds to present VLA-4-antagonist peptides and doxorubicin (Dox) conjugates, simultaneously, to selectively target MM cells and to overcome CAM-DR. Dox was conjugated to the nanoparticles through an acid-sensitive hydrazone bond. VLA-4-antagonist peptides were conjugated via a multifaceted synthetic procedure for generating precisely controlled number of targeting functionalities. The nanoparticles were efficiently internalized by MM cells and induced cytotoxicity. Mechanistic studies revealed that nanoparticles induced DNA double-strand breaks and apoptosis in MM cells. Importantly, multifunctional nanoparticles overcame CAM-DR, and were more efficacious than Dox when MM cells were cultured on fibronectin-coated plates. Finally, in a MM xenograft model, nanoparticles preferentially homed to MM tumors with ?10 fold more drug accumulation and demonstrated dramatic tumor growth inhibition with a reduced overall systemic toxicity. Altogether, we demonstrate the disease driven engineering of a nanoparticle-based drug delivery system, enabling the model of an integrative approach in the treatment of MM. PMID:22829966

Kiziltepe, T; Ashley, J D; Stefanick, J F; Qi, Y M; Alves, N J; Handlogten, M W; Suckow, M A; Navari, R M; Bilgicer, B

2012-04-20

226

Hodgkin's lymphoma associated T-cells exhibit a transcription factor profile consistent with distinct lymphoid compartments  

PubMed Central

Background Hodgkin's lymphoma (HL) is characterised by an ineffective immune response that is predominantly mediated by CD4+ T?cells. Aims To analyse the expression of the key regulatory T?cell transcription factors (TFs) in the T?cells of HL involved tissues in order to assess the nature of the TH immune response in HL. Methods and results By immunohistochemistry, GATA3 was strongly and T?bet exclusively expressed in a subset of interfollicular lymphocytes in the reactive lymphoid tissues. In classical HL (CHL), which is generally located in the interfollicular zones, a predominance of T?bet+ T?cells and lesser amounts of GATA3+ and c?Maf+ T?cells was found, concordant with the pattern of the normal interfollicular compartment. In reactive lymphoid tissues, c?Maf was observed mostly in T?lymphocytes within the germinal centres (GCs). Nodular lymphocyte predominance type of Hodgkin's lymphoma (NLPHL) and progressively transformed germinal centres cases, showed a majority of c?Maf+ T?cells, consistent with the pattern in normal GCs. NLPHL cases uniformly showed c?Maf+/CD57+ T?cell rosettes around the neoplastic cells; these rosettes were absent in “paragranuloma?type” T?cell/histiocyte rich B?cell lymphoma. Conclusions T?cell TF expression profiles of the reactive T?cells in both subtypes of HL are in accordance with the expression profile observed in the distinct lymphoid compartments.

Atayar, Cigdem; van den Berg, Anke; Blokzijl, Tjasso; Boot, Marcel; Gascoyne, Randy D; Visser, Lydia; Poppema, Sibrand

2007-01-01

227

Phytotoxic hazards of NiO-nanoparticles in tomato: a study on mechanism of cell death.  

PubMed

Nickel oxide nanoparticles (NiO-NPs) in the concentration range of 0.025-2.0mg/ml were examined for the induction of oxidative stress, mitochondrial dysfunction, apoptosis/necrosis in tomato seedling roots, as an in vivo model for nanotoxicity assessment in plants. Compared to the control, catalase (CAT), glutathione (GSH), superoxide dismutase (SOD) and lipid peroxidation (LPO) in 2.0mg/ml NiO-NPs treatments exhibited 6.8, 3.7, 1.7 and 2.6-fold higher activities of antioxidative enzymes. At 2.0mg/ml, 122% and 125.4% increase in intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (??m) of seedling roots confirmed the oxidative stress and mitochondrial dysfunction. Comet assay exhibited a significant increase in the number of apoptotic (21.8%) and necrotic (24.0%) cells in 2.0mg/ml treatment groups vis-á-vis in control 7% apoptotic and 9.6% of necrotic cells were observed. Flow cytometric analysis revealed 65.7% of apoptotic/necrotic cell populations and 2.14-fold higher caspase-3 like protease activity were recorded in 2.0mg/ml treatment groups. Ultrastructure analysis revealed NiO-NPs translocation, nuclear condensation, abundance in peroxisomes and degenerated mitochondrial cristae. The dissolution of Ni ions from NiO-NPs signifies its potential to induce cell death presumably by Ni ions, triggering the mitochondrial dependent intrinsic apoptotic pathway. PMID:23474406

Faisal, Mohammad; Saquib, Quaiser; Alatar, Abdulrahman A; Al-Khedhairy, Abdulaziz A; Hegazy, Ahmad K; Musarrat, Javed

2013-02-13

228

Specific biomolecule corona is associated with ring-shaped organization of silver nanoparticles in cells  

NASA Astrophysics Data System (ADS)

We correlate the localization of silver nanoparticles inside cells with respect to the cellular architecture with the molecular information in the vicinity of the particle surface by combining nanoscale 3D cryo-soft X-ray tomography (cryo-SXT) with surface-enhanced Raman scattering (SERS). The interaction of the silver nanoparticle surface with small molecules and biopolymers was monitored by SERS in vitro over time in living cells. The spectra indicate a stable, time-independent surface composition of silver nanoparticles, despite the changing environment in the endosomal structure. Cryo-SXT reveals a characteristic ring-shaped organization of the silver nanoparticles in endosomes of different cell types. The ring-like structures inside the endosomes suggest a strong association among silver particles and with membrane structures. The comparison of the data with those obtained with gold nanoparticles suggests that the interactions between the nanoparticles and with the endosomal component are influenced by the molecular composition of the corona.We correlate the localization of silver nanoparticles inside cells with respect to the cellular architecture with the molecular information in the vicinity of the particle surface by combining nanoscale 3D cryo-soft X-ray tomography (cryo-SXT) with surface-enhanced Raman scattering (SERS). The interaction of the silver nanoparticle surface with small molecules and biopolymers was monitored by SERS in vitro over time in living cells. The spectra indicate a stable, time-independent surface composition of silver nanoparticles, despite the changing environment in the endosomal structure. Cryo-SXT reveals a characteristic ring-shaped organization of the silver nanoparticles in endosomes of different cell types. The ring-like structures inside the endosomes suggest a strong association among silver particles and with membrane structures. The comparison of the data with those obtained with gold nanoparticles suggests that the interactions between the nanoparticles and with the endosomal component are influenced by the molecular composition of the corona. Electronic supplementary information (ESI) available: Description of additional experiments. Explanation of transmitted intensity and linear absorption coefficient in a cryo-XRT experiment (Fig. S1 and S2). Additional X-ray data (Fig. S3 and Movie S1). Toxicity of silver nanoparticles (Fig. S4). X-ray microscopy and SERS experiments with gold nanoparticles (Fig. S5 and S6). Size, plasmonic properties, and stability of silver and gold nanoparticles (Fig. S7-S9). Distribution of the silver nanoparticles in the cells using SERS mapping (Fig. S10). Tentative band assignments (Table S1). See DOI: 10.1039/c3nr02129g

Drescher, Daniela; Guttmann, Peter; Büchner, Tina; Werner, Stephan; Laube, Gregor; Hornemann, Andrea; Tarek, Basel; Schneider, Gerd; Kneipp, Janina

2013-09-01

229

Apoptosis induced by tungsten carbide-cobalt nanoparticles in JB6 cells involves ROS generation through both extrinsic and intrinsic apoptosis pathways.  

PubMed

In this study, apoptosis and related signaling induced by WC-Co nanoparticles were investigated in JB6 cells and rat lung macrophages. Electron spin resonance (ESR) and fluorescent staining indicated that both WC-Co nanoparticles and fine particles stimulated reactive oxygen species (ROS) generation. Catalase exhibited an inhibitory effect on WC-Co nanoparticle-induced ROS as well as mitochondrial membrane permeability damage. Further study indicated that WC-Co nanoparticles elicited higher cytotoxicity and apoptotic induction than fine particles. Western blot analysis showed activation of proapoptotic factors including Fas, Fas-associated protein with death domain (FADD), caspase 3, 8 and 9, BID and BAX. In addition, both cytochrome c and apoptosis-inducing factor (AIF) were upregulated and released from mitochondria to the cytoplasm. Our findings demonstrate that, on a mass basis, WC-Co nanoparticles exhibit higher cytotoxicity and apoptotic induction than fine particles. Apoptosis induced by WC-Co nanoparticles and fine particles involves both extrinsic and intrinsic apoptosis pathways. PMID:23417053

Zhao, Jinshun; Bowman, Linda; Magaye, Ruth; Leonard, Stephen S; Castranova, Vincent; Ding, Min

2013-02-15

230

Bio-molecule-conjugated fluorescent organically modified silica nanoparticles as optical probes for cancer cell imaging.  

PubMed

Organically modified silica nanoparticles doped with Nile Red were synthesized and characterized. Silica encapsulation is relatively transparent for light and can protect hydrophobic Nile Red against denaturalization induced by the extreme bio-environment, making the entire nanoparticle hydrophilic and possess stable optical properties. The nanoparticles were conjugated with bio-molecules (such as apo-transferrin and folic acid), and our in vitro experiments revealed that these functionalized nanoparticles can serve as effective optical probes for specific targeting of cancer cells. As a preliminary study for future in vivo animal experiment, ORMOSIL nanoparticles were further co-conjugated with polyethyleneglycol (PEG) and apo-transferrin and the conjugates were also very good for in vitro targeting of HeLa cells. These bio-molecule functionalized ORMOSIL nanoparticles may serve as a robust tool for early diagnosis/therapy of cancer and other diseases. PMID:19030044

Qian, Jun; Li, Xin; Wei, Ming; Gao, Xiangwei; Xu, Zhengping; He, Sailing

2008-11-24

231

LaB6 nanoparticles with carbon-doped silica coating for fluorescence imaging and near-IR photothermal therapy of cancer cells.  

PubMed

In this study, LaB6 nanoparticles are used as a novel nanomaterial for near-infrared (NIR) photothermal therapy because they are cheaper than nanostructured gold, are easy to prepare and have an excellent NIR photothermal conversion property. Furthermore, the surface of LaB6 nanoparticles is coated with a carbon-doped silica (C-SiO2) shell to introduce a fluorescent property and improve stability and biocompatibility. The resulting LaB6@C-SiO2 nanoparticles retain the excellent NIR photothermal conversion property and exhibit a bright blue emission under UV irradiation or a green emission under visible irradiation. Using a HeLa cancer cell line, it is demonstrated that LaB6@C-SiO2 nanoparticles have no significant cytotoxicity, but their presence leads to remarkable cell death after NIR irradiation. In addition, from the observation of cellular uptake, the fluorescence labeling function of LaB6@SiO2 (LaB6 core/SiO2 shell) nanoparticles is also confirmed. These results suggest that LaB6@C-SiO2 nanoparticles may potentially serve as an efficient multifunctional nano-platform for simultaneous fluorescent imaging and NIR-triggered photothermal therapy of cancer cells. PMID:23542555

Lai, B-H; Chen, D-H

2013-03-28

232

Gold nanoparticle sensitize radiotherapy of prostate cancer cells by regulation of the cell cycle  

Microsoft Academic Search

Glucose-capped gold nanoparticles (Glu-GNPs) have been used to improve cellular targeting and radio-sensitization. In this study, we explored the mechanism of Glu-GNP enhanced radiation sensitivity in radiation-resistant human prostate cancer cells. Cell survival and proliferation were measured using MTT and clonogenic assay. Flow cytometry with staining by propidium iodide (PI) was performed to study the cell cycle changes induced by

Wilson Roa; Xiaojing Zhang; Linghong Guo; Andrew Shaw; Xiuying Hu; Yeping Xiong; Sunil Gulavita; Samir Patel; Xuejun Sun; Jie Chen; Ronald Moore; James Z. Xing

2009-01-01

233

Endothelial cell-specific aryl hydrocarbon receptor knockout mice exhibit hypotension mediated, in part, by an attenuated angiotensin II responsiveness  

Microsoft Academic Search

Hypotension in aryl hydrocarbon receptor knockout mice (ahr?\\/?) is mediated, in part, by a reduced contribution of angiotensin (Ang) II to basal blood pressure (BP). Since AHR is highly expressed in endothelial cells (EC), we hypothesized that EC-specific ahr?\\/? (ECahr?\\/?) mice would exhibit a similar phenotype. We generated ECahr?\\/? mice by crossing AHR floxed mice (ahrfx\\/fx) to mice expressing Cre

Larry N. Agbor; Khalid M. Elased; Mary K. Walker

2011-01-01

234

Galactosylated Chitosan Oligosaccharide Nanoparticles for Hepatocellular Carcinoma Cell-Targeted Delivery of Adenosine Triphosphate  

PubMed Central

Nanoparticles composed of galactosylated chitosan oligosaccharide (Gal-CSO) and adenosine triphosphate (ATP) were prepared for hepatocellular carcinoma cell-specific uptake, and the characteristics of Gal-CSO/ATP nanoparticles were evaluated. CSO/ATP nanoparticles were prepared as a control. The average diameter and zeta potential of Gal-CSO/ATP nanoparticles were 51.03 ± 3.26 nm and 30.50 ± 1.25 mV, respectively, suggesting suitable properties for a drug delivery system. Subsequently, the cytotoxicity of Gal-CSO/ATP nanoparticles were examined by the methyl tetrazolium (MTT) assay, and the half maximal inhibitory concentration (IC50) values were calculated with HepG2 (human hepatocellular carcinoma cell line) cells. The results showed that the cytotoxic effect of nanoparticles on HepG2 cells was low. In the meantime, it was also found that the Gal-CSO/ATP nanoparticles could be uptaken by HepG2 cells, due to expression of the asialoglycoprotein receptor (ASGP-R) on their surfaces. The presented results indicate that the Gal-CSO nanoparticles might be very attractive to be used as an intracellular drug delivery carrier for hepatocellular carcinoma cell targeting, thus warranting further in vivo or clinical investigations.

Zhu, Xiu Liang; Du, Yong Zhong; Yu, Ri Sheng; Liu, Ping; Shi, Dan; Chen, Ying; Wang, Ying; Huang, Fang Fang

2013-01-01

235

LAMP-2-deficient human B cells exhibit altered MHC class II presentation of exogenous antigens  

PubMed Central

Major histocompatibility complex (MHC) class II molecules present antigenic peptides derived from engulfed exogenous proteins to CD4+ T cells. Exogenous antigens are processed in mature endosomes and lysosomes where acidic proteases reside and peptide-binding to class II alleles is favoured. Hence, maintenance of the microenvironment within these organelles is probably central to efficient MHC class II-mediated antigen presentation. Lysosome-associated membrane proteins such as LAMP-2 reside in mature endosomes and lysosomes, yet their role in exogenous antigen presentation pathways remains untested. In this study, human B cells lacking LAMP-2 were examined for changes in MHC class II-restricted antigen presentation. MHC class II presentation of exogenous antigen and peptides to CD4+ T cells was impaired in the LAMP-2-deficient B cells. Peptide-binding to MHC class II on LAMP-2-deficient B cells was reduced at physiological pH compared with wild-type cells. However, peptide-binding and class II-restricted antigen presentation were restored by incubation of LAMP-2-negative B cells at acidic pH, suggesting that efficient loading of exogenous epitopes by MHC class II molecules is dependent upon LAMP-2 expression in B cells. Interestingly, class II presentation of an epitope derived from an endogenous transmembrane protein was detected using LAMP-2-deficient B cells. Consequently, LAMP-2 may control the repertoire of peptides displayed by MHC class II molecules on B cells and influence the balance between endogenous and exogenous antigen presentation.

Crotzer, Victoria L; Glosson, Nicole; Zhou, Delu; Nishino, Ichizo; Blum, Janice S

2010-01-01

236

Laser nanothermolysis of human leukemia cells using functionalized plasmonic nanoparticles  

PubMed Central

In the present work, we present the use of gold nanorods as plasmonic nanoparticles for selective photothermal therapy of human acute (HL-60) and chronicle (K-562) leukemia cells using a near-infrared laser. We improved a published methodology of gold nanorods conjugation to generate high yields of narrow band gold nanorods with an optical absorption centered at 760 nm. The manufactured nanorods were pegylated and conjugated with monoclonal antibody to become non-toxic as biocompatible nanothermolysis agent. Gold nanorods are synthesized and conjugated to CD33 monoclonal antibody. After pegylation, or conjugation with CD33 antibody, gold nanorods were non-toxic to acute and chronic leukemia cells. Our modified gold nanorods CD33 conjugates shown high level of accumulation for both leukemia cell lines, and successful used for nanothermolysis of human leukemia cells in vitro. Each sample was illuminated with 1 or 3 laser shots as for low and for high laser fluence. The radiation was provided by a Quanta Systems q-switched titanium sapphire laser, and the system was designed for maximum sample coverage using non-focused illumination. HL-60 and K-562 cells were treated for 45 min with gold nanorods CD33 conjugated, or with pegylated gold nanorods. The effect of pulsed-laser nanothermolysis for acute and chronic leukemia cells were investigated with cell counting for number of living cells, percentage of cell death and functional parameters such as damage of cell membrane and metabolic activity. Gold nanorods CD33 conjugates significantly increase cell damage for low fluence laser and completely destroyed cancer cells after 3 pulses for low fluence (acute leukemia) and for high fluence laser as for HL-60 (acute) and for K-562 (chronicle) leukemia cells.

Liopo, Anton V.; Conjusteau, Andre; Konopleva, Marina; Andreeff, Michael; Oraevsky, Alexander A.

2012-01-01

237

The manipulation of natural killer cells to target tumor sites using magnetic nanoparticles  

PubMed Central

The present work demonstrates that Cy5.5 conjugated Fe3O4/SiO2 core/shell nanoparticles could allow us to control movement of human natural killer cells (NK-92MI) by an external magnetic field. Required concentration of the nanoparticles for the cell manipulation is as low as ~20 ?g Fe/mL. However, the relative ratio of the nanoparticles loaded NK-92MI cells infiltrated into the target tumor site is enhanced by 17-fold by applying magnetic field and their killing activity is still maintained as same as the NK-92MI cells without the nanoparticles. This approach allows us to open alternative clinical treatment with reduced toxicity of the nanoparticles and enhanced infiltration of immunology to the target site.

Jang, Eue-Soon; Shin, June-Ho; Ren, Gang; Park, Mi-Jin; Cheng, Kai; Chen, Xiaoyuan; Wu, Joseph C.; Sunwoo, John B.; Cheng, Zhen

2013-01-01

238

Circulating Breast Tumor Cells Exhibit Dynamic Changes in Epithelial and Mesenchymal Composition  

PubMed Central

Epithelial-mesenchymal transition (EMT) of adherent epithelial cells to a migratory mesenchymal state has been implicated in tumor metastasis in preclinical models. To investigate its role in human cancer, we characterized EMT in circulating tumor cells (CTCs) from breast cancer patients. Rare primary tumor cells simultaneously expressed mesenchymal and epithelial markers, but mesenchymal cells were highly enriched in CTCs. Serial CTC monitoring in 11 patients suggested an association of mesenchymal CTCs with disease progression. In an index patient, reversible shifts between these cell fates accompanied each cycle of response to therapy and disease progression. Mesenchymal CTCs occurred as both single cells and multicellular clusters, expressing known EMT regulators, including transforming growth factor (TGF)–? pathway components and the FOXC1 transcription factor. These data support a role for EMT in the blood-borne dissemination of human breast cancer.

Yu, Min; Bardia, Aditya; Wittner, Ben S.; Stott, Shannon L.; Smas, Malgorzata E.; Ting, David T.; Isakoff, Steven J.; Ciciliano, Jordan C.; Wells, Marissa N.; Shah, Ajay M.; Concannon, Kyle F.; Donaldson, Maria C.; Sequist, Lecia V.; Brachtel, Elena; Sgroi, Dennis; Baselga, Jose; Ramaswamy, Sridhar; Toner, Mehmet; Haber, Daniel A.; Maheswaran, Shyamala

2013-01-01

239

Aging Hematopoietic Stem Cells Decline in Function and Exhibit Epigenetic Dysregulation  

Microsoft Academic Search

Age-related defects in stem cells can limit proper tissue maintenance and hence contribute to a shortened lifespan. Using highly purified hematopoietic stem cells from mice aged 2 to 21 mo, we demonstrate a deficit in function yet an increase in stem cell number with advancing age. Expression analysis of more than 14,000 genes identified 1,500 that were age-induced and 1,600

Stuart M Chambers; Chad A Shaw; Catherine Gatza; C. Joseph Fisk; Lawrence A Donehower; Margaret A Goodell

2007-01-01

240

Notch1 and Notch2 exhibit unique patterns of expression in human B-lineage cells  

Microsoft Academic Search

The Notch genes encode a conserved family of receptors that influence developmental fate in many species. Prior studies have indicated that Notch-1 and Notch-2 signaling influence the development of hematopoietic stems cells and thymocytes, but little is known regarding Notch expression and function in B-lineage cells. We analyzed the expression of Notch receptors and Notch ligands in human B-lineage cells

FE Bertrand; CE Eckfeldt; AS Lysholm; TW LeBien

2000-01-01

241

Functionalised gold nanoparticles for selective induction of in vitro apoptosis among human cancer cell lines  

Microsoft Academic Search

The interaction of citrate- and polyethylene imine (PEI)-functionalised gold nanoparticles (GNP) with cancer cell lines with respect to the cellular response was studied. It was found that GNP\\/citrate nanoparticles were able to induce apoptosis in human carcinoma lung cell lines A549, but GNP\\/PEI did not show any reduction in the viability of the cells in human breast cancer cell line

Jithin C. Mohan; G. Praveen; K. P. Chennazhi; R. Jayakumar; S. V. Nair

2012-01-01

242

Rat embryo fibroblast cells expressing human papillomavirus 1a genes exhibit altered growth properties and tumorigenicity.  

PubMed Central

Human papillomavirus 1a (HPV1a) induces benign tumors (papillomas or warts) in humans under natural conditions of infection but has not been found to replicate significantly in cell culture or in experimental animals. To establish model systems to study the oncogenic properties and expression of HPV genes, we established cell lines by cotransfecting the 3Y1 rat fibroblast cell line with HPV1a DNA constructs containing an intact early gene region and the Tn5 neomycin resistance gene. Most cell lines selected for expression of the neomycin resistance gene by treatment with the antibiotic G-418 contained viral DNA in a high-molecular-weight form. The growth characteristics of several cell lines containing high copy numbers of HPV1a DNA were studied further. They were shown to differ from the parental cell line and from G-418-resistant cell lines that did not incorporate viral DNA in the following properties: morphological alteration, increased cell density at confluence, growth in 0.5% serum, efficient anchorage-independent growth in soft agar, and rapid formation of tumors in nude mice. Those cell lines that possessed altered growth properties and tumorigenicity were found to express abundant quantities of polyadenylated virus-specific RNA species in the cytoplasm. Images

Green, M; Brackmann, K H; Loewenstein, P M

1986-01-01

243

Colony Forming Unit Endothelial Cells Do not Exhibit Telomerase Alternative Splicing Variants and Activity  

PubMed Central

Introduction: Endothelial progenitor colony forming unit-endothelial cells (CFU-EC) were first believed to be the progenitors of endothelial cells, named endothelial progenitor cells. Further studies revealed that they are monocytes regulating vasculogenesis. The main hindrance of these cells for therapeutic purposes is their low frequency and limited replicative potentials. This study was undertaken to determine telomerase activity and alternative splicing variants in CFU-EC as a potential cause of limited replicative capacity in these cells. Methods: CFU-EC were isolated from peripheral blood using a standard cell culture assay. Colonies were detached mechanically and alternative splicing variant mRNA were evaluated using real-time PCR. Telomerase enzyme activity was assessed using telomerase repeat amplification protocol. The same procedures were done on the cancer cell line Calu6 as the positive control. Results: The cultured peripheral blood mononuclear cells formed colonies with spindle-shaped monocytic cells sprouted from the clusters. These morphological characteristics fulfill the definition of CFU-EC. Telomere length amplification protocol assay revealed no telomerase activity and real-time PCR showed no expression of telomerase enzyme mRNA in CFU-EC. Both parameters were significantly higher in the cancer cell line Calu6 taken as the positive control. Conclusion: The absence of telomerase activity in the CFU-EC is a result of pre-transcriptional regulation of gene expression rather than other mechanisms for controlling telomerase activity such as post-transcriptional modifications. This finding can explain the limited proliferative activity of CFU-EC cells. We propose that absence of telomerase activity in CFU-EC can be attributable to their more mature monocytic nature that needs further investigations.

Attar, Armin; Khosravi Maharlooi, Mohsen; Khoshkhou, Sara; Hosseini, Ahmad; Jaberipour, Mansoureh; Dehghan, Arman; Monabati, Ahmad

2013-01-01

244

Application in the Ethanol Fermentation of Immobilized Yeast Cells in Matrix of Alginate\\/Magnetic Nanoparticles, on Chitosan-Magnetite Microparticles and Cellulose-coated Magnetic Nanoparticles  

Microsoft Academic Search

Saccharomyces cerevisiae cells were entrapped in matrix of alginate and magnetic nanoparticles and covalently immobilized on magnetite-containing chitosan and cellulose-coated magnetic nanoparticles. Cellulose-coated magnetic nanoparticles with covalently immobilized thermostable {\\\\alpha}-amylase and chitosan particles with immobilized glucoamylase were also prepared. The immobilized cells and enzymes were applied in column reactors - 1\\/for simultaneous corn starch saccharification with the immobilized glucoamylase and

Viara Ivanova; Petia Petrova; Jordan Hristov

2011-01-01

245

Genotoxic responses to titanium dioxide nanoparticles and fullerene in gpt delta transgenic MEF cells  

PubMed Central

Background Titanium dioxide (TiO2) nanoparticles and fullerene (C60) are two attractive manufactured nanoparticles with great promise in industrial and medical applications. However, little is known about the genotoxic response of TiO2 nanoparticles and C60 in mammalian cells. In the present study, we determined the mutation fractions induced by either TiO2 nanoparticles or C60 in gpt delta transgenic mouse primary embryo fibroblasts (MEF) and identified peroxynitrite anions (ONOO-) as an essential mediator involved in such process. Results Both TiO2 nanoparticles and C60 dramatically increased the mutation yield, which could be abrogated by concurrent treatment with the endocytosis inhibitor, Nystatin. Under confocal scanning microscopy together with the radical probe dihydrorhodamine 123 (DHR 123), we found that there was a dose-dependent formation of ONOO- in live MEF cells exposed to either TiO2 nanoparticles or C60, and the protective effects of antioxidants were demonstrated by the nitric oxide synthase (NOS) inhibitor, NG-methyl-L-arginine (L-NMMA). Furthermore, suppression of cyclooxygenase-2 (COX-2) activity by using the chemical inhibitor NS-398 significantly reduced mutation frequency of both TiO2 nanoparticles and C60. Conclusion Our results provided novel information that both TiO2 nanoparticles and C60 were taken up by cells and induced kilo-base pair deletion mutations in a transgenic mouse mutation system. The induction of ONOO- may be a critical signaling event for nanoparticle genotoxicity.

Xu, An; Chai, Yunfei; Nohmi, Takehiko; Hei, Tom K

2009-01-01

246

Melittin exhibits necrotic cytotoxicity in gastrointestinal cells which is attenuated by cholesterol  

Microsoft Academic Search

Melittin, a cationic antimicrobial peptide isolated from the venom of Apis mellifera, has shown potential as a permeability enhancer, transiently increasing intestinal permeability and enhancing the absorption of paracellular markers. Although it is cytotoxic to eukaryotic cells, its cytotoxicity is significantly lower in polarised epithelia compared to non-polarised cells. The aim of this study was to explore the mechanism of

Sam Maher; Siobhán McClean

2008-01-01

247

Transgenic Chinese hamster V79 cell lines which exhibit variable levels of gpt mutagenesis  

SciTech Connect

The Escherichia coli gpt gene coding for xanthine-guanine phosphoribosyl transferase has been stably transfected into HPRT{sup {minus}} Chinese hamster V79 cells. Several gpt{sup {minus}} cell lines have been established, which retain the sequence(s) even after long-term culture without selection for gpt. While spontaneous mutagenesis to gpt{sup {minus}} occurs rather frequently for most cell lines, it cannot be correlated with either the number of plasmid integration sites or deletion of the plasmid sequence(s). One transgenic cell line (g12), which continuously maintains a low spontaneous mutation frequency was used in comparative mutagenesis studies with wild-type V79 cells (gpt vs. hprt). Alkylating agents such as N-methyl-N{prime}-nitro-N-nitrosoguanidine (MNNG) and {beta}-propiolactone (BPL) are shown to be equally toxic and mutagenic in both g12 and V79 cells. UV and X-rays are also equally toxic to both cell lines. The data presented here suggests that g12 cells may be useful to study mammalian mutagenesis by agents which yield limited response at the hprt locus.

Klein, C.B.; Rossman, T.G. (New York Univ. Medical Center, New York (USA))

1990-01-01

248

Human hepatocellular carcinoma cell lines exhibit multidrug resistance unrelated to MDR\\\\ gene expression  

Microsoft Academic Search

Summary Multidrug resistance of human cancer cells may result from expression of P-glycoprotein, the product of the MDRl gene, acting as an energy-dependent drug efflux pump. However, direct evidence that expression of the MDRl gene contributes to the multidrug resistance of human liver carcinomas has not been established. In this study, we tested five cell lines derived from human hepatocellular

D.-W. SHEN; YUAN-G. LU; KHEW-V. CfflN; M. M. GOTTESMAN

1991-01-01

249

In vitro release behavior and cytotoxicity of doxorubicin-loaded gold nanoparticles in cancerous cells  

Microsoft Academic Search

Doxorubicin (DOX), a common cancer chemotherapeutics, was conjugated to folate-modified thiolated-polyethylene glycol-functionalized\\u000a gold nanoparticles. The in vitro, controlled release behavior of DOX-loaded gold nanoparticles was observed using porous dialysis\\u000a membranes (cut-off = 2 kDa). DOX-loaded gold nanoparticles had higher cytotoxicity for folate-receptor-positive cells (KB\\u000a cells) compared to folate-receptor-negative cells (A549 cells) which were 48 and 62% viable for 10 ?M doxorubicin, respectively.\\u000a This indicates the

B. Asadishad; M. Vossoughi; I. Alamzadeh

2010-01-01

250

Cord Blood Natural Killer Cells Exhibit Impaired Lytic Immunological Synapse Formation That Is Reversed with IL-2 Ex Vivo Expansion  

PubMed Central

Peripheral blood natural killer (NK) cell therapy for acute myeloid leukemia has shown promise in clinical trials after allogeneic stem cell transplantation (SCT). Cord blood (CB) is another potentially rich source of NK cells for adoptive immune therapy after SCT. Tightly regulated receptor signaling between NK cells and susceptible tumor cells is essential for NK cell-mediated cytotoxicity. However, despite expressing normal surface activating and inhibitory NK receptors, CB-derived NK cells have poor cytolytic activity. In this study, we investigate the cellular mechanism and demonstrate that unmanipulated CB-NK cells exhibit an impaired ability to form F-actin immunological synapses with target leukemia cells compared with peripheral blood-derived NK cells. In addition, there was reduced recruitment of the activating receptor CD2, integrin LFA-1, and the cytolytic molecule perforin to the CB-NK synapse site. Ex vivo IL-2 expansion of CB-NK cells enhanced lytic synapse formation including CD2 and LFA-1 polarization and activity. Furthermore, the acquired anti-leukemic function of IL-2-expanded CB-NK cells was validated using a NOD-SCID-IL2R?null mouse model. We believe our results provide important mechanistic insights for the potential use of IL-2-expanded CB-derived NK cells for adoptive immune therapy in leukemia.

Xing, Dongxia; Ramsay, Alan G.; Gribben, John G.; Decker, William K.; Burks, Jared K.; Munsell, Mark; Li, Sufang; Robinson, Simon N.; Yang, Hong; Steiner, David; Shah, Nina; McMannis, John D.; Champlin, Richard E.; Hosing, Chitra; Zweidler-Mckay, Patrick A.; Shpall, Elizabeth J.; Bollard, Catherine M.

2011-01-01

251

In vitro toxicity of silica nanoparticles in human lung cancer cells  

SciTech Connect

The cytotoxicity of 15-nm and 46-nm silica nanoparticles was investigated by using crystalline silica (Min-U-Sil 5) as a positive control in cultured human bronchoalveolar carcinoma-derived cells. Exposure to 15-nm or 46-nm SiO{sub 2} nanoparticles for 48 h at dosage levels between 10 and 100 {mu}g/ml decreased cell viability in a dose-dependent manner. Both SiO{sub 2} nanoparticles were more cytotoxic than Min-U-Sil 5; however, the cytotoxicities of 15-nm and 46-nm silica nanoparticles were not significantly different. The 15-nm SiO{sub 2} nanoparticles were used to determine time-dependent cytotoxicity and oxidative stress responses. Cell viability decreased significantly as a function of both nanoparticle dosage (10-100 {mu}g/ml) and exposure time (24 h, 48 h, and 72 h). Indicators of oxidative stress and cytotoxicity, including total reactive oxygen species (ROS), glutathione, malondialdehyde, and lactate dehydrogenase, were quantitatively assessed. Exposure to SiO{sub 2} nanoparticles increased ROS levels and reduced glutathione levels. The increased production of malondialdehyde and lactate dehydrogenase release from the cells indicated lipid peroxidation and membrane damage. In summary, exposure to SiO{sub 2} nanoparticles results in a dose-dependent cytotoxicity in cultural human bronchoalveolar carcinoma-derived cells that is closely correlated to increased oxidative stress.

Lin Weisheng [Department of Chemistry and Environmental Research Center, University of Missouri-Rolla, Rolla, MO 65409 (United States); Huang Yuewern [Department of Biological Sciences and Environmental Research Center, University of Missouri-Rolla, Rolla, MO 65409 (United States); Zhou Xiaodong [Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Ma Yinfa [Department of Chemistry and Environmental Research Center, University of Missouri-Rolla, Rolla, MO 65409 (United States)]. E-mail: yinfa@umr.edu

2006-12-15

252

NY-ESO-1 antigen-reactive T cell receptors exhibit diverse therapeutic capability  

PubMed Central

The cancer-testis antigen NY-ESO-1 has been used as a target for different immunotherapies like vaccinations and adoptive transfer of antigen-specific cytotoxic T cells, as it is expressed in various tumor types and has limited expression in normal cells. The in vitro generation of T cells with defined antigen specificity by T cell receptor (TCR) gene transfer is an established method to create cells for immunotherapy. However, an extensive characterization of TCR which are candidates for treatment of patients is crucial for successful therapies. The TCR has to be efficiently expressed, their affinity to the desired antigen should be high enough to recognize low amounts of endogenously processed peptides on tumor cells, and the TCR should not be cross-reactive to other antigens. We characterized three NY-ESO-1 antigen-reactive cytotoxic T lymphocyte clones which were generated by different approaches of T cell priming (autologous, allogeneic), and transferred their TCR into donor T cells for more extensive evaluations. Although one TCR most efficiently bound MHC-multimers loaded with NY-ESO-1 peptide, T cells expressing this transgenic TCR were not able to recognize endogenously processed antigen. A second TCR recognized HLA-A2 independent of the bound peptide beside its much stronger recognition of NY-ESO-1 bound to HLA-A2. A third TCR displayed an intermediate but peptide-specific performance in all functional assays and, therefore, is the most promising candidate TCR for further clinical development. Our data indicate that multiple parameters of TCR gene-modified T cells have to be evaluated to identify an optimal TCR candidate for adoptive therapy.

Sommermeyer, Daniel; Conrad, Heinke; Kronig, Holger; Gelfort, Haike; Bernhard, Helga; Uckert, Wolfgang

2013-01-01

253

CYP26A1 knockout embryonic stem cells exhibit reduced differentiation and growth arrest in response to retinoic acid.  

PubMed

CYP26A1, a cytochrome P450 enzyme, metabolizes all-trans-retinoic acid (RA) into polar metabolites, e.g. 4-oxo-RA and 4-OH-RA. To determine if altering RA metabolism affects embryonic stem (ES) cell differentiation, we disrupted both alleles of Cyp26a1 by homologous recombination. CYP26a1(-/-) ES cells had a 11.0+/-3.2-fold higher intracellular RA concentration than Wt ES cells after RA treatment for 48 h. RA-treated CYP26A1(-/-) ES cells exhibited 2-3 fold higher mRNA levels of Hoxa1, a primary RA target gene, than Wt ES cells. Despite increased intracellular RA levels, CYP26a1(-/-) ES cells were more resistant than Wt ES cells to RA-induced proliferation arrest. Transcripts for parietal endodermal differentiation markers, including laminin, J6(Hsp 47), and J31(SPARC, osteonectin) were expressed at lower levels in RA-treated CYP26a1(-/-) ES cells, indicating that the lack of CYP26A1 activity inhibits RA-associated differentiation. Microarray analyses revealed that RA-treated CYP26A1(-/-) ES cells exhibited lower mRNA levels than Wt ES cells for genes involved in differentiation, particularly in neural (Epha4, Pmp22, Nrp1, Gap43, Ndn) and smooth muscle differentiation (Madh3, Nrp1, Tagln Calponin, Caldesmon1). In contrast, genes involved in the stress response (e.g. Tlr2, Stk2, Fcgr2b, Bnip3, Pdk1) were expressed at higher levels in CYP26A1(-/-) than in Wt ES cells without RA. Collectively, our results show that CYP26A1 activity regulates intracellular RA levels, cell proliferation, transcriptional regulation of primary RA target genes, and ES cell differentiation to parietal endoderm. PMID:18241852

Langton, Simne; Gudas, Lorraine J

2007-12-27

254

Breaking tolerance to self, circulating natural killer cells expressing inhibitory KIR for non-self HLA exhibit effector function after T cell-depleted allogeneic hematopoietic cell transplantation  

PubMed Central

Alloreactive natural killer (NK) cells are an important influence on hematopoietic stem cell transplantation (HSCT) outcome. In HLA-mismatched HSCT, alloreactivity occurs when licensed donor NK cells expressing inhibitory killer Ig-like receptors (KIR) for donor MHC class I ligands recognize the lack of the class I ligands in the mismatched recipient (“missing self”). Studies in HLA-matched HSCT, however, have also demonstrated improved outcome in patients lacking class I ligands for donor inhibitory KIR (“missing ligand”), indicating that classically nonlicensed donor NK cells expressing KIR for non-self MHC class I ligands may exhibit functional competence in HSCT. We examined NK function in 16 recipients of T cell–depleted allografts from HLA-identical or KIR-ligand matched donors after myeloablative therapy. After HSCT, nonlicensed NK cells expressing inhibitory KIR for non-self class I exhibit robust intracellular IFN-? and cytotoxic response to target cells lacking cognate ligand, gradually becoming tolerized to self by day 100. These findings could not be correlated with cytokine environment or phenotypic markers of NK development, nor could they be attributed to non-KIR receptors such as CD94/NKG2A. These findings confirm that NK alloreactivity can occur in HLA-matched HSCT, where tolerance to self is either acquired by the stem cell–derived NK cell after exiting the bone marrow or where tolerance to self can be temporarily overcome.

Yu, Junli; Venstrom, Jeffrey M.; Liu, Xiao-Rong; Pring, James; Hasan, Reenat S.; O'Reilly, Richard J.

2009-01-01

255

Poriferan survivin exhibits a conserved regulatory role in the interconnected pathways of cell cycle and apoptosis  

PubMed Central

Survivin orchestrates intracellular pathways during cell division and apoptosis. Its central function as mitotic regulator and inhibitor of cell death has major implications for tumor cell proliferation. Analyses in early-branching Metazoa so far propose an exclusive role of survivin as a chromosomal passenger protein, whereas only later during evolution a complementary antiapoptotic function might have arisen, concurrent with increased organismal complexity. To lift the veil on the ancestral function(s) of this key regulator, a survivin-like protein (SURVL) of one of the earliest-branching metazoan taxa was identified and functionally characterized. SURVL of the sponge Suberites domuncula shares considerable similarities with its metazoan homologs, ranging from conserved exon/intron structure to presence of protein-interaction domains. Whereas sponge tissue shows a low steady-state level, SURVL expression was significantly upregulated in rapidly proliferating primmorph cells. In addition, challenge of tissue and primmorphs with heavy metal or lipopeptide stimulated SURVL expression, concurrent with the expression of a newly discovered caspase. Complementary functional analyses in transfected HEK-293 cells revealed that heterologous expression of a SURVL–EFGP fusion not only promotes proliferation but also enhances resistance to cadmium-induced cell death. Taken together, these results suggest both a deep evolutionary conserved dual role of survivin and an equally conserved central position in the interconnected pathways of cell cycle and apoptosis.

Luthringer, B; Isbert, S; Muller, W E G; Zilberberg, C; Thakur, N L; Worheide, G; Stauber, R H; Kelve, M; Wiens, M

2011-01-01

256

Mature Hepatocytes Exhibit Unexpected Plasticity by Direct Dedifferentiation into Liver Progenitor Cells in Culture  

PubMed Central

Although there have been numerous reports describing the isolation of liver progenitor cells from adult liver, their exact origin has not been clearly defined; and the role played by mature hepatocytes as direct contributors to the hepatic progenitor cell pool has remained largely unknown. Here we report strong evidence that mature hepatocytes in culture have the capacity to dedifferentiate into a population of adult liver progenitors without genetic or epigenetic manipulations. By using highly-purified mature hepatocytes, which were obtained from untreated, healthy rat liver and labeled with fluorescent dye PKH2, we found that hepatocytes in culture gave rise to a population of PKH2-positive liver progenitor cells. These cells, Liver Derived Progenitor Cells or LDPCS, which share phenotypic similarities with oval cells, were previously reported to be capable of forming mature hepatocytes both in culture and in animals. Studies done at various time points during the course of dedifferentiation cultures revealed that hepatocytes rapidly transformed into liver progenitors within one week through a transient oval cell-like stage. This finding was supported by lineage-tracing studies involving double-transgenic AlbuminCreXRosa26 mice expressing ?-galactosidase exclusively in hepatocytes. Cultures set up with hepatocytes obtained from these mice resulted in generation of ?-galactosidase-positive liver progenitor cells demonstrating that they were a direct dedifferentiation product of mature hepatocytes. Additionally, these progenitors differentiated into hepatocytes in vivo when transplanted into rats that had undergone retrorsine pretreatment and partial hepatectomy. Conclusion Our studies provide strong evidence for the unexpected plasticity of mature hepatocytes to dedifferentiate into progenitor cells in culture; and this may potentially have a significant impact on the treatment of liver diseases requiring liver or hepatocyte transplantation.

Chen, Yixin; Wong, Philip P.; Sjeklocha, Lucas; Steer, Clifford J.; Sahin, M. Behnan

2011-01-01

257

Development of a dose-controlled multiculture cell exposure chamber for efficient delivery of airborne and engineered nanoparticles  

NASA Astrophysics Data System (ADS)

In order to study the various health influencing parameters related to engineered nanoparticles as well as to soot emitted by Diesel engines, there is an urgent need for appropriate sampling devices and methods for cell exposure studies that simulate the respiratory system and facilitate associated biological and toxicological tests. The objective of the present work was the further advancement of a Multiculture Exposure Chamber (MEC) into a dose-controlled system for efficient delivery of nanoparticles to cells. It was validated with various types of nanoparticles (Diesel engine soot aggregates, engineered nanoparticles for various applications) and with state-of-the-art nanoparticle measurement instrumentation to assess the local deposition of nanoparticles on the cell cultures. The dose of nanoparticles to which cell cultures are being exposed was evaluated in the normal operation of the in vitro cell culture exposure chamber based on measurements of the size specific nanoparticle collection efficiency of a cell free device. The average efficiency in delivering nanoparticles in the MEC was approximately 82%. The nanoparticle deposition was demonstrated by Transmission Electron Microscopy (TEM). Analysis and design of the MEC employs Computational Fluid Dynamics (CFD) and true to geometry representations of nanoparticles with the aim to assess the uniformity of nanoparticle deposition among the culture wells. Final testing of the dose-controlled cell exposure system was performed by exposing A549 lung cell cultures to fluorescently labeled nanoparticles. Delivery of aerosolized nanoparticles was demonstrated by visualization of the nanoparticle fluorescence in the cell cultures following exposure. Also monitored was the potential of the aerosolized nanoparticles to generate reactive oxygen species (ROS) (e.g. free radicals and peroxides generation), thus expressing the oxidative stress of the cells which can cause extensive cellular damage or damage on DNA.

Asimakopoulou, Akrivi; Daskalos, Emmanouil; Lewinski, Nastassja; Riediker, Michael; Papaioannou, Eleni; Konstandopoulos, Athanasios G.

2013-04-01

258

Interactions of lipid-based liquid crystalline nanoparticles with model and cell membranes.  

PubMed

Lipid-based liquid crystalline nanoparticles (LCNPs) are interesting candidates for drug delivery applications, for instance as solubilizing or encapsulating carriers for intravenous (i.v.) drugs. Here it is important that the carriers are safe and tolerable and do not have, e.g. hemolytic activity. In the present study we have studied LCNP particles of different compositions with respect to their mixing behavior and membrane destabilizing effects in model and cell membrane systems. Different types of non-lamellar LCNPs were studied including cubic phase nanoparticles (Cubosome) based on glycerol monooleate (GMO), hexagonal phase nanoparticles (Hexosome) based on diglycerol monooleate (DGMO) and glycerol dioleate (GDO), sponge phase nanoparticles based on DGMO/GDO/polysorbate 80 (P80) and non-lamellar nanoparticles based on soy phosphatidylcholine (SPC)/GDO. Importantly, the LCNPs based on the long-chain monoacyl lipid, GMO, were shown to display a very fast and complete lipid mixing with model membranes composed of multilamellar SPC liposomes as assessed by a fluorescence energy transfer (FRET) assay. The result correlated well with pronounced hemolytic properties observed when the GMO-based LCNPs were mixed with rat whole blood. In sharp contrast, LCNPs based on mixtures of the long-chain diacyl lipids, SPC and GDO, were found to be practically inert towards both hemolysis in rat whole blood as well as lipid mixing with SPC model membranes. The LCNP dispersions based on a mixture of long-chain monoacyl and diacyl lipids, DGMO/GDO, displayed an intermediate behavior compared to the GMO and SPC/GDO-based systems with respect to both hemolysis and lipid mixing. It is concluded that GMO-based LCNPs are unsuitable for parenteral drug delivery applications (e.g. i.v. administration) while the SPC/GDO-based LCNPs exhibit good properties with limited lipid mixing and hemolytic activity. The correlation between results from lipid mixing or FRET experiments and the in vitro hemolysis data indicates that FRET assays can be one useful screening tool for parenteral drug delivery systems. It is argued that the hemolytic potential is correlated with chemical activity of the monomers in the mixtures. PMID:20214966

Barauskas, Justas; Cervin, Camilla; Jankunec, Marija; Spandyreva, Marija; Ribokaite, Kristina; Tiberg, Fredrik; Johnsson, Markus

2010-03-07

259

Gold nanoparticle biodistribution: Cell, blood, and tissue interactions as a function of nanoparticle surface properties  

NASA Astrophysics Data System (ADS)

Intravenously injected gold nanoparticles (GNPs) hold a great promise for clinical diagnostic and therapeutic applications. A critical issue in their implementation is incomplete mechanistic understanding of their in vivo biodistribution. Two major limitations in optimizing the biodistribution of NPs are: (1) achieving the highest accumulation at the disease site, and (2) avoiding accumulation in healthy organs including liver and spleen. To overcome these limitations, the interactions of GNPs with biological system must be better understood. The research described in this dissertation sought to advance the field of GNP in vivo biodistribution by elucidating the effects of GNP surface properties such as surface charge, ligand, and polyethylene glycol (PEG) coverage. It was shown that the interactions of GNPs with cells and tissues were a function of their surface properties. A Confocal Raman Microscopy based technique was developed to study GNPs interactions with cells in vitro in fast, label-free, and non-invasive way. It was further shown that GNP surface properties strongly influence their blood circulation time in vivo. It was demonstrated that GNPs interact with circulating blood cells including platelets and monocytes, which may play a role in their clearance from blood stream. Most of the injected dose was shown to accumulate in liver and spleen; however, both organs displayed a different mechanism of uptake and distribution of GNPs. Long-term biodistribution studies further suggested that GNPs were still found in liver and spleen after 4 months, but GNPs showed clearance from liver overtime.

Shah, Neha B.

260

AS1411 aptamer tagged PLGA-lecithin-PEG nanoparticles for tumor cell targeting and drug delivery.  

PubMed

Liposomes and polymers are widely used drug carriers for controlled release since they offer many advantages like increased treatment effectiveness, reduced toxicity and are of biodegradable nature. In this work, anticancer drug-loaded PLGA-lecithin-PEG nanoparticles (NPs) were synthesized and were functionalized with AS1411 anti-nucleolin aptamers for site-specific targeting against tumor cells which over expresses nucleolin receptors. The particles were characterized by transmission electron microscope (TEM) and X-ray photoelectron spectroscopy (XPS). The drug-loading efficiency, encapsulation efficiency and in vitro drug release studies were conducted using UV spectroscopy. Cytotoxicity studies were carried out in two different cancer cell lines, MCF-7 and GI-1 cells and two different normal cells, L929 cells and HMEC cells. Confocal microscopy and flowcytometry confirmed the cellular uptake of particles and targeted drug delivery. The morphology analysis of the NPs proved that the particles were smooth and spherical in shape with a size ranging from 60 to 110?nm. Drug-loading studies indicated that under the same drug loading, the aptamer-targeted NPs show enhanced cancer killing effect compared to the corresponding non-targeted NPs. In addition, the PLGA-lecithin-PEG NPs exhibited high encapsulation efficiency and superior sustained drug release than the drug loaded in plain PLGA NPs. The results confirmed that AS1411 aptamer-PLGA-lecithin-PEG NPs are potential carrier candidates for differential targeted drug delivery. PMID:22615073

Aravind, Athulya; Jeyamohan, Prashanti; Nair, Remya; Veeranarayanan, Srivani; Nagaoka, Yutaka; Yoshida, Yasuhiko; Maekawa, Toru; Kumar, D Sakthi

2012-06-01

261

Interaction of multi-functional silver nanoparticles with living cells  

NASA Astrophysics Data System (ADS)

Silver nanoparticles (AgNPs) are widely used in household products and in medicine due to their antibacterial and to wound healing properties. In recent years, there is also an effort for their use in biomedical imaging and photothermal therapy. The primary reason behind the effort for their utility in biomedicine and therapy is their unique plasmonic properties and easy surface chemistry for a variety of functionalizations. In this study, AgNPs modified with glucose, lactose, oligonucleotides and combinations of these ligands are investigated for their cytotoxicity and cellular uptake in living non-cancer (L929) and cancer (A549) cells. It is found that the chemical nature of the ligand strongly influences the toxicity and cellular uptake into the model cells. While the lactose-and glucose-modified AgNPs enter the L929 cells at about the same rate, a significant increase in the rate of lactose-modified AgNPs into the A549 cells is observed. The binding of oligonucleotides along with the carbohydrate on the AgNP surfaces influences the differential uptake rate pattern into the cells. The cytotoxicity study with the modified AgNPs reveals that only naked AgNPs influence the viability of the A549 cells. The findings of this study may provide the key to developing effective applications in medicine such as cancer therapy.

Sur, Ilknur; Cam, Dilek; Kahraman, Mehmet; Baysal, Asli; Culha, Mustafa

2010-04-01

262

Functionalization of whole-cell bacterial reporters with magnetic nanoparticle.  

PubMed

We developed a biocompatible and highly efficient approach for functionalization of bacterial cell wall with magnetic nanoparticles (MNPs). Three Acinetobacter baylyi ADP1 chromosomally based bioreporters, which were genetically engineered to express bioluminescence in response to salicylate, toluene/ xylene and alkanes, were functionalized with 18 3 nm iron oxide MNPs to acquire magnetic function. The efficiency of MNPs functionalization of Acinetobacter bioreporters was 99.96 0.01%. The MNPs-functionalized bioreporters (MFBs) can be remotely controlled and collected by an external magnetic field. The MFBs were all viable and functional as good as the native cells in terms of sensitivity, specificity and quantitative response. More importantly, we demonstrated that salicylate sensing MFBs can be applied to sediments and garden soils, and semiquantitatively detect salicylate in those samples by discriminably recovering MFBs with a permanent magnet. The magnetically functionalized cells are especially useful to complex environments in which the indigenous cells, particles and impurities may interfere with direct measurement of bioreporter cells and conventional filtration is not applicable to distinguish and harvest bioreporters. The approach described here provides a powerful tool to remotely control and selectively manipulate MNPs-unctionalized cells in water and soils. It would have a potential in the application of environmental microbiology, such as bioremediation enhancement and environment monitoring and assessment. PMID:21255376

Zhang, Dayi; Fakhrullin, Rawil F; Özmen, Mustafa; Wang, Hui; Wang, Jian; Paunov, Vesselin N; Li, Guanghe; Huang, Wei E

2011-01-01

263

Glypican-3 Targeting of Liver Cancer Cells Using Multifunctional Nanoparticles  

PubMed Central

Imaging is essential in accurately detecting, staging, and treating primary liver cancer (hepatocellular carcinoma (HCC)), one of the most prevalent and lethal malignancies. We developed a novel multifunctional nanoparticle (NP) specifically targeting glypican-3 (GPC3), a proteoglycan implicated in promotion of cell growth that is over-expressed in most HCCs. Quantitative real-time PCR was performed to confirm the differential GPC3 expression in two human HCC cells, Hep G2 (high) and SK-HEP-1 (negligible). These cells were treated with biotin-conjugated GPC3 monoclonal antibody (?GPC3) and subsequently targeted using superparamagnetic iron oxide NPs conjugated to streptavidin and Alexa Fluor 647. Flow cytometry demonstrated that only GPC3-expressing Hep G2 cells were specifically targeted using this ?GPC3-NP conjugate (4-fold mean fluorescence over non-targeted NP), and magnetic resonance imaging (MRI) experiments showed similar findings (3-fold R2 relaxivity). Confocal fluorescence microscopy localized the ?GPC3-NPs only to the cell surface of GPC3-expressing Hep G2 cells. Further characterization of this construct demonstrated a negatively charged, monodisperse, 50 nm NP, ideally suited for tumor targeting. This GPC3-specific NP system, with dual imaging capability, may enhance pretreatment MRI, enable refined intra-operative HCC visualization by NIR fluorescence, and may be potentially used as a carrier for delivery of tumor-targeted therapies, improving patient outcomes.

Park, James O.; Stephen, Zachary; Sun, Conroy; Veiseh, Omid; Kievit, Forrest M.; Fang, Chen; Leung, Matthew; Mok, Hyejung; Zhang, Miqin

2010-01-01

264

Electrochemical study of the effect of functionalized nickel nanoparticles on cellular uptake of leukemia cancer cells in vitro  

Microsoft Academic Search

In this study, we have fabricated the functionalized nickel nanoparticles and investigated their effects on cellular uptake of quercetin in leukemia K562 cancer cells by using electrochemical assay. The results indicate that nickel nanoparticles could efficiently enhance the quercetin uptake and increase the intracellular accumulation in cancer cells, implying the great potential of functionalized nickel nanoparticles in target cancer therapy.

Da Dong Guo; Chun Hui Wu; Xue Mei Wang; Bao An Chen

2008-01-01

265

Syntheses of amorphous and crystalline cupric sulfide nanoparticles and study on the specific activities on different cells.  

PubMed

Copper sulfide amorphous nanoparticles and nanocrystals were prepared successfully by a special process. These CuS nanoparticles could specifically and significantly induce the apoptosis and inhibit the proliferation of human cancer cells rather than normal cells. Moreover, the biological activities of these nanoparticles are related to their polymorphs. PMID:20376385

Guo, Yuming; Zhang, Jie; Yang, Lin; Wang, Huajie; Wang, Feifei; Zheng, Zhi

2010-04-07

266

Cells lacking CIP1\\/WAF1 genes exhibit preferential sensitivity to cisplatin and nitrogen mustard  

Microsoft Academic Search

We have previously shown that p53 disruption sensitizes certain cancer cell types to cisplatin (CDDP) (Fan et al., 1995). In the present study we investigated the role of the p53 downstream effector, p21CIP1\\/WAF1 (p21), in this sensitization. Studies were performed in human colon cancer HCT-116 cells and murine embryonic fibroblasts (MEF) with intact versus disrupted p21 genes. For comparison, HCT-116

Saijun Fan; Johnny K Chang; Martin L Smith; Diane Duba; Albert J Fornace Jr; Patrick M O'Connor

1997-01-01

267

Transformed roots of Artemisia annua exhibit an unusual pattern of border cell release  

Microsoft Academic Search

Summary  Border cells from Artemisia annua were examined from hairy roots grown in shake flasks, culture plates, a bubble column reactor, and a nutrient mist (aeroponic)\\u000a reactor. When well-hydrated roots were subjected to shear, border cells were first released as an agglomerate and did not\\u000a disperse for several hours. Staining with neutral red and fluorescein diacetate (FDA) showed that both agglomerates

Pamela J. Weathers; Yoo Jeong Kim

2001-01-01

268

Cellular uptake of magnetic nanoparticle is mediated through energy-dependent endocytosis in A549 cells  

PubMed Central

Biocompatible silica-overcoated magnetic nanoparticles containing an organic fluorescence dye, rhodamine B isothiocyanate (RITC), within a silica shell [50 nm size, MNP@SiO2(RITC)s] were synthesized. For future application of the MNP@SiO2(RITC)s into diverse areas of research such as drug or gene delivery, bioimaging, and biosensors, detailed information of the cellular uptake process of the nanoparticles is essential. Thus, this study was performed to elucidate the precise mechanism by which the lung cancer cells uptake the magnetic nanoparticles. Lung cells were chosen for this study because inhalation is the most likely route of exposure and lung cancer cells were also found to uptake magnetic nanoparticles rapidly in preliminary experiments. The lung cells were pretreated with different metabolic inhibitors. Our results revealed that low temperature disturbed the uptake of magnetic nanoparticles into the cells. Metabolic inhibitors also prevented the delivery of the materials into cells. Use of TEM clearly demonstrated that uptake of the nanoparticles was mediated through endosomes. Taken together, our results demonstrate that magnetic nanoparticles can be internalized into the cells through an energy-dependent endosomal-lysosomal mechanism.

Kim, Jun-Sung; Yoon, Tae-Jong; Yu, Kyeong-Nam; Noh, Mi Suk; Woo, Minah; Kim, Byung-Geol; Lee, Kee-Ho; Sohn, Byung-Hyuk; Park, Seung-Bum

2006-01-01

269

Leukemia-initiating cells in human T-lymphoblastic leukemia exhibit glucocorticoid resistance.  

PubMed

T-cell acute lymphoblastic leukemia (T-ALL) is associated with a significant risk of disease relapse, but the biological basis for relapse is poorly understood. Here, we identify leukemiainitiating cells (L-ICs) on the basis of functional assays and prospective isolation and report a role for L-ICs in T-ALL disease and relapse. Long-term proliferation in response to NOTCH1 activating signals in OP9-DL1 coculture system or capacity to initiate leukemia in xenografts by the CD7(+)CD1a(-) subset of primary T-ALL samples was superior to other subsets, refining the identity of T-ALL L-ICs. T-ALL engraftment was improved in nonobese diabetic/severe combined immunodeficiency (NOD/scid)IL2R?(null) (NSG) mice compared with NOD/scid with anti-CD122 treatment (NS122), but both showed changes in leukemia immunophenotype. Clonal analysis of xenografts using the TCRG locus revealed the presence of subclones of T-ALL L-ICs, some of which possess a selective growth advantage and correlated with the capacity of CD7(+)CD1a(+) xenograft cells to engraft secondary NSG mice. Treatment of high-risk T-ALL xenografts eliminated CD1a(+) T-ALL cells, but CD1a(-) cells were resistant and their number was increased. Our results establish that primary CD1a(-) T-ALL cells are functionally distinct from CD1a(+) cells and that the CD7(+)CD1a(-) subset is enriched for L-IC activity that may be involved in mediating disease relapse after therapy. PMID:20810926

Chiu, Priscilla P L; Jiang, Hong; Dick, John E

2010-09-01

270

Synergistic Effect of Functionalized Nickel Nanoparticles and Quercetin on Inhibition of the SMMC-7721 Cells Proliferation.  

PubMed

The effect of functionalized nickel (Ni) nanoparticles capped with positively charged tetraheptylammonium on cellular uptake of drug quercetin into hepatocellular carcinoma cells (SMMC-7721) has been explored in this study via microscopy and electrochemical characterization as well as MTT assay. Meanwhile, the influence of Ni nanoparticles and/or quercetin on cell proliferation has been further evaluated by the real-time cell electronic sensing (RT-CES) study. Our observations indicate that Ni nanoparticles could efficiently improve the permeability of cancer cell membrane, and remarkably enhance the accumulation of quercetin in SMMC-7721 cells, suggesting that Ni nanoparticles and quercetin would facilitate the synergistic effect on inhibiting proliferation of cancer cells. PMID:20651919

Guo, Dadong; Wu, Chunhui; Li, Jingyuan; Guo, Airong; Li, Qingning; Jiang, Hui; Chen, Baoan; Wang, Xuemei

2009-08-23

271

Magnetite nanoparticles doped photoresist derived carbon as a suitable substratum for nerve cell culture.  

PubMed

A method which alters the substrate's physical and electrochemical properties by doping photoresist derived carbon with magnetite nanoparticles has been developed to enhance the existing substrate's ability to foster cell growth. Cyclic voltammetry, scanning electron microscopy and atomic force microscopy are used to evaluate the characters of the prepared film. And then, the magnetite nanoparticles doped carbon film is used as substrate for the growth of nerve cell. Here, rat pheochromocytoma cells are used for culture to test substrate-cell interactions. The results showed an increase in cell concentration and average neurite length with the increase of nanoparticle concentration on the surface. Importantly, the nerve cells can be grown on the magnetite nanoparticles doped carbon even in the absence of nerve growth factor. This finding will potentially provide a new material for nerve regeneration. PMID:23010126

Zhu, Zanzan; Rezhdo, Olijora; Perrone, Matthew; Bao, Zhengzheng; Munir, Ahsan; Wang, Jianlong; Zhou, H Susan; Shao, Jiahui

2012-08-14

272

Loading Erythrocytes with Maghemite Nanoparticles via Osmotic Pressure Induced Cell Membrane Pores  

NASA Astrophysics Data System (ADS)

Encapsulating magnetic nanoparticles within red blood cells is one strategy for extending the lifetime of magnetic resonance imaging contrast agents in the bloodstream. Human red blood cells were incubated for 12 hours with iron oxide (?-Fe2O3) nanoparticles with a broad range of particle and aggregate sizes (ranging from 10 to 600 nm) at different osmolarities ranging from 100 to 290 mOsm before being returned to an osmolarity of 300 mOsm. Concentrations of nanoparticles trapped within the cells were measured using transmission electron microscopy and iron-mapping by electron energy loss spectroscopy. An osmolarity of 200 mOsm was found to be the optimal condition for loading of the cells with nanoparticles. At this osmolarity, it was shown that the concentration of particles within the cells relative to the average concentration in the suspension is maximized. At 200 mOsm, the maximum size aggregate of particles that entered the cells was approximately 120 nm.

Ibrahim, Mounir; Wee, Leonard; Saunders, Martin; Woodward, Robert C.; Pierre, Timothy G. St

2010-12-01

273

Ligand modified nanoparticles increases cell uptake, alters endocytosis and elevates glioma distribution and internalization.  

PubMed

Nanoparticles (NPs) were widely used in drugs/probes delivery for improved disease diagnosis and/or treatment. Targeted delivery to cancer cells is a highly attractive application of NPs. However, few studies have been performed on the targeting mechanisms of these ligand-modified delivery systems. Additional studies are needed to understand the transport of nanoparticles in the cancer site, the interactions between nanoparticles and cancer cells, the intracellular trafficking of nanoparticles within the cancer cells and the subcellular destiny and potential toxicity. Interleukin 13 (IL-13) peptide can specifically bind IL-13R?2, a receptor that is highly expressed on glioma cells but is expressed at low levels on other normal cells. It was shown that the nanoparticels modification with the IL-13 peptide could improve glioma treatment by selectively increasing cellular uptake, facilitating cell internalization, altering the uptake pathway and increasing glioma localization. PMID:23982586

Gao, Huile; Yang, Zhi; Zhang, Shuang; Cao, Shijie; Shen, Shun; Pang, Zhiqing; Jiang, Xinguo

2013-08-28

274

The Influences of Cell Type and ZnO Nanoparticle Size on Immune Cell Cytotoxicity and Cytokine Induction  

NASA Astrophysics Data System (ADS)

Nanotechnology represents a new and enabling platform that promises to provide a range of innovative technologies for biological applications. ZnO nanoparticles of controlled size were synthesized, and their cytotoxicity toward different human immune cells evaluated. A differential cytotoxic response between human immune cell subsets was observed, with lymphocytes being the most resistant and monocytes being the most susceptible to ZnO nanoparticle-induced toxicity. Significant differences were also observed between previously activated memory lymphocytes and naive lymphocytes, indicating a relationship between cell-cycle potential and nanoparticle susceptibility. Mechanisms of toxicity involve the generation of reactive oxygen species, with monocytes displaying the highest levels, and the degree of cytotoxicity dependent on the extent of nanoparticle interactions with cellular membranes. An inverse relationship between nanoparticle size and cytotoxicity, as well as nanoparticle size and reactive oxygen species production was observed. In addition, ZnO nanoparticles induce the production of the proinflammatory cytokines, IFN-?, TNF-?, and IL-12, at concentrations below those causing appreciable cell death. Collectively, these results underscore the need for careful evaluation of ZnO nanoparticle effects across a spectrum of relevant cell types when considering their use for potential new nanotechnology-based biological applications.

Hanley, Cory; Thurber, Aaron; Hanna, Charles; Punnoose, Alex; Zhang, Jianhui; Wingett, Denise G.

2009-12-01

275

The Influences of Cell Type and ZnO Nanoparticle Size on Immune Cell Cytotoxicity and Cytokine Induction  

PubMed Central

Nanotechnology represents a new and enabling platform that promises to provide a range of innovative technologies for biological applications. ZnO nanoparticles of controlled size were synthesized, and their cytotoxicity toward different human immune cells evaluated. A differential cytotoxic response between human immune cell subsets was observed, with lymphocytes being the most resistant and monocytes being the most susceptible to ZnO nanoparticle-induced toxicity. Significant differences were also observed between previously activated memory lymphocytes and naive lymphocytes, indicating a relationship between cell-cycle potential and nanoparticle susceptibility. Mechanisms of toxicity involve the generation of reactive oxygen species, with monocytes displaying the highest levels, and the degree of cytotoxicity dependent on the extent of nanoparticle interactions with cellular membranes. An inverse relationship between nanoparticle size and cytotoxicity, as well as nanoparticle size and reactive oxygen species production was observed. In addition, ZnO nanoparticles induce the production of the proinflammatory cytokines, IFN-?, TNF-?, and IL-12, at concentrations below those causing appreciable cell death. Collectively, these results underscore the need for careful evaluation of ZnO nanoparticle effects across a spectrum of relevant cell types when considering their use for potential new nanotechnology-based biological applications.

2009-01-01

276

The influence of surface functionalization on the enhanced internalization of magnetic nanoparticles in cancer cells  

Microsoft Academic Search

The internalization and biocompatibility of iron oxide nanoparticles surface functionalized with four differently charged carbohydrates have been tested in the human cervical carcinoma cell line (HeLa). Neutral, positive, and negative iron oxide nanoparticles were obtained by coating with dextran, aminodextran, heparin, and dimercaptosuccinic acid, resulting in colloidal suspensions stable at pH 7 with similar aggregate size. No intracellular uptake was

Angeles Villanueva; Magdalena Cañete; Alejandro G Roca; Macarena Calero; Sabino Veintemillas-Verdaguer; Carlos J Serna; María del Puerto Morales; Rodolfo Miranda

2009-01-01

277

The physical state of lipid nanoparticles influences their effect on in vitro cell viability  

Microsoft Academic Search

Although lipid nanoparticles represent potent drug carriers, for many formulations toxicity data are rare. Thus, in this study, the effect of different lipid nanoparticles on the cell viability of L929 mouse fibroblasts was systematically investigated using the MTT assay. The formulations were composed of trimyristin, tristearin or cholesteryl myristate stabilized with poloxamer 188, polysorbate 80, polyvinyl alcohol or a blend

Silvia Petersen; Frank Steiniger; Dagmar Fischer; Alfred Fahr; Heike Bunjes

2011-01-01

278

Fluoridated HAp:Ln3+ (Ln = Eu or Tb) nanoparticles for cell-imaging.  

PubMed

Water-dispersible hydrophilic fluoridated HAp:Ln(3+) (Ln = Eu or Tb) nanoparticles were prepared via hydrophobic/hydrophilic transformation with surfactants (Pluronic F127). The HAp:Ln(3+) (Ln = Eu or Tb) nanoparticles with unique luminescent properties and excellent biocompatibility are promising for cell imaging applications. PMID:23076865

Hui, Junfeng; Zhang, Xiaoyong; Zhang, Zhicheng; Wang, Shiqi; Tao, Lei; Wei, Yen; Wang, Xun

2012-11-21

279

Synthesis and characterization of folate conjugated chitosan and cellular uptake of its nanoparticles in HT-29 cells.  

PubMed

Folate-chitosan (FA-CS) conjugates synthesized by coupling FA with CS render new and improved functions because the original properties of CS are maintained and the targeting ligand of FA is incorporated. In this work, FA-CS conjugates were synthesized based on chemical linking of carboxylic group of FA with amino group of CS as confirmed by Fourier transform spectroscopy (FTIR) and nuclear magnetic resonance ((1)H NMR). FA-CS conjugates displayed less crystal nature when compared to CS. The FA-CS nanoparticles (NPs) were prepared by crosslinking FA-CS conjugates with sodium tripolyphosphate (STPP). Positively charged FA-CS nanoparticles were spherical in shape with a particle size of about 100 nm. Cellular uptake of CS or FA-CS nanoparticles was assayed by fluorescent microscopy using calcein as fluorescent marker in colon cancer cells (HT-29). The FA-CS nanoparticles exhibited improved uptake of HT-29 and could become a potential targeted drug delivery system for colorectal cancer. PMID:21397214

Li, Puwang; Wang, Yichao; Zeng, Fanbo; Chen, Lijue; Peng, Zheng; Kong, Ling Xue

2011-05-01

280

Kupffer cells are central in the removal of nanoparticles from the organism  

PubMed Central

Background The study aims at revealing the fate of nanoparticles administered intravenously and intraperitoneally to adult female mice, some of which were pregnant. Gold nanoparticles were chosen as a model because these particles have been found to be chemically inert and at the same time are easily traced by autometallography (AMG) at both ultrastructural and light microscopic levels. Results Gold nanoparticles were injected intravenously (IV) or intraperitoneally (IP) and traced after 1, 4 or 24 hours. For IV injections 2 and 40 nm particles were used; for IP injections 40 nm particles only. The injected nanoparticles were found in macrophages only, and at moderate exposure primarily in the Kupffer cells in the liver. IV injections resulted in a rapid accumulation/clustering of nanoparticles in these liver macrophages, while the uptake in spleen macrophages was moderate. IP injections were followed by a delayed uptake in the liver and included a moderate uptake in macrophages located in mesenteric lymph nodes, spleen and small intestine. Ultrastructurally, the AMG silver enhanced nanocrystals were found in lysosome-like organelles of the Kupffer cells and other macrophages wherever located. Accumulations of gold nanoparticles were not found in any other organs analysed, i.e. kidneys, brain, lungs, adrenals, ovaries, placenta, and fetal liver, and the control animals were all void of AMG staining. Conclusion Our results suggest that: (1) inert gold nanoparticles do not penetrate cell membranes by non-endocytotic mechanisms, but are rather taken up by endocytosis; (2) gold nanoparticles, independent of size, are taken up primarily by Kupffer cells in the liver and secondarily by macrophages in other places; (3) gold nanoparticles do not seem to penetrate the placenta barrier; (4) the blood-brain barrier seems to protect the central nervous system from gold nanoparticles; (5) 2 nanometer gold particles seem to be removed not only by endocytosis by macrophages, and we hypothesize that part of these tiny nanoparticles are released into the urine as a result of simple filtration in the renal glomeruli.

Sadauskas, Evaldas; Wallin, Hakan; Stoltenberg, Meredin; Vogel, Ulla; Doering, Peter; Larsen, Agnete; Danscher, Gorm

2007-01-01

281

Single-cell response to stiffness exhibits muscle-like behavior  

PubMed Central

Living cells sense the rigidity of their environment and adapt their activity to it. In particular, cells cultured on elastic substrates align their shape and their traction forces along the direction of highest stiffness and preferably migrate towards stiffer regions. Although numerous studies investigated the role of adhesion complexes in rigidity sensing, less is known about the specific contribution of acto-myosin based contractility. Here we used a custom-made single-cell technique to measure the traction force as well as the speed of shortening of isolated myoblasts deflecting microplates of variable stiffness. The rate of force generation increased with increasing stiffness and followed a Hill force–velocity relationship. Hence, cell response to stiffness was similar to muscle adaptation to load, reflecting the force-dependent kinetics of myosin binding to actin. These results reveal an unexpected mechanism of rigidity sensing, whereby the contractile acto-myosin units themselves can act as sensors. This mechanism may translate anisotropy in substrate rigidity into anisotropy in cytoskeletal tension, and could thus coordinate local activity of adhesion complexes and guide cell migration along rigidity gradients.

Mitrossilis, Demosthene; Fouchard, Jonathan; Guiroy, Axel; Desprat, Nicolas; Rodriguez, Nicolas; Fabry, Ben; Asnacios, Atef

2009-01-01

282

bcl-x exhibits regulated expression during B cell development and activation and modulates lymphocyte survival in transgenic mice  

PubMed Central

We have assessed during B cell development, the regulation and function of bcl-x, a member of the bcl-2 family of apoptosis regulatory genes. Here we show that Bcl-xL, a product of bcl-x, is expressed in pre-B cells but downregulated at the immature and mature stages of B cell development. Bcl-xL but not Bcl-2 is rapidly induced in peripheral B cells upon surface immunoglobulin M (IgM) cross-linking, CD40 signaling, or LPS stimulation. Transgenic mice that overexpressed Bcl- xL within the B cell lineage exhibited marked accumulation of peripheral B cells in lymphoid organs and enhanced survival of developing and mature B cells. B cell survival was further increased by simultaneous expression of bcl-xL and bcl-2 transgenes. These studies demonstrate that Bcl-2 and Bcl-xL are regulated differentially during B cell development and activation of mature B cells. Induction of Bcl-xL after signaling through surface IgM and CD40 appears to provide mature B cells with an additional protective mechanism against apoptotic signals associated with antigen-induced activation and proliferation.

1996-01-01

283

Mass imaging of iron oxide nanoparticles inside cells for in vitro cytotoxicity.  

PubMed

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging analysis was performed on murine macrophage cells treated with various concentrations of iron oxide (Fe3O4) nanoparticles, which are used as MRI contrast agents. First, murine macrophage cells were seeded on a slide glass for 24 hrs and treated with varying concentrations of Fe3O4 nanoparticles for 24 hrs. To expose a cross section of each cell and obtain a distribution of the nanoparticles inside the cells, the cells were sputtered using Bi ions after which the cross section of each cell was scanned and imaged using the focused cluster ion beam with a spatial resolution of 300 nm. Fe3O4 nanoparticles were found mainly in the cytoplasm region of the cells, not in the nucleus region of cells, suggesting that the uptake of the Fe3O4 nanoparticles were into the cytoplasm of cell, not into the nucleus of cell. Based on these observations, our protocol using mass imaging analysis would be a useful addition to the study of in vitro nanoparticle cytotoxicity. PMID:21446514

Shon, Hyun Kyong; Park, Jungsin; Choi, Inhong; Park, Hyun Min; Moon, Dae Won; Lee, Tae Geol

2011-01-01

284

Red-emitting upconverting nanoparticles for photodynamic therapy in cancer cells under near-infrared excitation.  

PubMed

Upconverting nanoparticles (UCNPs) have attracted considerable attention as potential photosensitizer carriers for photodynamic therapy (PDT) in deep tissues. In this work, a new and efficient NIR photosensitizing nanoplatform for PDT based on red-emitting UCNPs is designed. The red emission band matches well with the efficient absorption bands of the widely used commercially available photosensitizers (Ps), benefiting the fluorescence resonance energy transfer (FRET) from UCNPs to the attached photosensitizers and thus efficiently activating them to generate cytotoxic singlet oxygen. Three commonly used photosensitizers, including chlorine e6 (Ce6), zinc phthalocyanine (ZnPc) and methylene blue (MB), are loaded onto the alpha-cyclodextrin-modified UCNPs to form Ps@UCNPs complexes that efficiently produce singlet oxygen to kill cancer cells under 980 nm near-infrared excitation. Moreover, two different kinds of drugs are co-loaded onto these nanoparticles: chemotherapy drug doxorubicin and PDT agent Ce6. The combinational therapy based on doxorubicin (DOX)-induced chemotherapy and Ce6-triggered PDT exhibits higher therapeutic efficacy relative to the individual means for cancer therapy in vitro. PMID:23239556

Tian, Gan; Ren, Wenlu; Yan, Liang; Jian, Shan; Gu, Zhanjun; Zhou, Liangjun; Jin, Shan; Yin, Wenyan; Li, Shoujian; Zhao, Yuliang

2012-12-13

285

Metre-long cell-laden microfibres exhibit tissue morphologies and functions.  

PubMed

Artificial reconstruction of fibre-shaped cellular constructs could greatly contribute to tissue assembly in vitro. Here we show that, by using a microfluidic device with double-coaxial laminar flow, metre-long core-shell hydrogel microfibres encapsulating ECM proteins and differentiated cells or somatic stem cells can be fabricated, and that the microfibres reconstitute intrinsic morphologies and functions of living tissues. We also show that these functional fibres can be assembled, by weaving and reeling, into macroscopic cellular structures with various spatial patterns. Moreover, fibres encapsulating primary pancreatic islet cells and transplanted through a microcatheter into the subrenal capsular space of diabetic mice normalized blood glucose concentrations for about two weeks. These microfibres may find use as templates for the reconstruction of fibre-shaped functional tissues that mimic muscle fibres, blood vessels or nerve networks in vivo. PMID:23542870

Onoe, Hiroaki; Okitsu, Teru; Itou, Akane; Kato-Negishi, Midori; Gojo, Riho; Kiriya, Daisuke; Sato, Koji; Miura, Shigenori; Iwanaga, Shintaroh; Kuribayashi-Shigetomi, Kaori; Matsunaga, Yukiko T; Shimoyama, Yuto; Takeuchi, Shoji

2013-03-31

286

Metre-long cell-laden microfibres exhibit tissue morphologies and functions  

NASA Astrophysics Data System (ADS)

Artificial reconstruction of fibre-shaped cellular constructs could greatly contribute to tissue assembly in vitro. Here we show that, by using a microfluidic device with double-coaxial laminar flow, metre-long core-shell hydrogel microfibres encapsulating ECM proteins and differentiated cells or somatic stem cells can be fabricated, and that the microfibres reconstitute intrinsic morphologies and functions of living tissues. We also show that these functional fibres can be assembled, by weaving and reeling, into macroscopic cellular structures with various spatial patterns. Moreover, fibres encapsulating primary pancreatic islet cells and transplanted through a microcatheter into the subrenal capsular space of diabetic mice normalized blood glucose concentrations for about two weeks. These microfibres may find use as templates for the reconstruction of fibre-shaped functional tissues that mimic muscle fibres, blood vessels or nerve networks in vivo.

Onoe, Hiroaki; Okitsu, Teru; Itou, Akane; Kato-Negishi, Midori; Gojo, Riho; Kiriya, Daisuke; Sato, Koji; Miura, Shigenori; Iwanaga, Shintaroh; Kuribayashi-Shigetomi, Kaori; Matsunaga, Yukiko T.; Shimoyama, Yuto; Takeuchi, Shoji

2013-06-01

287

A dodecapeptide (YQVTQSKVMSHR) exhibits antibacterial effect and induces cell aggregation in Escherichia coli.  

PubMed

Antimicrobial peptides play an important role in the innate immune response and host defense mechanism. In the present study, we employed phage display technique to screen for inhibitors which may block the phosphoenolpyruvatedependent phosphotransferase system (PTS) pathway and hence retard cell growth. The recombinant histidine-containing phosphocarrier HPr protein was prepared as the target to screen for the tight binders from the phage-displayed random peptide library Ph.D.-12. The biopanning processes were performed and the binding capabilities of the selected phage were further estimated by enzyme-linked immunosorbent assay (ELISA). The single-stranded DNAs of the 20 selected phages were isolated, sequenced, and five corresponding peptides were synthesized. Only one of the five peptides, AP1 (YQVTQSK VMSHR) was found to inhibit the growth of Escherichia coli cells efficiently (IC??~50 ?M). Molecular modeling reveals that AP1 may block the EI-HPr interaction and phosphotransfer. Interestingly, AP1 was also found to induce cell aggregation in a concentration-dependent manner. Since glycogen accumulation has been attributed to biofilm formation, the effects of AP1 on the intracellular glycogen levels were measured. The results strongly indicate that the cell aggregation may be caused by the binding of peptide AP1 with HPr to block the interaction of dephosphorylated HPr with glycogen phosphorylase (GP). Because glycogen phosphorylase activity can be activated by HPr-GP interaction, the binding of AP1 to HPr would cause a decreasing rate of glycogen breakdown in M9 medium and accumulation of glycogen, which may lead to eventual cell aggregation. To the best of our knowledge, this is the first study to demonstrate that an inhibitor bound to a dephosphorylated HPr can decouple its regulatory function and induce cell aggregation. PMID:22314514

Lin, Kuo-Chih; Chen, Chih-Yuan; Chang, Chih-Wei; Huang, Kuo-Jien; Lin, Shih-Pin; Lin, Shih-Hung; Chang, Ding-Kwo; Lin, Meei-Ru; Shiuan, David

2012-02-09

288

Oxidative stress induced by cerium oxide nanoparticles in cultured BEAS-2B cells  

Microsoft Academic Search

Cerium oxide nanoparticles of different sizes (15, 25, 30, 45nm) were prepared by the supercritical synthesis method, and cytotoxicity was evaluated using cultured human lung epithelial cells (BEAS-2B). Exposure of the cultured cells to nanoparticles (5, 10, 20, 40?g\\/ml) led to cell death, ROS increase, GSH decrease, and the inductions of oxidative stress-related genes such as heme oxygenase-1, catalase, glutathione

Eun-Jung Park; Jinhee Choi; Young-Kwon Park

2008-01-01

289

Enhanced relative biological effectiveness of proton radiotherapy in tumor cells with internalized gold nanoparticles  

NASA Astrophysics Data System (ADS)

The development and use of sensitizing agents to improve the effectiveness of radiotherapy have long been sought to improve our ability to treat cancer. In this letter, we have studied the relative biological effectiveness of proton beam radiotherapy on prostate tumor cells with and without internalized gold nanoparticles. The effectiveness of proton radiotherapy for the killing of prostate tumor cells was increased by approximately 15%-20% for those cells containing internalized gold nanoparticles.

Polf, Jerimy C.; Bronk, Lawrence F.; Driessen, Wouter H. P.; Arap, Wadih; Pasqualini, Renata; Gillin, Michael

2011-05-01

290

Synergistic Effect of Functionalized Nickel Nanoparticles and Quercetin on Inhibition of the SMMC-7721 Cells Proliferation  

Microsoft Academic Search

The effect of functionalized nickel (Ni) nanoparticles capped with positively charged tetraheptylammonium on cellular uptake\\u000a of drug quercetin into hepatocellular carcinoma cells (SMMC-7721) has been explored in this study via microscopy and electrochemical\\u000a characterization as well as MTT assay. Meanwhile, the influence of Ni nanoparticles and\\/or quercetin on cell proliferation\\u000a has been further evaluated by the real-time cell electronic sensing

Dadong Guo; Chunhui Wu; Jingyuan Li; Airong Guo; Qingning Li; Hui Jiang; Baoan Chen; Xuemei Wang

2009-01-01

291

Effects of MnO2 Nanoparticles on Liver and Kidney Cells of Rats  

Microsoft Academic Search

In order to study the effects of MnO2 nanoparticles on cells of rats liver and kidney, rats liver and kidney cells were exposed to different concentrations (0, 0.05, 0.50, 5.00, 50.00 ?g\\/mL) of MnO2 nanoparticles at 37?. An hour later, reactive oxygen species (ROS) levels, glutathione (GSH) concentrations and DNA-protein crosslinks (DPC) degrees in cells were measured to detect the

Huihui You; Jingyun Zhao; Lingling Li; Junlin Yuan

2011-01-01

292

Enhanced relative biological effectiveness of proton radiotherapy in tumor cells with internalized gold nanoparticles  

PubMed Central

The development and use of sensitizing agents to improve the effectiveness of radiotherapy have long been sought to improve our ability to treat cancer. In this letter, we have studied the relative biological effectiveness of proton beam radiotherapy on prostate tumor cells with and without internalized gold nanoparticles. The effectiveness of proton radiotherapy for the killing of prostate tumor cells was increased by approximately 15%–20% for those cells containing internalized gold nanoparticles.

Polf, Jerimy C.; Bronk, Lawrence F.; Driessen, Wouter H. P.; Arap, Wadih; Pasqualini, Renata; Gillin, Michael

2011-01-01

293

Enhancement of cell recognition in vitro by dual-ligand cancer targeting gold nanoparticles  

Microsoft Academic Search

A dual-ligand gold nanoparticle (DLGNP) was designed and synthesized to explore the therapeutic benefits of multivalent interactions between gold nanoparticles (GNPs) and cancer cells. DLGNP was tested on human epidermal cancer cells (KB), which had high expression of folate receptor. The cellular uptake of DLGNP was increased by 3.9 and 12.7 folds compared with GNP-folate or GNP-glucose. The enhanced cell

Xi Li; Hongyu Zhou; Lei Yang; Guoqing Du; Atmaram S. Pai-Panandiker; Xuefei Huang; Bing Yan

2011-01-01

294

Metallofullerene nanoparticles promote osteogenic differentiation of bone marrow stromal cells through BMP signaling pathway  

NASA Astrophysics Data System (ADS)

Although endohedral metallofullerenol [Gd@C82(OH)22]n nanoparticles have anti-tumor efficiency and mostly deposit in the bones of mice, how these nanoparticles act in bone marrow stromal cells (MSCs) remains largely unknown. Herein, we observed that [Gd@C82(OH)22]n nanoparticles facilitated the differentiation of MSCs toward osteoblasts, as evidenced by the enhancement of alkaline phosphatase (ALP) activity and mineralized nodule formation upon [Gd@C82(OH)22]n nanoparticle treatment. Mechanistically, the effect of [Gd@C82(OH)22]n nanoparticles on ALP activity was inhibited by the addition of noggin as an inhibitor of the BMP signaling pathway. Moreover, the in vivo results of the ovariectomized rats further indicated that [Gd@C82(OH)22]n nanoparticles effectively improved bone density and prevented osteoporosis.Although endohedral metallofullerenol [Gd@C82(OH)22]n nanoparticles have anti-tumor efficiency and mostly deposit in the bones of mice, how these nanoparticles act in bone marrow stromal cells (MSCs) remains largely unknown. Herein, we observed that [Gd@C82(OH)22]n nanoparticles facilitated the differentiation of MSCs toward osteoblasts, as evidenced by the enhancement of alkaline phosphatase (ALP) activity and mineralized nodule formation upon [Gd@C82(OH)22]n nanoparticle treatment. Mechanistically, the effect of [Gd@C82(OH)22]n nanoparticles on ALP activity was inhibited by the addition of noggin as an inhibitor of the BMP signaling pathway. Moreover, the in vivo results of the ovariectomized rats further indicated that [Gd@C82(OH)22]n nanoparticles effectively improved bone density and prevented osteoporosis. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr33575a

Yang, Kangning; Cao, Weipeng; Hao, Xiaohong; Xue, Xue; Zhao, Jing; Liu, Juan; Zhao, Yuliang; Meng, Jie; Sun, Baoyun; Zhang, Jinchao; Liang, Xing-Jie

2013-01-01

295

Orthopaedic applications of nanoparticle-based stem cell therapies  

PubMed Central

Stem cells have tremendous applications in the field of regenerative medicine and tissue engineering. These are pioneering fields that aim to create new treatments for disease that currently have limited therapies or cures. A particularly popular avenue of research has been the regeneration of bone and cartilage to combat various orthopaedic diseases. Magnetic nanoparticles (MNPs) have been applied to aid the development and translation of these therapies from research to the clinic. This review highlights contemporary research for the applications of iron-oxide-based MNPs for the therapeutic implementation of stem cells in orthopaedics. These MNPs comprise of an iron oxide core, coated with a choice of biological polymers that can facilitate the uptake of MNPs by cells through improving endocytic activity. The combined use of these oxides and the biological polymer coatings meet biological requirements, effectively encouraging the use of MNPs in regenerative medicine. The association of MNPs with stem cells can be achieved via the process of endocytosis resulting in the internalisation of these particles or the attachment to cell surface receptors. This allows for the investigation of migratory patterns through various tracking studies, the targeting of particle-labelled cells to desired locations via the application of an external magnetic field and, finally, for activation stem cells to initiate various cellular responses to induce the differentiation. Characterisation of cell localisation and associated tissue regeneration can therefore be enhanced, particularly for in vivo applications. MNPs have been shown to have the potential to stimulate differentiation of stem cells for orthopaedic applications, without limiting proliferation. However, careful consideration of the use of active agents associated with the MNP is suggested, for differentiation towards specific lineages. This review aims to broaden the knowledge of current applications, paving the way to translate the in vitro and in vivo work into further orthopaedic clinical studies.

2012-01-01

296

Beauty is Skin Deep: A Surface Monolayer Perspective on Nanoparticle Interactions with Cells and Biomacromolecules**  

PubMed Central

Surface recognition of biosystems is a critical component in the development of novel biosensors, delivery vehicles and for the therapeutic regulation of biological processes. Monolayer-protected nanoparticles present a highly versatile scaffold for selective interaction with biomacromolecules and cells. Through engineering of the monolayer surface, nanoparticles can be tailored for surface recognition of biomolecules and cells. This review highlights recent progress in nanoparticle-biomacromolecule/cellular interactions, emphasizing the effect of the surface monolayer structure on the interactions with proteins, DNA and cell surfaces. The extension of these tailored interactions to hybrid nanomaterials, biosensing platforms and delivery vehicles is also discussed.

Saha, Krishnendu; Bajaj, Avinash; Duncan, Bradley; Rotello, Vincent M.

2012-01-01

297

Vapor bubble generation around gold nano-particles and its application to damaging of cells  

PubMed Central

We investigated vapor bubbles generated upon irradiation of gold nanoparticles with nanosecond laser pulses. Bubble formation was studied both with optical and acoustic means on supported single gold nanoparticles and single nanoparticles in suspension. Formation thresholds determined at different wavelengths indicate a bubble formation efficiency increasing with the irradiation wavelength. Vapor bubble generation in Bac-1 cells containing accumulations of the same particles was also investigated at different wavelengths. Similarly, they showed an increasing cell damage efficiency for longer wavelengths. Vapor bubbles generated by single laser pulses were about half the cell size when inducing acute damage.

Kitz, M.; Preisser, S.; Wetterwald, A.; Jaeger, M.; Thalmann, G. N.; Frenz, M.

2011-01-01

298

Vascular endothelial cells cultured from patients with cerebral or uncomplicated malaria exhibit differential reactivity to TNF.  

PubMed

Plasmodium falciparum malaria is a major cause of morbidity and mortality in African children, and factors that determine the development of uncomplicated (UM) versus cerebral malaria (CM) are not fully understood. We studied the ex vivo responsiveness of microvascular endothelial cells to pro-inflammatory stimulation and compared the findings between CM and UM patients. In patients with fatal disease we compared the properties of vascular endothelial cells cultured from brain tissue to those cultured from subcutaneous tissue, and found them to be very similar. We then isolated, purified and cultured primary endothelial cells from aspirated subcutaneous tissue of patients with CM (EC(CM) ) or UM (EC(UM) ) and confirmed the identity of the cells before analysis. Upon TNF stimulation in vitro, EC(CM) displayed a significantly higher capacity to upregulate ICAM-1, VCAM-1 and CD61 and to produce IL-6 and MCP-1 but not RANTES compared with EC(UM) . The shedding of endothelial microparticles, a recently described parameter of severity in CM, and the cellular level of activated caspase-3 were both significantly greater in EC(CM) than in EC(UM) . These data suggest that inter-individual differences in the endothelial inflammatory response to TNF may be an additional factor influencing the clinical course of malaria. PMID:21029292

Wassmer, Samuel Crocodile; Moxon, Christopher Alan; Taylor, Terrie; Grau, Georges Emile; Molyneux, Malcolm Edward; Craig, Alister Gordon

2010-10-07

299

Tomato Spotted Wilt Virus Glycoproteins Exhibit Trafficking and Localization Signals That Are Functional in Mammalian Cells  

PubMed Central

The glycoprotein precursor (G1/G2) gene of tomato spotted wilt virus (TSWV) was expressed in BHK cells using the Semliki Forest virus expression system. The results reveal that in this cell system, the precursor is efficiently cleaved and the resulting G1 and G2 glycoproteins are transported from the endoplasmic reticulum (ER) to the Golgi complex, where they are retained, a process that could be blocked by tunicamycin. Expression of G2 alone resulted in transport to and retention in the Golgi complex, albeit less efficient, suggesting that G2 contains a Golgi retention signal. G1 alone was retained in the ER, irrespective of whether it contained the precursor's signal sequence or its own N-terminal hydrophobic sequence. Coexpression of G1 and G2 from separate gene constructs resulted in rescue of efficient G1 transport, as the proteins coaccumulated in the Golgi complex, indicating that their interaction is essential for proper targeting to this organelle. The results demonstrate that transport and targeting of the plant TSWV glycoproteins in mammalian BHK cells are strikingly similar to those of animal-infecting bunyavirus glycoproteins in mammalian cells. The observations are likely to reflect the dual tropism of TSWV, which replicates both in its plant host and in its animal (thrips) vector.

Kikkert, Marjolein; Verschoor, Ad; Kormelink, Richard; Rottier, Peter; Goldbach, Rob

2001-01-01

300

Sodium metavanadate exhibits carcinogenic tendencies in vitro in immortalized human bronchial epithelial cells.  

PubMed

Pentavalent vanadium compounds induce intracellular changes in vitro that are consistent with those of other carcinogenic substances. While there is no clear evidence that vanadium compounds cause cancer in humans, vanadium pentoxide causes lung cancer in rodents after long-term inhalation exposures and in turn IARC has categorized it as a group 2B possible human carcinogen. The goal of this study was to investigate the carcinogenicity of NaVO3 in the human immortalized bronchial epithelial cell line, Beas-2B. Cells were treated with 10 ?M NaVO3 for 5 weeks, with or without recovery time, followed by gene expression microarray analysis. In a separate experiment, cells were exposed to 1-10 ?M NaVO3 for 4 weeks and then grown in soft agar to test for anchorage-independent growth. A dose-dependent increase in the number of colonies was observed. In scratch tests, NaVO3-transformed clones could repair a wound faster than controls. In a gene expression microarray analysis of soft agar clones there were 2010 differentially expressed genes (DEG) (adjusted p-value ? 0.05) in NaVO3-transformed clones relative to control clones. DEG from this experiment were compared with the DEG of 5 week NaVO3 exposure with or without recovery, all with adjusted p-values < 0.05, and 469 genes were altered in the same direction for transformed clones, 5 week NaVO3-treated cells, and the recovered cells. The data from this study imply that chronic exposure to NaVO3 causes changes that are consistent with cellular transformation including anchorage-independent growth, enhanced migration ability, and gene expression changes that were likely epigenetically inherited. PMID:23963610

Passantino, Lisa; Muñoz, Alexandra B; Costa, Max

2013-09-25

301

Desulfurization activity and reusability of magnetite nanoparticle-coated Rhodococcus erythropolis FMF and R. erythropolis IGTS8 bacterial cells.  

PubMed

The application of Fe3 O4 nanoparticles to the separation of desulfurizing bacterial cells and their influence on the desulfurization activity and reusability of the two bacterial strains Rhodococcus erythropolis FMF and R. erythropolis IGTS8 were investigated. Magnetite nanoparticles were synthesized via the reverse coprecipitation method. Transmission electron microscopy (TEM) images showed that the magnetite nanoparticles had sizes of 5.35 ± 1.13 (F1 nanoparticles) and 8.74 ± 1.18 nm (F2 nanoparticles) when glycine was added during the synthesis of nanoparticles and when it was absent from the reaction mixture, respectively. Glycine was added after the synthesis of both F1 and F2 nanoparticles to stabilize the nanoparticle dispersion. TEM images of cells treated with magnetite nanoparticles indicated that F1 nanoparticles were immobilized on the surface of bacterial cells more evenly than the F2 nanoparticles. Desulfurization activities of the F1 magnetite nanoparticle-coated R. erythropolis FMF and R. erythropolis IGTS8 cells (with sulfur-removal percentage values of 70 ± 4 and 73 ± 3, respectively), as examined with the spectrophotometric Gibbs assay (based on dibenzothiophene degradation and sulfur-removal percentage), were not significantly different from those for the free bacterial cells (67 ± 3 and 69 ± 4, respectively). These results indicate that magnetite nanoparticles cannot affect the desulfurization activity of cells examined in this work. Isolation of bacterial cells from the suspension using a magnet and evaluation of desulfurization activity of separated cells showed that Fe3 O4 nanoparticles can provide a high-efficiency recovery of bacterial cells from a suspension, with the reused magnetite nanoparticle-coated bacterial cells being able to maintain their desulfurization activity efficiently. PMID:23656694

Bardania, Hassan; Raheb, Jamshid; Mohammad-Beigi, Hossein; Rasekh, Behnam; Arpanaei, Ayyoob

2013-05-08

302

Inhibition of the two-photon absorption response exhibited by a bilayer TiO2 film with embedded Au nanoparticles.  

PubMed

We use two different synthesis approaches for the preparation of TiO(2) films in order to study their resulting third order optical nonlinearity, and its modification by the inclusion of Au nanoparticles in one of the samples. An ultrasonic spray pyrolysis method was used for preparing a TiO(2) film in which we found two-photon absorption as a dominant nonlinear effect for 532 nm and 26 ps pulses; and a purely electronic nonlinearity at 830 nm for 80 fs pulses. A strong optical Kerr effect and the inhibition of the nonlinear optical absorption in 532 nm can be obtained for the first sample if Au nanoparticles embedded in a second TiO(2) film prepared by a sol-gel technique are added to it. We used an optical Kerr gate, z-scan, a multi-wave mixing experiment and an input-output transmittance experiment for measuring the optical nonlinearities. PMID:20721027

Torres-Torres, D; Trejo-Valdez, M; Castañeda, L; Torres-Torres, C; Tamayo-Rivera, L; Fernández-Hernández, R C; Reyes-Esqueda, J A; Muñoz-Saldaña, J; Rangel-Rojo, R; Oliver, A

2010-08-01

303

Oxidative stress and apoptosis induced by hydroxyapatite nanoparticles in C6 cells.  

PubMed

Hydroxyapatite (HA) nanoparticles have been reported to exhibit anti-tumor effects on various human cancers, but the effects of HA on glioma cells remain unclear. The aim of this study was to explore whether HA can inhibit the proliferation and induce the apoptosis of C6 cells. Use of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that HA induced C6 cell death in a concentration-dependent and time-dependent manner. Results from hoechst 33342 staining and flow cytometry assay showed that HA induced C6 cell apoptosis significantly. Meanwhile, the flow cytometric assay gave clear indication that HA induced intracellular accumulation of reactive oxygen species (ROS). The measurement of superoxide dismutase (SOD) generation showed that HA decreased the total SOD of cellular levels. Interestingly, pretreatment of N-(mercaptopropionyl)-glycine (N-MPG), known as a type of ROS scavenger formulations, could somehow inhibit C6 cell apoptosis induced by HA. These results may provide potential anti-glioma treatment in the future. PMID:22213249

Xu, Jing; Xu, Pengjuan; Li, Zhigui; Huang, Jie; Yang, Zhuo

2011-12-31

304

Detection of telomerase activity in high concentration of cell lysates using primer-modified gold nanoparticles.  

PubMed

Although the telomeric repeat amplification protocol (TRAP) has served as a powerful assay for detecting telomerase activity, its use has been significantly limited when performed directly in complex, interferant-laced samples. In this work, we report a modification of the TRAP assay that allows the detection of high-fidelity amplification of telomerase products directly from concentrated cell lysates. Briefly, we covalently attached 12 nm gold nanoparticles (AuNPs) to the telomere strand (TS) primer, which is used as a substrate for telomerase elongation. These TS-modified AuNPs significantly reduce polymerase chain reaction (PCR) artifacts (such as primer dimers) and improve the yield of amplified telomerase products relative to the traditional TRAP assay when amplification is performed in concentrated cell lysates. Specifically, because the TS-modified AuNPs eliminate most of the primer-dimer artifacts normally visible at the same position as the shortest amplified telomerase PCR product apparent on agarose gels, the AuNP-modified TRAP assay exhibits excellent sensitivity. Consequently, we observed a 10-fold increase in sensitivity for cancer cells diluted 1000-fold with somatic cells. It thus appears that the use of AuNP-modified primers significantly improves the sensitivity and specificity of the traditional TRAP assay and may be an effective method by which PCR can be performed directly in concentrated cell lysates. PMID:20932008

Xiao, Yi; Dane, Karen Y; Uzawa, Takanori; Csordas, Andrew; Qian, Jiangrong; Soh, H Tom; Daugherty, Patrick S; Lagally, Eric T; Heeger, Alan J; Plaxco, Kevin W

2010-11-01

305

DNA damage response to different surface chemistry of silver nanoparticles in mammalian cells  

SciTech Connect

Silver nanoparticles (Ag NPs) have recently received much attention for their possible applications in biotechnology and life sciences. Ag NPs are of interest to defense and engineering programs for new material applications as well as for commercial purposes as an antimicrobial. However, little is known about the genotoxicity of Ag NPs following exposure to mammalian cells. This study was undertaken to examine the DNA damage response to polysaccharide surface functionalized (coated) and non-functionalized (uncoated) Ag NPs in two types of mammalian cells; mouse embryonic stem (mES) cells and mouse embryonic fibroblasts (MEF). Both types of Ag NPs up-regulated the cell cycle checkpoint protein p53 and DNA damage repair proteins Rad51 and phosphorylated-H2AX expression. Furthermore both of them induced cell death as measured by the annexin V protein expression and MTT assay. Our observations also suggested that the different surface chemistry of Ag NPs induce different DNA damage response: coated Ag NPs exhibited more severe damage than uncoated Ag NPs. The results suggest that polysaccharide coated particles are more individually distributed while agglomeration of the uncoated particles limits the surface area availability and access to membrane bound organelles.

Ahamed, Maqusood; Karns, Michael; Goodson, Michael; Rowe, John [Department of Biology, Centre for Tissue Regeneration and Engineering, University of Dayton, Dayton-45469, OH (United States); Hussain, Saber M.; Schlager, John J. [Applied Biotechnology Branch, Human Effectiveness Directorate Air Force Research Laboratory/HEPB, Wright-Patterson Air Force Base-45433, OH (United States); Hong Yiling [Department of Biology, Centre for Tissue Regeneration and Engineering, University of Dayton, Dayton-45469, OH (United States)], E-mail: Yiling.Hong@notes.udayton.edu

2008-12-15

306

Hyaluronic acid modified mesoporous silica nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells.  

PubMed

In this paper, a targeted drug delivery system has been developed based on hyaluronic acid (HA) modified mesoporous silica nanoparticles (MSNs). HA-MSNs possess a specific affinity to CD44 over-expressed on the surface of a specific cancer cell line, HCT-116 (human colon cancer cells). The cellular uptake performance of fluorescently labelled MSNs with and without HA modification has been evaluated by confocal microscopy and fluorescence-activated cell sorter (FACS) analysis. Compared to bare MSNs, HA-MSNs exhibit a higher cellular uptake via HA receptor mediated endocytosis. An anticancer drug, doxorubicin hydrochloride (Dox), has been loaded into MSNs and HA-MSNs as drug delivery vehicles. Dox loaded HA-MSNs show greater cytotoxicity to HCT-116 cells than free Dox and Dox-MSNs due to the enhanced cell internalization behavior of HA-MSNs. It is expected that HA-MSNs have a great potential in targeted delivery of anticancer drugs to CD44 over-expressing tumors. PMID:23076766

Yu, Meihua; Jambhrunkar, Siddharth; Thorn, Peter; Chen, Jiezhong; Gu, Wenyi; Yu, Chengzhong

2012-10-18

307

Hydroxyapatite nanoparticles inhibit the growth of human glioma cells in vitro and in vivo  

PubMed Central

Hydroxyapatite nanoparticles (nano-HAPs) have been reported to exhibit antitumor effects on various human cancers, but the effects of nano-HAPs on human glioma cells remain unclear. The aim of this study was to explore the inhibitory effect of nano-HAPs on the growth of human glioma U251 and SHG44 cells in vitro and in vivo. Nano-HAPs could inhibit the growth of U251 and SHG44 cells in a dose- and time-dependent manner, according to methyl thiazoletetrazolium assay and flow cytometry. Treated with 120 mg/L and 240 mg/L nano-HAPs for 48 hours, typical apoptotic morphological changes were noted under Hoechst staining and transmission electron microscopy. The tumor growth of cells was inhibited after the injection in vivo, and the related side effects significantly decreased in the nano-HAP-and-drug combination group. Because of the function of nano-HAPs, the expression of c-Met, SATB1, Ki-67, and bcl-2 protein decreased, and the expression of SLC22A18 and caspase-3 protein decreased noticeably. The findings indicate that nano-HAPs have an evident inhibitory action and induce apoptosis of human glioma cells in vitro and in vivo. In a drug combination, they can significantly reduce the adverse reaction related to the chemotherapeutic drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU).

Chu, Sheng-Hua; Feng, Dong-Fu; Ma, Yan-Bin; Li, Zhi-Qiang

2012-01-01

308

SiC nanoparticles cyto- and genotoxicity to Hep-G2 cells  

NASA Astrophysics Data System (ADS)

While emerging nanotechnologies have seen significant development in recent years, knowledge on exposure levels as well as data on toxicity of nanoparticles are still quite limited. Indeed, there is a general agreement that development of nanotechnologies may lead to considerable dissemination of nanoparticles in the environment. Nevertheless, questions relative to toxicity versus innocuousness of such materials still remain. Our present study has thus been carried out with the purpose of assessing some aspects of toxicological capacities of three kinds of nano-sized particles: TiO2 and SiC nanoparticles, as well as multi-walled carbon nanotubes (CNT). In order to address the question of their potential toxicity toward living cells, we chose several cellular models. Assuming inhalation as the most probable exposure scenario, we used A549 alveolar epithelial cells as a model for mammalian primary target organ (lung). Furthermore, we considered that nanoparticles that would deposit into the pulmonary system may be translocated to the circulatory system. Thus, we decided to study the effect of nanoparticles on potentially secondary target organs: liver (WIF-B9, Can-10, HepG2) and kidneys (NRK-52E, LLC-PK1). Herein, we will focus our attention on results obtained on the HepG2 cell line exposed to SiC nanoparticles. Scarce literature exists on SiC nanotoxicology. According to the authors that have already carried out studies on this particular nanoparticle, it would seem that SiC nanoparticles do not induce cytotoxicity. That is one of the reasons of the potential use of these nanoparticles as biological labels [1]. We thus were interested in acquiring more data on biological effects induced by SiC nanoparticles. Furthermore, one of the particular aspects of the present study lies in the fact that we tried to specify the influence of physico-chemical characteristics of nanoparticles on toxicological endpoints (cytotoxicity and genotoxicity).

Barillet, Sabrina; Jugan, Mary-Line; Simon-Deckers, Angélique; Leconte, Yann; Herlin-Boime, Nathalie; Mayne-l'Hermite, Martine; Reynaud, Cécile; Carrière, Marie

2009-05-01

309

Mapping force of interaction between PLGA nanoparticle with cell membrane using optical tweezers  

NASA Astrophysics Data System (ADS)

Drug delivery using magnetic (Fe3O4) Poly Lactic-co-Glycolic Acid (PLGA) nanoparticles is finding increasing usage in therapeutic applications due to its biodegradability, biocompatibility and targeted localization. Since optical tweezers allow non-contact, highly sensitive force measurement, we utilized optical tweezers for studying interaction forces between the Fe3O4-PLGA nanoparticles with prostate cancer PC3 cells. Presence of Fe3O4 within the PLGA shell allowed efficient trapping of these nanoparticles in near-IR optical tweezers. The conglomerated PLGA nanoparticles could be dispersed by use of the optical tweezers. Calibration of trapping stiffness as a function of laser beam power was carried out using equipartition theorem method, where the mean square displacement was measured with high precision using time-lapse fluorescence imaging of the nanoparticles. After the trapped PLGA nanoparticle was brought in close vicinity of the PC3 cell membrane, displacement of the nanoparticle from trap center was measured as a function of time. In short time scale (< 30sec), while the force of interaction was within 0.2 pN, the force increased beyond 1pN at longer time scales (˜ 10 min). We will present the results of the time-varying force of interactions between PLGA nanoparticles with PC3 cells using optical tweezers.

Chhajed, Suyash; Gu, Ling; Homayoni, Homa; Nguyen, Kytai; Mohanty, Samarendra

2011-03-01

310

In vitro fermented nuts exhibit chemopreventive effects in HT29 colon cancer cells.  

PubMed

It is proven that nuts contain essential macro- and micronutrients, e.g. fatty acids, vitamins and dietary fibre (DF). Fermentation of DF by the gut microflora results in the formation of SCFA which are recognised for their chemopreventive potential, especially by influencing cell growth. However, little is known about cellular response to complex fermentation samples of nuts. Therefore, we prepared and analysed (pH, SCFA, bile acids, tocopherol, antioxidant capacity) fermentation supernatant (fs) fractions of nuts (almonds, macadamias, hazelnuts, pistachios, walnuts) after in vitro fermentation and determined their effects on growth of HT29 cells as well as their genotoxic/anti-genotoxic potential. The fermented nut samples contained 2- to 3-fold higher amounts of SCFA than the faeces control, but considerable reduced levels of bile acids. While most of the investigated native nuts comprised relatively high amounts of tocopherol (?-tocopherol in almonds and hazelnuts and ?- and ?-tocopherol in pistachios and walnuts), rather low concentrations were found in the fs. All nut extracts and nut fs showed a strong antioxidant potential. Furthermore, all fs, except the fs pistachio, reduced growth of HT29 cells significantly. DNA damage induced by H?O? was significantly reduced by the fs of walnuts after 15 min co-incubation of HT29 cells. In conclusion, this is the first study which presents the chemopreventive effects (reduction of tumour-promoting desoxycholic acid, rise in chemopreventive SCFA, protection against oxidative stress) of different nuts after in vitro digestion and fermentation, and shows the potential importance of nuts in the prevention of colon cancer. PMID:22172380

Lux, Stefanie; Scharlau, Daniel; Schlörmann, Wiebke; Birringer, Marc; Glei, Michael

2011-12-15

311

MicroRNA21 Exhibits Antiangiogenic Function by Targeting RhoB Expression in Endothelial Cells  

Microsoft Academic Search

BackgroundMicroRNAs (miRNAs) are endogenously expressed small non-coding RNAs that regulate gene expression at post-transcriptional level. The recent discovery of the involvement of these RNAs in the control of angiogenesis renders them very attractive in the development of new approaches for restoring the angiogenic balance. Whereas miRNA-21 has been demonstrated to be highly expressed in endothelial cells, the potential function of

Céline Sabatel; Ludovic Malvaux; Nicolas Bovy; Christophe Deroanne; Vincent Lambert; Maria-Luz Alvarez Gonzalez; Alain Colige; Jean-Marie Rakic; Agnès Noël; Joseph A. Martial; Ingrid Struman; Maurizio Capogrossi

2011-01-01

312

Magnetic nanoparticle effects on the red blood cells  

NASA Astrophysics Data System (ADS)

In vitro tests on magnetite colloidal nanoparticles effects upon animal red blood cells were carried out. Magnetite cores were stabilized with citric acid in the form of biocompatible magnetic fluid administrated in different dilutions in the whole blood samples. The hemolysis extent was found increased up to 2.75 in horse blood and respectively up to 2.81 in the dog blood. The electronic transitions assigned to the heme group were found shifted with about 500 cm-1 or, respectively, affected by supplementary vibronic structures. The Raman vibrations assigned to oxyhemoglobin were much diminished in intensity probably due to the bonding of OH group from citrate shell to the heme iron ion.

Creang?, D. E.; Culea, M.; N?dejde, C.; Oancea, S.; Curecheriu, L.; Racuciu, M.

2009-05-01

313

Wavelength-Dependent Differential Interference Contrast Microscopy: Selectively Imaging Nanoparticle Probes in Live Cells  

SciTech Connect

Gold and silver nanoparticles display extraordinarily large apparent refractive indices near their plasmon resonance (PR) wavelengths. These nanoparticles show good contrast in a narrow spectral band but are poorly resolved at other wavelengths in differential interference contrast (DIC) microscopy. The wavelength dependence of DIC contrast of gold/silver nanoparticles is interpreted in terms of Mie's theory and DIC working principles. We further exploit this wavelength dependence by modifying a DIC microscope to enable simultaneous imaging at two wavelengths. We demonstrate that gold/silver nanoparticles immobilized on the same glass slides through hybridization can be differentiated and imaged separately. High-contrast, video-rate images of living cells can be recorded both with and without illuminating the gold nanoparticle probes, providing definitive probe identification. Dual-wavelength DIC microscopy thus presents a new approach to the simultaneous detection of multiple probes of interest for high-speed live-cell imaging.

Sun, Wei; Wang, Gufeng; Fang, Ning; and Yeung, Edward S.

2009-11-15

314

Release of Magnetic Nanoparticles from Cell-Encapsulating Biodegradable Nanobiomaterials  

PubMed Central

The future of tissue engineering requires development of intelligent biomaterials using nanoparticles. Magnetic nanoparticles (MNPs) have several applications in biology and medicine; one example is Food and Drug Administration (FDA)-approved contrast agents in magnetic resonance imaging. Recently, MNPs have been encapsulated within cell-encapsulating hydrogels to create novel nanobiomaterials (i.e., M-gels), which can be manipulated and assembled in magnetic fields. The M-gels can be used as building blocks for bottom-up tissue engineering to create 3D tissue constructs. For tissue engineering applications of M-gels, it is essential to study the release of encapsulated MNPs from the hydrogel polymer network and the effect of MNPs on hydrogel properties, including mechanical characteristics, porosity, swelling behavior, and cellular response (e.g., viability, growth). Therefore, we evaluated the release of MNPs from photocrosslinkable gelatin methacrylate hydrogels as the polymer network undergoes biodegradation using inductively coupled plasma atomic emission spectroscopy. MNP release correlated linearly with hydrogel biodegradation rate with correlation factors (Pearson product moment correlation coefficient) of 0.96 ± 0.03 and 0.99 ± 0.01 for MNP concentrations of 1% and 5%, respectively. We also evaluated the effect of MNPs on hydrogel mechanical properties, porosity, and swelling behavior, as well as cell viability and growth in MNP-encapsulating hydrogels. Fibroblasts encapsulated with MNPs in hydrogels remained viable (>80% at t = 144 h) and formed microtissue constructs in culture (t = 144 h). These results indicated that MNP-encapsulating hydrogels show promise as intelligent nanobiomaterials, with great potential to impact broad areas of bioengineering, including tissue engineering, regenerative medicine, and pharmaceutical applications.

Xu, Feng; Inci, Fatih; Mullick, Omer; Gurkan, Umut Atakan; Sung, Yuree; Kavaz, Doga; Li, Baoqiang; Denkbas, Emir Baki; Demirci, Utkan

2013-01-01

315

Photothermal therapy of cancer cells mediated by blue hydrogel nanoparticles.  

PubMed

Aim: The aim of this study was to investigate in vitro the utility of biologically compatible, nontoxic and cell-specific targetable hydrogel nanoparticles (NPs), which have Coomassie(®) Brilliant Blue G dye (Sigma-Aldrich, MO, USA) covalently linked into their polyacrylamide matrix, as candidates for photothermal therapy (PTT) of cancer cells. Materials & methods: Hydrogel NPs with Coomassie Brilliant Blue G dye covalently linked into their polyacrylamide matrix were fabricated using a reverse micelle microemulsion polymerization method and were found to be 80-95 nm in diameter, with an absorbance value of 0.52. PTT-induced hyperthermia/thermolysis was achieved at 37°C using an inexpensive, portable, light-emitting diode array light source (590 nm, 25 mW/cm(2)). Results & conclusion: Hydrogel NPs with Coomassie Brilliant Blue G dye linked into their polyacrylamide matrix are effective in causing PTT-induced thermolysis in immortalized human cervical cancer cell line (HeLa) cells for varying NP concentrations and treatment times. These multifunctional particles have previously been used in cancer studies to enable delineation, for glioma surgery and in photoacoustic imaging studies. The addition of the PTT function would enable a three-pronged theranostic approach to cancer medicine, such as guided tumor surgery with intra-operative photoacoustic imaging and intra-operative PTT. Original submitted 21 May 2012; Revised submitted 13 September 2012. PMID:23432340

Curry, Taeyjuana; Epstein, Tamir; Smith, Ron; Kopelman, Raoul

2013-02-22

316

Gold nanoparticles cellular toxicity and recovery: Adipose Derived Stromal cells.  

PubMed

Abstract Gold nanoparticles (AuNPs) are currently used in numerous medical applications. Herein, we describe their in vitro impact on human adipose-derived stromal cells (ADSCs) using 13 nm and 45 nm citrate-coated AuNPs. In their non-differentiated state, ADSCs were penetrated by the AuNPs and stored in vacuoles. The presence of the AuNPs in ADSCs resulted in increased population doubling times, decreased cell motility and cell-mediated collagen contraction. The degree to which the cells were impacted was a function of particle concentration, where the smaller particles required a sevenfold higher concentration to have the same effect as the larger ones. Furthermore, AuNPs reduced adipogenesis as measured by lipid droplet accumulation and adiponectin secretion. These effects correlated with transient increases in DLK1 and with relative reductions in fibronectin. Upon removal of exogenous AuNPs, cellular NP levels decreased and normal ADSC functions were restored. As adiponectin helps regulate energy metabolism, local fluctuations triggered by AuNPs can lead to systemic changes. Hence, careful choice of size, concentration and clinical application duration of AuNPs is warranted. PMID:23330784

Mironava, Tatsiana; Hadjiargyrou, Michael; Simon, Marcia; Rafailovich, Miriam H

2013-02-01

317

Dynamic investigation of interaction of biocompatible iron oxide nanoparticles with epithelial cells for biomedical applications.  

PubMed

Magnetic nanoparticles have emerged as important players in current research in modern medicine since they can be used in medicine for diagnosis and/or therapeutic treatment of diseases. Among many therapeutic applications of iron-based nanoparticles, drug delivery and photothermal therapy are of particular interest. At cellular level their uptake has been studied and the mechanism by which nanoparticles enter into the cell has important implication not only for their fate but also for their impact on the biological systems. We present here a dynamic investigation of interaction of biocompatible iron oxide nanoparticles coated with L-3,4-dihydroxyphenylalanine and labeled with tetra-methylrhodamine-5/6-isothiocyanate with lung epithelial cells. Our data show that after macropinocytosis-mediated internalization, nanoparticles in form of vesicles approach the nucleus and converge in the more acidic compartments of the cells in a microtubule-dependent manner. During progression the nanoparticles aggregate. Finally, we have demonstrated that a converging laser radiation on the cells, causes the increase in the local temperature and thus damages the cells, suggesting that these nanoparticles may be applied for photothermal therapy studies. PMID:23980503

Panariti, Alice; Lettiero, Barbara; Alexandrescu, Rodica; Collini, Maddalena; Sironi, Laura; Chanana, Munish; Morjan, Ion; Wang, Dayan; Chirico, Giuseppe; Miserocchi, Giuseppe; Bucci, Cecilia; Rivolta, Ilaria

2013-09-01

318

The hyaluronan synthesis inhibitor 4-methylumbelliferone exhibits antitumor effects against mesenchymal-like canine mammary tumor cells  

PubMed Central

Hyaluronan (HA), a principal constituent of the extracellular matrix (ECM), mediates growth and metastasis of tumor cells. The role of HA in the epithelial-mesenchymal transition (EMT) is well known, and increased ECM remodeling is observed in mesenchymal-like cells. The HA synthesis inhibitor 4-methylumbelliferone (4-MU) is anti-tumorigenic for various malignant tumors. However, the antitumor effect of 4-MU against canine mammary tumor cells that possess a mesenchymal-like phenotype is unclear. We examined the antitumor effect of 4-MU on CF41.Mg mesenchymal-like canine mammary tumor cells. We investigated the influence of 4-MU on the expression of HA synthase (HAS) 1-3 mRNA and observed dose-dependent downregulation of HAS2 mRNA at 24-72 h; in contrast, HAS3 expression was elevated at 24 h. Thus, 4-MU inhibited HA synthesis via HAS2 repression. 4-MU also inhibited cell proliferation and induced apoptosis in the CF41.Mg cells. Our experiments showed that 4-MU-induced apoptosis in CF41.Mg cells involved induction of the pro-apoptotic gene BAX. We also assessed motility and found that 4-MU reduced chemokinesis and chemotaxis in CF41.Mg cells. Our data suggest that 4-MU may serve as a candidate therapeutic agent for the treatment of canine mammary tumors. Since 4-MU exhibits antitumor activity in mesenchymal-like cells, it may also be a useful inhibitor of canine mammary tumor invasion and metastasis.

SAITO, TERUYOSHI; DAI, TAMURA; ASANO, RYUJI

2013-01-01

319

Hematopoietic stem cells exhibit a specific ABC transporter gene expression profile clearly distinct from other stem cells  

Microsoft Academic Search

BACKGROUND: ATP-binding cassette (ABC) transporters protect cells against unrelated (toxic) substances by pumping them across cell membranes. Earlier we showed that many ABC transporters are highly expressed in hematopoietic stem cells (HSCs) compared to more committed progenitor cells. The ABC transporter expression signature may guarantee lifelong protection of HSCs but may also preserve stem cell integrity by extrusion of agents

Leilei Tang; Saskia M Bergevoet; Christian Gilissen; Theo de Witte; Joop H Jansen; Bert A van der Reijden; Reinier AP Raymakers

2010-01-01

320

Three fluorescent protein voltage sensors exhibit low plasma membrane expression in mammalian cells  

Microsoft Academic Search

Three first-generation fluorescent protein voltage sensitive probes (FP-voltage sensors) were characterized in mammalian cells. Flare, a Kv1.4 variant of FlaSh [Siegel MS, Isacoff EY. Neuron 1997;19(October (4)):735–41], SPARC [Ataka K, Pieribone VA. Biophys J 2002;82(January (1 Pt 1)):509–16], and VSFP-1 [Sakai R, Repunte-Canonigo V, Raj CD, Knopfel T. Eur J Neurosci 2001;13(June (12)):2314–18] were expressed, imaged and voltage clamped in

B. J. Baker; H. Lee; V. A. Pieribone; L. B. Cohen; E. Y. Isacoff; T. Knopfel; E. K. Kosmidis

2007-01-01

321

3-O-Acetyloleanolic acid exhibits anti-angiogenic effects and induces apoptosis in human umbilical vein endothelial cells.  

PubMed

3-O-Acetyloleanolic acid, a pentacyclic triterpenoid isolated from cowpea seeds, inhibited proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. HUVECs. The induced apoptosis was characterized by detection of cell surface annexin V and sub-G1 populations. The number of cells immunostained with annexin V-fluorescein isothiocyanate increased after treatment with 3-O-acetyloleanolic acid. The sub-G1 cell populations were also increased in treated HUVECs. 3-O-Acetyloleanolic acid induced activation of caspase 3, a critical mediator of apoptosis signaling. It also significantly inhibited angiogenesis in an in vivo Matrigel plug assay. 3-O-Acetyloleanolic acid thus exhibits anti-angiogenic effects and induces apoptosis in HUVECs and the results suggest that it has a potential use for suppression of the tumor growth stimulated by angiogenesis. PMID:23801119

Cui, En-Ji; Hwang-Bo, Jeon; Park, Jong-Hwa; Baek, Nam-In; Kim, Jiyoung; Hong, Seong Gil; Chung, In Sik

2013-06-26

322

Differential cytotoxicity and particle action of hydroxyapatite nanoparticles in human cancer cells.  

PubMed

Aim: While hydroxyapatite nanoparticles (HAPNs) have been reported to exhibit anticancer effects on several types of human cancer cells, no investigation has been performed to compare their cytotoxicity with different types of cancer cells. The objective of the present study is to investigate the cytotoxic action of HAPNs in different types of human cancer cell and to explore the possible mechanisms involved. Materials & methods: Rod-shaped HAPNs were prepared by the aqueous precipitation method and then labeled with ?uorescein isothiocyanate to visualize the cellular uptake and distribution. Their cytotoxicity to three human carcinoma cell lines (gastric cancer cells [MGC80-3], cervical adenocarcinoma epithelial cells [HeLa] and hepatoma cells [HepG2], as well as to normal human hepatocyte cells [L-02]) was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis was characterized by the changes in nuclear morphology with 4',6-diamidino-2-phenylindole staining and by ?ow cytometric analysis with Annexin V-?uorescein isothiocyanate/propidium iodide double staining. Furthermore, the activity of apoptotic proteins (caspase-3, -8 and -9), intracellular reactive oxygen species and glutathione levels were analyzed in HAPN-treated cells. The cellular uptake of HAPNs was studied using flow cytometry analysis, and changes in intracellular calcium levels were investigated using the Ca(2+)-sensitive fluorescent dye, fluo-3 AM. Results: HAPNs significantly inhibited cell proliferation and induced apoptosis of cancer cells with an order of MGC80-3 > HepG2 > HeLa, but had no impact on normal hepatic cells (L-02). The increase in apoptosis was accompanied by the activation of caspase-3 and -9, but not activation of caspase-8. Moreover, HAPN treatment led to reactive oxygen species generation and decreased intracellular glutathione in cancer cells, with the most remarkable reactive oxygen species burst in HeLa cells. The degree of cytotoxicity did not correlate with the cellular uptake efficiency of HAPNs. However, more HAPNs were found inside the nucleus of MGC80-3 cells, and an increase in the intracellular calcium level was observed in all cancer cells, with the highest level also detected in MGC80-3. Conclusion: Varying cytotoxicity of HAPNs was observed in different cancer cell types. Our results suggest that possible mechanisms of cytotoxicity in various types of cancer cells could be different. The elevated calcium concentration and nuclear localization of the particles might be the main mechanism of growth inhibition by HAPNs in cancer cells. Original submitted 18 April 2012; Revised submitted 14 September 2012. PMID:23614636

Tang, Wei; Yuan, Yuan; Liu, Changsheng; Wu, Yuequn; Lu, Xun; Qian, Jiangchao

2013-04-24

323

CEBPG Exhibits Allele-Specific Expression in Human Bronchial Epithelial Cells.  

PubMed

Inter-individual variation in CCAAT/enhancer binding protein gamma (CEBPG) transcript expression in normal human bronchial epithelial cells (NBEC) is associated with predisposition to lung cancer. We hypothesize that this inter-individual variation is in part explained by cis-acting genetic variation in CEBPG. To test this hypothesis we measured transcript expression derived from each parental copy of CEBPG (ie, allele-specific expression; ASE). There was a significant 2.9-fold higher cell cycle-specific variation in ASE of CEBPG rs2772 A compared to C allele (P < 0.001). In 20% of NBEC samples, CEBPG rs2772 A allele was expressed on average 2.10 fold greater than rs2772 C allele. These data support the hypothesis that genetic variation in linkage disequilibrium with rs2772 influences regulation of CEBPG transcript expression through a trans-effect downstream of RNA polymerase II transcription and confirm that cis-acting genetic variation contributes to inter-individual variation in CEBPG transcript expression in NBEC, which is associated with variation in lung cancer risk. PMID:23888109

Blomquist, Thomas M; Brown, Ronald D; Crawford, Erin L; de la Serna, Ivana; Williams, Kandace; Yoon, Youngsook; Hernandez, Dawn-Alita; Willey, James C

2013-07-04

324

Microvascular Endothelial Cells Exhibit Optimal Aspect Ratio for Minimizing Flow Resistance  

PubMed Central

A recent analytical solution of the three-dimensional Stokes flow through a bumpy tube predicts that for a given bump area, there exists an optimal circumferential wavenumber which minimizes flow resistance. This study uses measurements of microvessel endothelial cell morphology to test whether this prediction holds in the microvasculature. Endothelial cell (EC) morphology was measured in blood perfused in situ microvessels in anesthetized mice using confocal intravital microscopy. EC borders were identified by immunofluorescently labeling the EC surface molecule ICAM-1 which is expressed on the surface but not in the EC border regions. Comparison of this theory with extensive in situ measurements of microvascular EC geometry in mouse cremaster muscle using intravital microscopy reveals that the spacing of EC nuclei in venules ranging from 27 to 106 ?m in diameter indeed lies quite close to this predicted optimal configuration. Interestingly, arteriolar ECs are configured to minimize flow resistance not in the resting state, but at the dilated vessel diameter. These results raise the question of whether less organized circulatory systems, such as that found in newly formed solid tumors or in the developing embryo, may deviate from the optimal bump spacing predicted to minimize flow resistance.

Sumagin, Ronen; Brown, Carl W.; Sarelius, Ingrid H.

2008-01-01

325

Proper design of silica nanoparticles combines high brightness, lack of cytotoxicity and efficient cell endocytosis  

NASA Astrophysics Data System (ADS)

Silica-based luminescent nanoparticles (SiNPs) show promising prospects in nanomedicine in light of their chemical properties and versatility. In this study, we have characterized silica core-PEG shell SiNPs derivatized with PEG moieties (NP-PEG), with external amino- (NP-PEG-amino) or carboxy-groups (NP-PEG-carbo), both in cell cultures as well as in animal models. By using different techniques, we could demonstrate that these SiNPs were safe and did not exhibit appreciable cytotoxicity in different relevant cell models, of normal or cancer cell types, growing either in suspension (JVM-2 leukemic cell line and primary normal peripheral blood mononuclear cells) or in adherence (human hepatocarcinoma Huh7 and umbilical vein endothelial cells). Moreover, by multiparametric flow cytometry, we could demonstrate that the highest efficiency of cell uptake and entry was observed with NP-PEG-amino, with a stable persistence of the fluorescence signal associated with SiNPs in the loaded cell populations both in vitro and in vivo settings suggesting this as an innovative method for cell traceability and detection in whole organisms. Finally, experiments performed with the endocytosis inhibitor Genistein clearly suggested the involvement of a caveolae-mediated pathway in SiNP endocytosis. Overall, these data support the safe use of these SiNPs for diagnostic and therapeutic applications.Silica-based luminescent nanoparticles (SiNPs) show promising prospects in nanomedicine in light of their chemical properties and versatility. In this study, we have characterized silica core-PEG shell SiNPs derivatized with PEG moieties (NP-PEG), with external amino- (NP-PEG-amino) or carboxy-groups (NP-PEG-carbo), both in cell cultures as well as in animal models. By using different techniques, we could demonstrate that these SiNPs were safe and did not exhibit appreciable cytotoxicity in different relevant cell models, of normal or cancer cell types, growing either in suspension (JVM-2 leukemic cell line and primary normal peripheral blood mononuclear cells) or in adherence (human hepatocarcinoma Huh7 and umbilical vein endothelial cells). Moreover, by multiparametric flow cytometry, we could demonstrate that the highest efficiency of cell uptake and entry was observed with NP-PEG-amino, with a stable persistence of the fluorescence signal associated with SiNPs in the loaded cell populations both in vitro and in vivo settings suggesting this as an innovative method for cell traceability and detection in whole organisms. Finally, experiments performed with the endocytosis inhibitor Genistein clearly suggested the involvement of a caveolae-mediated pathway in SiNP endocytosis. Overall, these data support the safe use of these SiNPs for diagnostic and therapeutic applications. Electronic supplementary information (ESI) available: Synthetic procedures, 1H and 13C NMR spectra, TEM and DLS measurements, and absorption and emission spectra. See DOI: 10.1039/c3nr02563b

Rampazzo, Enrico; Voltan, Rebecca; Petrizza, Luca; Zaccheroni, Nelsi; Prodi, Luca; Casciano, Fabio; Zauli, Giorgio; Secchiero, Paola

2013-08-01

326

Human Embryonic and Induced Pluripotent Stem Cell-Derived Cardiomyocytes Exhibit Beat Rate Variability and Power-Law Behavior  

PubMed Central

Background The sinoatrial node is the main impulse-generating tissue in the heart. Atrioventricular conduction block and arrhythmias caused by sinoatrial node dysfunction are clinically important and generally treated with electronic pacemakers. Although an excellent solution, electronic pacemakers incorporate limitations that have stimulated research on biological pacing. To assess the suitability of potential biological pacemakers, we tested the hypothesis that the spontaneous electric activity of human embryonic stem cell– derived cardiomyocytes (hESC-CMs) and induced pluripotent stem cell– derived cardiomyocytes (iPSC-CMs) exhibit beat rate variability and power-law behavior comparable to those of human sinoatrial node. Methods and Results We recorded extracellular electrograms from hESC-CMs and iPSC-CMs under stable conditions for up to 15 days. The beat rate time series of the spontaneous activity were examined in terms of their power spectral density and additional methods derived from nonlinear dynamics. The major findings were that the mean beat rate of hESC-CMs and iPSC-CMs was stable throughout the 15-day follow-up period and was similar in both cell types, that hESC-CMs and iPSC-CMs exhibited intrinsic beat rate variability and fractal behavior, and that isoproterenol increased and carbamylcholine decreased the beating rate in both hESC-CMs and iPSC-CMs. Conclusions This is the first study demonstrating that hESC-CMs and iPSC-CMs exhibit beat rate variability and power-law behavior as in humans, thus supporting the potential capability of these cell sources to serve as biological pacemakers. Our ability to generate sinoatrial-compatible spontaneous cardiomyocytes from the patient’s own hair (via keratinocyte-derived iPSCs), thus eliminating the critical need for immunosuppression, renders these myocytes an attractive cell source as biological pacemakers.

Mandel, Yael; Weissman, Amir; Schick, Revital; Barad, Lili; Novak, Atara; Meiry, Gideon; Goldberg, Stanislav; Lorber, Avraham; Rosen, Michael R.; Itskovitz-Eldor, Joseph; Binah, Ofer

2013-01-01

327

The Effect of Titanium Dioxide Nanoparticles on Keratinocyte Cell (KC) and Squamous Cell Carcinoma (SCC-13)  

NASA Astrophysics Data System (ADS)

We have studied the effects of TiO2 nanoparticles on cell keratinocyte and SCC (Squamous Cell Carcinoma) cells. We found that the concentration of particles required to adversely affect the cells was many times higher for keratinocyte than SCC cells. Confocal microscope shows that the particles in keratinocyte culture are sequestered in membranes between the cell colonies. The particles penetrated into the cells in the case of the SCC cells. TEM images revealed very few particles in the keratinocyte, many more particles were observed sequestered in vacuole of the SCC cells. These results indicate that the keratinocyte layer behaves very different from the fibroblast layers which are much more sensate to TiO2 nanoparticle damage and may suggest a protection mechanism of the dermal tissue. The effect of UV exposure in the presence of DNA was also investigated. We found that adsorbed proteins, as well as grafted polymer provided a measure of protection against free radical formation. The effects of low level UV exposure when the particles are near in-vitro cell culture will be presented.

Lin, Chienhsiu; Simon, Marcia; Jurukovski, Vladimir; Lee, Wilson; Rafailovich, Miriam

2009-03-01

328

Aquaporin 4-Specific T Cells in Neuromyelitis Optica Exhibit a Th17 Bias and Recognize Clostridium ABC Transporter  

PubMed Central

Objective Aquaporin 4 (AQP4)-specific autoantibodies in neuromyelitis optica (NMO) are immunoglobulin (Ig)G1, a T cell-dependent Ig subclass, indicating that AQP4-specific T cells participate in NMO pathogenesis. Our goal was to identify and characterize AQP4-specific T cells in NMO patients and healthy controls (HC). Methods Peripheral blood T cells from NMO patients and HC were examined for recognition of AQP4 and production of proinflammatory cytokines. Monocytes were evaluated for production of T cell-polarizing cytokines and expression of costimulatory molecules. Results T cells from NMO patients and HC proliferated to intact AQP4 or AQP4 peptides (p11–30, p21–40, p61–80, p131–150, p156–170, p211–230, and p261–280). T cells from NMO patients demonstrated greater proliferation to AQP4 than those from HC, and responded most vigorously to p61–80, a naturally processed immunodominant determinant of intact AQP4. T cells were CD4+, and corresponding to association of NMO with human leukocyte antigen (HLA)-DRB1*0301 and DRB3, AQP4 p61–80-specific T cells were HLA-DR restricted. The T-cell epitope within AQP4 p61–80 was mapped to 63–76, which contains 10 residues with 90% homology to a sequence within Clostridium perfringens adenosine triphosphate-binding cassette (ABC) transporter permease. T cells from NMO patients proliferated to this homologous bacterial sequence, and cross-reactivity between it and self-AQP4 was observed, supporting molecular mimicry. In NMO, AQP4 p61–80-specific T cells exhibited Th17 polarization, and furthermore, monocytes produced more interleukin 6, a Th17-polarizing cytokine, and expressed elevated CD40 and CD80 costimulatory molecules, suggesting innate immunologic dysfunction. Interpretation AQP4-specific T-cell responses are amplified in NMO, exhibit a Th17 bias, and display cross-reactivity to a protein of an indigenous intestinal bacterium, providing new perspectives for investigating NMO pathogenesis. ANN NEUROL 2012;

Varrin-Doyer, Michel; Spencer, Collin M; Schulze-Topphoff, Ulf; Nelson, Patricia A; Stroud, Robert M; C Cree, Bruce A; Zamvil, Scott S

2012-01-01

329

Factors affecting T cell responses induced by fully synthetic glyco-gold-nanoparticles  

NASA Astrophysics Data System (ADS)

We have synthesized and characterized nearly monodisperse and highly pure gold nanoparticles (2 and 5 nm) coated with non-immunoactive mono- and disaccharides, modelled after the capsular polysaccharide of serogroup A of the Neisseria meningitidis bacterium. We have used them to test their ability to induce immune cell responses as a consequence of their multivalency. The results indicate that they are indeed immunoactive and that immunoactivity is strongly dependent on size, and larger, 5 nm nanoparticles perform far better than smaller, 2 nm ones. Immune response (activation of macrophages) initiates with the whole nanoparticle recognition by the surface of antigen-presenting cells, independent of the saccharide oligomerization (or charge) on the nanoparticle surface. The induction of T cell proliferation and the increase of IL-2 levels, a consequence of the expression of MHC II involved in antigen presentation, require the presence of a disaccharide on the nanoparticle, not just a monosaccharide. A possible explanation is that, at this stage, the saccharides are detached from the gold surface. These results may provide leads for designing new saccharide-based, nanoparticle-conjugate vaccines.We have synthesized and characterized nearly monodisperse and highly pure gold nanoparticles (2 and 5 nm) coated with non-immunoactive mono- and disaccharides, modelled after the capsular polysaccharide of serogroup A of the Neisseria meningitidis bacterium. We have used them to test their ability to induce immune cell responses as a consequence of their multivalency. The results indicate that they are indeed immunoactive and that immunoactivity is strongly dependent on size, and larger, 5 nm nanoparticles perform far better than smaller, 2 nm ones. Immune response (activation of macrophages) initiates with the whole nanoparticle recognition by the surface of antigen-presenting cells, independent of the saccharide oligomerization (or charge) on the nanoparticle surface. The induction of T cell proliferation and the increase of IL-2 levels, a consequence of the expression of MHC II involved in antigen presentation, require the presence of a disaccharide on the nanoparticle, not just a monosaccharide. A possible explanation is that, at this stage, the saccharides are detached from the gold surface. These results may provide leads for designing new saccharide-based, nanoparticle-conjugate vaccines. Electronic supplementary information (ESI) available: Fig. S1-S10 mentioned in the text related to the syntheses of nanosystems, nanoparticle characterization, and biological tests. See DOI: 10.1039/c2nr32338a

Fallarini, Silvia; Paoletti, Tiziana; Battaglini, Carolina Orsi; Ronchi, Paolo; Lay, Luigi; Bonomi, Renato; Jha, Satadru; Mancin, Fabrizio; Scrimin, Paolo; Lombardi, Grazia

2012-12-01

330

Biocompatibility of chitosan-coated iron oxide nanoparticles with osteoblast cells  

PubMed Central

Background: Bone disorders (including osteoporosis, loosening of a prosthesis, and bone infections) are of great concern to the medical community and are difficult to cure. Therapies are available to treat such diseases, but all have drawbacks and are not specifically targeted to the site of disease. Chitosan is widely used in the biomedical community, including for orthopedic applications. The aim of the present study was to coat chitosan onto iron oxide nanoparticles and to determine its effect on the proliferation and differentiation of osteoblasts. Methods: Nanoparticles were characterized using transmission electron microscopy, dynamic light scattering, x-ray diffraction, zeta potential, and vibrating sample magnetometry. Uptake of nanoparticles by osteoblasts was studied by transmission electron microscopy and Prussian blue staining. Viability and proliferation of osteoblasts were measured in the presence of uncoated iron oxide magnetic nanoparticles or those coated with chitosan. Lactate dehydrogenase, alkaline phosphatase, total protein synthesis, and extracellular calcium deposition was studied in the presence of the nanoparticles. Results: Chitosan-coated iron oxide nanoparticles enhanced osteoblast proliferation, decreased cell membrane damage, and promoted cell differentiation, as indicated by an increase in alkaline phosphatase and extracellular calcium deposition. Chitosan-coated iron oxide nanoparticles showed good compatibility with osteoblasts. Conclusion: Further research is necessary to optimize magnetic nanoparticles for the treatment of bone disease.

Shi, Si-Feng; Jia, Jing-Fu; Guo, Xiao-Kui; Zhao, Ya-Ping; Chen, De-Sheng; Guo, Yong-Yuan; Cheng, Tao; Zhang, Xian-Long

2012-01-01

331

Amorphous silica nanoparticles promote monocyte adhesion to human endothelial cells: size-dependent effect.  

PubMed

There is evidence that nanoparticles can induce endothelial dysfunction. Here, the effect of monodisperse amorphous silica nanoparticles (SiO(2)-NPs) of different diameters on endothelial cells function is examined. Human endothelial cell line (EA.hy926) or primary human pulmonary artery endothelial cells (hPAEC) are seeded in inserts introduced or not above triple cell co-cultures (pneumocytes, macrophages, and mast cells). Endothelial cells are incubated with SiO(2)-NPs at non-cytotoxic concentrations for 12 h. A significant increase (up to 2-fold) in human monocytes adhesion to endothelial cells is observed for 18 and 54 nm particles. Exposure to SiO(2)-NPs induces protein expression of adhesion molecules (ICAM-1 and VCAM-1) as well as significant up-regulation in mRNA expression of ICAM-1 in both endothelial cell types. Experiments performed with fluorescent-labelled monodisperse amorphous SiO(2)-NPs of similar size evidence nanoparticle uptake into the cytoplasm of endothelial cells. It is concluded that exposure of human endothelial cells to amorphous silica nanoparticles enhances their adhesive properties. This process is modified by the size of the nanoparticle and the presence of other co-cultured cells. PMID:23042701

Napierska, Dorota; Quarck, Rozenn; Thomassen, Leen C J; Lison, Dominique; Martens, Johan A; Delcroix, Marion; Nemery, Benoit; Hoet, Peter H

2012-10-08

332

Functionalized magnetic nanoparticles for the detection and quantitative analysis of cell surface antigen.  

PubMed

Cell surface antigens as biomarkers offer tremendous potential for early diagnosis, prognosis, and therapeutic response in a variety of diseases such as cancers. In this research, a simple, rapid, accurate, inexpensive, and easily available in vitro assay based on magnetic nanoparticles and magnetic cell separation principle was applied to identify and quantitatively analyze the cell surface antigen expression in the case of prostate cancer cells. Comparing the capability of the assay with flow cytometry as a gold standard method showed similar results. The results showed that the antigen-specific magnetic cell separation with antibody-coated magnetic nanoparticles has high potential for quantitative cell surface antigen detection and analysis. PMID:23484112

Shahbazi-Gahrouei, Daryoush; Abdolahi, Mohammad; Zarkesh-Esfahani, Sayyed Hamid; Laurent, Sophie; Sermeus, Corine; Gruettner, Cordula

2012-12-31

333

Neurons and ?-Cells of the Pancreas Express Connexin36, Forming Gap Junction Channels that Exhibit Strong Cationic Selectivity  

PubMed Central

We examined the permeability of connexin36 (Cx36) homotypic gap junction (GJ) channels, expressed in neurons and ?-cells of the pancreas, to dyes differing in molecular mass and net charge. Experiments were performed in HeLa cells stably expressing Cx36 tagged with EGFP by combining a dual whole-cell voltage clamp and fluorescence imaging. To assess the permeability of the single GJ channel (P?), we used a dual-mode excitation of fluorescent dyes that allowed us to measure cell-to-cell dye transfer at levels not resolvable using whole-field excitation solely. We demonstrate that P? of Cx36 for cationic dyes (EAM-1+ and EAM-2+) is ?10-fold higher than that for an anionic dye of the same net charge and similar molecular mass, Alexa fluor-350 (AFl-350?). In addition, P? for Lucifer yellow (LY2?) is approximately fourfold smaller than that for AFl-350?, which suggests that the higher negativity of LY2? significantly reduces permeability. The P? of Cx36 for AFl-350 is approximately 358, 138, 23 and four times smaller than the P?s of Cx43, Cx40, Cx45, and Cx57, respectively. In contrast, it is 6.5-fold higher than the P? of mCx30.2, which exhibits a smaller single-channel conductance. Thus, Cx36 GJs are highly cation-selective and should exhibit relatively low permeability to numerous vital negatively charged metabolites and high permeability to K+, a major charge carrier in cellcell communication.

2013-01-01

334

Silica nanoparticles for cell imaging and intracellular sensing.  

PubMed

There is increasing interest in the use of nanoparticles (NPs) for biomedical applications. In particular, nanobiophotonic approaches using fluorescence offers the potential of high sensitivity and selectivity in applications such as cell imaging and intracellular sensing. In this review, we focus primarily on the use of fluorescent silica NPs for these applications and, in so doing, aim to enhance and complement the key recent review articles on these topics. We summarize the main synthetic approaches, namely the Stöber and microemulsion processes, and, in this context, we deal with issues in relation to both covalent and physical incorporation of different types of dyes in the particles. The important issue of NP functionalization for conjugation to biomolecules is discussed and strategies published in the recent literature are highlighted and evaluated. We cite recent examples of the use of fluorescent silica NPs for cell imaging in the areas of cancer, stem cell and infectious disease research, and we review the current literature on the use of silica NPs for intracellular sensing of oxygen, pH and ionic species. We include a short final section which seeks to identify the main challenges and obstacles in relation to the potential widespread use of these particles for in vivo diagnostics and therapeutics. PMID:24113689

Korzeniowska, B; Nooney, R; Wencel, D; McDonagh, C

2013-10-10

335

Silica nanoparticles for cell imaging and intracellular sensing  

NASA Astrophysics Data System (ADS)

There is increasing interest in the use of nanoparticles (NPs) for biomedical applications. In particular, nanobiophotonic approaches using fluorescence offers the potential of high sensitivity and selectivity in applications such as cell imaging and intracellular sensing. In this review, we focus primarily on the use of fluorescent silica NPs for these applications and, in so doing, aim to enhance and complement the key recent review articles on these topics. We summarize the main synthetic approaches, namely the Stöber and microemulsion processes, and, in this context, we deal with issues in relation to both covalent and physical incorporation of different types of dyes in the particles. The important issue of NP functionalization for conjugation to biomolecules is discussed and strategies published in the recent literature are highlighted and evaluated. We cite recent examples of the use of fluorescent silica NPs for cell imaging in the areas of cancer, stem cell and infectious disease research, and we review the current literature on the use of silica NPs for intracellular sensing of oxygen, pH and ionic species. We include a short final section which seeks to identify the main challenges and obstacles in relation to the potential widespread use of these particles for in vivo diagnostics and therapeutics.

Korzeniowska, B.; Nooney, R.; Wencel, D.; McDonagh, C.

2013-11-01

336

Carbon black nanoparticles induce type II epithelial cells to release chemotaxins for alveolar macrophages  

PubMed Central

Background Alveolar macrophages are a key cell in dealing with particles deposited in the lungs and in determining the subsequent response to that particle exposure. Nanoparticles are considered a potential threat to the lungs and the mechanism of pulmonary response to nanoparticles is currently under intense scrutiny. The type II alveolar epithelial cell has previously been shown to release chemoattractants which can recruit alveolar macrophages to sites of particle deposition. The aim of this study was to assess the responses of a type II epithelial cell line (L-2) to both fine and nanoparticle exposure in terms of secretion of chemotactic substances capable of inducing macrophage migration. Results Exposure of type II cells to carbon black nanoparticles resulted in significant release of macrophage chemoattractant compared to the negative control and to other dusts tested (fine carbon black and TiO2 and nanoparticle TiO2) as measured by macrophage migration towards type II cell conditioned medium. SDS-PAGE analysis of the conditioned medium from particle treated type II cells revealed that a higher number of protein bands were present in the conditioned medium obtained from type II cells treated with nanoparticle carbon black compared to other dusts tested. Size-fractionation of the chemotaxin-rich supernatant determined that the chemoattractants released from the epithelial cells were between 5 and 30 kDa in size. Conclusion The highly toxic nature and reactive surface chemistry of the carbon black nanoparticles has very likely induced the type II cell line to release pro-inflammatory mediators that can potentially induce migration of macrophages. This could aid in the rapid recruitment of inflammatory cells to sites of particle deposition and the subsequent removal of the particles by phagocytic cells such as macrophages and neutrophils. Future studies in this area could focus on the exact identity of the substance(s) released by the type II cells in response to particle exposure.

Barlow, Peter G; Clouter-Baker, Anna; Donaldson, Ken; MacCallum, Janis; Stone, Vicki

2005-01-01

337

Fluorescence Modified Chitosan-Coated Magnetic Nanoparticles for High-Efficient Cellular Imaging  

PubMed Central

Labeling of cells with nanoparticles for living detection is of interest to various biomedical applications. In this study, novel fluorescent/magnetic nanoparticles were prepared and used in high-efficient cellular imaging. The nanoparticles coated with the modified chitosan possessed a magnetic oxide core and a covalently attached fluorescent dye. We evaluated the feasibility and efficiency in labeling cancer cells (SMMC-7721) with the nanoparticles. The nanoparticles exhibited a high affinity to cells, which was demonstrated by flow cytometry and magnetic resonance imaging. The results showed that cell-labeling efficiency of the nanoparticles was dependent on the incubation time and nanoparticles’ concentration. The minimum detected number of labeled cells was around 104by using a clinical 1.5-T MRI imager. Fluorescence and transmission electron microscopy instruments were used to monitor the localization patterns of the magnetic nanoparticles in cells. These new magneto-fluorescent nanoagents have demonstrated the potential for future medical use.

2009-01-01

338

Comprehensive studies on the interactions between chitosan nanoparticles and some live cells  

Microsoft Academic Search

As more and more oral formulations of nanoparticles are used in clinical contexts, a comprehensive study on the mechanisms\\u000a of interaction between polymer nanoparticles and live cells seems merited. Such a study was conducted and the results were\\u000a compared to the polymer itself in order to demonstrate different kinds of effects that are brought into the cell by polymer\\u000a and

Ai-ping Zheng; Hui-xue Liu; Lan Yuan; Meng Meng; Jian-cheng Wang; Xuan Zhang; Qiang Zhang

339

Targeting to carcinoma cells with chitosan- and starch-coated magnetic nanoparticles for magnetic hyperthermia.  

PubMed

The delivery of hyperthermic thermoseeds to a specific target site with minimal side effects is an important challenge in targeted hyperthermia, which employs magnetic method and functional polymers. An external magnetic field is used to control the site-specific targeting of the magnetic nanoparticles. Polymer-coated magnetic nanoparticles can confer a higher affinity to the biological cell membranes. In this study, uncoated, chitosan-coated, and starch-coated magnetic nanoparticles were synthesized for use as a hyperthermic thermoseed. Each sample was examined with respect to their applications to hyperthermia using XRD, VSM, and FTIR. In addition, the temperature changes under an alternating magnetic field were observed. As in vitro tests, the magnetic responsiveness of chitosan- and starch-coated magnetite was determined by a simple blood vessel model under various intensities of magnetic field. L929 normal cells and KB carcinoma cells were used to examine the cytotoxicity and affinity of each sample using the MTT method. The chitosan-coated magnetic nanoparticles generated a higher DeltaT of 23 degrees C under an AC magnetic field than the starch-coated magnetite, and the capturing rate of the particles was 96% under an external magnetic field of 0.4 T. The highest viability of L929 cells was 93.7%. Comparing the rate of KB cells capture with the rate of L929 cells capture, the rate of KB cells capture relatively increased with 10.8% in chitosan-coated magnetic nanoparticles. Hence, chitosan-coated magnetic nanoparticles are biocompatible and have a selective affinity to KB cells. The targeting of magnetic nanoparticles in hyperthermia was improved using a controlled magnetic field and a chitosan-coating. Therefore, chitosan-coated magnetic nanoparticles are expected to be promising materials for use in magnetic targeted hyperthermia. PMID:18257079

Kim, Dong-Hyun; Kim, Kyoung-Nam; Kim, Kwang-Mahn; Lee, Yong-Keun

2009-01-01

340

Electron microscopy localization and characterization of functionalized composite organic-inorganic SERS nanoparticles on leukemia cells  

Microsoft Academic Search

We demonstrate the use of electron microscopy as a powerful characterization tool to identify and locate antibody-conjugated composite organic-inorganic nanoparticle (COINs) surface enhanced Raman scattering (SERS) nanoparticles on cells. U937 leukemia cells labeled with antibody CD54-conjugated COINs were characterized in their native, hydrated state using wet scanning electron microscopy (SEM) and in their dehydrated state using high-resolution SEM. In both

Ai Leen Koh; Catherine M. Shachaf; Sailaja Elchuri; Garry P. Nolan; Robert Sinclair

2008-01-01

341

Biocompatibility of Fe3O4 nanoparticles evaluated by in vitro cytotoxicity assays using normal, glia and breast cancer cells  

NASA Astrophysics Data System (ADS)

In order to reveal the biocompatibility of Fe3O4 nanoparticles and bipolar surfactant tetramethylammonium 11-aminoundecanoate cytotoxicity tests were performed as a function of concentration from low (0.1 µg ml-1) to higher concentration (100 µg ml-1) using various human glia, human breast cancer and normal cell lines. Cytotoxicity tests for human glia (D54MG, G9T, SF126, U87, U251, U373), human breast cancer (MB157, SKBR3, T47D) and normal (H184B5F5/M10, WI-38, SVGp12) cell lines exhibited almost nontoxicity and reveal biocompatibility of Fe3O4 nanoparticles in the concentration range of 0.1-10 µg ml-1, while accountable cytotoxicity can be seen at 100 µg ml-1. The results of our studies suggest that Fe3O4 nanoparticles coated with bipolar surfactant tetramethylammonium 11-aminoundecanoate are biocompatible and promising for bio-applications such as drug delivery, magnetic resonance imaging and magnetic hyperthermia.

Ankamwar, B.; Lai, T. C.; Huang, J. H.; Liu, R. S.; Hsiao, M.; Chen, C. H.; Hwu, Y. K.

2010-02-01

342

Tumour-initiating stem-like cells in human prostate cancer exhibit increased NF-?B signalling  

PubMed Central

Androgen depletion is a key strategy for treating human prostate cancer, but the presence of hormone-independent cells escaping treatment remains a major therapeutic challenge. Here, we identify a minor subset of stem-like human prostate tumour-initiating cells (TICs) that do not express prostate cancer markers, such as androgen receptor or prostate specific antigen. These TICs possess stem cell characteristics and multipotency as demonstrated by in vitro sphere-formation and in vivo tumour-initiation, respectively. The cells represent an undifferentiated subtype of basal cells and can be purified from prostate tumours based on coexpression of the human pluripotent stem cell marker TRA-1-60 with CD151 and CD166. Such triple-marker-positive TICs recapitulate the original parent tumour heterogeneity in serial xeno-transplantations indicating a tumour cell hierarchy in human prostate cancer development. These TICs exhibit increased nuclear factor-?B activity. These findings are important in understanding the molecular basis of human prostate cancer.

Rajasekhar, Vinagolu K.; Studer, Lorenz; Gerald, William; Socci, Nicholas D.; Scher, Howard I.

2011-01-01

343

Nanoparticle mediated thermal ablation of breast cancer cells using a nanosecond pulsed electric field.  

PubMed

In the past, ablation of cancer cells using radiofrequency heating techniques has been demonstrated, but the current methodology has many flaws, including inconsistent tumor ablation and significant ablation of normal cells. Other researchers have begun to develop a treatment that is more selective for cancer cells using metallic nanoparticles and constant electric field exposure. In these studies, cell necrosis is induced by heating antibody functionalized metallic nanoparticles attached to cancer cells. Our approach to studying this phenomenon is to use similarly functionalized metallic nanoparticles that are specific for the T47D breast cancer cell line, exposing these nanoparticle cell conjugates to a nanosecond pulsed electric field. Using fluorescent, polystyrene-coated, iron-oxide nanoparticles, the results of our pilot study indicated that we were able to ablate up to approximately 80% of the cells using 60 ns pulses in increasing numbers of pulses and up to approximately 90% of the cells using 300 ns pulses in increasing numbers of pulses. These quantities of ablated cells were achieved using a cumulative exposure time 6 orders of magnitude less than most in vitro constant electric field studies. PMID:23694696

Burford, Christopher D; Bhattacharyya, Kiran D; Boriraksantikul, Nattaphong; Whiteside, Paul J D; Robertson, Benjamin P; Peth, Sarah M; Islam, Naz E; Viator, John A

2013-05-16

344

In vitro developmental toxicity test detects inhibition of stem cell differentiation by silica nanoparticles  

SciTech Connect

While research into the potential toxic properties of nanomaterials is now increasing, the area of developmental toxicity has remained relatively uninvestigated. The embryonic stem cell test is an in vitro screening assay used to investigate the embryotoxic potential of chemicals by determining their ability to inhibit differentiation of embryonic stem cells into spontaneously contracting cardiomyocytes. Four well characterized silica nanoparticles of various sizes were used to investigate whether nanomaterials are capable of inhibition of differentiation in the embryonic stem cell test. Nanoparticle size distributions and dispersion characteristics were determined before and during incubation in the stem cell culture medium by means of transmission electron microscopy (TEM) and dynamic light scattering. Mouse embryonic stem cells were exposed to silica nanoparticles at concentrations ranging from 1 to 100 {mu}g/ml. The embryonic stem cell test detected a concentration dependent inhibition of differentiation of stem cells into contracting cardiomyocytes by two silica nanoparticles of primary size 10 (TEM 11) and 30 (TEM 34) nm while two other particles of primary size 80 (TEM 34) and 400 (TEM 248) nm had no effect up to the highest concentration tested. Inhibition of differentiation of stem cells occurred below cytotoxic concentrations, indicating a specific effect of the particles on the differentiation of the embryonic stem cells. The impaired differentiation of stem cells by such widely used particles warrants further investigation into the potential of these nanoparticles to migrate into the uterus, placenta and embryo and their possible effects on embryogenesis.

Park, Margriet V.D.Z. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment, 3720 BA, Bilthoven (Netherlands); Department of Health Risk Analysis and Toxicology, Maastricht University, 6200 MD Maastricht (Netherlands)], E-mail: Margriet.Park@rivm.nl; Annema, Wijtske [Laboratory for Health Protection Research, National Institute for Public Health and the Environment, 3720 BA, Bilthoven (Netherlands); Salvati, Anna; Lesniak, Anna [Centre for BioNano Interactions, School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4 (Ireland); Elsaesser, Andreas; Barnes, Clifford; McKerr, George; Howard, C. Vyvyan [Centre for Molecular Bioscience, University of Ulster, Coleraine, BT52 1SA (United Kingdom); Lynch, Iseult; Dawson, Kenneth A. [Centre for BioNano Interactions, School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4 (Ireland); Piersma, Aldert H. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment, 3720 BA, Bilthoven (Netherlands); Institute for Risk Assessment Sciences, University of Utrecht, 3508 TD, Utrecht (Netherlands); Jong, Wim H. de [Laboratory for Health Protection Research, National Institute for Public Health and the Environment, 3720 BA, Bilthoven (Netherlands)

2009-10-01

345

Disruption of HepG2 cell adhesion by gold nanoparticle and Paclitaxel disclosed by in situ QCM measurement  

Microsoft Academic Search

Cell adhesion is a crucial issue for cytotoxicity or anticancer effectiveness for tumor cells. However, how both nanoparticles and drugs affect cell adhesion has not yet been defined. Herein, we report for the first time that gold nanoparticles and Paclitaxel can disrupt adhesion, as well as enhance apoptosis of HepG2 cell individually and synergistically, as observed by in situ measurement

Xiao-Lan Wei; Zhi-Hong Mo; Biao Li; Jin-Min Wei

2007-01-01

346

Microbubbles-overlapping mode for laser killing of cancer cells with absorbing nanoparticle clusters  

NASA Astrophysics Data System (ADS)

Laser-induced bubble formation around nanoparticles may play a crucial role in selective laser nanophotothermolysis of cancer cells targeted with nanoparticles. In this paper, we propose theoretically, and confirm experimentally, a new dynamic mode for selective cancer treatment that involves the overlapping of bubbles inside the cell volume. This bubbles-overlapping mode (BOM) can dramatically increase the efficiency of cancer treatment by laser-heated nanoparticles as a result of the large damage range. On the basis of nanoparticle optics below the diffraction limit and the kinetic model of bubble dynamics, we found the criteria and conditions (interparticle distance and particle size and concentration) for BOM initiation in cancer cells by laser radiation. Using MDA-MB-231 breast cancer cells, we showed that the optimal size range of the gold nanoparticles for effective laser initiation of BOM is 30-40 nm and the lower concentration limit is n ap 2.44 × 1011 cm-3 (i.e. the absolute number of particles homogeneously distributed inside a tumour cell is n ap 430). It was demonstrated that the formation of nanoclusters on the cell surface with sizes larger than the sizes of individual nanoparticles, may further increase the efficiency of the laser treatment of cancer.

Zharov, V. P.; Letfullin, R. R.; Galitovskaya, E. N.

2005-08-01

347

Targeting Mantle Cell Lymphoma with Anti-SYK Nanoparticles  

PubMed Central

The pentapeptide mimic 1,4-bis(9-O-dihydroquinidinyl)phthalazine / hydroquinidine 1,4-phathalazinediyl diether (“compound 61”) (C-61) is the first reported inhibitor targeting the P-site of SYK. Here we report a nanotechnology platform to target C-61 to mantle cell lymphoma (MCL) cells. Liposomal nanoparticles (NP) loaded with C-61 were prepared using the standard thin film evaporation method. The entrapment of C-61 was obtained using the pH gradient procedure with lactobionic acid (LBA) being used as a low pH buffer inside the NP. Formulation F6A was selected as a lead candidate for further biological testing. The average diameter, zeta potential and C-61 content of the F6A NP was 40 nm, 0.1 mV, and 12.6 mg/ml, respectively. F6A induces apoptosis in SYK+ but not SYK? leukemia/lymphoma cells. We also evaluated the cytotoxic activity of F6A in the context of an in vitro artificial bone marrow assay platform based on a 3D scaffold with inverted colloidal crystal geometry mimicking the structural topology of actual bone marrow matrix. The ability of C-61 to induce apoptosis in ALL-1 cells was not adversely affected by the scaffolds. F6A, but not the drug-free NP formulation F6B, caused apoptosis of MCL cell lines MAVER-1 and MINO within 24h. Further development of rationally designed SYK inhibitors and their nanoscale formulations may provide the foundation for therapeutic innovation against a broad spectrum of lymphoid malignancies, including MCL.

Cely, Ingrid; Yiv, Seang; Yin, Qian; Shahidzadeh, Anoush; Tang, Li; Cheng, Jianjun; Uckun, Fatih M.

2013-01-01

348

Nitric oxide releasing iron oxide magnetic nanoparticles for biomedical applications: cell viability, apoptosis and cell death evaluations  

NASA Astrophysics Data System (ADS)

Nitric oxide (NO) is involved in several physiological and pathophysiological processes, such as control of vascular tone and immune responses against microbes. Thus, there is great interest in the development of NO-releasing materials to carry and deliver NO for biomedical applications. Magnetic iron oxide nanoparticles have been used in important pharmacological applications, including drug-delivery. In this work, magnetic iron oxide nanoparticles were coated with thiol-containing hydrophilic ligands: mercaptosuccinic acid (MSA) and dimercaptosuccinic acid (DMSA). Free thiol groups on the surface of MSA- or DMSA- coated nanoparticles were nitrosated, leading to the formation of NO-releasing iron oxide nanoparticles. The cytotoxicity of MSA- or DMSA-coated magnetic nanoparticles (MNP) (thiolated nanoparticles) and nitrosated MSA- or nitrosated DMSA- coated MNPs (NO-releasing nanoparticles) were evaluated towards human lymphocytes. The results showed that MNP-MSA and MNP-DMSA have low cytotoxicity effects. On the other hand, NO-releasing MNPs were found to increase apoptosis and cell death compared to free NO-nanoparticles. Therefore, the cytotoxicity effects observed for NO-releasing MNPs may result in important biomedical applications, such as the treatment of tumors cells.

de Lima, R.; de Oliveira, J. L.; Ludescher, A.; Molina, M. M.; Itri, R.; Seabra, A. B.; Haddad, P. S.

2013-04-01

349

Mesenchymal stem cell-based cell engineering with multifunctional mesoporous silica nanoparticles for tumor delivery.  

PubMed

Stem cell engineering, the manipulation and control of cells, harnesses tremendous potential for diagnosis and therapy of disease; however, it is still challenging to impart multifunctionalization onto stem cells to achieve both. Here we describe a mesenchymal stem cell (MSC)-based multifunctional platform to target orthotopic glioblastoma by integrating the tumor targeted delivery of mesenchymal stem cells and the multimodal imaging advantage of mesoporous silica nanoparticles (MSNs). Rapid cellular uptake, long retention time and stability of particles exemplify the potential that the combination of MSNs and MSCs has as a stem cell-based multifunctional platform. Using such a platform, we verified tumor-targeted delivery of MSCs by in vivo multimodal imaging in an orthotopic U87MG glioblastoma model, displaying higher tumor uptake than particles without MSCs. As a proof-of-concept, this MSC platform opens a new vision for multifunctional applications of cell products by combining the superiority of stem cells and nanoparticles for actively targeted delivery. PMID:23228423

Huang, Xinglu; Zhang, Fan; Wang, Hui; Niu, Gang; Choi, Ki Young; Swierczewska, Magdalena; Zhang, Guofeng; Gao, Haokao; Wang, Zhe; Zhu, Lei; Choi, Hak Soo; Lee, Seulki; Chen, Xiaoyuan

2012-12-08

350

In vivo targeting of dendritic cells in lymph nodes with poly(propylene sulfide) nanoparticles.  

PubMed

Delivery of biodegradable nanoparticles to antigen-presenting cells (APCs), specifically dendritic cells (DCs), has potential for immunotherapy. This study investigates the delivery of 20, 45, and 100nm diameter poly(ethylene glycol)-stabilized poly(propylene sulfide) (PPS) nanoparticles to DCs in the lymph nodes. These nanoparticles consist of a cross-linked rubbery core of PPS surrounded by a hydrophilic corona of poly(ethylene glycol). The PPS domain is capable of carrying hydrophobic drugs and degrades within oxidative environments. 20 nm particles were most readily taken up into lymphatics following interstitial injection, while both 20 and 45nm nanoparticles showed significant retention in lymph nodes, displaying a consistent and strong presence at 24, 72, 96 and 120h post-injection. Nanoparticles were internalized by up to 40-50% of lymph node DCs (and APCs) without the use of a targeting ligand, and the site of internalization was in the lymph nodes rather than at the injection site. Finally, an increase in nanoparticle-containing DCs (and other APCs) was seen at 96h vs. 24h, suggesting an infiltration of these cells to lymph nodes. Thus, PPS nanoparticles of 20-45nm have the potential for immunotherapeutic applications that specifically target DCs in lymph nodes. PMID:16529839

Reddy, Sai T; Rehor, Annemie; Schmoekel, Hugo G; Hubbell, Jeffrey A; Swartz, Melody A

2006-03-10

351

Gold nanoparticles as physiological markers of urine internalization into urothelial cells in vivo  

PubMed Central

Background Urothelial bladder is the reservoir of urine and the urothelium minimizes the exchange of urine constituents with this tissue. Our aim was to test 1.9 nm biocompatible gold nanoparticles as a novel marker of internalization into the urothelial cells under physiological conditions in vivo. Methods We compared normal and neoplastic mice urothelium. Neoplastic lesions were induced by 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in drinking water for 10 weeks. Nanoparticles, intravenously injected into normal and BBN-treated mice, were filtered through the kidneys and became constituents of the urine within 90 minutes after injection. Results Gold nanoparticles were densely accumulated in the urine, while their internalization into urothelial cells depended on the cell differentiation stage. In the terminally differentiated superficial urothelial cells of normal animals, nanoparticles were occasionally found in the endosomes, but not in the fusiform vesicles. Regions of exfoliated cells were occasionally found in the normal urothelium. Superficial urothelial cells located next to exfoliated regions contained gold nanoparticles in the endosomes and in the cytosol beneath the apical plasma membrane. The urothelium of BBN-treated animals developed fat hyperplasia with moderate dysplasia. The superficial cells of BBN-treated animals were partially differentiated as demonstrated by the lack of fusiform vesicles. These cells contained the gold nanoparticles distributed in the endosomes and throughout their cytosol. Conclusion Gold nanoparticles are a valuable marker to study urine internalization into urothelial cells in vivo. Moreover, they can be used as a sensitive marker of differentiation and functionality of urothelial cells.

Hudoklin, Samo; Zupancic, Dasa; Makovec, Darko; Kreft, Mateja Erdani; Romih, Rok

2013-01-01

352

In vitro nanoparticle toxicity to rat alveolar cells and coelomocytes from the earthworm Lumbricus rubellus.  

PubMed

Abstract Sensitivity of immune cells (coelomocytes) of Lumbricus rubellus earthworms was investigated for exposure to selected nanoparticles, in order to obtain further insight in mechanisms of effects observed after in vivo C(60) exposure. In the in vivo study, tissue damage appeared to occur without accompanying increased immune responses. Coelomocytes exposed in vitro to C(60) showed no decrease of their cellular viability, but demonstrated a decrease in gene expression of the cytokine-like protein CCF-1, indicating immunosuppression. Experiments with NR8383 rat macrophage cells and tri-block copolymer nanoparticles were used to compare sensitivity and to demonstrate the usefulness of coelomocytes as a test system for nano-immunotoxicity, respectively. Overall, the results imply that sensitivity towards nanoparticles differs between cell types and nanoparticles. Moreover, this study indicates that injuries in absence of an immune response, observed after in vivo C(60) exposure in our earlier work, are caused by immunosuppression rather than coelomocyte mortality. PMID:23102209

van der Ploeg, Merel Jc; van den Berg, Johannes Hj; Bhattacharjee, Sourav; de Haan, Laura Hj; Ershov, Dmitry S; Fokkink, Remco G; Zuilhof, Han; Rietjens, Ivonne McM; van den Brink, Nico W

2012-11-27

353

Enhancement of silicon solar cell performances due to light trapping by colloidal metal nanoparticles  

NASA Astrophysics Data System (ADS)

Photovoltaics is the most promising technology for the future of green energy production. To fully realize the potential use of photovoltaic technology, low manufacturing cost and high working photoconversion efficiency must be obtained. Light trapping by metal nanoparticles is an attractive strategy in thin film as well as in bulk silicon solar cells aimed to confine light within the active layer to promote the photon absorption and therefore achieving higher efficiency. In this paper, we tested the deposition of silver and gold nanoparticles on bulk silicon solar cells by colloidal technique in order to enhance their photovoltaic conversion efficiency by means of Plasmonic Light Scattering by metal nanoparticles. The feasible Plasmonic Light Scattering related enhancement was examined using spectral response and I-V measurements. Relative increases of the total delivered power under simulated solar irradiation were observed for cells both with and without antireflection coating using silver and gold nanoparticles.

Jana, Sourav Kanti; Le Donne, Alessia; Binetti, Simona

2012-02-01

354

The significance of a Cripto-1 positive subpopulation of human melanoma cells exhibiting stem cell-like characteristics.  

PubMed

Cripto-1 (CR-1) protein function differs according to cellular or extracellular expression. In this study, we explore the significance of cell surface CR-1 expression in human melanoma cells. Cell surface CR-1-expressing human melanoma cells (CR1-CS+) were selected by fluorescence-activated cell sorting (FACS) and grown in vitro and in vivo in nude mice to study their growth characteristics. The CR1-CS+ melanoma cells were found to express increased levels of Oct4, MDR-1 and activated c-Src compared with cells lacking this subpopulation (CR1-CS-) or unsorted cells, used as control. CR1-CS+ show reduced proliferation rates and diminished spherical colony formation compared with control cells when cultured in vitro. Orthotopic injections of CR1-CS+ in nude mice formed slow growing tumors with histologic variability across different areas of the CR1-CS+ xenografts. CR-1-expressing cells from first generation CR1-CS+ tumors showed significantly increased tumor-forming rate and aggressiveness following subsequent transplants in nude mice. These data demonstrate that within a heterogeneous melanoma cell population there resides a slow proliferating, cell surface CR-1-expressing subpopulation capable of giving rise to a fast growing, aggressive progeny that may contribute to disease recurrence and progression. PMID:23574716

Strizzi, Luigi; Margaryan, Naira V; Gilgur, Alina; Hardy, Katharine M; Normanno, Nicola; Salomon, David S; Hendrix, Mary J C

2013-04-10

355

The significance of a Cripto-1-positive subpopulation of human melanoma cells exhibiting stem cell-like characteristics  

PubMed Central

Cripto-1 (CR-1) protein function differs according to cellular or extracellular expression. In this study, we explore the significance of cell surface CR-1 expression in human melanoma cells. Cell surface CR-1-expressing human melanoma cells (CR1-CS+) were selected by fluorescence-activated cell sorting (FACS) and grown in vitro and in vivo in nude mice to study their growth characteristics. The CR1-CS+ melanoma cells were found to express increased levels of Oct4, MDR-1 and activated c-Src compared with cells lacking this subpopulation (CR1-CS?) or unsorted cells, used as control. CR1-CS+ show reduced proliferation rates and diminished spherical colony formation compared with control cells when cultured in vitro. Orthotopic injections of CR1-CS+ in nude mice formed slow growing tumors with histologic variability across different areas of the CR1-CS+ xenografts. CR-1-expressing cells from first generation CR1-CS+ tumors showed significantly increased tumor-forming rate and aggressiveness following subsequent transplants in nude mice. These data demonstrate that within a heterogeneous melanoma cell population there resides a slow proliferating, cell surface CR-1-expressing subpopulation capable of giving rise to a fast growing, aggressive progeny that may contribute to disease recurrence and progression.

Strizzi, Luigi; Margaryan, Naira V.; Gilgur, Alina; Hardy, Katharine M.; Normanno, Nicola; Salomon, David S.; Hendrix, Mary J.C.

2013-01-01

356

Smooth Muscle Cells Isolated from Thoracic Aortic Aneurysms Exhibit Increased Genomic Damage, but Similar Tendency for Apoptosis  

PubMed Central

Aortic aneurysms (AA) are characterized by structural deterioration leading to progressive dilation. During the development of AA, two key structural changes are pronounced, one being degradation of extracellular matrix and the other loss of smooth muscle cells (SMCs) through apoptosis. Reactive oxygen species (ROS) are produced above physiological levels in dilated (aneurismal) part of the aorta compared to the nondilated part and they are known to be associated with both the extracellular matrix degradation and the loss of SMCs. In this study, we hypothesized that aneurismal SMCs are more prone to apoptosis and that at least some cells undergo apoptosis due to elevated ROS in the aortic wall. To test this hypothesis, we first isolated SMCs from thoracic aneurismal tissue and compared their apoptotic tendency with normal SMCs in response to H2O2, oxidized sterol, or UV treatment. Exposed cells exhibited morphological changes characteristic of apoptosis, such as cell shrinkage, membrane blebbing, chromatin condensation, and DNA fragmentation. Terminal deoxynucleotidyl transferased UTP nick end labeling (TUNEL) further confirmed the fragmentation of nuclear DNA in these cells. Vascular SMCs were analyzed for their micronuclei (MN) and binucleate (BN) frequency as indicators of genomic abnormality. These data were then compared to patient parameters, including age, gender, hypertension, or aortic diameter for existing correlations. While the tendency for apoptosis was not significantly different compared to normal cells, both the %MN and %BN were higher in aneurismal SMCs. The data suggest that there is increased DNA damage in TAA samples, which might play a pivotal role in disease development.

Serhatli, Muge; Kacar, Omer; Adiguzel, Zelal; Tuncer, Altug; Hayran, Mutlu; Baysal, Kemal

2012-01-01

357

Highly specific and ultrasensitive graphene-enhanced electrochemical detection of low-abundance tumor cells using silica nanoparticles coated with antibody-conjugated quantum dots.  

PubMed

A dual signal amplification immunosensing strategy that offers high sensitivity and specificity for the detection of low-abundance tumor cells was designed. High sensitivity was achieved by using graphene to modify the immunosensor surface to accelerate electron transfer and quantum dot (QD)-coated silica nanoparticles as tracing tags. High specificity was further obtained by the simultaneous measurement of two disease-specific biomarkers on the cell surface using different QD-coated silica nanoparticle tracers. The immunosensor was constructed by covalently immobilized capture antibodies on a chitosan/electrochemically reduced graphene oxide film-modified glass carbon electrode. Cells were captured with a sandwich-type immunoreaction and the different QD-coated silica nanoparticle tracers were captured on the surface of the cells. Each biorecognition event yields a distinct voltammetric peak, which position and size reflects the corresponding identity and amount of the respective antigen. This strategy was vividly demonstrated by the simultaneous immunoassay of EpCAM and GPC3 antigens on the surface of the human liver cancer cell line Hep3B using anti-EpCAM-CdTe- and anti-GPC3-ZnSe-coated silica nanoparticle tracers. The two tracers gave comparable sensitivity, and the immunosensor exhibited high sensitivity and specificity with excellent stability, reproducibility, and accuracy, indicating its wide range of potential applications in clinical and molecular diagnostics. PMID:23402311

Wu, Yafeng; Xue, Peng; Kang, Yuejun; Hui, Kam M

2013-02-27

358

Iron nanoparticles increase 7-ketocholesterol-induced cell death, inflammation, and oxidation on murine cardiac HL1-NB cells  

PubMed Central

Objective: To evaluate the cytotoxicity of iron nanoparticles on cardiac cells and to determine whether they can modulate the biological activity of 7-ketocholesterol (7KC) involved in the development of cardiovascular diseases. Nanoparticles of iron labeled with Texas Red are introduced in cultures of nonbeating mouse cardiac cells (HL1-NB) with or without 7-ketocholesterol 7KC, and their ability to induce cell death, pro-inflammatory and oxidative effects are analyzed simultaneously. Study design: Flow cytometry (FCM), confocal laser scanning microscopy (CLSM), and subsequent factor analysis image processing (FAMIS) are used to characterize the action of iron nanoparticles and to define their cytotoxicity which is evaluated by enhanced permeability to SYTOX Green, and release of lactate deshydrogenase (LDH). Pro-inflammatory effects are estimated by ELISA in order to quantify IL-8 and MCP-1 secretions. Pro-oxidative effects are measured with hydroethydine (HE). Results: Iron Texas Red nanoparticles accumulate at the cytoplasmic membrane level. They induce a slight LDH release, and have no inflammatory or oxidative effects. However, they enhance the cytotoxic, pro-inflammatory and oxidative effects of 7KC. The accumulation dynamics of SYTOX Green in cells is measured by CLSM to characterize the toxicity of nanoparticles. The emission spectra of SYTOX Green and nanoparticles are differentiated, and corresponding factor images specify the possible capture and cellular localization of nanoparticles in cells. Conclusion: The designed protocol makes it possible to show how Iron Texas Red nanoparticles are captured by cardiomyocytes. Interestingly, whereas these fluorescent iron nanoparticles have no cytotoxic, pro-inflammatory or oxidative activities, they enhance the side effects of 7KC.

Kahn, Edmond; Baarine, Mauhamad; Pelloux, Sophie; Riedinger, Jean-Marc; Frouin, Frederique; Tourneur, Yves; Lizard, Gerard

2010-01-01

359

Hydrothermal synthesis of PtRu nanoparticles supported on graphene sheets for methanol oxidation in direct methanol fuel cell  

Microsoft Academic Search

Platinum–ruthenium (PtRu) nanoparticles are dispersed on graphene nanosheets and multi-walled carbon nanotubes (MWCNTs) via a hydrothermal method. Transmission electron microsocopy (TEM) observation shows the uniformly dispersed nanoparticles and the average nanoparticle size has been calculated. The electrochemical measurements demonstrate that the Pt–Ru\\/graphene catalyst exhibits about two times higher mass activity and better tolerance to poisoning species in methanol electro-oxidation than

Seok Hee Lee; Nitul Kakati; Seung Hyun Jee; Jatindranath Maiti; Young-Soo Yoon

2011-01-01

360

Evaluation of cytotoxic, genotoxic and inflammatory responses of nanoparticles from photocopiers in three human cell lines  

PubMed Central

Background Photocopiers emit nanoparticles with complex chemical composition. Short-term exposures to modest nanoparticle concentrations triggered upper airway inflammation and oxidative stress in healthy human volunteers in a recent study. To further understand the toxicological properties of copier-emitted nanoparticles, we studied in-vitro their ability to induce cytotoxicity, pro-inflammatory cytokine release, DNA damage, and apoptosis in relevant human cell lines. Methods Three cell types were used: THP-1, primary human nasal- and small airway epithelial cells. Following collection in a large volume photocopy center, nanoparticles were extracted, dispersed and characterized in the cell culture medium. Cells were doped at 30, 100 and 300 ?g/mL administered doses for up to 24 hrs. Estimated dose delivered to cells, was ~10% and 22% of the administered dose at 6 and 24 hrs, respectively. Gene expression analysis of key biomarkers was performed using real time quantitative PCR (RT-qPCR) in THP-1 cells at 5 ?g nanoparticles/mL for 6-hr exposure for confirmation purposes. Results Multiple cytokines, GM-CSF, IL-1?, IL-6, IL-8, IFN?, MCP-1, TNF-? and VEGF, were significantly elevated in THP-1 cells in a dose-dependent manner. Gene expression analysis confirmed up-regulation of the TNF-? gene in THP-1 cells, consistent with cytokine findings. In both primary epithelial cells, cytokines IL-8, VEGF, EGF, IL-1?, TNF-?, IL-6 and GM-CSF were significantly elevated. Apoptosis was induced in all cell lines in a dose-dependent manner, consistent with the significant up-regulation of key apoptosis-regulating genes P53 and Casp8 in THP-1 cells. No significant DNA damage was found at any concentration with the comet assay. Up-regulation of key DNA damage and repair genes, Ku70 and Rad51, were also observed in THP-1 cells, albeit not statistically significant. Significant up-regulation of the key gene HO1 for oxidative stress, implicates oxidative stress induced by nanoparticles. Conclusions Copier-emitted nanoparticles induced the release of pro-inflammatory cytokines, apoptosis and modest cytotoxicity but no DNA damage in all three-human cell lines. Taken together with gene expression data in THP-1 cells, we conclude that these nanoparticles are directly responsible for inflammation observed in human volunteers. Further toxicological evaluations of these nanoparticles, including across different toner formulations, are warranted.

2013-01-01