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1

Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries  

PubMed Central

Prostacyclin analogues are standard therapeutic options for vasoconstrictive diseases, including pulmonary hypertension and Raynaud’s phenomenon. Although effective, these treatment strategies are expensive and have several side effects. To improve drug efficiency, we tested liposomal nanoparticles as carrier systems. In this study, we synthesized liposomal nanoparticles tailored for the prostacyclin analogue iloprost and evaluated their pharmacologic efficacy on mouse intrapulmonary arteries, using a wire myograph. The use of cationic lipids, stearylamine, or 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (DOTAP) in liposomes promoted iloprost encapsulation to at least 50%. The addition of cholesterol modestly reduced iloprost encapsulation. The liposomal nanoparticle formulations were tested for toxicity and pharmacologic efficacy in vivo and ex vivo, respectively. The liposomes did not affect the viability of human pulmonary artery smooth muscle cells. Compared with an equivalent concentration of free iloprost, four out of the six polymer-coated liposomal formulations exhibited significantly enhanced vasodilation of mouse pulmonary arteries. Iloprost that was encapsulated in liposomes containing the polymer polyethylene glycol exhibited concentration-dependent relaxation of arteries. Strikingly, half the concentration of iloprost in liposomes elicited similar pharmacologic efficacy as nonencapsulated iloprost. Cationic liposomes can encapsulate iloprost with high efficacy and can serve as potential iloprost carriers to improve its therapeutic efficacy.

Jain, Pritesh P; Leber, Regina; Nagaraj, Chandran; Leitinger, Gerd; Lehofer, Bernhard; Olschewski, Horst; Olschewski, Andrea; Prassl, Ruth; Marsh, Leigh M

2014-01-01

2

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

3

Nanoparticles of cationic chimeric peptide and sodium polyacrylate exhibit striking antinociception activity at lower dose.  

PubMed

The current study investigates the performance of polyelectrolyte complexes based nanoparticles in improving the antinociceptive activity of cationic chimeric peptide-YFa at lower dose. Size, Zeta potential and morphology of the nanoparticles were determined. Size of the nanoparticles decreases and zeta potential increases with concomitant increase in charge ratio (Z(+/-)). The nanoparticles at Z(+/-)12 are spherical with 70+/-7 nm diameter in AFM and displayed positive surface charge and similar sizes (83+/-8 nm) by Zetasizer. The nanoparticles of Z(+/-) 12 are used in this study. Cytotoxicity by MTT assay on three different mammalian cell lines (liver, neuronal and kidney) revealed lower toxicity of nanoparticles. Hematological parameters were also not affected by nanoparticles compared to normal counts of water treated control group. Nanoparticles containing 10 mg/kg YFa produced increased antinociception, approximately 36%, in tail-flick latency test in mice, whereas the neat peptide at the same concentration did not show any antinociception activity. This enhancement in activity is attributed to the nanoparticle associated protection of peptide from proteolytic degradation. In vitro peptide release study in plasma also supported the antinociception profile of nanoparticles. Thus, our results suggest of a potential nanoparticle delivery system for cationic peptide drug candidates for improving their stability and bioavailability. PMID:19014986

Gupta, Kshitij; Singh, Vijay P; Kurupati, Raj K; Mann, Anita; Ganguli, Munia; Gupta, Yogendra K; Singh, Yogendra; Saleem, Kishwar; Pasha, Santosh; Maiti, Souvik

2009-02-20

4

Magnetofluorescent nanoparticles for bimodal detection of breast cancer cells  

NASA Astrophysics Data System (ADS)

Silica-encapsulated iron oxide composite nanoparticles were synthesized and characterized in terms of morphological and physico-chemical properties. These nanoparticles exhibited both fluorescent and magnetic properties useful for labeling of breast cancer cells. The mechanism of uptake by tumor cells, the pathway of degradation and the potential toxicity of these magnetofluorescent nanoparticles were investigated, suggesting that they could be developed as an efficient and safe bimodal contrast agent for detection of breast cancer cells.

Ronchi, Silvia; Colombo, Miriam; Verderio, Paolo; Mazzucchelli, Serena; Corsi, Fabio; de Palma, Clara; Allevi, Raffaele; Clementi, Emilio; Prosperi, Davide

2010-10-01

5

Core-shell silver nanoparticles for optical labeling of cells.  

PubMed

Silver nanoparticles have been modified with self-assembled monolayers of hydroxyl-terminated long chain thiols and encapsulated with a silica shell. The resulting core-shell nanoparticles were used as optical labels for cell analysis using flow cytometry and microscopy. The excitation of plasmon resonances in nanoparticles results in strong depolarized scattering of visible light, permitting detection at the single nanoparticle level. The nanoparticles were modified with neutravidin via epoxide-azide coupling chemistry, to which biotinylated antibodies targeting cell surface receptors were bound. The nanoparticle labels exhibited long-term stability in solutions with high salt concentrations without aggregation or silver etching. Labeled cells exhibited two orders of magnitude enhancement of the scattering intensity compared with unlabeled cells. PMID:24755004

Dukes, Kyle D; Christensen, Kenneth A; Chumanov, George

2014-08-01

6

Enhancement of cell radiation sensitivity by pegylated gold nanoparticles  

Microsoft Academic Search

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

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

2010-01-01

7

Thymoquinone Poly(lactide-co-glycolide) Nanoparticles Exhibit Enhanced Anti-proliferative, Anti-inflammatory, and Chemosensitization Potential  

PubMed Central

Thymoquinone (TQ), derived from the medicinal spice Nigella sativa (also called black cumin), has been shown to exhibit anti-inflammatory and anti-cancer activities. In this report we employed polymer-based nanoparticle approach to improve upon its effectiveness and bioavailability. TQ was encapsulated with 97.5% efficiency in biodegradable nanoparticulate formulation based on poly (lactide-co-glycolide) (PLGA) and the stabilizer polyethylene glycol (PEG)-5000. Dynamic laser light scattering and transmission electron microscopy confirmed particle diameter ranged between 150–200 nm. Electrophoretic gel shift mobility assay showed that TQ nanoparticles (NP) were more active than TQ in inhibiting NF-?B activation and in suppressing the expression of cyclin D1, matrix metalloproteinase (MMP)-9, vascular endothelial growth factor (VEGF), markers of cell proliferation, metastasis and angiogenesis, respectively. TQ-NP was also more potent than TQ in suppressing proliferation of colon cancer, breast cancer, prostate cancer, and multiple myeloma cells. Esterase staining for plasma membrane integrity revealed that TQ-NP was more potent than TQ in sensitizing leukemic cells to TNF- and paclitaxel-induced apoptosis. Overall our results demonstrate that encapsulation of TQ into nanoparticles enhances its anti-proliferative, anti-inflammatory, and chemosensitizing effects.

Ravindran, Jayaraj; Nair, Hareesh B; Sung, Bokyung; Prasad, Sahdeo; Tekmal, Rajeshwar R.; Aggarwal, Bharat B.

2010-01-01

8

Novel, silver-ion-releasing nanofibrous scaffolds exhibit excellent antibacterial efficacy without the use of silver nanoparticles.  

PubMed

Nanofibers, with their morphological similarities to the extracellular matrix of skin, hold great potential for skin tissue engineering. Over the last decade, silver nanoparticles have been extensively investigated in wound-healing applications for their ability to provide antimicrobial benefits to nanofibrous scaffolds. However, the use of silver nanoparticles has raised concerns as these particles can penetrate into the stratum corneum of skin, or even diffuse into the cellular plasma membrane. We present and evaluate a new silver ion release polymeric coating that we have found can be applied to biocompatible, biodegradable poly(l-lactic acid) nanofibrous scaffolds. Using this compound, custom antimicrobial silver-ion-releasing nanofibers were created. The presence of a uniform, continuous silver coating on the nanofibrous scaffolds was verified by XPS analysis. The antimicrobial efficacy of the antimicrobial scaffolds against Staphylococcus aureus and Escherichia coli bacteria was determined via industry-standard AATCC protocols. Cytotoxicity analyses of the antimicrobial scaffolds toward human epidermal keratinocytes and human dermal fibroblasts were performed via quantitative analyses of cell viability and proliferation. Our results indicated that the custom antimicrobial scaffolds exhibited excellent antimicrobial properties while also maintaining human skin cell viability and proliferation for silver ion concentrations below 62.5?gml(-1) within the coating solution. This is the first study to show that silver ions can be effectively delivered with nanofibrous scaffolds without the use of silver nanoparticles. PMID:24365706

Mohiti-Asli, Mahsa; Pourdeyhimi, Behnam; Loboa, Elizabeth G

2014-05-01

9

Shear-regulated Uptake of Nanoparticles by Endothelial Cells and Development of Endothelial-targeting Nanoparticles  

PubMed Central

The purpose of this research project was to develop nanoparticles with improved targeting, adhesion, and cellular uptake to activated or inflamed endothelial cells (ECs) under physiological flow conditions. Our hypothesis is that by mimicking platelet binding to activated ECs through the interaction between platelet glycoprotein Ib? (GP Ib?) and P-selectin on activated endothelial cells, GP Ib?-conjugated nanoparticles could exhibit increased targeting and higher cellular uptake in injured or activated endothelial cells under physiological flow conditions. To test this hypothesis, fluorescent carboxylated polystyrene nanoparticles were selected for the study as a model particle due to its narrow size distribution as a “proof-of-concept”. Using confocol microscopy, fluorescent measurement, and protein assays, cellular uptake properties were characterized for these polystyrene nanoparticles. The study also found that conjugation of 100 nm polystyrene nanoparticles with glycocalicin (the extracellular segment of GP Ib?) significantly increased the particle adhesion on P-selectin-coated surfaces and cellular uptake of nanoparticles by activated endothelial cells under physiological flow conditions. The results demonstrate that these novel endothelial-targeting nanoparticles could be the first step towards developing a targeted and sustained drug delivery system that can improve shear-regulated particle adhesion and cellular uptake.

Lin, Arthur; Sabnis, Abhimanyu; Kona, Soujanya; Nattama, Sivaniaravindapriya; Patel, Hemang; Dong, Jing-Fei; Nguyen, Kytai T.

2009-01-01

10

Mature adipocyte-derived dedifferentiated fat cells exhibit multilineage potential.  

PubMed

When mature adipocytes are subjected to an in vitro dedifferentiation strategy referred to as ceiling culture, these mature adipocytes can revert to a more primitive phenotype and gain cell proliferative ability. We refer to these cells as dedifferentiated fat (DFAT) cells. In the present study, we examined the multilineage differentiation potential of DFAT cells. DFAT cells obtained from adipose tissues of 18 donors exhibited a fibroblast-like morphology and sustained high proliferative activity. Flow cytometric analysis revealed that DFAT cells comprised a highly homogeneous cell population compared with that of adipose-derived stem/stromal cells (ASCs), although the cell-surface antigen profile of DFAT cells was very similar to that of ASCs. DFAT cells lost expression of mature adipocytes marker genes but retained or gained expression of mesenchymal lineage-committed marker genes such as peroxisome proliferator-activated receptor gamma (PPARgamma), RUNX2, and SOX9. In vitro differentiation analysis revealed that DFAT cells could differentiate into adipocytes, chondrocytes, and osteoblasts under appropriate culture conditions. DFAT cells also formed osteoid matrix when implanted subcutaneously into nude mice. In addition, clonally expanded porcine DFAT cells showed the ability to differentiate into multiple mesenchymal cell lineages. These results indicate that DFAT cells represent a type of multipotent progenitor cell. The accessibility and ease of culture of DFAT cells support their potential application for cell-based therapies. PMID:18064604

Matsumoto, Taro; Kano, Koichiro; Kondo, Daisuke; Fukuda, Noboru; Iribe, Yuji; Tanaka, Nobuaki; Matsubara, Yoshiyuki; Sakuma, Takahiro; Satomi, Aya; Otaki, Munenori; Ryu, Jyunnosuke; Mugishima, Hideo

2008-04-01

11

Vaccinia virus exhibits cell-type-dependent entry characteristics  

PubMed Central

Differing and sometimes conflicting data have been reported regarding several aspects of vaccinia virus (VV) entry. To address this, we used a ?-galactosidase reporter virus to monitor virus entry into multiple cell types under varying conditions. Entry into HeLa, B78H1 and L cells was strongly inhibited by heparin whereas entry into Vero and BSC-1 cells was unaffected. Bafilomycin also exhibited variable and cell-type-specific effects on VV entry. Entry into B78H1 and BSC-1 cells was strongly inhibited by bafilomycin whereas entry into Vero and HeLa cells was only partially inhibited suggesting the co-existence of both pH-dependent and pH-independent VV entry pathways in these cell types. Finally, entry into HeLa, B78H1, L and BSC-1 cells exhibited a lag of 6–9 min whereas this delay was undetectable in Vero cells. Our results suggest that VV exploits multiple cell attachment and entry pathways allowing it to infect a broad range of cells.

Whitbeck, J. Charles; Foo, Chwan-Hong; de Leon, Manuel Ponce; Eisenberg, Roselyn J.; Cohen, Gary H.

2014-01-01

12

Green synthesis of silver nanoparticles using Delphinium denudatum root extract exhibits antibacterial and mosquito larvicidal activities  

NASA Astrophysics Data System (ADS)

Green synthesis of silver nanoparticles (AgNPs) using aqueous root extract of Delphinium denudatum (Dd) by reduction of Ag+ ions from silver nitrate solution has been investigated. The synthesized DdAgNPs were characterized by using UV-Vis spectroscopy, X-ray diffraction (XRD), Field emission scanning electron microscope (FESEM) and Fourier transform infrared spectroscopy (FTIR). The prepared DdAgNPs showed maximum absorbance at 416 nm and particles were polydispersed in nature, spherical in shape and the size of the particle obtained was ?85 nm. The DdAgNPs exhibited antibacterial activity against Staphylococcus aureus ATCC 6538, Bacillus cereus NCIM 2106, Escherichia coli ATCC 8739 and Pseudomonas aeruginosa ATCC 9027. The DdAgNPs showed potent larvicidal activity against second instar larvae of dengue vector Aedes aegypti with a LC50 value of 9.6 ppm.

Suresh, Gopal; Gunasekar, Poosali Hariharan; Kokila, Dhanasegaran; Prabhu, Durai; Dinesh, Devadoss; Ravichandran, Nagaiya; Ramesh, Balasubramanian; Koodalingam, Arunagirinathan; Vijaiyan Siva, Ganesan

2014-06-01

13

Nanoparticles of cationic chimeric peptide and sodium polyacrylate exhibit striking antinociception activity at lower dose  

Microsoft Academic Search

The current study investigates the performance of polyelectrolyte complexes based nanoparticles in improving the antinociceptive activity of cationic chimeric peptide-YFa at lower dose. Size, Zeta potential and morphology of the nanoparticles were determined. Size of the nanoparticles decreases and zeta potential increases with concomitant increase in charge ratio (Z+\\/?). The nanoparticles at Z+\\/?12 are spherical with 70±7 nm diameter in AFM

Kshitij Gupta; Vijay P. Singh; Raj K. Kurupati; Anita Mann; Munia Ganguli; Yogendra K. Gupta; Yogendra Singh; Kishwar Saleem; Santosh Pasha; Souvik Maiti

2009-01-01

14

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

2013-10-01

15

Cell type-dependent uptake, localization, and cytotoxicity of 1.9 nm gold nanoparticles  

PubMed Central

Background This follow-up study aims to determine the physical parameters which govern the differential radiosensitization capacity of two tumor cell lines and one immortalized normal cell line to 1.9 nm gold nanoparticles. In addition to comparing the uptake potential, localization, and cytotoxicity of 1.9 nm gold nanoparticles, the current study also draws on comparisons between nanoparticle size and total nanoparticle uptake based on previously published data. Methods We quantified gold nanoparticle uptake using atomic emission spectroscopy and imaged intracellular localization by transmission electron microscopy. Cell growth delay and clonogenic assays were used to determine cytotoxicity and radiosensitization potential, respectively. Mechanistic data were obtained by Western blot, flow cytometry, and assays for reactive oxygen species. Results Gold nanoparticle uptake was preferentially observed in tumor cells, resulting in an increased expression of cleaved caspase proteins and an accumulation of cells in sub G1 phase. Despite this, gold nanoparticle cytotoxicity remained low, with immortalized normal cells exhibiting an LD50 concentration approximately 14 times higher than tumor cells. The surviving fraction for gold nanoparticle-treated cells at 3 Gy compared with that of untreated control cells indicated a strong dependence on cell type in respect to radiosensitization potential. Conclusion Gold nanoparticles were most avidly endocytosed and localized within cytoplasmic vesicles during the first 6 hours of exposure. The lack of significant cytotoxicity in the absence of radiation, and the generation of gold nanoparticle-induced reactive oxygen species provide a potential mechanism for previously reported radiosensitization at megavoltage energies.

Coulter, Jonathan A; Jain, Suneil; Butterworth, Karl T; Taggart, Laura E; Dickson, Glenn R; McMahon, Stephen J; Hyland, Wendy B; Muir, Mark F; Trainor, Coleman; Hounsell, Alan R; O'Sullivan, Joe M; Schettino, Giuseppe; Currell, Fred J; Hirst, David G; Prise, Kevin M

2012-01-01

16

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

PubMed

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

2013-11-01

17

Electronic and surface properties of PbS nanoparticles exhibiting efficient multiple exciton generation.  

PubMed

Ultrafast transient absorption measurements have been used to study multiple exciton generation in solutions of PbS nanoparticles vigorously stirred to avoid the effects of photocharging. The threshold and slope efficiency of multiple exciton generation are found to be 2.5 ± 0.2 ×E(g) and 0.34 ± 0.08, respectively. Photoemission measurements as a function of nanoparticle size and ageing show that the position of the valence band maximum is pinned by surface effects, and that a thick layer of surface oxide is rapidly formed at the nanoparticle surfaces on exposure to air. PMID:21993370

Hardman, Samantha J O; Graham, Darren M; Stubbs, Stuart K; Spencer, Ben F; Seddon, Elaine A; Fung, Ho-Ting; Gardonio, Sandra; Sirotti, Fausto; Silly, Mathieu G; Akhtar, Javeed; O'Brien, Paul; Binks, David J; Flavell, Wendy R

2011-12-01

18

Cytotoxicity of monodispersed chitosan nanoparticles against the Caco-2 cells  

SciTech Connect

Published toxicology data on chitosan nanoparticles (NP) often lack direct correlation to the in situ size and surface characteristics of the nanoparticles, and the repeated NP assaults as experienced in chronic use. The aim of this paper was to breach these gaps. Chitosan nanoparticles synthesized by spinning disc processing were characterised for size and zeta potential in HBSS and EMEM at pHs 6.0 and 7.4. Cytotoxicity against the Caco-2 cells was evaluated by measuring the changes in intracellular mitochondrial dehydrogenase activity, TEER and sodium fluorescein transport data and cell morphology. Cellular uptake of NP was observed under the confocal microscope. Contrary to established norms, the collective data suggest that the in vitro cytotoxicity of NP against the Caco-2 cells was less influenced by positive surface charges than by the particle size. Particle size was in turn determined by the pH of the medium in which the NP was dispersed, with the mean size ranging from 25 to 333 nm. At exposure concentration of 0.1%, NP of 25 ± 7 nm (zeta potential 5.3 ± 2.8 mV) was internalised by the Caco-2 cells, and the particles were observed to inflict extensive damage to the intracellular organelles. Concurrently, the transport of materials along the paracellular pathway was significantly facilitated. The Caco-2 cells were, however, capable of recovering from such assaults 5 days following NP removal, although a repeat NP exposure was observed to produce similar effects to the 1st exposure, with the cells exhibiting comparable resiliency to the 2nd assault. -- Highlights: ? Chitosan nanoparticles reduced mitochondrial dehydrogenase activity. ? Cellular uptake of chitosan nanoparticles was observed. ? Chitosan nanoparticles inflicted extensive damage to the cell morphology. ? The transport of materials along the paracellular pathway was facilitated.

Loh, Jing Wen [Laboratory for Drug Delivery, Pharmacy, Characterisation and Analysis, University of Western Australia (Australia)] [Laboratory for Drug Delivery, Pharmacy, Characterisation and Analysis, University of Western Australia (Australia); Saunders, Martin [Centre for Microscopy, Characterisation and Analysis, University of Western Australia (Australia)] [Centre for Microscopy, Characterisation and Analysis, University of Western Australia (Australia); Lim, Lee-Yong, E-mail: lee.lim@uwa.edu.au [Laboratory for Drug Delivery, Pharmacy, Characterisation and Analysis, University of Western Australia (Australia) [Laboratory for Drug Delivery, Pharmacy, Characterisation and Analysis, University of Western Australia (Australia); School of Biomedical, Biomolecular and Chemical Sciences, 35 Stirling Hwy, Crawley 6009 (Australia)

2012-08-01

19

Thymoquinone poly (lactide-co-glycolide) nanoparticles exhibit enhanced anti-proliferative, anti-inflammatory, and chemosensitization potential  

Microsoft Academic Search

Thymoquinone (TQ), derived from the medicinal spice Nigella sativa (also called black cumin), has been shown to exhibit anti-inflammatory and anti-cancer activities. In this report we employed polymer-based nanoparticle approach to improve upon its effectiveness and bioavailability. TQ was encapsulated with 97.5% efficiency in biodegradable nanoparticulate formulation based on poly (lactide-co-glycolide) (PLGA) and the stabilizer polyethylene glycol (PEG)-5000. Dynamic laser

Jayaraj Ravindran; Hareesh B. Nair; Bokyung Sung; Sahdeo Prasad; Rajeshwar R. Tekmal; Bharat B. Aggarwal

2010-01-01

20

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

21

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

22

Interactions of Model Cell Membranes with Nanoparticles  

NASA Astrophysics Data System (ADS)

The same properties that give nanoparticles their enhanced function, such as high surface area, small size, and better conductivity, can also alter the cytotoxicity of nanomaterials. Ultimately, many of these nanomaterials will be released into the environment, and can cause cytotoxic effects to environmental bacteria, aquatic organisms, and humans. Previous results from our laboratory suggest that nanoparticles can have a detrimental effect on cells, depending on nanoparticle size. It is our goal to characterize the properties of nanomaterials that can result in membrane destabilization. We tested the effects of nanoparticle size and chemical functionalization on nanoparticle-membrane interactions. Gold nanoparticles at 2, 5,10, and 80 nm were investigated, with a concentration of 1.1x1010 particles/mL. Model cell membranes were constructed of of L-?-phosphatidylcholine (egg PC), which has negatively charged lipid headgroups. A quartz crystal microbalance with dissipation (QCM-D) was used to measure frequency changes at different overtones, which were related to mass changes corresponding to nanoparticle interaction with the model membrane. In QCM-D, a lipid bilayer is constructed on a silicon dioxide crystal. The crystals, oscillate at different harmonic frequencies depending upon changes in mass or energy dissipation. When mass is added to the crystal surface, such as through addition of a lipid vesicle solution, the frequency change decreases. By monitoring the frequency and dissipation, we could verify that a supported lipid bilayer (SLB) formed on the silica surface. After formation of the SLB, the nanoparticles can be added to the system, and the changes in frequency and dissipation are monitored in order to build a mechanistic understanding of nanoparticle-cell membrane interactions. For all of the smaller nanoparticles (2, 5, and 10 nm), nanoparticle addition caused a loss of mass from the lipid bilayer, which appears to be due to the formation of holes or pores in the cell membrane. The dissipation changes were small, which indicates that even with the membrane destabilization that occurs, the overall structure of the bilayer is not greatly perturbed. For the 80 nm nanoparticles, we initially saw the same pattern as the smaller nanoparticles with a mass loss from the membrane, but eventually we saw a large decrease in frequency, representing an increase in mass. This addition of mass may be attributed to adsorption of the gold nanoparticles onto the bilayer. The 80 nm particles also created a change in the energy dissipation, which suggests that the formation of the bilayer was altered with the adsorbed particles. This study suggests that nanoparticle size controls the mechanism by which nanoparticles interact with model cell membranes. We are extending this work to other types of gold nanoparticles. We are interested in examining the role of nanoparticle hydrophobicity and type of chemical functionalization on the interactions of the nanoparticle with a model membrane. We are also conducting studies on environmental bacteria, to correlate the mechanisms of nanoparticle cytoxicity with killing data on bacterial cells.

D'Angelo, S. M.; Camesano, T. A.; Nagarajan, R.

2011-12-01

23

Iron(II,III)-polyphenol complex nanoparticles derived from green tea exhibit a high ecotoxicological hazard  

EPA Science Inventory

There are several greener methods exist to synthesize zero–valent iron nanoparticles (nZVI) using different bio-based reducing agents. Although their useful properties in degradation of organic dyes, chlorinated organics, or arsenic have been described earlier, their charac...

24

Nanoparticles and cells: an interdisciplinary approach.  

PubMed

In this article we present an overview of some of our research in the field of nanoscience. By combining two different scientific backgrounds (chemistry and biology), we investigate nanoparticle-cell interactions from different angles. This requires an interdisciplinary approach involving material synthesis and characterization, cell biology (biochemistry) and microscopy. In particular, we describe the synthesis and magnetic properties of superparamagnetic iron oxide nanoparticles as well as their behavior in cell culture, evaluate different visualization and detection methods, and investigate the interaction of such magnetic particles with immune cells. PMID:22546253

Petri-Fink, Alke; Rothen-Rutishauser, Barbara

2012-01-01

25

Optically induced cell fusion using bispecific nanoparticles.  

PubMed

Redirecting the immune system to eliminate tumor cells is a promising alternative to traditional cancer therapies, most often requiring direct interaction between an immune system effector cell and its target. Herein, a novel approach for selective attachment of malignant cells to antigen-presenting cells by using bispecific nanoparticles is presented. The engaged cell pairs are then irradiated by a sequence of resonant femtosecond pulses, which results in widespread cell fusion and the consequent formation of hybrid cells. The dual role of gold nanoparticles as conjugating agents and fusion promoters offers a simple yet effective means for specific fusion between different cells. This technology could be useful for a variety of in vitro and in vivo applications that call for selective fusion between cells within a large heterogenic cell population. PMID:23788508

Yeheskely-Hayon, Daniella; Minai, Limor; Golan, Lior; Dann, Eldad J; Yelin, Dvir

2013-11-25

26

Iron-oxide nanoparticles embedded silica microsphere resonator exhibiting broadband all-optical wavelength tunability.  

PubMed

In this Letter, a novel silica microsphere resonator (MSR) embedded with iron-oxide nanoparticles, which possesses broadband all-optical wavelength tunability, is demonstrated. It is generated by using in-line 1550 nm laser ablation of a microfiber with the assistance of magnetic fluid. To the best of our knowledge, this simple method of fabricating such MSRs is reported for the first time. Prominent photothermal effect is realized by the iron-oxide nanoparticles absorbing light pumped via the fiber stem, leading to a wavelength shift of over 13 nm (1.6 THz). Moreover, a linear tuning efficiency up to 0.2??nm/mW is realized. With excellent robustness and being fiberized, the spheres can be attractive elements in building up novel micro-illuminators, point heaters, optical sensors, and fiber communication modules. PMID:24978752

Zhao, Ping; Shi, Lei; Liu, Yang; Wang, Zheqi; Pu, Shengli; Zhang, Xinliang

2014-07-01

27

Stem cell tracking with optically active nanoparticles  

PubMed Central

Stem-cell-based therapies hold promise and potential to address many unmet clinical needs. Cell tracking with modern imaging modalities offers insight into the underlying biological process of the stem-cell-based therapies, with the goal to reveal cell survival, migration, homing, engraftment, differentiation, and functions. Adaptability, sensitivity, resolution, and non-invasiveness have contributed to the longstanding use of optical imaging for stem cell tracking and analysis. To identify transplanted stem cells from the host tissue, optically active probes are usually used to label stem cells before the administration. In comparison to the traditional fluorescent probes like fluorescent proteins and dyes, nanoparticle-based probes are advantageous in terms of the photo-stabilities and minimal changes to the cell phenotype. The main focus here is to overview the recent development of optically active nanoparticles for stem cells tracking. The related optical imaging modalities include fluorescence imaging, photoacoustic imaging, Raman and surface enhanced Raman spectroscopy imaging.

Gao, Yu; Cui, Yan; Chan, Jerry KY; Xu, Chenjie

2013-01-01

28

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

29

Protamine sulfate-nanodiamond hybrid nanoparticles as a vector for MiR-203 restoration in esophageal carcinoma cells.  

PubMed

We report an innovative approach for miRNA-203 delivery in esophageal cancer cells using protamine sulphate (PS)-nanodiamond (ND) nanoparticles. The efficient delivery of miR-203 significantly suppressed the proliferation and migration of cancer cells through targeting Ran and ?Np63, exhibiting a great potential for PS@ND nanoparticles in miRNA-based cancer therapy. PMID:24154605

Cao, Minjun; Deng, Xiongwei; Su, Shishuai; Zhang, Fang; Xiao, Xiangqian; Hu, Qin; Fu, Yongwei; Yang, Burton B; Wu, Yan; Sheng, Wang; Zeng, Yi

2013-12-21

30

Growth of gold nanoparticles in human cells.  

PubMed

Gold nanoparticles of 20-100 nm diameter were synthesized within HEK-293 (human embryonic kidney), HeLa (human cervical cancer), SiHa (human cervical cancer), and SKNSH (human neuroblastoma) cells. Incubation of 1 mM tetrachloroaurate solution, prepared in phosphate buffered saline (PBS), pH 7.4, with human cells grown to approximately 80% confluency yielded systematic growth of nanoparticles over a period of 96 h. The cells, stained due to nanoparticle growth, were adherent to the bottom of the wells of the tissue culture plates, with their morphology preserved, indicating that the cell membrane was intact. Transmission electron microscopy of ultrathin sections showed the presence of nanoparticles within the cytoplasm and in the nucleus, the latter being much smaller in dimension. Scanning near field microscopic images confirmed the growth of large particles within the cytoplasm. Normal cells gave UV-visible signatures of higher intensity than the cancer cells. Differences in the cellular metabolism of cancer and noncancer cells were manifested, presumably in their ability to carry out the reduction process. PMID:16316080

Anshup, Anshup; Venkataraman, J Sai; Subramaniam, Chandramouli; Kumar, R Rajeev; Priya, Suma; Kumar, T R Santhosh; Omkumar, R V; John, Annie; Pradeep, T

2005-12-01

31

Human intestinal M cells exhibit enterocyte-like intermediate filaments  

PubMed Central

Background—The derivation and ultrastructural composition of M cells covering the lymphoid follicles of Peyer's patches is still unknown. Results from different animal models have shown that there are species specific differences in the composition of intermediate filaments between M cells and neighbouring enterocytes. Little is known, however, about intermediate filaments of human M cells. ?Aims—To compare components of the cytoskeleton of human M cells with those of adjacent absorptive enterocytes. ?Methods—The expression and localisation of different cytokeratins, vimentin, and desmin in M cells was determined on follicle associated epithelia of human appendix using immunohistochemistry and immunogold electron microscopy. ?Results—Cytokeratins specific for human intestinal epithelial cells such as cytokeratins 8, 18, 19, and 20 were expressed in both absorptive enterocytes and M cells with no differences in intensity and cellular distribution between both cell types. Vimentin and desmin, tissue specific markers of either mesenchymal or myogenic cells, as well as other cytokeratins were not detectable in enterocytes or M cells. ?Conclusion—This is the first study on the structure of intermediate filaments in human intestinal M cells. Our results show that in contrast to several animal models, human M cells apparently do not differ from adjacent enterocytes in the composition of their intermediate filament cytoskeleton. The presence of enterocyte like cytokeratins and the absence of other cytokeratins as well as of vimentin and desmin supports the hypothesis of an epithelial origin of human intestinal M cells and suggests that M cells may derive from differentiated enterocytes. ?? Keywords: human intestinal M cells; appendix; cytokeratin; intermediate filaments; follicle associated epithelium

Kucharzik, T; Lugering, N; Schmid, K; Schmidt, M; Stoll, R; Domschke, W

1998-01-01

32

Hybrid silver nanoparticle/conjugated polyelectrolyte nanocomposites exhibiting controllable metal-enhanced fluorescence  

NASA Astrophysics Data System (ADS)

Metal-enhanced fluorescence of conjugated polyelectrolytes (CPs) is realized using a simple, green hybrid Ag nanocomposite film. Ag nanoparticles (Ag NPs) are pre-prepared by sodium citrate reduction and incorporated into agarose by mixing to form an Ag-containing agarose film (Ag@agarose). Through variation of the amount of Ag NPs in the Ag@agarose film as well as the thickness of the interlayer between CPs and the Ag@agarose film prepared of layer-by-layer assembly of chitosan and sodium alginate, a maximum 8.5-fold increase in the fluorescence of CPs is obtained. After introducing tyrosinase, this system also can be used to detect phenolic compounds with high sensitivity and good visualization under ultraviolet light.

Wang, Xiaoyu; He, Fang; Zhu, Xi; Tang, Fu; Li, Lidong

2014-03-01

33

Hybrid silver nanoparticle/conjugated polyelectrolyte nanocomposites exhibiting controllable metal-enhanced fluorescence  

PubMed Central

Metal-enhanced fluorescence of conjugated polyelectrolytes (CPs) is realized using a simple, green hybrid Ag nanocomposite film. Ag nanoparticles (Ag NPs) are pre-prepared by sodium citrate reduction and incorporated into agarose by mixing to form an Ag-containing agarose film (Ag@agarose). Through variation of the amount of Ag NPs in the Ag@agarose film as well as the thickness of the interlayer between CPs and the Ag@agarose film prepared of layer-by-layer assembly of chitosan and sodium alginate, a maximum 8.5-fold increase in the fluorescence of CPs is obtained. After introducing tyrosinase, this system also can be used to detect phenolic compounds with high sensitivity and good visualization under ultraviolet light.

Wang, Xiaoyu; He, Fang; Zhu, Xi; Tang, Fu; Li, Lidong

2014-01-01

34

A universal nanoparticle cell secretion capture assay.  

PubMed

Secreted proteins play an important role in intercellular interactions, especially between cells of the immune system. Currently, there is no universal assay that allows a simple noninvasive identification and isolation of cells based on their secretion of various products. We have developed such a method. Our method is based on the targeting, to the cell surface, of heterofunctional nanoparticles coupled to a cell surface-specific antibody and to a secreted protein-specific antibody, which captures the secreted protein on the surface of the producing cell. Importantly, this method does not compromise cellviability and is compatible with further culture and expansion of the secreting cells. PMID:22996967

Fitzgerald, Wendy; Grivel, Jean-Charles

2013-02-01

35

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

36

Uptake and cytotoxicity of chitosan nanoparticles in human liver cells  

Microsoft Academic Search

Despite extensive research into the biomedical and pharmaceutical applications of nanoparticles, and the liver being the main detoxifying organ in the human body, there are limited studies which delineate the hepatotoxicity of nanoparticles. This paper reports on the biological interactions between liver cells and chitosan nanoparticles, which have been widely recognised as biocompatible. Using the MTT assay, human liver cells

Jing Wen Loh; George Yeoh; Martin Saunders; Lee-Yong Lim

2010-01-01

37

Effects of cobalt nanoparticles on human T cells in vitro.  

PubMed

Limited information is available on the potential risk of degradation products of metal-on-metal bearings in joint arthroplasty. The aim of this study was to investigate the cytotoxicity and genotoxicity of orthopedic-related cobalt nanoparticles on human T cells in vitro. T cells were collected using magnetic CD3 microbeads and exposed to different concentrations of cobalt nanoparticles and cobalt chloride. Cytotoxicity was evaluated by methyl thiazolyl tetrazolium and lactate dehydrogenase release assay. Cobalt nanoparticles dissolution in culture medium was determined by inductively coupled plasma-mass spectrometry. To study the probable mechanism of cobalt nanoparticles effects on T cells, superoxide dismutase, catalase, and glutathione peroxidase level was measured. Cobalt nanoparticles and cobalt ions could inhibit cell viability and enhance lactate dehydrogenase release in a concentration- and time-dependent manner (P?nanoparticles in the culture medium were less than 40% and increased with cobalt nanoparticles concentration. Cobalt nanoparticles could induce primary DNA damage in a concentration-dependent manner, and the DNA damage caused by cobalt nanoparticles was heavier than that caused by cobalt ions. Cobalt nanoparticles exposure could significantly decrease superoxide dismutase, catalase, and glutathione peroxidase activities at subtoxic concentrations (6 ?M, nanoparticles could generate potential risks to the T cells of patients suffer from metal-on-metal total hip arthroplasty, and the inhibition of antioxidant capacity may play important role in cobalt nanoparticles effects on T cells. PMID:21968949

Jiang, Haitao; Liu, Fan; Yang, Huilin; Li, Yang

2012-04-01

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.  

PubMed

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. PMID:22101191

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

Fullerene nanoparticles exhibit greater retention in freshwater sediment than in model porous media.  

PubMed

Increasing production and use of fullerene-based nanomaterials underscore the need to determine their mobility in environmental transport pathways and potential ecological exposures. This study investigated the transport of two fullerenes (i.e., aqu/C(60) and water-soluble C(60) pyrrolidine tris-acid [C(60) PTA]) in columns packed with model porous media (Iota quartz and Ottawa sand) and a sediment from Call's creek under saturated and unsaturated steady-state flows. The fullerenes had the least retention in Iota quartz, and the greatest retention in the sediment at near neutral pH, correlating with the degree of grain surface chemical heterogeneity (e.g., amorphous Al hydroxides concentration increasing in the order of Iota quartzexhibited a strong dependency on solution pH that could be explained partly by the pH-dependent surface charge of fullerenes and grain surface, and partly by increased hydrophobicity of C(60) PTA when solution pH approaches its isoelectric point (IEP). Finally, fullerene retention was enhanced in unsaturated media, implying that fullerenes may be more attenuated in the vadose zone than in groundwater. PMID:22445188

Zhang, Wei; Isaacson, Carl W; Rattanaudompol, U-sa; Powell, Tremaine B; Bouchard, Dermont

2012-06-01

42

Endocytosis and exocytosis of nanoparticles in mammalian cells  

PubMed Central

Engineered nanoparticles that can be injected into the human body hold tremendous potential to detect and treat complex diseases. Understanding of the endocytosis and exocytosis mechanisms of nanoparticles is essential for safe and efficient therapeutic application. In particular, exocytosis is of significance in the removal of nanoparticles with drugs and contrast agents from the body, while endocytosis is of great importance for the targeting of nanoparticles in disease sites. Here, we review the recent research on the endocytosis and exocytosis of functionalized nanoparticles based on various sizes, shapes, and surface chemistries. We believe that this review contributes to the design of safe nanoparticles that can efficiently enter and leave human cells and tissues.

Oh, Nuri; Park, Ji-Ho

2014-01-01

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

Ginger phytochemicals exhibit synergy to inhibit prostate cancer cell proliferation  

PubMed Central

Dietary phytochemicals offer non-toxic 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 due to individual phytochemicals rather may be ascribed to but 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 0.03-0.88. 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.

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

2014-01-01

45

Synergistic targeting of cell membrane, cytoplasm, and nucleus of cancer cells using rod-shaped nanoparticles.  

PubMed

Design of carriers for effective delivery and targeting of drugs to cellular and subcellular compartments is an unmet need in medicine. Here, we report pure drug nanoparticles comprising camptothecin (CPT), trastuzumab (TTZ), and doxorubicin (DOX) to enable cell-specific interactions, subcellular accumulation, and growth inhibition of breast cancer cells. CPT is formulated in the form of nanorods which are coated with TTZ. DOX is encapsulated in the TTZ corona around the CPT nanoparticle. Our results show that TTZ/DOX-coated CPT nanorods exhibit cell-specific internalization in BT-474 breast cancer cells, after which TTZ is recycled to the plasma membrane, leaving CPT nanorods in the perinuclear region and delivering DOX into the nucleus of the cells. The effects of CPT-TTZ-DOX nanoparticles on growth inhibition are synergistic (combination index = 0.17 ± 0.03) showing 10-10?000-fold lower inhibitory concentrations (IC50) compared to those of individual drugs. The design of antibody-targeted pure drug nanoparticles offers a promising design strategy to facilitate intracellular delivery and therapeutic efficiency of anticancer drugs. PMID:24053162

Barua, Sutapa; Mitragotri, Samir

2013-11-26

46

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

2012-08-30

47

Single live cell refractometer using nanoparticle coated fiber tip  

Microsoft Academic Search

We present a nano-optical probe for real-time refractive index measurement of single live cell. The probe was made of a tapered fiber tip coated with 13 nm diameter gold nanoparticles. The evanescent wave near the tip excited localized surface plasmon resonance of gold nanoparticles. By measuring the optical intensity scattered from the nanoparticles, the probe showed an intensity sensitivity up

Jung-Yan Lee; Chia-Wei Lee; En-Hong Lin; Pei-Kuen Wei

2008-01-01

48

Carbon and clay nanoparticles induce minimal stress responses in gram negative bacteria and eukaryotic fish cells.  

PubMed

We investigated in vitro the potential mutagenic and toxic effects of two clay-based nanoparticles, Cloisite® Na(+) (Cloisite) and halloysite; and multi-walled carbon nanotubes (MWCNT), commonly used in the polymer composite industry. Using the Ames test, the three nanoparticles did not have a true mutagenic effect, although growth of Salmonella enterica var. Typhimurium (S.typhimurium) was diminished at higher nanoparticle concentrations. We investigated the impact of nanoparticles on Escherichia coli and S. typhimurium including oxyR and rpoS mutants, which are susceptible to oxidative stress. The oxyR mutants were inhibited in the presence of nanoparticles, when grown aerobically with light. Toxicity was not observed in the absence of light or during anaerobic growth. E. coli rpoS mutants exhibited some toxicity when cultured with Cloisite and MWCNT only when grown aerobically with light. There was no effect with other nanoparticles, or with S. typhimurium rpoS mutants. MWCNT exhibited a slight toxic effect against Epithelioma papulosum cyprini (EPC) cells only at the highest concentration tested. There was no discernable toxicity to EPC cells caused by the clay nanoparticles. We conclude that clay-based nanoparticles and MWCNT do not exert a mutagenic effect and do not have a general toxic effect across all bacterial species or between prokaryotic and eukaryotic cells. Modest toxicity was only observed in eukaryotic EPC cells against MWCNT at the highest concentration tested. Limited species-specific toxicity to clay based and MWCNT nanoparticles was seen in bacterial strains primarily due to culture conditions and mutations that exacerbate oxidative stress. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 961-968, 2014. PMID:23125163

Taylor, Alicia A; Aron, Gary M; Beall, Gary W; Dharmasiri, Nihal; Zhang, Yixin; McLean, Robert J C

2014-08-01

49

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

50

Effect of hydroxyapatite nanoparticles on K562 cells in vitro  

Microsoft Academic Search

Stable and single-dispersed hydroxyapatite (HAP) nanoparticles were synthesized with ultrasonic-assisted method. HAP nanoparticles\\u000a were characterized by dynamic light scattering, XRD (X-ray diffraction) and TEM (Transmission Electron Microscopy). The effect\\u000a of HAP nanoparticles on the K562 human myelogenous leukemia cell line was investigated by MTT assay and cell count test, and\\u000a the mechanism was studied through the changes of cell cycle

Pei Chen; Honglian Dai; Yingchao Han; Meizhen Yin; Shipu Li

2008-01-01

51

Thiolated chitosan nanoparticles: transfection study in the Caco-2 differentiated cell culture  

NASA Astrophysics Data System (ADS)

The aim of this study was to monitor the expression of secreted protein in differentiated Caco-2 cells after transfection with nanoparticles, in order to improve gene delivery. Based on unmodified chitosan and thiolated chitosan conjugates, nanoparticles with the gene reporter pSEAP (recombinant Secreted Alkaline Phosphatase) were generated at pH 4.0. Transfection studies of thiolated chitosan in Caco-2 cells during the exponential growth phase and differentiation growth phase of the cells led to a 5.0-fold and 2.0-fold increase in protein expression when compared to unmodified chitosan nanoparticles. The mean particle size for both unmodified chitosan and cross-linked thiolated chitosan nanoparticles is 212.2 ± 86 and 113.6 ± 40 nm, respectively. The zeta potential of nanoparticles was determined to be 7.9 ± 0.38 mV for unmodified chitosan nanoparticles and 4.3 ± 0.74 mV for cross-linked thiolated chitosan nanoparticles. Red blood cell lysis evaluation was used to evaluate the membrane damaging properties of unmodified and thiolated chitosan nanoparticles and led to 4.61 ± 0.36% and 2.29 ± 0.25% lysis, respectively. Additionally, cross-linked thiolated chitosan nanoparticles were found to exhibit higher stability toward degradation in gastric juices. Furthermore the reversible effect of thiolated chitosan on barrier properties was monitored by measuring the transepithelial electrical resistance (TEER) and is supported by immunohistochemical staining for the tight junction protein claudin. According to these results cross-linked thiolated chitosan nanoparticles have the potential to be used as a non-viral vector system for gene therapy.

Martien, Ronny; Loretz, Brigitta; Sandbichler, Adolf Michael; Bernkop Schnürch, Andreas

2008-01-01

52

pH-sensitive pullulan-based nanoparticle carrier for adriamycin to overcome drug-resistance of cancer cells.  

PubMed

Urocanic acid was conjugated to pullulan to synthesize O-urocanyl pullulan (URPA) with degree of substitution (DS) of 8.2%. URPA nanoparticles prepared by dialysis method had spherical shapes and a mean diameter of 156.8±16.8nm. Adriamycin (ADR) was successfully loaded into URPA nanoparticles and exhibited pH-sensitive in vitro release property. MTT assay showed that ADR-loaded URPA (ADR/URPA) nanoparticles had a significant higher toxicity against drug resistant MCF-7/ADR cells than free ADR, and the reversal index reached up to 9.6. The results of flow cytometry and confocal microscopy showed that URPA nanoparticles efficiently enhanced accumulation and retention of ADR in MCF-7/ADR cells and successfully delivered ADR into cell nucleus. The reversal effect of ADR/URPA nanoparticles on the drug resistance of MCF-7/ADR cells was perhaps related with their cell entry and intracellular drug release mechanisms. PMID:25037431

Guo, Hua; Liu, Yuanyuan; Wang, Yan; Wu, Jing; Yang, Xiaoying; Li, Rongshan; Wang, Yinsong; Zhang, Ning

2014-10-13

53

Bio-synthesis of gold nanoparticles by human epithelial cells, in vivo  

NASA Astrophysics Data System (ADS)

Healthy epithelial cells, in vivo, have the ability to synthesize gold nanoparticles when aqueous tetrachloroauric acid is made to react with human skin. Neither a reducing agent nor a protecting chemical is needed for this bio-synthesis method. The first indication of gold nanoparticle formation is the staining of the skin, which turns deep purple. Stereoscopic optical micrographs of human skin tissue in contact with aqueous tetrachloroauric acid clearly show the staining of the epithelial cells. The UV-Vis spectrum of these epithelial cells shows an absorption band with a maximum at 553 nm. This absorption peak is within the wavelength region where the surface plasmon resonance (SPR) band of aqueous colloidal gold exhibits a maximum. Transmission electron micrographs show that gold nanoparticles synthesized by epithelial cells have sizes between 1 and 100 nm. The electron diffraction pattern of these nanoparticles reveals a crystalline structure whose interplanar distances correspond to fcc metallic gold. Transmission electron micrographs of ultra-thin (70 nm thick) slices of epithelial cells clearly and undoubtedly demonstrate that gold nanoparticles are inside the cell. According to high resolution transmission electron micrographs of intracellular single gold nanoparticles, they have the shape of a polyhedron.

Larios-Rodriguez, E.; Rangel-Ayon, C.; Castillo, S. J.; Zavala, G.; Herrera-Urbina, R.

2011-09-01

54

Gold nanoparticles enhanced electroporation for mammalian cell transfection.  

PubMed

Electroporation figured prominently as an effective nonviral gene delivery approach for its balance on the transfection efficiency and cell viability, no restrictions of probe or cell type, and operation simplicity. The commercial electroporation systems have been widely adopted in the past two decades while still carry drawbacks associated with the high applied electric voltage, unsatisfied delivery efficiency, and/or low cell viability. By adding highly conductive gold nanoparticles (AuNPs) in electroporation solution, we demonstrated enhanced electroporation performance (i.e., better DNA delivery efficiency and higher cell viability) on mammalian cells from two different aspects: the free, naked AuNPs reduce the resistance of the electroporation solution so that the local pulse strength on cells was enhanced; targeting AuNPs (e.g., Tf-AuNPs) were brought to the cell membrane to work as virtual microelectrodes to porate cells with limited area from many different sites. The enhancement was confirmed with leukemia cells in both a commercial batch electroporation system and a home-made flow-through system using pWizGFP plasmid DNA probes. Such enhancement depends on the size, concentration, and the mixing ratio of free AuNPs/Tf-AuNPs. An equivalent mixture of free AuNPs and Tf-AuNPs exhibited the best enhancement with the transfection efficiency increased 2-3 folds at minimum sacrifice of cell viability. This new delivery concept, the combination of nanoparticles and electroporation technologies, may stimulate various in vitro and in vivo biomedical applications which rely on the efficient delivery of nucleic acids, anticancer drugs, or other therapeutic materials. PMID:24749393

Zu, Yingbo; Huang, Shuyan; Liao, Wei-Ching; Lu, Yang; Wang, Shengnian

2014-06-01

55

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

56

Cytotoxicity and apoptotic effects of tea polyphenol-loaded chitosan nanoparticles on human hepatoma HepG2 cells.  

PubMed

Tea polyphenols have strong antioxidant and antitumor activities. However, these health benefits are limited due to their poor in vivo stability and low bioavailability. Chitosan nanoparticles as delivery systems may provide an alternative approach for enhancing bioavailability of poorly absorbed drugs. In this study, tea polyphenol-loaded chitosan nanoparticles have been prepared using two different chitosan biomaterials, and their antitumor effects were evaluated in HepG2 cells, including cell cytotoxicity comparison, cell morphology analysis, cell apoptosis and cell cycle detection. The results indicated that the tea polyphenol-loaded chitosan nanoparticles showed a branch shape and heterogeneous distribution in prepared suspension. MTT assay suggested that tea polyphenol-loaded chitosan nanoparticles could inhibit the proliferation of HepG2 cells, and the cytotoxicity rates were increased gradually and appeared an obvious dose-dependent relationship. Transmission electron microscope images showed that the HepG2 cells treated with tea polyphenol-loaded chitosan nanoparticles exhibited some typical apoptotic features, such as microvilli disappearance, margination of nuclear chromatin, intracytoplasmic vacuoles and the mitochondrial swelling. In addition, the tea polyphenol-loaded chitosan nanoparticles had relatively weak inhibitory effects on HepG2 cancer cells compared with tea polyphenols. Tea polyphenols not only induced cancer cell apoptosis, but also promoted their necrosis. However, tea polyphenol-loaded chitosan nanoparticles exhibited their antitumor effects mainly through inducing cell apoptosis. Our results revealed that the inhibition effects of tea polyphenol-loaded chitosan nanoparticles on tumor cells probably depended on their controlled drug release and effective cell delivery. The chitosan nanoparticles themselves as the delivery carrier showed limited antitumor effects compared with their encapsulated drugs. PMID:24433880

Liang, Jin; Li, Feng; Fang, Yong; Yang, Wenjian; An, Xinxin; Zhao, Liyan; Xin, Zhihong; Cao, Lin; Hu, Qiuhui

2014-03-01

57

Aluminum plasmonic nanoparticles enhanced dye sensitized solar cells.  

PubMed

We present an investigation on utilizing plasmonic aluminium (Al) nanoparticles (NPs) to enhance the optical absorption of dye-sensitized solar cells (DSCs). The Al NPs exhibit not only the light absorption enhancement in solar cells with localized surface plasmon (LSP) effect but also the chemical stability to iodide/triiodide electrolyte. Besides, the lower work function (~4.06 eV), compared with that of TiO2 (~4.6 eV), may suppress the quenching processes, such as charge transfer to metal NPs, to reduce the loss. Thus, high concentration of Al NPs could be incorporated into the TiO2 anodes, and the power conversion efficiency (PCE) of DSCs is improved by nearly 13%. Moreover, electrochemical impedance spectroscopy (EIS) characterization also indicates that the plasmonic DSCs with Al NPs present better electrochemical performance than regular ones, which contributes to the improvement of PCE of the device. PMID:24922239

Xu, Qi; Liu, Fang; Liu, Yuxiang; Meng, Weisi; Cui, Kaiyu; Feng, Xue; Zhang, Wei; Huang, Yidong

2014-03-10

58

Cervical Cancer Cells with Positive Sox2 Expression Exhibit the Properties of Cancer Stem Cells  

PubMed Central

Background Although Sox2 expression has been found in several types of cancer, it has not yet been used to identify or isolate CSCs in somatic carcinoma. Methods SiHa and C33A cells stably transfected with a plasmid containing human Sox2 transcriptional elements driving the enhanced green fluorescent protein (EGFP) reporter were sorted into the Sox2-positive and the Sox2-negative populations by FACS, and Sox2 expression was detected by western blot and immunohistochemistry. The differentiation, self-renewal and tumor formation abilities, as well as the expression of the stemness and the EMT related genes of the Sox2-positive and the Sox2-negative cervical cancer cells were characterized in vitro and in vivo. Results A pSox2/EGFP system was used to separate the Sox2-positive and the Sox2-negative cells from cervical cancer cell lines, SiHa and C33A cells. Compared with the Sox2-negative cells, the Sox2-positive SiHa and C33A cells exhibited greater capacities for self-renewal, differentiation and tumor formation. Furthermore, Sox2-positive SiHa and C33A cells expressed higher levels of stemness-related genes, such as Sox2/Bmi-1/Oct4/ALDH1, and EMT-related genes, such as vimentin/snail/?-catenin. Taken together, all these results indicated that cells expressing endogenous Sox2 are CSCs in cervical carcinomas. Conclusion This study is the first to establish a functional link between endogenous Sox2 expression and CSCs in cervical carcinomas. Additionally, this study demonstrated that it is feasible to develop a tool to isolate CSCs from somatic tumors based on the expression of the endogenous nuclear protein Sox2 instead of cell surface markers.

Xu, Rui; Liu, Jun-Tian; Zheng, Peng-Sheng

2014-01-01

59

Drug-loaded nanoparticles induce gene expression in human pluripotent stem cell derivatives.  

PubMed

Tissue engineering and advanced manufacturing of human stem cells requires a suite of tools to control gene expression spatiotemporally in culture. Inducible gene expression systems offer cell-extrinsic control, typically through addition of small molecules, but small molecule inducers typically contain few functional groups for further chemical modification. Doxycycline (DXC), a potent small molecule inducer of tetracycline (Tet) transgene systems, was conjugated to a hyperbranched dendritic polymer (Boltorn H40) and subsequently reacted with polyethylene glycol (PEG). The resulting PEG-H40-DXC nanoparticle exhibited pH-sensitive drug release behavior and successfully controlled gene expression in stem-cell-derived fibroblasts with a Tet-On system. While free DXC inhibited fibroblast proliferation and matrix metalloproteinase (MMP) activity, PEG-H40-DXC nanoparticles maintained higher fibroblast proliferation levels and MMP activity. The results demonstrate that the PEG-H40-DXC nanoparticle system provides an effective tool to controlling gene expression in human stem cell derivatives. PMID:24232694

Gajbhiye, Virendra; Escalante, Leah; Chen, Guojun; Laperle, Alex; Zheng, Qifeng; Steyer, Benjamin; Gong, Shaoqin; Saha, Krishanu

2014-01-01

60

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

61

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

62

Engineered cobalt oxide nanoparticles readily enter cells.  

PubMed

Magnetic nanoparticles (NPs) have great potential for applications not only as catalysts or energy storage devices, but also in biomedicine, as contrast enhancement agents for magnetic resonance imaging, or for drug delivery. The same characteristics that make cobalt-based NPs so attractive raise serious questions about their safety. In this context, we investigated Co3O4-NPs. Believing that the characterization of NPs is relevant for understanding their biological activity, we analyzed them by atomic force and electron microscopy to define size, shape, and aggregation. To clarify whether their biological effects could be due to a potential release of cobalt ions, we evaluated spontaneous dissolution in different media. To determine their potential toxicity to human cells, we measured cell viability and ROS formation in two human cell lines using CoCl2 for comparison. Co3O(4)-NPs induced a concentration- and time-dependent impairment of cellular viability, although cobalt ions were more toxic. We also demonstrated that cobalt causes a rapid induction of ROS if supplied in the form of Co3O4-NPs rather than as ions. Moreover, we evaluated the cellular uptake of NPs. Interestingly, Co3O4-NPs are able to enter the cell very rapidly, remaining confined in vesicles inside the cytoplasm. They were found also inside the cell nuclei, though less frequently. PMID:19539014

Papis, Elena; Rossi, Federica; Raspanti, Mario; Dalle-Donne, Isabella; Colombo, Graziano; Milzani, Aldo; Bernardini, Giovanni; Gornati, Rosalba

2009-09-28

63

Role of cell cycle on the cellular uptake and dilution of nanoparticles in a cell population  

NASA Astrophysics Data System (ADS)

Nanoparticles are considered a primary vehicle for targeted therapies because they can pass biological barriers and enter and distribute within cells by energy-dependent pathways. So far, most studies have shown that nanoparticle properties, such as size and surface, can influence how cells internalize nanoparticles. Here, we show that uptake of nanoparticles by cells is also influenced by their cell cycle phase. Although cells in different phases of the cell cycle were found to internalize nanoparticles at similar rates, after 24 h the concentration of nanoparticles in the cells could be ranked according to the different phases: G2/M > S > G0/G1. Nanoparticles that are internalized by cells are not exported from cells but are split between daughter cells when the parent cell divides. Our results suggest that future studies on nanoparticle uptake should consider the cell cycle, because, in a cell population, the dose of internalized nanoparticles in each cell varies as the cell advances through the cell cycle.

Kim, Jong Ah; Åberg, Christoffer; Salvati, Anna; Dawson, Kenneth A.

2012-01-01

64

Uptake and cytotoxicity of chitosan nanoparticles in human liver cells  

SciTech Connect

Despite extensive research into the biomedical and pharmaceutical applications of nanoparticles, and the liver being the main detoxifying organ in the human body, there are limited studies which delineate the hepatotoxicity of nanoparticles. This paper reports on the biological interactions between liver cells and chitosan nanoparticles, which have been widely recognised as biocompatible. Using the MTT assay, human liver cells were shown to tolerate up to 4 h of exposure to 0.5% w/v of chitosan nanoparticles (18 {+-} 1 nm, 7.5 {+-} 1.0 mV in culture medium). At nanoparticle concentrations above 0.5% w/v, cell membrane integrity was compromised as evidenced by leakage of alanine transaminase into the extracellular milieu, and there was a dose-dependent increase in CYP3A4 enzyme activity. Uptake of chitosan nanoparticles into the cell nucleus was observed by confocal microscopic analysis after 4 h exposure with 1% w/v of chitosan nanoparticles. Electron micrographs further suggest necrotic or autophagic cell death, possibly caused by cell membrane damage and resultant enzyme leakage.

Loh, Jing Wen [Laboratory for Drug Delivery, Pharmacy, University of Western Australia, 35 Stirling Hwy, Crawley, 6009 (Australia); Yeoh, George [School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, 35 Stirling Hwy, Crawley, 6009 (Australia); Centre for Medical Research, Western Australian Institute for Medical Research, Nedlands, WA 6009 (Australia); Saunders, Martin [Centre for Microscopy, Characterisation and Analysis, University of Western Australia, 35 Stirling Hwy, Crawley, 6009 (Australia); Lim, Lee-Yong, E-mail: limly@cyllene.uwa.edu.a [Laboratory for Drug Delivery, Pharmacy, University of Western Australia, 35 Stirling Hwy, Crawley, 6009 (Australia); School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, 35 Stirling Hwy, Crawley, 6009 (Australia)

2010-12-01

65

Porous Silicon Nanoparticle Photosensitizers for Singlet Oxygen and Their Phototoxicity Against Cancer Cells  

PubMed Central

Porous Si nanoparticles, prepared from electrochemically etched single crystal Si wafers, function as photosensitizers to generate 1O2 in ethanol and in aqueous media. The preparation conditions for the porous Si nanoparticles were optimized to maximize (1) the yield of material; (2) its quantum yield of 1O2 production; and (3) its in vitro degradation properties. The optimal formulation was determined to consist of nanoparticles 146 ± 7 nm in diameter, with nominal pore sizes of 12 ± 4 nm. The quantum yield for 1O2 production is 0.10 ± 0.02 in ethanol and 0.17 ± 0.01 in H2O. HeLa or NIH-3T3 cells treated with 100 µg/mL porous Si nanoparticles and exposed to 60 J/cm2 white light (infrared filtered, 100 mW/cm2 for 10 min) exhibit ~ 45% cell death, while controls containing no nanoparticles show 10% or 25% cell death, respectively. The dark control experiment yields < 10% cytotoxicity for either cell type.

Xiao, Ling; Gu, Luo; Howell, Stephen B.; Sailor, Michael J.

2011-01-01

66

Gold nanoparticle-enhanced electroporation for leukemia cell transfection.  

PubMed

Electroporation serves as an attractive nonviral gene delivery approach for its effectiveness, operational simplicity, and no restrictions of probe or cell type. The commercial electroporation systems have been widely adopted in research and clinics with protocols usually compromising appropriate transfection efficiency and cell viability. By introducing gold nanoparticles (AuNPs), we demonstrated greatly enhanced performance of electroporation from two aspects: the highly conductive, naked AuNPs help reduce the potential drop consumed by the electroporation solution so that the majority of the applied voltage of an electric pulse is truly imposed on cells with enhanced field strength; AuNPs with targeting ligands (e.g., transferrin-AuNPs or Tf-AuNPs) are bound to the cell membrane, working as virtual microelectrodes to create pores on cells with limited opening area while from many different sites. The addition of AuNPs during electroporation therefore benefits not only quicker recovery and better survival of cells but also more efficient uptake of the subjected probes. Such enhancement was successfully confirmed on a chronic myeloid leukemia cell line (i.e., K562 cells) in both a commercial batch electroporation system and a homemade flow system with pWizGFP plasmid DNA probes. The efficiency was found to be dependent on the size, concentration, and mixing ratio of free AuNPs/Tf-AuNPs. An equivalent mixture of free AuNPs and Tf-AuNPs exhibited the best enhancement with the transfection efficiency increase of two to threefold at a minimum sacrifice of the cell viability. PMID:24510813

Huang, Shuyan; Zu, Yingbo; Wang, Shengnian

2014-01-01

67

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

2011-12-01

68

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

69

Fabrication of micropatterned arrays of gold nanoparticles for photothermal manipulation of living cells.  

PubMed

The fabrication of micro/nanostructured surfaces functionalized with stimulus-responsive chemical groups proved to be an interesting approach to simultaneously confine cell adhesion and manipulate cell-substrate interactions down to the single cell level. However, reversibility of stimulus-triggered systems is often not possible or exhibits slow switching kinetics. In contrast to such setups, gold nanoparticles have the properties to efficiently and reversibly generate heat under illumination at their plasmon resonance band. Thus, photo-induced heating could be used to directly and locally interface living cells and dynamically tailor the interactions to their adhesive environment. In the present chapter, we will first detail the preparation of micropatterned and functionalized gold nanoparticles immobilized on glass coverslips, and then report how to reliably characterize the photothermal properties of such substrates that enable the dynamic manipulation of cells. PMID:24484663

Polleux, Julien; Baffou, Guillaume

2014-01-01

70

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

71

The DG75 B-cell lymphoma line exhibits biclonal immunoglobulin gene rearrangement  

PubMed Central

Immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangement (GR) studies have been successfully employed to investigate the clonality and cell lineage of various lymphoid malignancies. Several lymphoma cell lines, such as BJAB, RAJI, DG75 and Jurkat cell lines, were often used as the positive controls in GR detection assays. Of those, the DG75 B-cell lymphoma line was found to exhibit biclonality [two or more homoduplex and heteroduplex bands in a polymerase chain reaction (PCR) product of clonality assay] in the PCR of GR detection assays. To further explore these characteristics of the biclonal phenomenon, the PCR products were purified and cloned into a pEGM-T clone vector. The sequences were analyzed using DNA analysis software. The results demonstrated that the two bands originated from two forms of GR of DG75 cell lines, i.e., DG75 is a biclonal cell line in Ig GRs, which has not been reported before.

QI, ZONGLI; LI, YUAN; HU, JUN; GUO, HUA; ZHAO, XIANGRONG; WANG, GUANGHUA; GAO, JINWEI; HU, QIAOXIA

2013-01-01

72

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

73

Micropatterned mammalian cells exhibit phenotype-specific left-right asymmetry  

PubMed Central

Left-right (LR) asymmetry (handedness, chirality) is a well-conserved biological property of critical importance to normal development. Changes in orientation of the LR axis due to genetic or environmental factors can lead to malformations and disease. While the LR asymmetry of organs and whole organisms has been extensively studied, little is known about the LR asymmetry at cellular and multicellular levels. Here we show that the cultivation of cell populations on micropatterns with defined boundaries reveals intrinsic cell chirality that can be readily determined by image analysis of cell alignment and directional motion. By patterning 11 different types of cells on ring-shaped micropatterns of various sizes, we found that each cell type exhibited definite LR asymmetry (p value down to 10-185) that was different between normal and cancer cells of the same type, and not dependent on surface chemistry, protein coating, or the orientation of the gravitational field. Interestingly, drugs interfering with actin but not microtubule function reversed the LR asymmetry in some cell types. Our results show that micropatterned cell populations exhibit phenotype-specific LR asymmetry that is dependent on the functionality of the actin cytoskeleton. We propose that micropatterning could potentially be used as an effective in vitro tool to study the initiation of LR asymmetry in cell populations, to diagnose disease, and to study factors involved with birth defects in laterality.

Wan, Leo Q.; Ronaldson, Kacey; Park, Miri; Taylor, Grace; Zhang, Yue; Gimble, Jeffrey M.; Vunjak-Novakovic, Gordana

2011-01-01

74

Biodesulfurization of Dibenzothiophene by Microbial Cells Coated with Magnetite Nanoparticles  

PubMed Central

Microbial cells of Pseudomonas delafieldii were coated with magnetic Fe3O4 nanoparticles and then immobilized by external application of a magnetic field. Magnetic Fe3O4 nanoparticles were synthesized by a coprecipitation method followed by modification with ammonium oleate. The surface-modified Fe3O4 nanoparticles were monodispersed in an aqueous solution and did not precipitate in over 18 months. Using transmission electron microscopy (TEM), the average size of the magnetic particles was found to be in the range from 10 to 15 nm. TEM cross section analysis of the cells showed further that the Fe3O4 nanoparticles were for the most part strongly absorbed by the surfaces of the cells and coated the cells. The coated cells had distinct superparamagnetic properties. The magnetization (?s) was 8.39 emu · g?1. The coated cells not only had the same desulfurizing activity as free cells but could also be reused more than five times. Compared to cells immobilized on Celite, the cells coated with Fe3O4 nanoparticles had greater desulfurizing activity and operational stability.

Shan, GuoBin; Xing, JianMin; Zhang, HuaiYing; Liu, HuiZhou

2005-01-01

75

Electrical transport and optical studies of ferromagnetic cobalt doped ZnO nanoparticles exhibiting a metal insulator transition  

Microsoft Academic Search

The observed correlation of oxygen vacancies and room temperature ferromagnetic ordering in Co doped ZnO1-delta nanoparticles reported earlier (Naeem et al 2006 Nanotechnology 17 2675-80) has been further explored by transport and optical measurements. In these particles room temperature ferromagnetic ordering had been observed to occur only after annealing in forming gas. In the current work the optical properties have

M. Naeem; S. K. Hasanain; A. Mumtaz

2008-01-01

76

Nanoparticle accumulation and transcytosis in brain endothelial cell layers  

NASA Astrophysics Data System (ADS)

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.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. Electronic supplementary information (ESI) available: Nanoparticle characterization in relevant media by Dynamic Light Scattering and SDS-PAGE. Transport study for silica nanoparticles across the BBB layer. Additional Electron Microscopy images of cells treated with the different nanoparticles investigated and details of the filters of the transwell systems. See DOI: 10.1039/c3nr02905k

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

2013-10-01

77

Nanoparticles: molecular targets and cell signalling.  

PubMed

Increasing evidence linking nanoparticles (NPs) with different cellular outcomes necessitate an urgent need for the better understanding of cellular signalling pathways triggered by NPs. Oxidative stress has largely been reported to be implicated in NP-induced toxicity. It could activate a wide variety of cellular events such as cell cycle arrest, apoptosis, inflammation and induction of antioxidant enzymes. These responses occur after the activation of different cellular pathways. In this context, three groups of MAP kinase cascades [ERK (extracellular signal-regulated kinases), p38 mitogen-activated protein kinase and JNK (c-Jun N-terminal kinases)] as well as redox-sensitive transcription factors such as NF?B and Nrf-2 were specially investigated. The ability of NPs to interact with these signalling pathways could partially explain their cytotoxicity. The induction of apoptosis is also closely related to the modulation of signalling pathways induced by NPs. Newly emerged scientific areas of research are the studies on interactions between NPs and biological molecules in body fluids, cellular microenvironment, intracellular components or secreted cellular proteins such as cytokines, growth factors and enzymes and use of engineered NPs to target various signal transduction pathways in cancer therapy. Recently published data present the ability of NPs to interact with membrane receptors leading to a possible aggregation of these receptors. These interactions could lead to a sustained modulation of specific signalling in the target cells or paracrine and even "by-stander" effects of the neighbouring cells or tissues. However, oxidative stress is not sufficient to explain specific mechanisms which could be induced by NPs, and these new findings emphasize the need to revise the paradigm of oxidative stress to explain the effects of NPs. PMID:20502881

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

2011-07-01

78

The Effects of Silica Nanoparticles in Macrophage Cells  

PubMed Central

Silica nanoparticles, which are applicable in many industrial fields, have been reported to induce cellular changes such as cytotoxicity in various cells and fibrosis in lungs. Because the immune system is the primary targeting organ reacting to internalized exogenous nanoparticles, we tried to figure out the immunostimulatory effect of silica nanoparticles in macrophages using differently sized silica nanoparticles. Using U937 cells we assessed cytotoxicity by CCK-8 assay, ROS generation by CM-H2DCFDA, intracellular Ca++ levels by staining with Fluo4-AM and IL-8 production by ELISA. At non-toxic concentration, the intracellular Ca++ level has increased immediately after exposure to 15 nm particles, not to larger particles. ROS generation was detected significantly in response to 15 nm particles. However, all three different sizes of silica nanoparticles induced IL-8 production. 15 nm silica nanoparticles are more stimulatory than larger particles in cytotoxicity, intracellular Ca++ increase and ROS generation. But IL-8 production was induced to same levels with 50 or 100 nm particles. Therefore, IL-8 production induced by silica nanoparticles may be dependent on other mechanisms rather than intracellular Ca++ increase and ROS generation.

Kim, Seungjae; Jang, Jiyoung; Kim, Hyojin; Choi, Hoon; Lee, Kangtaek

2012-01-01

79

Metal nanoparticles amplify photodynamic effect on skin cells in vitro  

NASA Astrophysics Data System (ADS)

We report on an investigation aimed to increase the efficiency of photodynamic therapy (PDT) through the influence of localized surface plasmon resonances (LSPR's) in metal nanoparticles. PDT is based on photosensitizers that generate singlet oxygen at the tumour site upon exposure to visible light. Although PDT is a well-established treatment for skin cancer, a major drawback is the low quantum yield for singlet-oxygen production. This motivates the development of novel methods that enhance singlet oxygen generation during treatment. In this context, we study the photodynamic effect on cultured human skin cells in the presence or absence of gold nanoparticles with well established LSPR and field-enhancement properties. The cultured skin cells were exposed to protoporphyrin IX and gold nanoparticles and subsequently illuminated with red light. We investigated the differences in cell viability by tuning different parameters, such as incubation time and light dose. In order to find optimal parameters for specific targeting of tumour cells, we compared normal human epidermal keratinocytes with a human squamous skin cancer cell line. The study indicates significantly enhanced cell death in the presence of nanoparticles and important differences in treatment efficiency between normal and tumour cells. These results are thus promising and clearly motivate further development of nanoparticle enhanced clinical PDT treatment.

Bauer, Brigitte; Chen, Si; Käll, Mikael; Gunnarsson, Linda; Ericson, Marica B.

2011-02-01

80

T cells expanded in presence of IL-15 exhibit increased antioxidant capacity and innate effector molecules  

PubMed Central

Persistence of effector cytotoxic T lymphocytes (CTLs) during an immunological response is critical for successfully controlling a viral infection or tumor growth. Various cytokines are known to play an important part in regulating the immune response. The IL-2 family of cytokines that includes IL-2 and IL-15 are known to function as growth and survival factors for antigen-experienced T cells. IL-2 and IL-15 possess similar properties, including the ability to induce T cell proliferation. Whereas long term IL-2 exposure has been shown to promote apoptosis and limit CD8+ memory T cell survival and proliferation, it is widely believed that IL-15 can inhibit apoptosis and helps maintain a memory CD8+ T-cell population. However, mechanisms for superior outcomes for IL-15 as compared to IL-2 are still under investigation. Our data shows that human T cells cultured in the presence of IL-15 exhibit increased expression of anti-oxidant molecules Glutathione reductase (GSR), Thioredoxin reductase 1 (TXNDR1), Peroxiredoxin (PRDX), Superoxide dismutase (SOD). An increased expression of cell-surface thiols, intracellular glutathione, and thioredoxins was also noted in IL-15 cultured T cells. Additionally, IL-15 cultured T cells also showed an increase in cytolytic effector molecules. Apart from increased level of Granzyme A and Granzyme B, IL-15 cultured T cells exhibit increased accumulation of reactive oxygen (ROS) and reactive nitrogen (RNS) species as compared to IL-2 cultured T cells. Overall, this study suggests that T cells cultured in IL-15 show increase persistence not only due to increased anti-apoptotic proteins but also due to increased anti-oxidant levels, which is further complimented by increased cytolytic effector functions.

Kaur, Navtej; Naga, Osama S.; Norell, Hakan; Al-Khami, Amir A.; Scheffel, Matthew J.; Chakraborty, Nitya G.; Voelkel-Johnson, Christina; Mukherji, Bijay; Mehrotra, Shikhar

2011-01-01

81

Clonally expanded human airway smooth muscle cells exhibit morphological and functional heterogeneity  

PubMed Central

Background Mesenchyme-derived airway cell populations including airway smooth muscle (ASM) cells, fibroblasts and myofibroblasts play key roles in the pathogenesis of airway inflammation and remodeling. Phenotypic and functional characterisation of these cell populations are confounded by their heterogeneity in vitro. It is unclear which mechanisms underlie the creation of these different sub-populations. The study objectives were to investigate whether ASM cells are capable of clonal expansion and if so (i) what proportion possess this capability and (ii) do clonal populations exhibit variation in terms of morphology, phenotype, proliferation rates and pro-relaxant or pro-contractile signaling pathways. Methods Early passage human ASM cells were subjected to single-cell cloning and their doubling time was recorded. Immunocytochemistry was performed to assess localization and levels of markers previously reported to be specifically associated with smooth muscle or fibroblasts. Finally functional assays were used to reveal differences between clonal populations specifically assessing mitogen-induced proliferation and pro-relaxant and pro-contractile signaling pathways. Results Our studies provide evidence that a high proportion (58%) of single cells present within early passage human ASM cell cultures have the potential to create expanded cell populations. Despite being clonally-originated, morphological heterogeneity was still evident within these clonal populations as assessed by the range in expression of markers associated with smooth muscle cells. Functional diversity was observed between clonal populations with 10 ?M isoproterenol-induced cyclic AMP responses ranging from 1.4 - 5.4 fold cf basal and bradykinin-induced inositol phosphate from 1.8 - 5.2 fold cf basal. Conclusion In summary we show for the first time that primary human ASM cells are capable of clonal expansion and that the resulting clonal populations themselves exhibit phenotypic plasticity.

2014-01-01

82

Nanoparticle-GFP "chemical nose" sensor for cancer cells identification  

PubMed Central

Summary 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 nanoparticle 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.

Moyano, Daniel F.; Rotello, Vincent M.

2014-01-01

83

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

2012-01-01

84

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

PubMed Central

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.

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

2012-01-01

85

Nanogel-quantum dot hybrid nanoparticles for live cell imaging  

Microsoft Academic Search

We report here a novel carrier of quantum dots (QDs) for intracellular labeling. Monodisperse hybrid nanoparticles (38nm in diameter) of QDs were prepared by simple mixing with nanogels of cholesterol-bearing pullulan (CHP) modified with amino groups (CHPNH2). The CHPNH2–QD nanoparticles were effectively internalized into the various human cells examined. The efficiency of cellular uptake was much higher than that of

Urara Hasegawa; Shin-ichiro M. Nomura; Sunil C. Kaul; Takashi Hirano; Kazunari Akiyoshi

2005-01-01

86

Human myogenic endothelial cells exhibit chondrogenic and osteogenic potentials at the clonal level.  

PubMed

We have previously reported the high regenerative potential of murine muscle-derived stem cells (mMDSCs) that are capable of differentiating into multiple mesodermal cell lineages, including myogenic, endothelial, chondrocytic, and osteoblastic cells. Recently, we described a putative human counterpart of mMDSCs, the myogenic endothelial cells (MECs), in adult human skeletal muscle, which efficiently repair/regenerate the injured and dystrophic skeletal muscle as well as the ischemic heart in animal disease models. Nevertheless it remained unclear whether human MECs, at the clonal level, preserve mMDSC-like chondrogenic and osteogenic potentials and classic stem cell characteristics including high proliferation and resistance to stress. Herein, we demonstrated that MECs, sorted from fresh postnatal human skeletal muscle biopsies, can be grown clonally and exhibit robust resistance to oxidative stress with no tumorigeneity. MEC clones were capable of differentiating into chondrocytes and osteoblasts under inductive conditions in vitro and participated in cartilage and bone formation in vivo. Additionally, adipogenic and angiogenic potentials of clonal MECs (cMECs) were observed. Overall, our study showed that cMECs not only display typical properties of adult stem cells but also exhibit chondrogenic and osteogenic capacities in vitro and in vivo, suggesting their potential applications in articular cartilage and bone repair/regeneration. PMID:23553740

Zheng, Bo; Li, Guangheng; Chen, William C W; Deasy, Bridget M; Pollett, Jonathan B; Sun, Bin; Drowley, Lauren; Gharaibeh, Burhan; Usas, Arvydas; Péault, Bruno; Huard, Johnny

2013-07-01

87

Antibacterial titanium plate anodized by being discharged in NaCl solution exhibits cell compatibility.  

PubMed

Implant surfaces should be modified to achieve excellent cell compatibility as well as antibacterial activity. Our previous study demonstrated that titanium plates anodized by being discharged in NaCl (Ti-Cl) exhibited high antibacterial activity. Since Ti-Cl was prepared with a NaCl solution, we hypothesized that Ti-Cl would exhibit low toxicity toward cells. The aims of this study were to characterize the surface of Ti-Cl and investigate the cell compatibility (MC3T3-E1 and L929 cells) of Ti-Cl. The results demonstrated that, since the TiCl(3) formed on the Ti-Cl surface was hydrolyzed into HCl, HClO, and TiOH after immersion in pure distilled water, TiCl(3) contributed to the antibacterial activity of Ti-Cl. On the other hand, TiO formed on the Ti-Cl surface enhanced cell extension and cell growth through a larger adsorption of fibronectin compared with the pure titanium control. These findings suggest that antibacterial titanium is a promising material for use in dental implant systems. PMID:14742647

Shibata, Y; Kawai, H; Yamamoto, H; Igarashi, T; Miyazaki, T

2004-02-01

88

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

2013-10-01

89

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

90

Nanoparticle derived contacts for photovoltaic cells  

SciTech Connect

Contacts are becoming increasingly important as PV devices move to higher efficiency and lower cost. The authors present an approach to developing contacts using nanoparticle-based precursors. Both elemental, alloy and compound nanoparticles can be employed for contacts. Ink based approaches can be utilized at low temperatures and utilize direct write techniques such as ink jet and screen printing. The ability to control the composition of the nanoparticle allows improved control of the contact metallurgy and the potential for thermodynamically stable interfaces. A key requirement is the ability to control the interface between particles and between particles and the substrate. The authors illustrate some of these principals with recent results on Al, Cu and (Hg,Cu)Te. They show that for the elemental materials control of the surface can prevent oxide formation and act as glue to control the reactivity of the nanoparticles.

Ginley, D.S.

1999-10-20

91

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

PubMed Central

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.

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

2013-01-01

92

Cell toxicity of superparamagnetic iron oxide nanoparticles  

Microsoft Academic Search

The performance of nanoparticles for biomedical applications is often assessed by their narrow size distribution, suitable magnetic saturation and low toxicity effects. In this work, superparamagnetic iron oxide nanoparticles (SPIONs) with different size, shape and saturation magnetization levels were synthesized via a co-precipitation technique using ferrous salts with a Fe3+\\/Fe2+ mole ratio equal to 2. A parametric study is conducted,

M. Mahmoudi; A. Simchi; A. S. Milani; P. Stroeve

2009-01-01

93

The novel SMAC mimetic birinapant exhibits potent activity against human melanoma cells  

PubMed Central

Purpose Inhibitor of apoptosis proteins (IAPs) promote cancer cell survival and confer resistance to therapy. We report on the ability of second mitochondria-derived activator of caspases (SMAC) mimetic, birinapant, which acts as antagonist to cIAP1 and cIAP2, to restore the sensitivity to apoptotic stimuli such as tumor necrosis factor (TNF)-? in melanomas Experimental Design Seventeen melanoma cell lines, representing five major genetic subgroups of cutaneous melanoma, were treated with birinapant as a single agent or in combination with TNF-?. Effects on cell viability, target inhibition, and initiation of apoptosis were assessed and findings were validated in in 2D, 3D spheroid and in vivo xenograft models. Results When birinapant was combined with TNF-?, strong combination activity, i.e. neither compound was effective individually but the combination was highly effective, was observed in twelve out of eighteen cell lines. This response was conserved in spheroid models, whereas in vivo birinapant inhibited tumor growth without adding TNF-? in in vitro resistant cell lines. Birinapant combined with TNF-? inhibited the growth of a melanoma cell line with acquired resistance to BRAF inhibition to the same extent as in the parental cell line. Conclusions Birinapant in combination with TNF-? exhibits a strong anti-melanoma effect in vitro. Birinapant as a single agent shows in vivo anti-tumor activity, even if cells are resistant to single agent therapy in vitro. Birinapant in combination with TNF-? is effective in a melanoma cell line with acquired resistance to BRAF inhibitors.

Krepler, Clemens; Chunduru, Srinivas K.; Halloran, Molly B.; He, Xu; Xiao, Min; Vultur, Adina; Villanueva, Jessie; Mitsuuchi, Yasuhiro; Neiman, Eric M.; Benetatos, Christopher; Nathanson, Katherine L.; Amaravadi, Ravi K.; Pehamberger, Hubert; McKinlay, Mark; Herlyn, Meenhard

2013-01-01

94

Proliferating versus differentiating stem and cancer cells exhibit distinct midbody-release behaviour  

PubMed Central

The central portion of the midbody, a cytoplasmic bridge between nascent daughter cells at the end of cell division, has generally been thought to be retained by one of the daughter cells, but has, recently, also been shown to be released into the extracellular space. The significance of midbody-retention versus -release is unknown. Here we show, by quantitatively analysing midbody-fate in various cell lines under different growth conditions, that the extent of midbody-release is significantly greater in stem cells than cancer-derived cells. Induction of cell differentiation is accompanied by an increase in midbody-release. Knockdown of the endosomal sorting complex required for transport family members, Alix and tumour-suppressor gene 101, or of their interaction partner, centrosomal protein 55, impairs midbody-release, suggesting mechanistic similarities to abscission. Cells with such impaired midbody-release exhibit enhanced responsiveness to a differentiation stimulus. Taken together, midbody-release emerges as a characteristic feature of cells capable of differentiation.

Ettinger, Andreas W.; Wilsch-Brauninger, Michaela; Marzesco, Anne-Marie; Bickle, Marc; Lohmann, Annett; Maliga, Zoltan; Karbanova, Jana; Corbeil, Denis; Hyman, Anthony A.; Huttner, Wieland B.

2011-01-01

95

Antitumor effect of TRAIL on oral squamous cell carcinoma using magnetic nanoparticle-mediated gene expression.  

PubMed

We developed a new magnetic nanovector to improve the efficiency and targeting of transgene therapy for oral squamous cell carcinoma (OSCC). Positively charged polymer PEI-modified Fe(3)O(4) magnetic nanoparticles were tested as gene transfer vectors in the presence of a magnetic field. The Fe(3)O(4) nanoparticles were prepared by a co-precipitation method and had good dispersibility in water. These nanoparticles modified by PEI were combined with negatively charged pACTERT-EGFP via electrostatic interaction. The transfection efficiency of the magnetic nano-gene vector with the magnetic field was determined by a fluorescence-inverted microscope and flow cytometry. The results showed significant improvement compared with the control group (p < 0.05). The magnetic complexes also exhibited up to 6-times higher transfection efficiency compared with commonly used PEI or lipofectin. On the basis of these results, the antitumor effect with suicide gene therapy using pACTERT-TRAIL in vitro and vivo was evaluated. In vitro apoptosis was determined with the Annexin V-FITC Apoptosis Detection Kit. The results suggested that PEI-modified Fe(3)O(4) nanoparticles could mediate the killing of Tca83 cells. Furthermore, treatment with pACTERT-TRAIL delivered by magnetic nanoparticles showed a significant cytostatic effect through the induction of apoptosis in a xenograft model. This indicates that magnetic nano-gene vectors could improve the transgene efficiency for Tca83 cells and could exhibit antitumor functions with the plasmid pACTERT-TRAIL. This may be a new way to treat OSCC. PMID:24563116

Miao, Leiying; Liu, Chao; Ge, Jiuyu; Yang, Weidong; Liu, Jinzhong; Sun, Weibin; Yang, Bai; Zheng, Changyu; Sun, Hongchen; Hu, Qingang

2014-07-01

96

Nanoparticle-dependent labeling of mesenchymal stem cell.  

PubMed

Mesenchymal stem cells (MSCs) are able to differentiate into osteoblasts, adipocytes and chondroblasts. They hold great promise for tissue regeneration and treatment of immune-related diseases. Efficient application of MSCs requires safe cell tracking to follow stem cell fate over time in the host environment after infusion. This review discusses the nanoparticle-mediated MSC labeling, with special emphasis on the influence of nanoparticles on MSC bioactivities. We emphasize the importance of establishing guidelines, protocols and standards for labeling of MSCs in future clinical trials, so that MSCs can become a therapeutic agent with a reliable safety. PMID:24730312

Liao, Lianming

2014-01-01

97

Epithelial and mesenchymal subpopulations within normal basal breast cell lines exhibit distinct stem cell/progenitor properties.  

PubMed

It has been proposed that epithelial-mesenchymal transition (EMT) in mammary epithelial cells and breast cancer cells generates stem cell features, and that the presence of EMT characteristics in claudin-low breast tumors reveals their origin in basal stem cells. It remains to be determined, however, whether EMT is an inherent property of normal basal stem cells, and if the presence of a mesenchymal-like phenotype is required for the maintenance of all their stem cell properties. We used nontumorigenic basal cell lines as models of normal stem cells/progenitors and demonstrate that these cell lines contain an epithelial subpopulation ("EpCAM+," epithelial cell adhesion molecule positive [EpCAM(pos)]/CD49f(high)) that spontaneously generates mesenchymal-like cells ("Fibros," EpCAM(neg)/CD49f(med/low)) through EMT. Importantly, stem cell/progenitor properties such as regenerative potential, high aldehyde dehydrogenase 1 activity, and formation of three-dimensional acini-like structures predominantly reside within EpCAM+ cells, while Fibros exhibit invasive behavior and mammosphere-forming ability. A gene expression profiling meta-analysis established that EpCAM+ cells show a luminal progenitor-like expression pattern, while Fibros most closely resemble stromal fibroblasts but not stem cells. Moreover, Fibros exhibit partial myoepithelial traits and strong similarities with claudin-low breast cancer cells. Finally, we demonstrate that Slug and Zeb1 EMT-inducers control the progenitor and mesenchymal-like phenotype in EpCAM+ cells and Fibros, respectively, by inhibiting luminal differentiation. In conclusion, nontumorigenic basal cell lines have intrinsic capacity for EMT, but a mesenchymal-like phenotype does not correlate with the acquisition of global stem cell/progenitor features. Based on our findings, we propose that EMT in normal basal cells and claudin-low breast cancers reflects aberrant/incomplete myoepithelial differentiation. PMID:22102611

Sarrio, David; Franklin, Chris K; Mackay, Alan; Reis-Filho, Jorge S; Isacke, Clare M

2012-02-01

98

Sickle cell mice exhibit mechanical allodynia and enhanced responsiveness in light touch cutaneous mechanoreceptors  

PubMed Central

Background Sickle cell disease (SCD) is associated with both acute vaso-occlusive painful events as well as chronic pain syndromes, including heightened sensitivity to touch. We have previously shown that mice with severe SCD (HbSS mice; express 100% human sickle hemoglobin in red blood cells; RBCs) have sensitized nociceptors, which contribute to increased mechanical sensitivity. Yet, the hypersensitivity in these neural populations alone may not fully explain the mechanical allodynia phenotype in mouse and humans. Findings Using the Light Touch Behavioral Assay, we found HbSS mice exhibited increased responses to repeated application of both innocuous punctate and dynamic force compared to control HbAA mice (100% normal human hemoglobin). HbSS mice exhibited a 2-fold increase in percent response to a 0.7mN von Frey monofilament when compared to control HbAA mice. Moreover, HbSS mice exhibited a 1.7-fold increase in percent response to the dynamic light touch “puffed” cotton swab stimulus. We further investigated the mechanisms that drive this behavioral phenotype by focusing on the cutaneous sensory neurons that primarily transduce innocuous, light touch. Low threshold cutaneous afferents from HbSS mice exhibited sensitization to mechanical stimuli that manifested as an increase in the number of evoked action potentials to suprathreshold force. Rapidly adapting (RA) A? and A? D-hair fibers showed the greatest sensitization, each with a 75% increase in suprathreshold firing compared to controls. Slowly adapting (SA) A? afferents had a 25% increase in suprathreshold firing compared to HbAA controls. Conclusions These novel findings demonstrate mice with severe SCD exhibit mechanical allodynia to both punctate and dynamic light touch and suggest that this behavioral phenotype may be mediated in part by the sensitization of light touch cutaneous afferent fibers to suprathreshold force. These findings indicate that A? fibers can be sensitized to mechanical force and should potentially be examined for sensitization in other tissue injury and disease models.

2012-01-01

99

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

100

Rare somatic cells from human breast tissue exhibit extensive lineage plasticity  

PubMed Central

We identified cell surface markers associated with repression of p16INK4a/cyclin-dependent kinase inhibitor 2A(CDKN2A), a critical determinant in the acquisition of a plastic state. These cell surface markers allowed direct isolation of rare cells from healthy human breast tissue that exhibit extensive lineage plasticity. This subpopulation is poised to transcribe plasticity markers, OCT3/4, SOX2, and NANOG, at levels similar to those measured in human embryonic stem cells and to acquire a plastic state sensitive to environmental programming. In vitro, in vivo, and teratoma assays demonstrated that either a directly sorted (uncultured) or a single-cell (clonogenic) cell population from primary tissue can differentiate into functional derivatives of each germ layer, ectodermal, endodermal, and mesodermal. In contrast to other cells that express OCT3/4, SOX2, and NANOG, these human endogenous plastic somatic cells are mortal, express low telomerase activity, expand for an extensive but finite number of population doublings, and maintain a diploid karyotype before arresting in G1.

Roy, Somdutta; Gascard, Philippe; Dumont, Nancy; Zhao, Jianxin; Pan, Deng; Petrie, Sarah; Margeta, Marta; Tlsty, Thea D.

2013-01-01

101

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

102

Immunosuppressive compounds exhibit particular effects on functional properties of human anti-Aspergillus Th1 cells.  

PubMed

Allogeneic hematopoietic stem cell transplant (HSCT) recipients are at high risk for invasive aspergillosis. Whereas adoptive immunotherapy transferring donor-derived anti-Aspergillus TH1 cells has been shown to be beneficial for HSCT recipients suffering from invasive aspergillosis, little is known about the impact of commonly used immunosuppressants on the functional properties of anti-Aspergillus TH1 cells. Anti-Aspergillus TH1 cells were coincubated with different concentrations of methylprednisolone, cyclosporine (CsA), mycophenolic acid (MPA), the active component of mycophenolate mofetil, and rapamycin. Immunosuppressants were tested in concentrations reflecting common target levels in serum and in significantly lower and higher concentrations. Apoptosis of anti-Aspergillus TH1 cells, as well as proliferation and production of gamma interferon (IFN-?) and CD154 upon restimulation, was evaluated in the presence and absence of immunosuppressive compounds. All dosages of CsA, MPA, and methylprednisolone significantly decreased the number of viable anti-Aspergillus TH1 cells in the cell culture, which was due partly to an impaired proliferative capacity of the cells and partly to an increased rate of apoptosis. In addition, CsA significantly decreased the number of IFN-?-producing cells and had the highest impact of all immunosuppressants on IFN-? levels in the supernatant. CsA also significantly decreased the expression of CD154 by anti-Aspergillus TH1 cells. Variant dosages of immunosuppressants exhibit particular effects on essential functional properties of anti-Aspergillus TH1 cells. Our findings may have an important impact on the design of clinical trials evaluating the therapeutic benefit of anti-Aspergillus TH1 cells in allogeneic HSCT recipients suffering from invasive aspergillosis. PMID:24711569

Tramsen, Lars; Schmidt, Stanislaw; Roeger, Frauke; Schubert, Ralf; Salzmann-Manrique, Emilia; Latgé, Jean-Paul; Klingebiel, Thomas; Lehrnbecher, Thomas

2014-06-01

103

Mouse hematopoietic stem cells, unlike human and mouse embryonic stem cells, exhibit checkpoint-apoptosis coupling.  

PubMed

Previously, we reported that the spindle assembly checkpoint (SAC), which is coupled in somatic cells, is uncoupled from apoptosis-initiation in mouse and human embryonic stem cells (ESCs). This condition allows ESCs to tolerate and proliferate as polyploidy/aneuploid cells. Proper function of the SAC is vital to prevent polyploidy/aneuploidy during ex vivo hematopoietic stem cell (HSC) expansion. Here we address, for the first time, whether HSCs are more like ESCs or somatic cells with respect to SAC-apoptosis coupling. Using multiparametric permeablized cell flow-cytometric analysis to identify and analyze the mouse sca 1(+)/c-kit(+)/lin(-) (LSK) population, we found the mitotic spindle checkpoint to be functional in primary murine LSK cells, a population enriched in primitive hematopoietic stem/progenitor cells, after prolonged activation of the SAC by microtubule-depolymerizing agents such as nocodazole. HSCs can efficiently initiate apoptosis after activation of the SAC in LSK cells as indicated by increased hypodiploidy and increased levels of activated caspase 3, suggesting that HSCs behave more like somatic cells instead of ESCs with respect to this important cell cycle checkpoint. We conclude that mouse HSCs are not subject to the same kinds of chromosomal instability as are ESCs, knowledge that might aid in optimizing in vitro culture and expansion of human bone marrow or cord blood HSC for clinical applications. PMID:18788999

Rohrabaugh, Sara; Mantel, Charlie; Broxmeyer, Hal E

2008-10-01

104

Cultured buffalo umbilical cord matrix cells exhibit characteristics of multipotent mesenchymal stem cells.  

PubMed

Recent findings have demonstrated umbilical cord, previously considered as a biomedical waste, as a source of stem cells with promising therapeutic applications in human as well as livestock species. The present study was carried out to isolate the umbilical cord matrix cells and culture for a prolonged period, cryopreserve these cells and test their post-thaw viability, characterize these cells for expression of stem cell markers and differentiation potential in vitro. The intact umbilical cord was taken out of the amniotic sac of a fetus and then incised longitudinally to remove umbilical vessels. Wharton's jelly containing tissue was diced into small pieces and placed in tiny drops of re-calcified buffalo plasma for establishing their primary culture. Confluent primary culture was trypsinized and passaged with a split ratio of 1:2 for multiplication of cells. Cryopreservation of cells was performed at three different passages in cryopreservation medium containing 15%, 20% and 25% fetal bovine serum (FBS). A significant increase in post-thaw viability was observed in cells cryopreserved in freezing medium with higher concentration of FBS. After re-culturing, frozen-thawed cells started adhering, and spike formation occurred within 4-6 h with similar morphology to their parent representative cultures. The normal karyotype and positive expression of alkaline phosphatase and pluripotency genes OCT4, NANOG and SOX2 were observed at different passages of culture. When induced, these cells differentiated into adipogenic and osteogenic cells as confirmed by oil red O and alizarin red stains, respectively. This study indicates that buffalo umbilical cord matrix cells have stemness properties with mesenchymal lineage restricted differentiation and limited proliferation potential in vitro. PMID:23708916

Singh, Jarnail; Mann, Anita; Kumar, D; Duhan, J S; Yadav, P S

2013-06-01

105

Photothermal Therapy of Cancer Cells mediated by Blue Hydrogel Nanoparticles  

NASA Astrophysics Data System (ADS)

Coomassie Blue dye has been covalently linked into a polyacrylamide nanoparticle matrix, so as to form nontoxic, biologically compatible, biodegradable and cell-specific targetable nanoparticles for photothermal therapy (PTT) of cancer. The nanoparticles were found to be approximately 80-95 nm in diameter, with an absorbance value of 0.52. Using an inexpensive, low intensity LED array light source (590nm, 25mW/cm2), with 20 minute excitation times, at 37^o, PTT induced hyperthermia/thermolysis in HeLa cells, in vitro, resulting in virtually complete cell death when observed 3 hours after exposure. These multifunctional particles have been previously used in cancer delineation, for surgery, and in photoacoustic imaging studies; the addition of the PTT function now enables a multi-pronged medical approach to cancer.

Curry, Taeyjuana; Epstein, Tamir; Kopelman, Raoul

2012-02-01

106

Photothermal Therapy of Cancer Cells mediated by Blue Hydrogel Nanoparticles  

NASA Astrophysics Data System (ADS)

Coomassie Blue dye has been covalently linked into a polyacrylamide nanoparticle matrix, so as to form nontoxic, biologically compatible, biodegradable and cell-specific targetable nanoparticles for photothermal therapy (PTT) of cancer. The nanoparticles were found to be approximately 80-95 nm in diameter, with an absorbance value of 0.52. Using an inexpensive, low intensity LED array light source (590nm, 25mW/cm^2), with 20 minute excitation times, at 37 , PTT induced hyperthermia/thermolysis in HeLa cells, in vitro, resulting in virtually complete cell death when observed 3 hours after exposure. These multifunctional particles have been previously used in cancer delineation, for surgery, and in photoacoustic imaging studies; the addition of the PTT function now enables a multi-pronged medical approach to cancer.

Curry, Taeyjuana; Epstein, Tamir; Kopelman, Raoul

2012-10-01

107

Kidney transplant recipients treated with belatacept exhibit increased naïve and transitional B cells.  

PubMed

Phase III clinical studies have shown that kidney transplant (KT) recipients treated with the costimulation blocker belatacept exhibited a better renal allograft function and lower donor-specific anti-HLA immunization when compared to recipients treated with calcineurin inhibitors (CNI). We analyzed B cell phenotype in KT recipients treated with belatacept and stable renal function (N?=?13). Results were compared to those observed in stable patients treated with CNI (N?=?12), or with chronic antibody-mediated rejection (N?=?5). Both transcriptional profile and phenotypic characterization of peripheral B cells were performed by real-time polymerase chain reaction and flow cytometry, respectively. In belatacept group, the frequency and absolute number of transitional B cells as defined by both phenotypes: CD19(+) CD24(hi) CD38(hi) and CD19(+) IgD(hi) CD38(hi) CD27(-) , as well as naïve B cells were significantly higher compared with CNI group. B cell activating factor (BAFF) and BAFF receptor mRNA levels were significantly lower in belatacept group than in CNI group. These results show for the first time that belatacept influences B cell compartment by favoring the occurrence of transitional B cells with potential regulatory properties, as described in operational tolerant patients. This role may explain the lower alloimmunization rate observed in belatacept-treated patients. PMID:24730563

Leibler, C; Matignon, M; Pilon, C; Montespan, F; Bigot, J; Lang, P; Carosella, E D; Cohen, J; Rouas-Freiss, N; Grimbert, P; Menier, C

2014-05-01

108

Amorphous-Silicon-Based Thin-Film Solar Cells Exhibiting Low Light-Induced Degradation  

NASA Astrophysics Data System (ADS)

We have applied a triode electrode configuration in the plasma-enhanced chemical vapor deposition (PECVD) process to grow intrinsic hydrogenated amorphous silicon (a-Si:H) light absorbers for the fabrication of p--i--n junction solar cells. Although the deposition rate is lower (0.1--0.3 Å/s) than that of the conventional diode PECVD process, the light-soaking stability of the solar cell is markedly improved and less sensitive to the cell thickness due to the reduced Si--H2 bond density in the a-Si:H i-layer. The a-Si:H single-junction solar cells exhibit low light-induced degradation of conversion efficiency (??/?ini˜ 10%) in comparison with that of high-efficiency solar cells reported to date. By applying the improved a-Si:H layers as top-cell absorbers in a-Si:H/hydrogenated microcrystalline silicon (?c-Si:H) tandem device, the light-induced degradation can be reduced even further (??/?ini? 5%). As a result, we obtain confirmed stabilized efficiencies of 9.6 and 11.3% for a-Si:H single-junction and a-Si:H/?c-Si:H tandem solar cells, respectively.

Matsui, Takuya; Sai, Hitoshi; Saito, Kimihiko; Kondo, Michio

2012-10-01

109

Vaccinium corymbosum L. (blueberry) extracts exhibit protective action against cadmium toxicity in Saccharomyces cerevisiae cells.  

PubMed

Blueberries (Vaccinium corymbosum L.) are a rich source of antioxidants and their consumption is believed to contribute to food-related protection against oxidative stress. In the present study, the chemoprotective action of blueberry extracts against cadmium toxicity was investigated using a cadmium-hypersensitive strain of Saccharomyces cerevisiae. Four varieties of blueberries were used in the study, and it was found that the extracts with high content of total anthocyanidins exhibited significant protective effect against the toxicity of cadmium and H2O2. Both the blueberry extracts and pure cyanidin exhibited protective effects against cadmium in a dose-dependent manner, but without significantly interfering with the cadmium accumulation by the yeast cells. The results imply that the blueberry extracts might be a potentially valuable food supplement for individuals exposed to high cadmium. PMID:24444969

Oprea, Eliza; Ruta, Lavinia L; Nicolau, Ioana; Popa, Claudia V; Neagoe, Aurora D; Farcasanu, Ileana C

2014-06-01

110

Chitosan cross-linked docetaxel loaded EGF receptor targeted nanoparticles for lung cancer cells.  

PubMed

Lung cancer, associated with the up-regulated epidermal growth factor receptor (EGFR) led to the development of EGFR targeted anticancer therapeutics. The biopolymeric nanoparticles form an outstanding system for the targeted delivery of therapeutic agents. The present work evaluated the in vitro effects of chitosan cross-linked ?-poly(glutamic acid) (?-PGA) nanoparticles (Nps) loaded with docetaxel (DTXL) and decorated with Cetuximab (CET), targeted to EGFR over-expressing non-small-cell-lung-cancer (NSCLC) cells (A549). CET-DTXL-?-PGA Nps was prepared by ionic gelation and CET conjugation via EDC/NHS chemistry. EGFR specificity of targeted Nps was confirmed by the higher uptake rates of EGFR +ve A549 cells compared to that of EGFR -ve cells (NIH3T3). The cytotoxicity of Nps quantified using cell based (MTT/LDH) and flowcytometry (Cell-cycle analysis, Annexin V/PI and JC-1) assays showed superior antiproliferative activity of CET-DTXL-?-PGA Nps over DTXL-?-PGA Nps. The A549 cells treated with CET-DTXL-?-PGA NPs underwent a G2/M phase cell cycle arrest followed by reduction in mitochondrial membrane potential of A549 cells, inducing apoptosis and necrosis resulting in enhanced cancer cell death. CET-DTXL-?-PGA Nps exhibited enhanced cellular internalization and therapeutic activity, by actively targeting EGFR on NSCLC cells and hence could be an effective alternative to non-specific, conventional chemotherapy by increasing its efficiency by many folds. PMID:24950310

Maya, S; Sarmento, Bruno; Lakshmanan, Vinoth-Kumar; Menon, Deepthy; Seabra, Vitor; Jayakumar, R

2014-08-01

111

Nevus unius lateralis exhibiting intraepidermal basaloid cell formation simulating superficial basal cell epithelioma.  

PubMed

A unilateral verrucous lesion with clinical characteristics of nevus unius lateralis (NUL) in an 18-year-old boy, showed histopathological features of intraepidermal basaloid cell formation simulating superficial basal cell epitheliomas. Biological significance of this phenomenon is discussed. The lesion is considered a most peculiar variant of NUL. PMID:478072

Bedi, T R

1979-01-01

112

Muscle satellite cells are multipotential stem cells that exhibit myogenic, osteogenic, and adipogenic differentiation  

Microsoft Academic Search

Muscle satellite cells are believed to represent a committed stem cell population that is responsible for the postnatal growth and regeneration of skeletal muscle. However, the observation that cultured myoblasts differentiate into osteocytes or adipocytes following treatment with bone morphogenetic proteins (BMPs) or adipogenic inducers, respectively, suggests some degree of plasticity within the mesenchymal lineage. To further investigate this phenomenon,

Atsushi Asakura; Michael A. Rudnicki; Motohiro Komaki

2001-01-01

113

Preparation and characterization of fullerene (C60) amino acid nanoparticles for liver cancer cell treatment.  

PubMed

The properties of an ideal photosensitizer are water solubility, low cytotoxicity in the dark, high ability to produce reactive oxygen species (ROS). The characteristics of water-soluble fullerene (C60) amino acid nanoparticles as a photosensitizer were evaluated. C60 modified with l-phenylalanine (C60-phe) or glycine (C60-gly) was very efficient to carry out photodynamic activity leading to cleavage of plasmid DNA in vitro. These C60 amino acid nanoparticles were the most active photosensitizer against human Liver cancer cells and induced cancer cells apoptosis after illumination. However, these derivatives exhibited no significant cytotoxicity in dark. It produced diffuse intracellular fluorescence when 2',7'-dichlorfluorescein-diacetate (DCFH-DA) was added as an ROS probe, suggesting phototoxicity of these derivatives related with the generation of intracellular ROS. These findings indicate that these fullerene derivatives may be excellent candidate PDT enhancing agents. PMID:24738422

Li, Zhi; Pan, Li-Li; Zhang, Fei-Long; Wang, Zhiyuan; Shen, Ying-Ying; Zhang, Zhen-Zhong

2014-06-01

114

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

115

A new class of red fluorescent organic nanoparticles: noncovalent fabrication and cell imaging applications.  

PubMed

Cyano-substituted diarylethlene derivatives R-OMe (-H, -CF3) with different peripheral substituted groups were synthesized in high yield. Water-soluble red fluorescent organic nanoparticles (FONs) could be facilely prepared from them via hydrophobic interaction with polyoxyethylene-polyoxypropylene-polyoxyethylene triblock copolymer (Pluronic F127). The optical properties and surface morphology of the synthesized FONs were characterized, and their biocompatibilities as well as their applications in cell imaging were further investigated. We demonstrate that such red FONs exhibit antiaggregation-caused quenching properties, broad excitation wavelengths, excellent water dispersibilities, and biocompatibilities, making them promising for cell imaging. PMID:24555855

Zhang, Xiqi; Zhang, Xiaoyong; Yang, Bin; Zhang, Yaling; Wei, Yen

2014-03-12

116

The Transcription Factor NFAT Exhibits Signal Memory during Serial T Cell Interactions with Antigen Presenting Cells  

PubMed Central

Summary Interactions with antigen-presenting cells (APCs) interrupt T cell migration through tissues and trigger signaling pathways that converge on the activation of transcriptional regulators, including NFAT, which control T cell function and differentiation. Both stable and unstable modes of cognate T cell-APC interactions have been observed in vivo, but the functional significance of unstable, serial contacts has remained unclear. Here we used multiphoton intravital microscopy in lymph nodes and tumors to show that while NFAT nuclear import was fast (t1/2 max~1min), nuclear export was slow (t1/2~20min) in T cells. During delayed export, nuclear NFAT constituted a short-term imprint of transient TCR signals and remained transcriptionally active for the T cell tolerance gene Egr2, but not for the effector gene Ifng, which required continuous TCR triggering for expression. This provides a potential mechanistic basis for the observation that a predominance of unstable APC interactions correlates with the induction of T cell tolerance.

Marangoni, Francesco; Murooka, Thomas T.; Manzo, Teresa; Kim, Edward Y.; Carrizosa, Esteban; Elpek, Natalie M.; Mempel, Thorsten R.

2012-01-01

117

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

118

Mice deficient in heparanase exhibit impaired dendritic cell migration and reduced airway inflammation.  

PubMed

Heparanase is a ?-d-endoglucuronidase that cleaves heparan sulphate, a key component of the ECM and basement membrane. The remodelling of the ECM by heparanase has been proposed to regulate both normal physiological and pathological processes, including wound healing, inflammation, tumour angiogenesis and cell migration. Heparanase is also known to exhibit non-enzymatic functions by regulating cell adhesion, cell signalling and differentiation. In this study, constitutive heparanase-deficient (Hpse(-/-) ) mice were generated on a C57BL/6 background using the Cre/loxP recombination system, with a complete lack of heparanase mRNA, protein and activity. Although heparanase has been implicated in embryogenesis and development, Hpse(-/-) mice are anatomically normal and fertile. Interestingly, consistent with the suggested function of heparanase in cell migration, the trafficking of dendritic cells from the skin to the draining lymph nodes was markedly reduced in Hpse(-/-) mice. Furthermore, the ability of Hpse(-/-) mice to generate an allergic inflammatory response in the airways, a process that requires dendritic cell migration, was also impaired. These findings establish an important role for heparanase in immunity and identify the enzyme as a potential target for regulation of an immune response. PMID:24532362

Poon, Ivan K H; Goodall, Katharine J; Phipps, Simon; Chow, Jenny D Y; Pagler, Eloisa B; Andrews, Daniel M; Conlan, Carly L; Ryan, Gemma F; White, Julie A; Wong, Michael K L; Horan, Catherine; Matthaei, Klaus I; Smyth, Mark J; Hulett, Mark D

2014-04-01

119

Gold nanoparticles delivery in mammalian live cells: a critical review.  

PubMed

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. PMID:22110850

Lévy, Raphaël; Shaheen, Umbreen; Cesbron, Yann; Sée, Violaine

2010-01-01

120

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

121

Human T-cell leukemia virus types I and II exhibit different DNase I protection patterns  

SciTech Connect

Human T-cell leukemia virus types I (HTLV-I) and II (HTLV-II) are human retroviruses which normally infect T-lymphoid cells. HTLV-I infection is associated with adult T-cell leukemia-lymphoma, and HTLV-II is associated with an indolent form of hairy-cell leukemia. To identify potential transcriptional regulatory elements of these two related human retroviruses, the authors performed DNase I footprinting of both the HTLV-I and HTLV-II long terminal repeats (LTRs) by using extracts prepared from uninfected T cells, HTLV-I and HTLV-II transformed T cells, and HeLa cells. Five regions of the HTLV-I LTR and three regions of the HTLV-II LTR showed protection by DNase I footprinting. All three of the 21-base-pair repeats previously shown to be important in HTLV transcriptional regulation were protected in the HTLV-I LTR, whereas only one of these repeats was protected in the HTLV-II LTR. Several regions exhibited altered protection in extracts prepared from lymphoid cells as compared with HeLa cells, but there were minimal differences in the protection patterns between HTLV-infected and uninfected lymphoid extracts. A number of HTLV-I and HTLV-II LTR fragments which contained regions showing protection in DNase I footprinting were able to function as inducible enhancer elements in transient CAT gene expression assays in the presence of the HTLV-II tat protein. The alterations in the pattern of the cellular proteins which bind to the HTLV-I and HTLV-II LTRs may in part be responsible for differences in the transcriptional regulation of these two related viruses.

Altman, R.; Harrich, D.; Garcia, J.A. (Univ. of California Los Angeles School of Medicine (USA)); Gaynor, R.B. (Univ. of California Los Angeles School of Medicine (USA) Wadsworth Veterans Hospital, Los Angeles, CA (USA))

1988-04-01

122

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

123

Colloidal gold nanoparticle modified carbon paste interface for studies of tumor cell adhesion and viability.  

PubMed

A non-toxic biomimetic interface for immobilization of living cells and electrochemical exogenous effect study of cell viability was constructed by mixing colloidal gold nanoparticles in carbon paste. A new approach to study the effects of anti-tumor drug and other exogenous factors on cell viability was proposed. The nanoparticles were efficient for preserving the activity of immobilized living cells and preventing their leakage from the electrode surface. The immobilized living AsPC-1 cells (pancreatic adenocarcinoma cells derived from ascites) exhibited an irreversible voltammetric response related to the oxidation of guanine. The presence of guanine was verified by liquid chromatography-mass spectrometry. The contents of guanine in cytoplasm of each AsPC-1 and normal pancreatic cell were detected to be 370 and 22amol, respectively. The cytotoxic effect of adriamycin resulted in a decrease in peak current of guanine. The optimal exogenous factors that affected cell viability, including pH, temperature and salt concentration of electrolyte, were just consistent with cell growth conditions in culture. This simple and rapid method could be applied for the electrochemical investigation of exogenous effect and characterization of the viability of living cells. PMID:15951013

Du, Dan; Liu, Shengli; Chen, Jing; Ju, Huangxian; Lian, Hongzhen; Li, Jianxin

2005-11-01

124

Spontaneously immortalised bovine mammary epithelial cells exhibit a distinct gene expression pattern from the breast cancer cells  

PubMed Central

Background Spontaneous immortalisation of cultured mammary epithelial cells (MECs) is an extremely rare event, and the molecular mechanism behind spontaneous immortalisation of MECs is unclear. Here, we report the establishment of a spontaneously immortalised bovine mammary epithelial cell line (BME65Cs) and the changes in gene expression associated with BME65Cs cells. Results BME65Cs cells maintain the general characteristics of normal mammary epithelial cells in morphology, karyotype and immunohistochemistry, and are accompanied by the activation of endogenous bTERT (bovine Telomerase Reverse Transcriptase) and stabilisation of the telomere. Currently, BME65Cs cells have been passed for more than 220 generations, and these cells exhibit non-malignant transformation. The expression of multiple genes was investigated in BME65Cs cells, senescent BMECs (bovine MECs) cells, early passage BMECs cells and MCF-7 cells (a human breast cancer cell line). In comparison with early passage BMECs cells, the expression of senescence-relevant apoptosis-related gene were significantly changed in BME65Cs cells. P16INK4a was downregulated, p53 was low expressed and Bax/Bcl-2 ratio was reversed. Moreover, a slight upregulation of the oncogene c-Myc, along with an undetectable level of breast tumor-related gene Bag-1 and TRPS-1, was observed in BME65Cs cells while these genes are all highly expressed in MCF-7. In addition, DNMT1 is upregulated in BME65Cs. These results suggest that the inhibition of both senescence and mitochondrial apoptosis signalling pathways contribute to the immortality of BME65Cs cells. The expression of p53 and p16INK4a in BME65Cs was altered in the pattern of down-regulation but not "loss", suggesting that this spontaneous immortalization is possibly initiated by other mechanism rather than gene mutation of p53 or p16INK4a. Conclusions Spontaneously immortalised BME65Cs cells maintain many characteristics of normal BMEC cells and exhibit non-malignant transformation. Although this cell line displays altered patterns of gene expression, it is clearly distinct from malignant breast cancer cell line. It showed that co-inhibition of cellular senescence and mitochondrial apoptosis pathways coordinates BME65Cs cells immortalisation. Additionally, mechanisms other than gene mutation are likely to be involved in regulation of cellular functions. This study provides an insight into the relationship between cell senescence and immortalisation. BME65Cs cells will be useful in future studies of cellular senescence and tumorigenesis.

2010-01-01

125

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

126

Firefly Luciferase and Rluc8 Exhibit Differential Sensitivity to Oxidative Stress in Apoptotic Cells  

PubMed Central

Over the past decade, firefly Luciferase (fLuc) has been used in a wide range of biological assays, providing insight into gene regulation, protein-protein interactions, cell proliferation, and cell migration. However, it has also been well established that fLuc activity can be highly sensitive to its surrounding environment. In this study, we found that when various cancer cell lines (HeLa, MCF-7, and 293T) stably expressing fLuc were treated with staurosporine (STS), there was a rapid loss in bioluminescence. In contrast, a stable variant of Renilla luciferase (RLuc), RLuc8, exhibited significantly prolonged functionality under the same conditions. To identify the specific underlying mechanism(s) responsible for the disparate sensitivity of RLuc8 and fLuc to cellular stress, we conducted a series of inhibition studies that targeted known intracellular protein degradation/modification pathways associated with cell death. Interestingly, these studies suggested that reactive oxygen species, particularly hydrogen peroxide (H2O2), was responsible for the diminution of fLuc activity. Consistent with these findings, the direct application of H2O2 to HeLa cells also led to a reduction in fLuc bioluminescence, while H2O2 scavengers stabilized fLuc activity. Comparatively, RLuc8 was far less sensitive to ROS. These observations suggest that fLuc activity can be substantially altered in studies where ROS levels become elevated and can potentially lead to ambiguous or misleading findings.

Czupryna, Julie; Tsourkas, Andrew

2011-01-01

127

Hepatitis B virus X protein mutants exhibit distinct biological activities in hepatoma Huh7 cells  

SciTech Connect

The role of the hepatitis B virus X protein (HBx) in hepatocarcinogenesis remains controversial. To investigate the biological impact of hepatitis B virus x gene (HBx) mutation on hepatoma cells, plasmids expressing the full-length HBx or HBx deletion mutants were constructed. The biological activities in these transfectants were analyzed by a series of assays. Results showed that HBx3'-20 and HBx3'-40 amino acid deletion mutants exhibited an increase in cellular proliferation, focus formation, tumorigenicity, and invasive growth and metastasis through promotion of the cell cycle from G0/G1 to the S phase, when compared with the full-length HBx. In contrast, HBx3'-30 amino acid deletion mutant repressed cell proliferation by blocking in G1 phase. The expression of P53, p21{sup WAF1}, p14{sup ARF}, and MDM2 proteins was regulated by expression of HBx mutants. In conclusions, HBx variants showed different effects and functions on cell proliferation and invasion by regulation of the cell cycle progression and its associated proteins expression.

Liu Xiaohong; Zhang Shuhui; Lin Jing; Zhang Shunmin [Department of Pathology, Changhai Hospital, Second Military Medical University, 174 Changhai Road, Shanghai 200433 (China); Feitelson, Mark A. [Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122 (United States); Gao Hengjun [National Engineering Center for Biochip at Shanghai, Shanghai 201203 (China); Zhu Minghua [Department of Pathology, Changhai Hospital, Second Military Medical University, 174 Changhai Road, Shanghai 200433 (China)], E-mail: mhzhu2000@hotmail.com

2008-09-05

128

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

129

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

2011-03-11

130

Human Endometrial Side Population Cells Exhibit Genotypic, Phenotypic and Functional Features of Somatic Stem Cells  

Microsoft Academic Search

During reproductive life, the human endometrium undergoes around 480 cycles of growth, breakdown and regeneration should pregnancy not be achieved. This outstanding regenerative capacity is the basis for women's cycling and its dysfunction may be involved in the etiology of pathological disorders. Therefore, the human endometrial tissue must rely on a remarkable endometrial somatic stem cells (SSC) population. Here we

Irene Cervelló; Claudia Gil-Sanchis; Aymara Mas; Francisco Delgado-Rosas; José Antonio Martínez-Conejero; Amparo Galán; Alicia Martínez-Romero; Sebastian Martínez; Ismael Navarro; Jaime Ferro; José Antonio Horcajadas; Francisco José Esteban; José Enrique O'Connor; Antonio Pellicer; Carlos Simón; Joanna Mary Bridger

2010-01-01

131

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

132

Synthetic and biogenic magnetite nanoparticles for tracking of stem cells and dendritic cells  

NASA Astrophysics Data System (ADS)

Accurate delivery of cells to target organs is critical for success of cell-based therapies with stem cells or immune cells such as antigen-presenting dendritic cells (DC). Labeling with contrast agents before implantation provides a powerful means for monitoring cellular migration using magnetic resonance imaging (MRI). In this study, we investigated the uptake of fully synthesized or bacterial magnetic nanoparticles (MNPs) into hematopoietic Flt3 + stem cells and DC from mouse bone marrow. We show that (i) uptake of both synthetic and biogenic nanoparticles into cells endow magnetic activity and (ii) low numbers of MNP-loaded cells are readily detected by MRI.

Schwarz, Sebastian; Fernandes, Fabiana; Sanroman, Laura; Hodenius, Michael; Lang, Claus; Himmelreich, Uwe; Schmitz-Rode, Thomas; Schueler, Dirk; Hoehn, Mathias; Zenke, Martin; Hieronymus, Thomas

2009-05-01

133

Water soluble nanoporous nanoparticle for in vivo targeted drug delivery and controlled release in B cells tumor context  

NASA Astrophysics Data System (ADS)

Multitasking nanoparticles are gaining great attention for smart drug delivery systems. The exploration of the nano-scale opens new concrete opportunities for revealing new properties and undiscovered cell-particle interactions. Here we present a biodegradable nanoporous silicon nanoparticle that can be successfully employed for in vivo targeted drug delivery and sustained release. The bare nanoporous nanocarriers can be accurately designed and fabricated with an effective control of porosity, surface chemistry and particle size, up to a few nm. The proposed nanoparticles exhibit several remarkable features including high payload, biodegradability, no toxicity, and multiple loading in water without the need of additional chemical reagents at room temperature. The targeting strategy is based on phage display technology that was successfully used to discover cell surface binding peptide for murine B lymphoma A20 cell line. The peptide used in combination with the nanoporous nanoparticles allows an efficient in vivo targeting, a sustained release and a sensible therapeutic effect.Multitasking nanoparticles are gaining great attention for smart drug delivery systems. The exploration of the nano-scale opens new concrete opportunities for revealing new properties and undiscovered cell-particle interactions. Here we present a biodegradable nanoporous silicon nanoparticle that can be successfully employed for in vivo targeted drug delivery and sustained release. The bare nanoporous nanocarriers can be accurately designed and fabricated with an effective control of porosity, surface chemistry and particle size, up to a few nm. The proposed nanoparticles exhibit several remarkable features including high payload, biodegradability, no toxicity, and multiple loading in water without the need of additional chemical reagents at room temperature. The targeting strategy is based on phage display technology that was successfully used to discover cell surface binding peptide for murine B lymphoma A20 cell line. The peptide used in combination with the nanoporous nanoparticles allows an efficient in vivo targeting, a sustained release and a sensible therapeutic effect. Electronic supplementary information (ESI) available: Nanoparticles fabrication; payload evaluation; dissolution and release profiles; multivalent loading; targeting specifity on A20 Cells; cell cycle analysis; in vitro cytotoxicity assay; in vivo cytotoxicity assay. See DOI: 10.1039/c0nr00161a

de Angelis, F.; Pujia, A.; Falcone, C.; Iaccino, E.; Palmieri, C.; Liberale, C.; Mecarini, F.; Candeloro, P.; Luberto, L.; de Laurentiis, A.; Das, G.; Scala, G.; di Fabrizio, E.

2010-10-01

134

In vitro cell imaging using multifunctional small sized KGdF4:Yb3+,Er3+ upconverting nanoparticles synthesized by a one-pot solvothermal process.  

PubMed

Multifunctional KGdF4:18%Yb(3+),2%Er(3+) nanoparticles with upconversion fluorescence and paramagnetism are synthesized. The average sizes of the nanoparticles capped with branched polyethyleneimine (PEI) and 6-aminocaproic acid (6AA) are ~14 and ~13 nm, respectively. Our KGdF4 host does not exhibit any phase change with the decrease of particle size, which can prevent the detrimental significant decrease in upconversion luminescence caused by this effect observed in the well-known NaYF4 host. The branched PEI and 6AA capping ligands endow our nanoparticles with water-dispersibility and biocompatibility, which can favor internalization of our nanoparticles into the cytoplasm of HeLa cells and relatively high cell viability. The strong upconversion luminescence detected at the cytoplasm of HeLa cells incubated with the branched PEI-capped nanoparticles is probably attributed to the reported high efficiency of cellular uptake. The magnetic mass susceptibility of our nanoparticle is 8.62 × 10(-5) emu g(-1) Oe(-1). This is the highest value ever reported in trivalent rare-earth ion-doped KGdF4 nanoparticles of small size (?14 nm), and is very close to that of nanoparticles used as T1 contrast agents in magnetic resonance imaging. These suggest the potential of our KGdF4:Yb(3+),Er(3+) nanoparticles as small-sized multifunctional bioprobes. PMID:23475279

Wong, Hon-Tung; Tsang, Ming-Kiu; Chan, Chi-Fai; Wong, Ka-Leung; Fei, Bin; Hao, Jianhua

2013-04-21

135

The effect of Ag nanoparticles on PC3 cells ultraweak bioluminescence  

NASA Astrophysics Data System (ADS)

Ultraweak intrinsic bioluminescence of cancer cell is a noninvasive method of assessing bioenergetic status of the investigated cells. This weak emission generated by PC3 cell line was measured during various stages of growth with or without the presence of Ag nanoparticles. The comparison between nanoparticles concentration, bioluminescence and cell survival showed that even though Ag nanoparticles doesn't significantly affect cell survival at used concentration it affects cell metabolism, possibly making them more susceptible to other form of therapies.

Hossu, Marius; Zou, Xiaoju; Ma, Lun; Chen, Wei

2011-03-01

136

Particle-Cell Contact Enhances Antibacterial Activity of Silver Nanoparticles  

PubMed Central

Background It is generally accepted that antibacterial properties of Ag nanoparticles (AgNPs) are dictated by their dissolved fraction. However, dissolution-based concept alone does not fully explain the toxic potency of nanoparticulate silver compared to silver ions. Methodology/Principal Findings Herein, we demonstrated that the direct contact between bacterial cell and AgNPs' surface enhanced the toxicity of nanosilver. More specifically, cell-NP contact increased the cellular uptake of particle-associated Ag ions – the single and ultimate cause of toxicity. To prove that, we evaluated the toxicity of three different AgNPs (uncoated, PVP-coated and protein-coated) to six bacterial strains: Gram-negative Escherichia coli, Pseudomonas fluorescens, P. putida and P. aeruginosa and Gram-positive Bacillus subtilis and Staphylococcus aureus. While the toxicity of AgNO3 to these bacteria varied only slightly (the 4-h EC50 ranged from 0.3 to 1.2 mg Ag/l), the 4-h EC50 values of protein-coated AgNPs for various bacterial strains differed remarkably, from 0.35 to 46 mg Ag/l. By systematically comparing the intracellular and extracellular free Ag+ liberated from AgNPs, we demonstrated that not only extracellular dissolution in the bacterial test environment but also additional dissolution taking place at the particle-cell interface played an essential role in antibacterial action of AgNPs. The role of the NP-cell contact in dictating the antibacterial activity of Ag-NPs was additionally proven by the following observations: (i) separation of bacterial cells from AgNPs by particle-impermeable membrane (cut-off 20 kDa, ?4 nm) significantly reduced the toxicity of AgNPs and (ii) P. aeruginosa cells which tended to attach onto AgNPs, exhibited the highest sensitivity to all forms of nanoparticulate Ag. Conclusions/Significance Our findings provide new insights into the mode of antibacterial action of nanosilver and explain some discrepancies in this field, showing that “Ag-ion” and “particle-specific” mechanisms are not controversial but, rather, are two faces of the same coin.

Bondarenko, Olesja; Ivask, Angela; Kakinen, Aleksandr; Kurvet, Imbi; Kahru, Anne

2013-01-01

137

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

138

Protamine sulfate-nanodiamond hybrid nanoparticles as a vector for MiR-203 restoration in esophageal carcinoma cells  

NASA Astrophysics Data System (ADS)

We report an innovative approach for miRNA-203 delivery in esophageal cancer cells using protamine sulphate (PS)-nanodiamond (ND) nanoparticles. The efficient delivery of miR-203 significantly suppressed the proliferation and migration of cancer cells through targeting Ran and ?Np63, exhibiting a great potential for PS@ND nanoparticles in miRNA-based cancer therapy.We report an innovative approach for miRNA-203 delivery in esophageal cancer cells using protamine sulphate (PS)-nanodiamond (ND) nanoparticles. The efficient delivery of miR-203 significantly suppressed the proliferation and migration of cancer cells through targeting Ran and ?Np63, exhibiting a great potential for PS@ND nanoparticles in miRNA-based cancer therapy. Electronic supplementary information (ESI) available: (1) Experimental section; (2) Results: serum stability of miR-203/PS@NDs and miR-203 release curve (Fig. S1). Cytotoxicity assay of PS@NDs to Ec-109 cells (Fig. S2); confocal image and FACS analysis of intracellular uptake of cy3-labeled miR-203 (Fig. S3 and S4); real-time PCR analysis of miR-203 restoration (Fig. S5); Ran and ?Np63 expression (Fig. S6); the sizes and zeta potentials of miRNA/PS@NDs (Table S1); the sequences of the microRNA mimics and primers (Table S2, S3 and S4). See DOI: 10.1039/c3nr04056a

Cao, Minjun; Deng, Xiongwei; Su, Shishuai; Zhang, Fang; Xiao, Xiangqian; Hu, Qin; Fu, Yongwei; Yang, Burton B.; Wu, Yan; Sheng, Wang; Zeng, Yi

2013-11-01

139

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

140

Synthesizing Biofunctionalized Nanoparticles to Image Cell Signaling Pathways  

Microsoft Academic Search

This minireview outlines the synthetic efforts, from our research group, to produce nanomaterials for use as imaging agents to study cell signaling pathways. An overview of our approach to the synthesis and biofunctionalization of metal, semiconductor, and ceramic nanomaterials is presented. The probes investigated include coinage metals, Cd-based, Gedeg, naturally occurring fluorescent (NOF) minerals, and Ln-based nanoparticles which were synthesized

Bernadette A. Hernandez-Sanchez; Timothy N. Lambert; Sherrika D. Daniel-Taylor; Janet M. Oliver; Bridget S. Wilson; Diane S. Lidke; Nicholas L. Andrews

2006-01-01

141

T cells from CLL patients exhibit features of T-cell exhaustion but retain capacity for cytokine production  

PubMed Central

T-cell exhaustion, originally described in chronic viral infections, was recently reported in solid and hematologic cancers. It is not defined whether exhaustion contributes to T-cell dysfunction observed in chronic lymphocytic leukemia (CLL). We investigated the phenotype and function of T cells from CLL patients and age-matched controls. CD8+ and CD4+ T cells from CLL patients had increased expression of exhaustion markers CD244, CD160, and PD1, with expansion of a PD1+BLIMP1HI subset. These molecules were most highly expressed in the expanded population of effector T cells in CLL. CLL CD8+ T cells showed functional defects in proliferation and cytotoxicity, with the cytolytic defect caused by impaired granzyme packaging into vesicles and nonpolarized degranulation. In contrast to virally induced exhaustion, CLL T cells showed increased production of interferon-? and TNF? and increased expression of TBET, and normal IL2 production. These defects were not restricted to expanded populations of cytomegalovirus (CMV)–specific cells, although CMV seropositivity modulated the distribution of lymphocyte subsets, the functional defects were present irrespective of CMV serostatus. Therefore, although CLL CD8+ T cells exhibit features of T-cell exhaustion, they retain the ability to produce cytokines. These findings also exclude CMV as the sole cause of T-cell defects in CLL.

Davies, Jeffrey K.; McClanahan, Fabienne; Fatah, Rewas; Iqbal, Sameena; Agrawal, Samir; Ramsay, Alan G.; Gribben, John G.

2013-01-01

142

T cells from CLL patients exhibit features of T-cell exhaustion but retain capacity for cytokine production.  

PubMed

T-cell exhaustion, originally described in chronic viral infections, was recently reported in solid and hematologic cancers. It is not defined whether exhaustion contributes to T-cell dysfunction observed in chronic lymphocytic leukemia (CLL). We investigated the phenotype and function of T cells from CLL patients and age-matched controls. CD8+ and CD4+ T cells from CLL patients had increased expression of exhaustion markers CD244, CD160, and PD1, with expansion of a PD1+BLIMP1HI subset. These molecules were most highly expressed in the expanded population of effector T cells in CLL. CLL CD8+ T cells showed functional defects in proliferation and cytotoxicity, with the cytolytic defect caused by impaired granzyme packaging into vesicles and nonpolarized degranulation. In contrast to virally induced exhaustion, CLL T cells showed increased production of interferon-? and TNF? and increased expression of TBET, and normal IL2 production. These defects were not restricted to expanded populations of cytomegalovirus (CMV)–specific cells, although CMV seropositivity modulated the distribution of lymphocyte subsets, the functional defects were present irrespective of CMV serostatus. Therefore, although CLL CD8+ T cells exhibit features of T-cell exhaustion, they retain the ability to produce cytokines. These findings also exclude CMV as the sole cause of T-cell defects in CLL. PMID:23247726

Riches, John C; Davies, Jeffrey K; McClanahan, Fabienne; Fatah, Rewas; Iqbal, Sameena; Agrawal, Samir; Ramsay, Alan G; Gribben, John G

2013-02-28

143

Lactoferrin and ceruloplasmin derivatized superparamagnetic iron oxide nanoparticles for targeting cell surface receptors  

Microsoft Academic Search

Tissue and cell-specific drug targeting can be achieved by employing nanoparticle coatings or carrier-drug conjugates that contain a ligand recognized by a receptor on the target cell. Superparamagnetic iron oxide nanoparticles have been used for many years in various biomedical applications. In this study, superparamagnetic nanoparticles with specific shape and size have been prepared and coupled to various proteins. These

Ajay Kumar Gupta; Adam S. G Curtis

2004-01-01

144

Cell labeling with magnetic nanoparticles: Opportunity for magnetic cell imaging and cell manipulation  

PubMed Central

This tutorial describes a method of controlled cell labeling with citrate-coated ultra small superparamagnetic iron oxide nanoparticles. This method may provide basically all kinds of cells with sufficient magnetization to allow cell detection by high-resolution magnetic resonance imaging (MRI) and to enable potential magnetic manipulation. In order to efficiently exploit labeled cells, quantify the magnetic load and deliver or follow-up magnetic cells, we herein describe the main requirements that should be applied during the labeling procedure. Moreover we present some recommendations for cell detection and quantification by MRI and detail magnetic guiding on some real-case studies in vitro and in vivo.

2013-01-01

145

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

2013-10-22

146

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

147

Mechanism of the uptake of cationic and anionic calcium phosphate nanoparticles by cells.  

PubMed

The uptake of calcium phosphate nanoparticles (diameter 120nm) with different charge by HeLa cells was studied by flow cytometry. The amount of uptaken nanoparticles increased with increasing concentration of nanoparticles in the cell culture medium. Several inhibitors of endocytosis and macropinocytosis were applied to elucidate the uptake mechanism of nanoparticles into HeLa cells: wortmannin, LY294002, nocodazole, chlorpromazine and nystatin. Wortmannin and LY294002 strongly reduced the uptake of anionic nanoparticles, which indicates macropinocytosis as uptake mechanism. For cationic nanoparticles, the uptake was reduced to a lesser extent, indicating a different uptake mechanism. The localization of nanoparticles inside the cells was investigated by conjugating them with the pH-sensitive dye SNARF-1. The nanoparticles were localized in lysosomes after 3h of incubation. PMID:23454056

Sokolova, Viktoriya; Kozlova, Diana; Knuschke, Torben; Buer, Jan; Westendorf, Astrid M; Epple, Matthias

2013-07-01

148

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

PubMed Central

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.

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

2013-01-01

149

A simple method for the synthesis of hyaluronic acid coated magnetic nanoparticles for highly efficient cell labelling and in vivo imaging†  

PubMed Central

Highly stable colloidal hyaluronic acid coated magnetic nano-particles were prepared via a ligand exchange method. These particles exhibited excellent cell labeling efficiencies and superior potential as MRI contrast agents, which are useful to target tumor cells expressing hyaluronic acid receptors such as CD44.

El-Dakdouki, Mohammad H.; El-Boubbou, Kheireddine; Zhu, David C.; Huang, Xuefei

2012-01-01

150

DNA strand breaks produced by oxidative stress in mammalian cells exhibit 3'-phosphoglycolate termini.  

PubMed Central

In recent years two mechanisms have been proposed for the production of DNA strand breaks in cells undergoing oxidative stress: (i) DNA attack by OH radical, produced by Fenton reaction catalyzed by DNA-bound iron; and (ii) DNA attack by calcium-activated nucleases, due to the increase of cytosolic and nuclear calcium induced by oxidative stress. We set out to investigate the participation of the former mechanism by detecting and quantifying 3'-phosphoglycolate, a 3' DNA terminus known to be formed by OH radical attack to the deoxyribose moiety, followed by sugar ring rupture and DNA strand rupture. These structures were found in DNA of monkey kidney cells exposed to hydrogen peroxide, iron nitrilotriacetate or ascorbate, all species known to favor a cellular pro-oxidant status. The method employed to measure 3' phosphoglycolate was the 32P-postlabeling assay. Repair time course experiments showed that it takes 10 h for 3'-phosphoglycolate to be removed from DNA. It was found that the DNA of both control cells and cells exposed to hydrogen peroxide had a very poor capacity of supporting in vitro DNA synthesis, catalyzed by DNA polymerase I. If the DNA was previously incubated with exonuclease III, an enzyme able to expose 3'-OH primers by removal of 3'-phosphoglycolate and 3'-phosphate termini the in vitro synthesis was substantially increased. This result shows that either of these termini are present at the break and that 3'-hydroxyl termini are virtually absent. At least 25% of the strand breaks exhibited 3'-phosphoglycolate termini as determined by the 32P-postlabeling assay, but due to the characteristic of the method this percentage is likely to be higher. These results favor the hypothesis that an oxidative agent generated by Fenton reaction is responsible for DNA strand breakage in cells undergoing oxidative stress. Images

Bertoncini, C R; Meneghini, R

1995-01-01

151

In vitro effects of chitosan nanoparticles on proliferation of human gastric carcinoma cell line MGC803 cells  

Microsoft Academic Search

Abstract Abstract Abstract Abstract AIM: To investigate the effects of chitosan nanoparticles on proliferation of human gastric carcinoma cell line MGC803 in vitro and the possible mechanisms involved. METHODS: Chitosan nanoparticles were characterized by particle size, zeta potential, and morphology. After treatment with various concentrations of chitosan nanoparticles (25, 50, 75, 100 µg\\/mL) at various time intervals, cell proliferation, ultrastructural

Li-Feng Qi; Zi-Rong Xu; Yan Li; Xia Jiang; Xin-Yan Han

152

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

153

Congenital amegakaryocytic thrombocytopenia iPS cells exhibit defective MPL-mediated signaling.  

PubMed

Congenital amegakaryocytic thrombocytopenia (CAMT) is caused by the loss of thrombopoietin receptor-mediated (MPL-mediated) signaling, which causes severe pancytopenia leading to bone marrow failure with onset of thrombocytopenia and anemia prior to leukopenia. Because Mpl(-/-) mice do not exhibit the human disease phenotype, we used an in vitro disease tracing system with induced pluripotent stem cells (iPSCs) derived from a CAMT patient (CAMT iPSCs) and normal iPSCs to investigate the role of MPL signaling in hematopoiesis. We found that MPL signaling is essential for maintenance of the CD34+ multipotent hematopoietic progenitor (MPP) population and development of the CD41+GPA+ megakaryocyte-erythrocyte progenitor (MEP) population, and its role in the fate decision leading differentiation toward megakaryopoiesis or erythropoiesis differs considerably between normal and CAMT cells. Surprisingly, complimentary transduction of MPL into normal or CAMT iPSCs using a retroviral vector showed that MPL overexpression promoted erythropoiesis in normal CD34+ hematopoietic progenitor cells (HPCs), but impaired erythropoiesis and increased aberrant megakaryocyte production in CAMT iPSC-derived CD34+ HPCs, reflecting a difference in the expression of the transcription factor FLI1. These results demonstrate that impaired transcriptional regulation of the MPL signaling that normally governs megakaryopoiesis and erythropoiesis underlies CAMT. PMID:23908116

Hirata, Shinji; Takayama, Naoya; Jono-Ohnishi, Ryoko; Endo, Hiroshi; Nakamura, Sou; Dohda, Takeaki; Nishi, Masanori; Hamazaki, Yuhei; Ishii, Ei-ichi; Kaneko, Shin; Otsu, Makoto; Nakauchi, Hiromitsu; Kunishima, Shinji; Eto, Koji

2013-09-01

154

Quantitative Photoacoustic Imaging of Nanoparticles in Cells and Tissues  

PubMed Central

Quantitative visualization of nanoparticles in cells and tissues, while preserving the spatial information, is very challenging. A photoacoustic imaging technique to depict the presence and quantity of nanoparticles is presented. This technique is based on the dependence of the photoacoustic signal with both the nanoparticle quantity and the laser fluence. Quantitative photoacoustic imaging is a robust technique that doesn’t require knowledge of the local fluence, but a relative change in the fluence. This eliminates the need for sophisticated methods or models to determine the energy distribution of light in turbid media. Quantitative photoacoustic imaging was first applied to nanoparticle-loaded cells and quantitation was validated by inductively coupled plasma mass spectrometry. Quantitative photoacoustic imaging was then extended to xenograft tumor tissue sections, and excellent agreement with traditional histopathological analysis was demonstrated. Our results suggest that quantitative photoacoustic imaging may be used in many applications including the determination of the efficiency and effectiveness of molecular targeting strategies for cell studies and animal models, the quantitative assessment of photoacoustic contrast agent biodistribution, and the validation of in vivo photoacoustic imaging.

Cook, Jason R.; Frey, Wolfgang; Emelianov, Stanislav

2013-01-01

155

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

156

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

157

Effect of hydroxyapatite nanoparticles on the ultrastructure and function of hepatocellular carcinoma cells in vitro  

Microsoft Academic Search

The interaction of Bel-7402 hepatocellular carcinoma cells (HCC) as a single cell suspension with hydroxyapatite (HAP) nanoparticles was investigated. It was observed by an inverted microscope that the cells were still homogeneously distributed in the culture medium after 24 h. A TEM analysis showed that the HAP nanoparticles attached to the Bel-7402 cells were finally swallowed by the cells after

Mei-Zhen Yin; Ying-Chao Han; Ingo W. Bauer; Pei Chen; Shi-Pu Li

2006-01-01

158

Polylactide-based Paclitaxel-loaded nanoparticles fabricated by dispersion polymerization: characterization, evaluation in cancer cell lines, and preliminary biodistribution studies.  

PubMed

The macromonomer method was used to prepare cross-linked, paclitaxel-loaded polylactide (PLA)-polyethylene glycol (stealth) nanoparticles using free-radical dispersion polymerization. The method can facilitate the attachment of other molecules to the nanoparticle surface to make it multifunctional. Proton nuclear magnetic resonance and Fourier transform infrared spectra confirm the synthesis of PLA macromonomer and cross-linking agent. The formation of stealth nanoparticles was confirmed by scanning and transmission electron microscopy. The drug release isotherm of paclitaxel-loaded nanoparticles shows that the encapsulated drug is released over 7 days. In vitro cytotoxicity assay in selected breast and ovarian cancer cell lines reveal that the blank nanoparticle is biocompatible compared with medium-only treated controls. In addition, the paclitaxel-loaded nanoparticles exhibit similar cytotoxicity compared with paclitaxel in solution. Confocal microscopy reveals that the nanoparticles are internalized by MCF-7 breast cancer cells within 1 h. Preliminary biodistribution studies also show nanoparticle accumulation in tumor xenograft model. The nanoparticles are suitable for the controlled delivery of bioactive agents. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2546-2555, 2014. PMID:24961596

Adesina, Simeon K; Holly, Alesia; Kramer-Marek, Gabriela; Capala, Jacek; Akala, Emmanuel O

2014-08-01

159

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

PubMed Central

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.

Costa, Pedro M; Cardoso, Ana L; Mendonca, Liliana S; Serani, Angelo; Custodia, Carlos; Conceicao, Mariana; Simoes, Sergio; Moreira, Joao N; Pereira de Almeida, Luis; Pedroso de Lima, Maria C

2013-01-01

160

Targeted sonocatalytic cancer cell injury using avidin-conjugated titanium dioxide nanoparticles.  

PubMed

In this study, we applied sonodynamic therapy to cancer cells based on the delivery of titanium dioxide (TiO2) nanoparticles (NPs) modified with avidin protein, which preferentially discriminated cancerous cells from healthy cells. Subsequently, hydroxyl radicals were generated from the TiO2 NPs after activation by external ultrasound irradiation (TiO2/US treatment). Although 30% of the normal breast cells (human mammary epithelial cells) exhibited the uptake of avidin-modified TiO2 NPs, over 80% of the breast cancer cells (MCF-7) exhibited the uptake of avidin-TiO2 NPs. Next the effect of the TiO2/US treatment on MCF-7 cell growth was examined for up to 96h after 1-MHz ultrasound was applied (0.1W/cm(2), 30s) to cells that incorporated the TiO2 NPs. No apparent cell injury was observed until 24h after the treatment, but the viable cell concentration declined to 68% compared with the control at 96h. PMID:24717690

Ninomiya, Kazuaki; Fukuda, Aya; Ogino, Chiaki; Shimizu, Nobuaki

2014-09-01

161

Selective effects of hydroxyapatite nanoparticles on osteosarcoma cells and osteoblasts.  

PubMed

The effects of hydroxyapatite nanoparticles (HA-NPs) on two kinds of cells, human MG63 cells and the normal osteoblasts were investigated. According to the MTT assay and fluorescent staining assay, it was proved that HA-NPs could inhibit the growth of MG63 cells but slightly support proliferation of the osteoblasts. Meanwhile, transmission electron microscopy (TEM) was employed to observe the ultrastructural alterations of both cells. The TEM results showed that HA-NPs had entered the two kinds of cells. Typical apoptosis was observed in the MG63 cells, especially in the group of 250 ?g/mL with 5 days culture. While no apoptosis could be found in the normal osteoblasts at any concentration group of HA-NPs. Our results suggested that the HA-NPs had selective effects to different kinds of cells: supporting proliferation to the normal bone cells while causing apoptosis to the osteosarcoma cells. PMID:22903597

Qing, Fangzhu; Wang, Zhe; Hong, Youliang; Liu, Ming; Guo, Bo; Luo, Hongrong; Zhang, Xingdong

2012-09-01

162

Maltooligosaccharides from JEG-3 Trophoblast-Like Cells Exhibit Immunoregulatory Properties  

PubMed Central

Problem To better understand the immunoregulatory properties of trophoblasts, we have searched for small immunologically active carbohydrates derived from intact trophoblast-like cells. Method of study Using solid phase extraction coupled with HPLC and mass spectrometry methods, we have characterized a low molecular weight carbohydrate-rich fraction associated with JEG-3 cells. We have also tested the bioactivities of selected authentic oligosaccharides found in the oligosaccharide fraction. Results The most abundant components of the low molecular weight carbohydrate-rich fraction were maltotriose and maltotetraose, with detectable amounts of maltopentaose. When authentic maltooligosaccharides were tested using lymphocytes, IL-2 inhibition was observed. This activity was dependent upon the number of saccharide subunits, stereochemistry and concentration. To further test maltooligosaccharide properties, maltopentose was attached to glass cover slips. Although spontaneous neutrophil motility was observed on unmodified and control surfaces, it was inhibited on maltooligosaccharide-derivatized surfaces. Conclusion Maltooligosaccharides are associated with the trophoblast’s surface where they may exhibit immunoregulatory activities.

Zhu, Aiping; Romero, Roberto; Huang, J.-B; Clark, Andrea; Petty, Howard R.

2010-01-01

163

The effects of different size gold nanoparticles on mechanical properties of vascular smooth muscle cells under mechanical stretching  

NASA Astrophysics Data System (ADS)

Nanotechnology is an emerging and promising frontier for medicine and biomedical research due to its potential for applications such as drug delivery, imaging enhancement, and cancer treatment. While these materials may possess significant possibilities, the effects of these particles in the body and how the particles affect the cells is not fully understood. In this study, vascular smooth muscle cells (VSMCs) will be exposed to 5 and 20 nm diameter citrate AuNPs under mechanical conditions. The cytotoxicity properties of these particles will be investigated using LDH and MTT assays. Atomic force microscopy will be used to study how the size of the nanoparticles affect the mechanical properties of the VSMCs. Immunofluorescence staining for alpha actin will also be performed to enhance understanding of the phenotypic shift. The LDH and MTT cytotoxicity assay results demonstrated that neither 5 nor 20 nm diameter nanoparticles are cytotoxic to the cells. However, the mechanical properties and cell morphology of the VSMCs was altered. Under static conditions, both AuNP treatments decreased the mechanical properties of the cells. The size of the nanoparticles had a softening effect on elastic modulus of the cell and sign of a synthetic phenotype was observed. The VSMCs subjected to mechanical stretching exhibited higher elastic modulus compared to the static experimental groups. Again, both AuNPs treatments decreased the mechanical properties of the cells and signs of more synthetic phenotype was seen. However, the size of the nanoparticles did not have any influence on cell's elastic modulus unlike the static treated cells. The mechanical testing condition provided a better look at how these particles would affect the cells in vivo. While the nanoparticles are not cytotoxic to the VSMCs, they are altering the mechanical properties and phenotype of the cell.

Kieu, Tri Minh

164

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

NASA Astrophysics Data System (ADS)

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.

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

2009-12-01

165

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

166

Graphene nanosheets inserted by silver nanoparticles as zero-dimensional nanospacers for dye sensitized solar cells  

NASA Astrophysics Data System (ADS)

Three-dimensional Ag nanoparticle/GNs (Ag/GNs) hybrids as highly efficient counter electrode (CE) materials for dye sensitized solar cells (DSSCs) is described, highlighting the Ag nanoparticles as zero-dimensional nanospacers inserting into GNs to lift the interspacing layer between individual GNs. It is demonstrated that, when the hybrids are used as CE materials for DSSCs, compared to their pure GNs, Ag/GNs hybrids without agglomerates have a significant improvement in their electrochemical properties such as high current density, narrow peak-to-peak separation (Epp) and low charge transfer resistance (RCT). The enhancement of electrochemical performance can be attributed to the increased electrode conductivity, an extended interlayer distance and the reduction of the restacking of graphene sheets due to the insertion of metallic Ag nanoparticles into GNs. The DSSC with this hybrid CE exhibited an energy conversion efficiency (?) of 7.72% with an open circuit voltage (VOC), short circuit photocurrent density (JSC), and fill factor (FF) of 732 mV, 14.67 mA cm-2, and 71.8%, respectively.Three-dimensional Ag nanoparticle/GNs (Ag/GNs) hybrids as highly efficient counter electrode (CE) materials for dye sensitized solar cells (DSSCs) is described, highlighting the Ag nanoparticles as zero-dimensional nanospacers inserting into GNs to lift the interspacing layer between individual GNs. It is demonstrated that, when the hybrids are used as CE materials for DSSCs, compared to their pure GNs, Ag/GNs hybrids without agglomerates have a significant improvement in their electrochemical properties such as high current density, narrow peak-to-peak separation (Epp) and low charge transfer resistance (RCT). The enhancement of electrochemical performance can be attributed to the increased electrode conductivity, an extended interlayer distance and the reduction of the restacking of graphene sheets due to the insertion of metallic Ag nanoparticles into GNs. The DSSC with this hybrid CE exhibited an energy conversion efficiency (?) of 7.72% with an open circuit voltage (VOC), short circuit photocurrent density (JSC), and fill factor (FF) of 732 mV, 14.67 mA cm-2, and 71.8%, respectively. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr06340b

Chang, Quanhong; Wang, Zhenping; Wang, Jinzhong; Yan, Yuan; Ma, Zhoujing; Zhu, Jianxiao; Shi, Wangzhou; Chen, Qi; Yu, Qingjiang; Huang, Lei

2014-04-01

167

Use of nanoparticles for targeted, noninvasive thermal destruction of malignant cells.  

PubMed

Shortwave (MHz range) radiofrequency (RF) energy is nonionizing, penetrates deeply into biological tissues with no adverse side effects, and heats metallic nanoparticles efficiently. Targeted delivery of these nanoparticles to cancer cells should result in hyperthermic cytotoxicity upon exposure to a focused, noninvasive RF field. We have demonstrated that gold nanoparticles conjugated with cetuximab (C225) are quickly internalized by Panc-1 (pancreatic adenocarcinoma) and Difi (colorectal adenocarcinoma) cancer cells overexpressing epidermal growth factor receptor (EGFR). Panc-1 or Difi cells treated with naked gold nanoparticles or nonspecific IgG-conjugated gold nanoparticles demonstrated minimal intracellular uptake of gold nanoparticles by transmission electron microscopy (TEM). In contrast, there were dense concentrations of cytoplasmic vesicles containing gold nanoparticles following treatment with cetuximab-conjugated gold nanoparticles. Exposure of cells to a noninvasive RF field produced nearly 100% cytotoxicity in cells treated with the cetuximab-conjugated gold nanoparticles, but significantly lower levels of cytotoxicity in the two control groups (p < 0.00012). Treatment of a breast cancer cell line (CAMA-1) that does not express EGFR with cetuximab-conjugated gold nanoparticles produced no enhanced cytotoxicity following treatment in the RF field. Conjugation of cancer cell-directed targeting agents to gold nanoparticles may represent an effective and cancer-specific therapy to treat numerous types of human malignant disease using noninvasive RF hyperthermia. PMID:20217608

Cherukuri, Paul; Curley, Steven A

2010-01-01

168

Internalization pathways into cancer cells of gadolinium-based radiosensitizing nanoparticles.  

PubMed

Over the last few decades, nanoparticles have been studied in theranostic field with the objective of exhibiting a long circulation time through the body coupled to major accumulation in tumor tissues, rapid elimination, therapeutic potential and contrast properties. In this context, we developed sub-5 nm gadolinium-based nanoparticles that possess in vitro efficient radiosensitizing effects at moderate concentration when incubated with head and neck squamous cell carcinoma cells (SQ20B). Two main cellular internalization mechanisms were evidenced and quantified: passive diffusion and macropinocytosis. Whereas the amount of particles internalized by passive diffusion is not sufficient to induce in vitro a significant radiosensitizing effect, the cellular uptake by macropinocytosis leads to a successful radiotherapy in a limited range of particles incubation concentration. Macropinocytosis processes in two steps: formation of agglomerates at vicinity of the cell followed by their collect via the lamellipodia (i.e. the "arms") of the cell. The first step is strongly dependent on the physicochemical characteristics of the particles, especially their zeta potential that determines the size of the agglomerates and their distance from the cell. These results should permit to control the quantity of particles internalized in the cell cytoplasm, promising ambitious opportunities towards a particle-assisted radiotherapy using lower radiation doses. PMID:23046756

Rima, Wael; Sancey, Lucie; Aloy, Marie-Thérèse; Armandy, Emma; Alcantara, Gustavo B; Epicier, Thierry; Malchère, Annie; Joly-Pottuz, Lucile; Mowat, Pierre; Lux, François; Tillement, Olivier; Burdin, Béatrice; Rivoire, Annie; Boulé, Christelle; Anselme-Bertrand, Isabelle; Pourchez, Jérémie; Cottier, Michèle; Roux, Stéphane; Rodriguez-Lafrasse, Claire; Perriat, Pascal

2013-01-01

169

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

2009-11-01

170

A multifunctional core-shell nanoparticle for dendritic cell-based cancer immunotherapy  

NASA Astrophysics Data System (ADS)

Dendritic cell-based cancer immunotherapy requires tumour antigens to be delivered efficiently into dendritic cells and their migration to be monitored in vivo. Nanoparticles have been explored as carriers for antigen delivery, but applications have been limited by the toxicity of the solvents used to make nanoparticles, and by the need to use transfection agents to deliver nanoparticles into cells. Here we show that an iron oxide-zinc oxide core-shell nanoparticle can deliver carcinoembryonic antigen into dendritic cells while simultaneously acting as an imaging agent. The nanoparticle-antigen complex is efficiently taken up by dendritic cells within one hour and can be detected in vitro by confocal microscopy and in vivo by magnetic resonance imaging. Mice immunized with dendritic cells containing the nanoparticle-antigen complex showed enhanced tumour antigen specific T-cell responses, delayed tumour growth and better survival than controls.

Cho, Nam-Hyuk; Cheong, Taek-Chin; Min, Ji Hyun; Wu, Jun Hua; Lee, Sang Jin; Kim, Daehong; Yang, Jae-Seong; Kim, Sanguk; Kim, Young Keun; Seong, Seung-Yong

2011-10-01

171

Effects of internalized gold nanoparticles with respect to cytotoxicity and invasion activity in lung cancer cells.  

PubMed

The effect of gold nanoparticles on lung cancer cells is not yet clear. In this study, we investigated the cytotoxicity and cell invasion activity of lung cancer cells after treatment with gold nanoparticles and showed that small gold nanoparticles can be endocytosed by lung cancer cells and that they facilitate cell invasion. The growth of A549 cells was inhibited after treatment with 5-nm gold nanoparticles, but cell invasion increased. Endocytosed gold nanoparticles (size, 10 nm) notably promoted the invasion activity of 95D cells. All these effects of gold nanoparticles were not seen after treatment with larger particles (20 and 40 nm). The enhanced invasion activity may be associated with the increased expression of matrix metalloproteinase 9 and intercellular adhesion molecule-1. In this study, we obtained evidence for the effect of gold nanoparticles on lung cancer cell invasion activity in vitro. Moreover, matrix metalloproteinase 9 and intercellular adhesion molecule-1, key modulators of cell invasion, were found to be regulated by gold nanoparticles. These data also demonstrate that the responses of the A549 and 95D cells to gold nanoparticles have a remarkable relationship with their unique size-dependent physiochemical properties. Therefore, this study provides a new perspective for cell biology research in nanomedicine. PMID:24901215

Liu, Zhengxia; Wu, Yucheng; Guo, Zhirui; Liu, Ying; Shen, Yujie; Zhou, Ping; Lu, Xiang

2014-01-01

172

Effects of Internalized Gold Nanoparticles with Respect to Cytotoxicity and Invasion Activity in Lung Cancer Cells  

PubMed Central

The effect of gold nanoparticles on lung cancer cells is not yet clear. In this study, we investigated the cytotoxicity and cell invasion activity of lung cancer cells after treatment with gold nanoparticles and showed that small gold nanoparticles can be endocytosed by lung cancer cells and that they facilitate cell invasion. The growth of A549 cells was inhibited after treatment with 5-nm gold nanoparticles, but cell invasion increased. Endocytosed gold nanoparticles (size, 10 nm) notably promoted the invasion activity of 95D cells. All these effects of gold nanoparticles were not seen after treatment with larger particles (20 and 40 nm). The enhanced invasion activity may be associated with the increased expression of matrix metalloproteinase 9 and intercellular adhesion molecule-1. In this study, we obtained evidence for the effect of gold nanoparticles on lung cancer cell invasion activity in vitro. Moreover, matrix metalloproteinase 9 and intercellular adhesion molecule-1, key modulators of cell invasion, were found to be regulated by gold nanoparticles. These data also demonstrate that the responses of the A549 and 95D cells to gold nanoparticles have a remarkable relationship with their unique size-dependent physiochemical properties. Therefore, this study provides a new perspective for cell biology research in nanomedicine.

Guo, Zhirui; Liu, Ying; Shen, Yujie; Zhou, Ping; Lu, Xiang

2014-01-01

173

Iron oxide nanoparticles as drug delivery agents in MIA PaCa-2 pancreatic cells  

NASA Astrophysics Data System (ADS)

Oleic acid (OA)-Pluronic-coated iron oxide nanoparticles were synthesized and characterized by Fourier Transform Infrared Spectroscopy (FT-IR) and Atomic Force Microscopy (AFM). FT-IR confirmed the bonding of oleic acid and Pluronic (surfactant) to the nanoparticles. AFM measurements on these nanoparticles indicated a root mean square (RMS) roughness, a measure of nanoparticle size of (50 +/- 20) nm. The efficiency of these functionalized nanoparticles was investigated by loading with 5-Fluorouracil (5-FU) in aqueous solution. AFM measurements were used to characterize modified iron oxide nanoparticles and pancreatic MIA PaCa-2 cells, including size distribution, stability and cellular uptake. Nanoparticles were added to MIA PaCa-2 cells and assayed for their cytotoxic effects after 24 and 48 hours. The outcome of this study demonstrated the effectiveness of oleic acid (OA)-Pluronic-coated iron oxide nanoparticles as a non-toxic drug delivery agent for pancreatic cancer.

Perry, Christopher; Randriamahefa, Alexandrine; Lokko, Carl; Evans, Whitney; Watkins, Julian; Carrell, Holly; King, Natalie; Patel, Darayas

2007-03-01

174

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

175

Exocytosis of peptide functionalized gold nanoparticles in endothelial cells  

NASA Astrophysics Data System (ADS)

We present the exocytosis profile of two types of peptide-coated nanoparticles, which have similar charge and size but different functionality. While one kind of particles appears to progressively exocytose, the other one has a more complex profile, suggesting that some of the particles are re-uptaken by the cells. Both types of particles retain their colloidal stability after exocytosis.We present the exocytosis profile of two types of peptide-coated nanoparticles, which have similar charge and size but different functionality. While one kind of particles appears to progressively exocytose, the other one has a more complex profile, suggesting that some of the particles are re-uptaken by the cells. Both types of particles retain their colloidal stability after exocytosis. Electronic supplementary information (ESI) available: ICP-AES DLS and zeta potential measurements. See DOI: 10.1039/c2nr31064c

Bartczak, Dorota; Nitti, Simone; Millar, Timothy M.; Kanaras, Antonios G.

2012-07-01

176

Hepatitis C virus proteins exhibit conflicting effects on the interferon system in human hepatocyte cells.  

PubMed

We previously found that hepatitis C virus (HCV) core protein (Core) activated the interferon (IFN)-inducible 40/46 kDa 2'-5'-oligoadenylate synthetase (2'-5'-OAS) gene through an IFN-stimulated response element (ISRE) in non-neoplastic human hepatocyte PH5CH8 cells. Here, we found that Core and NS5B synergistically enhanced the 2'-5'-OAS gene promoter activity through ISRE. Further analysis revealed that amino acid positions 12 and/or 13 of Core and RNA-dependent RNA polymerase activity of NS5B were essential for the activation of the 2'-5'-OAS gene promoter. Interestingly, we observed that the activation by Core or NS5B was still partially enhanced by even the NS5B or Core mutant lacking the activating ability, respectively, suggesting an indirect interaction between Core and NS5B. Furthermore, we showed that the activation by NS5B could be explained by NS5B's induction of IFN-beta, however, IFN-beta was not induced by Core. Moreover, we showed that the synergistic effect of Core and NS5B was not invalidated by NS3-4A, although NS3-4A significantly inhibited the activation by combination of Core and NS5B. Taken together, our findings reveal that NS5B/Core and NS3-4A exhibit conflicting effects (activation and inhibition) on the IFN system in PH5CH8 cells, and suggest that such effects may promote the distraction of the host defense system to lead to persistent infection. PMID:16139243

Dansako, Hiromichi; Naka, Kazuhito; Ikeda, Masanori; Kato, Nobuyuki

2005-10-21

177

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

178

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

179

nanoparticles  

NASA Astrophysics Data System (ADS)

In this work, we present the role of vanadium ions (V+5 and V+3), oxygen vacancies (VO), and interstitial zinc (Zni) to the contribution of specific magnetization for a mixture of ZnO-V2O5 nanoparticles (NPs). Samples were obtained by mechanical milling of dry powders and ethanol-assisted milling for 1 h with a fixed atomic ratio V/Zn?=?5% at. For comparison, pure ZnO samples were also prepared. All samples exhibit a room temperature magnetization ranging from 1.18?×?10-3 to 3.5?×?10-3 emu/gr. Pure ZnO powders (1.34?×?10-3 emu/gr) milled with ethanol exhibit slight increase in magnetization attributed to formation of Zni, while dry milled ZnO powders exhibit a decrease of magnetization due to a reduction of VO concentration. For the ZnO-V2O5 system, dry milled and thermally treated samples under reducing atmosphere exhibit a large paramagnetic component associated to the formation of V2O3 and secondary phases containing V+3 ions; at the same time, an increase of VO is observed with an abrupt fall of magnetization to ??~?0.7?×?10-3 emu/gr due to segregation of V oxides and formation of secondary phases. As mechanical milling is an aggressive synthesis method, high disorder is induced at the surface of the ZnO NPs, including VO and Zni depending on the chemical environment. Thermal treatment restores partially structural order at the surface of the NPs, thus reducing the amount of Zni at the same time that V2O5 NPs segregate reducing the direct contact with the surface of ZnO NPs. Additional samples were milled for longer time up to 24 h to study the effect of milling on the magnetization; 1-h milled samples have the highest magnetizations. Structural characterization was carried out using X-ray diffraction and transmission electron microscopy. Identification of VO and Zni was carried out with Raman spectra, and energy-dispersive X-ray spectroscopy was used to verify that V did not diffuse into ZnO NPs as well to quantify O/Zn ratios.

Olive-Méndez, Sion F.; Santillán-Rodríguez, Carlos R.; González-Valenzuela, Ricardo A.; Espinosa-Magaña, Francisco; Matutes-Aquino, José A.

2014-04-01

180

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

181

Cytotoxicity evaluation of silica nanoparticles using fish cell lines.  

PubMed

Nanoparticles (NPs) have extensive industrial, biotechnological, and biomedical/pharmaceutical applications, leading to concerns over health risks to humans and biota. Among various types of nanoparticles, silica nanoparticles (SiO2 NPs) have become popular as nanostructuring, drug delivery, and optical imaging agents. SiO2 NPs are highly stable and could bioaccumulate in the environment. Although toxicity studies of SiO2 NPs to human and mammalian cells have been reported, their effects on aquatic biota, especially fish, have not been significantly studied. Twelve adherent fish cell lines derived from six species (rainbow trout, fathead minnow, zebrafish, goldfish, haddock, and American eel) were used to comparatively evaluate viability of cells by measuring metabolic impairment using Alamar Blue. Toxicity of SiO2 NPs appeared to be size-, time-, temperature-, and dose-dependent as well as tissue-specific. However, dosages greater than 100 ?g/mL were needed to achieve 24 h EC50 values (effective concentrations needed to reduce cell viability by 50%). Smaller SiO2 NPs (16 nm) were relatively more toxic than larger sized ones (24 and 44 nm) and external lining epithelial tissue (skin, gills)-derived cells were more sensitive than cells derived from internal tissues (liver, brain, intestine, gonads) or embryos. Higher EC50 values were achieved when toxicity assessment was performed at higher incubation temperatures. These findings are in overall agreement with similar human and mouse cell studies reported to date. Thus, fish cell lines could be valuable for screening emerging contaminants in aquatic environments including NPs through rapid high-throughput cytotoxicity bioassays. PMID:24357037

Vo, Nguyen T K; Bufalino, Mary R; Hartlen, Kurtis D; Kitaev, Vladimir; Lee, Lucy E J

2014-05-01

182

Surface modification of monodisperse magnetite nanoparticles for improved intracellular uptake to breast cancer cells  

Microsoft Academic Search

Nanoparticles have been widely used for a variety of biomedical\\u000a applications and there is a growing need for highly specific and\\u000a efficient uptake of the nanoparticles into target cells. Poly(ethylene\\u000a glycol) (PEG), folic acid (FA), and their conjugate PEG-FA were attached\\u000a to magnetite nanoparticles to compare their effects on the improvement\\u000a of intracellular uptake of the nanoparticles to human breast

Y Zhang; Jing Zhang

2005-01-01

183

Hydrazone ligation strategy to assemble multifunctional viral nanoparticles for cell imaging and tumor targeting.  

PubMed

Multivalent nanoparticle platforms are attractive for biomedical applications because of their improved target specificity, sensitivity, and solubility. However, their controlled assembly remains a considerable challenge. An efficient hydrazone ligation chemistry was applied to the assembly of Cowpea mosaic virus (CPMV) nanoparticles with individually tunable levels of a VEGFR-1 ligand and a fluorescent PEGylated peptide. The nanoparticles recognized VEGFR-1 on endothelial cell lines and VEGFR1-expressing tumor xenografts in mice, validating targeted CPMV as a nanoparticle platform in vivo. PMID:20163184

Brunel, Florence M; Lewis, John D; Destito, Giuseppe; Steinmetz, Nicole F; Manchester, Marianne; Stuhlmann, Heidi; Dawson, Philip E

2010-03-10

184

Hydrazinocurcumin Encapsuled Nanoparticles "Re-Educate" Tumor-Associated Macrophages and Exhibit Anti-Tumor Effects on Breast Cancer Following STAT3 Suppression  

PubMed Central

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-10high, IL-12low, 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-10low, IL-12high, 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.

Tian, Wenxia; Cai, Xiaozhong; Wang, Xiaofei; Dang, Weiqi; Tang, Hao; Cao, Hong; Wang, Lin

2013-01-01

185

Reactive oxygen species mediated DNA damage in human lung alveolar epithelial (A549) cells from exposure to non-cytotoxic MFI-type zeolite nanoparticles.  

PubMed

Increasing utilization of engineered nanoparticles in the field of electronics and biomedical applications demands an assessment of risk associated with deliberate or accidental exposure. Metal based nanoparticles are potentially most important of all the nanoparticles in terms of health risks. Microporous alumino-silicates and pure silicates named as zeolites and zeo-type materials with variety of structures, chemical compositions, particle sizes and morphologies have a significant number of industrial uses such as in catalysis, sorption and ion-exchange processes. In particular, the nanosized particles due to their unique properties are used in hybrid organic-inorganic materials for photography, photonics, electronics, labeling, imaging, and sensing. The aim of the current study is to investigate pure silica MFI-type zeolites nanoparticles with sizes of 50nm and 100nm (samples MFI-50 and MFI-100) under suspended conditions and their toxicological effects on human lung alveolar (A549) cells under in vitro conditions. Live cell imaging showed that the nanoparticles precipitated from the colloidal suspension of cell culture media as large agglomerates, coming in contact with the cell surface through sedimentation. A cellular proliferative capacity test showed the zeolite nanoparticles to exhibit no significant cytotoxicity below a concentration of 100?g/ml. However, both the MFI-50 and MFI-100 nanoparticles induced high intracellular reactive oxygen species (ROS) generation and elevated mitochondrial membrane potential in the A549 cells over the measured time period of 12h and at concentrations up to ?50?g/ml. DNA fragmentation analysis using the comet assay showed that the MFI-50 and MFI-100 nanoparticles cause genotoxicity in a concentration dependent manner. Furthermore, the rate at which maximum genomic damage was caused by MFI-100 nanoparticles in the A549 cells was found to be high as compared to the MFI-50 nanoparticles. However, the damage caused by the MFI-50 nanoparticles was found to accumulate over a longer period of time as compared to MFI-100 nanoparticles. The study therefore points towards the capability of the non-cytotoxic zeolite nanoparticles to induce oxidative stress resulting in short-term altered cellular metabolism up-regulation and genomic instability. Although the damage was found to be short-lived, its persistence over longer durations, or stabilization cannot be neglected. Further studies are in progress to yield a better understanding of the mechanisms for oxidative stress and resulting cascade of events leading to genetic damage in the human lung alveolar epithelial cells following exposure to zeolite nanoparticles of different sizes. PMID:23103338

Bhattacharya, Kunal; Naha, Pratap C; Naydenova, Izabela; Mintova, Svetlana; Byrne, Hugh J

2012-12-17

186

Iron Oxide Nanoparticle Assisted Purification and Mass Spectrometry Based Proteolytic Mapping of Intact CD4T Cells from Human Blood  

Microsoft Academic Search

Iron oxide nanoparticles have been used for many years as clinical applications. We have developed a rapid immunoaffinity isolation method of CD4T cells from a mixed cell population of human blood using iron oxide nanoparticles. Anti CD4-antibody has been attached to iron oxide nanoparticles after its surface modification. The antibody tagged iron oxide nanoparticle beads are simply incubated with the

Santi M. Mandal; Ananta K. Ghosh; Mahitosh Mandal

2008-01-01

187

Micro-Raman Spectroscopy of Silver Nanoparticle Induced Stress on Optically-Trapped Stem Cells  

Microsoft Academic Search

We report here results of a single-cell Raman spectroscopy study of stress effects induced by silver nanoparticles in human mesenchymal stem cells (hMSCs). A high-sensitivity, high-resolution Raman Tweezers set-up has been used to monitor nanoparticle-induced biochemical changes in optically-trapped single cells. Our micro-Raman spectroscopic study reveals that hMSCs treated with silver nanoparticles undergo oxidative stress at doping levels in excess

Aseefhali Bankapur; R. Sagar Krishnamurthy; Elsa Zachariah; Chidangil Santhosh; Basavaraj Chougule; Bhavishna Praveen; Manna Valiathan; Deepak Mathur

2012-01-01

188

Quantitative intracellular magnetic nanoparticle uptake measured by live cell magnetophoresis  

PubMed Central

Superparamagnetic iron oxide (SPIO) particles have been used successfully as an intracellular contrast agent for nuclear MRI cell tracking in vivo. We present a method of detecting intracellular SPIO colloid uptake in live cells using cell magnetophoresis, with potential applications in measuring intracellular MRI contrast uptake. The method was evaluated by measuring shifts in mean and distribution of the cell magnetophoretic mobility, and the concomitant changes in population frequency of the magnetically positive cells when compared to the unmanipulated negative control. Seven different transfection agent (TA) -SPIO complexes based on dendrimer, lipid, and polyethylenimine compounds were used as test standards, in combination with 3 different cell types: mesenchymal stem cells, cardiac fibroblasts, and cultured KG-1a hematopoietic stem cells. Transfectol (TRA) -SPIO incubation resulted in the highest frequency of magnetically positive cells (>90%), and Fugene 6 (FUG) -SPIO incubation the lowest, below that when using SPIO alone. A highly regular process of cell magnetophoresis was amenable to intracellular iron mass calculations. The results were consistent in all the cell types studied and with other reports. The cell magnetophoresis depends on the presence of high-spin iron species and is therefore expected to be directly related to the cell MRI contrast level.—Jing, Y., Mal, N., Williams, P. S., Mayorga, M., Penn, M. S., Chalmers, J. J., Zborowski, M. Quantitative intracellular magnetic nanoparticle uptake measured by live cell magnetophoresis.

Jing, Ying; Mal, Niladri; Williams, P. Stephen; Mayorga, Maritza; Penn, Marc S.; Chalmers, Jeffrey J.; Zborowski, Maciej

2008-01-01

189

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

190

Shape effects of nanoparticles conjugated with cell-penetrating peptides (HIV Tat PTD) on CHO cell uptake  

PubMed Central

In order to probe the nanoparticle shape/size effect on cellular uptake, a spherical and two cylindrical nanoparticles, whose lengths were distinctively varied, were constructed by the selective crosslinking of amphiphilic block copolymer micelles. Herein, we demonstrate that, when the nanoparticles were functionalized with the protein transduction domain of human immunodeficiency virus type 1 Tat protein (HIV Tat PTD), the smaller, spherical nanoparticles had a higher rate of cell entry into Chinese Hamster Ovary (CHO) cells than did the larger, cylindrical nanoparticles. It was also found that nanoparticles were released after internalization, and that the rate of cell exit was dependent on both the nanoparticle shape and the amount of surface-bound PTD.

Zhang, Ke; Fang, Huafeng; Chen, Zhiyun; Taylor, John-Stephen A.; Wooley, Karen L.

2009-01-01

191

Manganese Nanoparticle Activates Mitochondrial Dependent Apoptotic Signaling and Autophagy in Dopaminergic Neuronal Cells  

PubMed Central

The production of man-made nanoparticles for various modern applications has increased exponentially in recent years, but the potential health effects of most nanoparticles are not well characterized. Unfortunately, in vitro nanoparticle toxicity studies are extremely limited by yet unresolved problems relating to dosimetry. In the present study, we systematically characterized manganese (Mn) nanoparticle sizes and examined the nanoparticle-induced oxidative signaling in dopaminergic neuronal cells. Differential interference contrast (DIC) microscopy and transmission electron microscopy (TEM) studies revealed that Mn nanoparticles range in size from single nanoparticles (~25 nM) to larger agglomerates when in treatment media. Manganese nanoparticles were effectively internalized in N27 dopaminergic neuronal cells, and they induced a time-dependent upregulation of the transporter protein transferrin. Exposure to 25–400 µg/mL Mn nanoparticles induced cell death in a time- and dose-dependent manner. Mn nanoparticles also significantly increased ROS, accompanied by a caspase-mediated proteolytic cleavage of proapoptotic protein kinase C? (PKC?), as well as activation loop phosphorylation. Blocking Mn nanoparticle-induced ROS failed to protect against the neurotoxic effects, suggesting the involvement of other pathways. Further mechanistic studies revealed changes in Beclin1 and LC3, indicating that Mn nanoparticles induce autophagy. Primary mesencephalic neuron exposure to Mn nanoparticles induced loss of TH positive dopaminergic neurons and neuronal processes. Collectively, our results suggest that Mn nanoparticles effectively enter dopaminergic neuronal cells and exert neurotoxic effects by activating an apoptotic signaling pathway and autophagy, emphasizing the need for assessing possible health risks associated with an increased use of Mn nanoparticles in modern applications.

Ngwa, Hilary Afeseh; Kanthasamy, Arthi; Gu, Yan; Fang, Ning; Anantharam, Vellareddy; Kanthasamy, Anumantha G.

2011-01-01

192

NKp46+ CD3+ cells: a novel nonconventional T cell subset in cattle exhibiting both NK cell and T cell features.  

PubMed

The NKp46 receptor demonstrates a high degree of lineage specificity, being expressed almost exclusively in NK cells. Previous studies have demonstrated NKp46 expression by T cells, but NKp46+ CD3+ cells are rare and almost universally associated with NKp46 acquisition by T cells following stimulation. In this study we demonstrate the existence of a population of NKp46+ CD3+ cells resident in normal bovine PBMCs that includes cells of both the ?? TCR+ and ?? TCR+ lineages and is present at a frequency of 0.1-1.7%. NKp46+ CD3+ cells express transcripts for a broad repertoire of both NKRs and TCRs and also the CD3?, DAP10, and Fc?R1? but not DAP12 adaptor proteins. In vitro functional analysis of NKp46+ CD3+ cells confirm that NKp46, CD16, and CD3 signaling pathways are all functionally competent and capable of mediating/redirecting cytolysis. However, only CD3 cross-ligation elicits IFN-? release. NKp46+ CD3+ cells exhibit cytotoxic activity against autologous Theileria parva-infected cells in vitro, and during in vivo challenge with this parasite an expansion of NKp46+ CD3+ cells was observed in some animals, indicating the cells have the potential to act as an anti-pathogen effector population. The results in this study identify and describe a novel nonconventional NKp46+ CD3+ T cell subset that is phenotypically and functionally distinct from conventional NK and T cells. The ability to exploit both NKRs and TCRs suggests these cells may fill a functional niche at the interface of innate and adaptive immune responses. PMID:24639352

Connelley, Timothy K; Longhi, Cassandra; Burrells, Alison; Degnan, Kathryn; Hope, Jayne; Allan, Alasdair J; Hammond, John A; Storset, Anne K; Morrison, W Ivan

2014-04-15

193

Manganese nanoparticle activates mitochondrial dependent apoptotic signaling and autophagy in dopaminergic neuronal cells  

SciTech Connect

The production of man-made nanoparticles for various modern applications has increased exponentially in recent years, but the potential health effects of most nanoparticles are not well characterized. Unfortunately, in vitro nanoparticle toxicity studies are extremely limited by yet unresolved problems relating to dosimetry. In the present study, we systematically characterized manganese (Mn) nanoparticle sizes and examined the nanoparticle-induced oxidative signaling in dopaminergic neuronal cells. Differential interference contrast (DIC) microscopy and transmission electron microscopy (TEM) studies revealed that Mn nanoparticles range in size from single nanoparticles ({approx} 25 nM) to larger agglomerates when in treatment media. Manganese nanoparticles were effectively internalized in N27 dopaminergic neuronal cells, and they induced a time-dependent upregulation of the transporter protein transferrin. Exposure to 25-400 {mu}g/mL Mn nanoparticles induced cell death in a time- and dose-dependent manner. Mn nanoparticles also significantly increased ROS, accompanied by a caspase-mediated proteolytic cleavage of proapoptotic protein kinase C{delta} (PKC{delta}), as well as activation loop phosphorylation. Blocking Mn nanoparticle-induced ROS failed to protect against the neurotoxic effects, suggesting the involvement of other pathways. Further mechanistic studies revealed changes in Beclin 1 and LC3, indicating that Mn nanoparticles induce autophagy. Primary mesencephalic neuron exposure to Mn nanoparticles induced loss of TH positive dopaminergic neurons and neuronal processes. Collectively, our results suggest that Mn nanoparticles effectively enter dopaminergic neuronal cells and exert neurotoxic effects by activating an apoptotic signaling pathway and autophagy, emphasizing the need for assessing possible health risks associated with an increased use of Mn nanoparticles in modern applications. -- Highlights: Black-Right-Pointing-Pointer Mn nanoparticles activate mitochondrial cell death signaling in dopaminergic neuron. Black-Right-Pointing-Pointer Mn nanoparticles activate caspase-mediated proteolytic cleavage of PKC{delta} cascade. Black-Right-Pointing-Pointer Mn nanoparticles induce autophagy in dopaminergic neuronal cells. Black-Right-Pointing-Pointer Mn nanoparticles induce loss of TH{sup +} neurons in primary mesencephalic cultures. Black-Right-Pointing-Pointer Study emphasizes neurotoxic risks of Mn nanoparticles to nigral dopaminergic system.

Afeseh Ngwa, Hilary; Kanthasamy, Arthi [Department of Biomedical Sciences, Iowa Center for Advanced Neurotoxicology, Iowa State University, Ames, IA 50011 (United States)] [Department of Biomedical Sciences, Iowa Center for Advanced Neurotoxicology, Iowa State University, Ames, IA 50011 (United States); Gu, Yan; Fang, Ning [Department of Chemistry, Iowa State University, Ames, IA 50011 (United States)] [Department of Chemistry, Iowa State University, Ames, IA 50011 (United States); Anantharam, Vellareddy [Department of Biomedical Sciences, Iowa Center for Advanced Neurotoxicology, Iowa State University, Ames, IA 50011 (United States)] [Department of Biomedical Sciences, Iowa Center for Advanced Neurotoxicology, Iowa State University, Ames, IA 50011 (United States); Kanthasamy, Anumantha G., E-mail: akanthas@iastate.edu [Department of Biomedical Sciences, Iowa Center for Advanced Neurotoxicology, Iowa State University, Ames, IA 50011 (United States)

2011-11-15

194

Salivary ?-amylase exhibits antiproliferative effects in primary cell cultures of rat mammary epithelial cells and human breast cancer cells  

PubMed Central

Background Breast cancer is one of the most diagnosed cancers in females, frequently with fatal outcome, so that new strategies for modulating cell proliferation in the mammary tissue are urgently needed. There is some, as yet inconclusive evidence that ?-amylase may constitute a novel candidate for affecting cellular growth. Methods The present investigation aimed to examine if salivary ?-amylase, an enzyme well known for the metabolism of starch and recently introduced as a stress marker, is able to exert antiproliferative effects on the growth of mammary gland epithelial cells. For this purpose, primary epithelial cultures of breast tissue from two different inbred rat strains, Fischer 344 (F344) and Lewis, as well as breast tumor cells of human origin were used. Treatment with human salivary ?-amylase was performed once daily for 2 days followed by cell counting (trypan blue assay) to determine alterations in cell numbers. Cell senescence after ?-amylase treatment was assessed by ?-galactosidase assay. Endogenous ?-amylase was detected in cells from F344 and Lewis by immunofluorescence. Results Salivary ?-amylase treatment in vitro significantly decreased the proliferation of primary cells from F344 and Lewis rats in a concentration-dependent manner. Noticeably, the sensitivity towards ?-amylase was significantly higher in Lewis cells with stronger impact on cell growth after 5 and 50 U/ml compared to F344 cells. An antiproliferative effect of ?-amylase was also determined in mammary tumor cells of human origin, but this effect varied depending on the donor, age, and type of the cells. Conclusions The results presented here indicate for the first time that salivary ?-amylase affects cell growth in rat mammary epithelial cells and in breast tumor cells of human origin. Thus, ?-amylase may be considered a novel, promising target for balancing cellular growth, which may provide an interesting tool for tumor prophylaxis and treatment.

2011-01-01

195

Adult Cardiac Progenitor Cell Aggregates Exhibit Survival Benefit Both In Vitro and In Vivo  

PubMed Central

Background A major hurdle in the use of exogenous stems cells for therapeutic regeneration of injured myocardium remains the poor survival of implanted cells. To date, the delivery of stem cells into myocardium has largely focused on implantation of cell suspensions. Methodology and Principal Findings We hypothesize that delivering progenitor cells in an aggregate form would serve to mimic the endogenous state with proper cell-cell contact, and may aid the survival of implanted cells. Microwell methodologies allow for the culture of homogenous 3D cell aggregates, thereby allowing cell-cell contact. In this study, we find that the culture of cardiac progenitor cells in a 3D cell aggregate augments cell survival and protects against cellular toxins and stressors, including hydrogen peroxide and anoxia/reoxygenation induced cell death. Moreover, using a murine model of cardiac ischemia-reperfusion injury, we find that delivery of cardiac progenitor cells in the form of 3D aggregates improved in vivo survival of implanted cells. Conclusion Collectively, our data support the notion that growth in 3D cellular systems and maintenance of cell-cell contact improves exogenous cell survival following delivery into myocardium. These approaches may serve as a strategy to improve cardiovascular cell-based therapies.

Wu, Jinhui; Peng, Michelle; Chen, Howard H.; Camci-Unal, Gulden; Bayomy, Ahmad F.; Sosnovik, David E.; Khademhosseini, Ali; Liao, Ronglih

2012-01-01

196

Comparative evaluation of novel biodegradable nanoparticles for the drug targeting to breast cancer cells.  

PubMed

Nanomedicine formulations such as biodegradable nanoparticles (nps) and liposomes offer several advantages over traditional routes of administration: due to their small size, nanocarriers are able to selectively accumulate inside tumours or inflammatory tissues, resulting in improved drug efficacy and reduced side effects. To further augment targeting ability of nanoparticles towards tumour cells, specific ligands or antibodies that selectively recognise biomarkers over-expressed on cancer cells, can be attached to the surface either by chemical bond or by hydrophilic/hydrophobic interactions. In the present work, Herceptin (HER), a monoclonal antibody (mAb) able to selectively recognise HER-2 over-expressing tumour cells (such as breast and ovarian cancer cells), was absorbed on the surface of nanoparticles through hydrophilic/hydrophobic interactions. Nps were prepared by a modified single emulsion solvent evaporation method with five different polymers: three commercial polyesters (poly(?-caprolactone) (PCL), poly (D,L-lactide) (PLA) and poly (D,L-lactide-co-.glycolide) (PLGA)) and two novel biodegradable polyesterurethanes (PURs) based on Poly(?-caprolactone) blocks, synthesised with different chain extenders (1,4-cyclohexane dimethanol (CDM) and N-Boc-serinol). Polyurethanes were introduced as matrix-forming materials for nanoparticles due to their high chemical versatility, which allows tailoring of the materials final properties by properly selecting the reagents. All nps exhibited a small size and negative surface charge, suitable for surface functionalisation with mAb through hydrophilic/hydrophobic interactions. The extent of cellular internalisation was tested on two different cell lines: MCF-7 and SK-BR-3 breast cancer cells showing a normal and a high expression of the HER-2 receptor, respectively. Paclitaxel, a model anti-neoplastic drug, was encapsulated inside all nps, and release profiles and cytotoxicity on SK-BR-3 cells were also assessed. Interestingly, PUR nps were superior to commercial polyester-based nps in terms of higher cellular internalisation and cytotoxic activity on the tested cell lines. Results obtained warrants further investigation on the application of these PUR nps for controlled drug delivery and targeting. PMID:23916461

Mattu, C; Pabari, R M; Boffito, M; Sartori, S; Ciardelli, G; Ramtoola, Z

2013-11-01

197

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...

198

Dye-sensitized solar cells based on a nanoparticle/nanotube bilayer structure and their equivalent circuit analysis  

NASA Astrophysics Data System (ADS)

Dye-sensitized solar cells (DSSCs) were prepared by capitalizing on a TiO2 bilayer structure composed of P-25 nanoparticles and freestanding crystalline nanotube arrays as photoanodes. After being subjected to sequential TiCl4 treatment and O2 plasma exposure, the bilayer photoanode was sensitized with N719 dye. DSSCs based on a 20 ?m TiO2 nanoparticle film solely and a bilayer of 13 ?m TiO2 nanoparticles and 7 ?m TiO2 nanotubes exhibited the highest power conversion efficiency, PCE, of 8.02% and 7.00%, respectively, compared to the devices made of different TiO2 thicknesses. On the basis of J-V parameter analysis acquired by equivalent circuit model simulation, in comparison to P-25 nanoparticles, charge transport in nanotubes was found to be facilitated due to the presence of advantageous nanotubular structures, while photocurrent was reduced owing to their small surface area, which in turn resulted in low dye loading, as well as the lack of cooperative effect of anatase and rutile phases.Dye-sensitized solar cells (DSSCs) were prepared by capitalizing on a TiO2 bilayer structure composed of P-25 nanoparticles and freestanding crystalline nanotube arrays as photoanodes. After being subjected to sequential TiCl4 treatment and O2 plasma exposure, the bilayer photoanode was sensitized with N719 dye. DSSCs based on a 20 ?m TiO2 nanoparticle film solely and a bilayer of 13 ?m TiO2 nanoparticles and 7 ?m TiO2 nanotubes exhibited the highest power conversion efficiency, PCE, of 8.02% and 7.00%, respectively, compared to the devices made of different TiO2 thicknesses. On the basis of J-V parameter analysis acquired by equivalent circuit model simulation, in comparison to P-25 nanoparticles, charge transport in nanotubes was found to be facilitated due to the presence of advantageous nanotubular structures, while photocurrent was reduced owing to their small surface area, which in turn resulted in low dye loading, as well as the lack of cooperative effect of anatase and rutile phases. Electronic supplementary information (ESI) available: Calculation of the porosity of nanoparticle and nanotube films, respectively. I-V curve fitting parameters. See DOI: 10.1039/c2nr11617k

Xin, Xukai; Wang, Jun; Han, Wei; Ye, Meidan; Lin, Zhiqun

2012-01-01

199

Functions of corneal endothelial cells do not change after uptake of superparamagnetic iron oxide nanoparticles.  

PubMed

To avoid donor tissue shortages, ex vivo cultured human corneal endothelial cell (HCEC) transplantation is a promising therapeutic resource. Superparamagnetic iron oxide nanoparticle (SPION) cell labeling assists HCEC transplantation by attaching the posterior corneal stroma in ex vivo animal models. However, possible functional changes of the HCECs following SPION labeling remain to be determined. In this study, we used SPIONs to label cultured rabbit CECs (RCECs) in order to observe important cell functions and the levels of cell markers. The synthetic SPIONs exhibited superparamagnetism at room temperature, with saturation magnetization of 55.4 emu/g and negligible remanence or coercivity. The ?-potential was -24.5 mV and the diameter was 101 ± 55 nm. Immunostaining demonstrated a normal density of zonula occluden-1 (ZO-1), nestin and Ki-67 at cellular junctions or in nuclei from RCECs following SPION labeling at 16 µg/ml. MTT cytotoxicity assay, homotypic adhesion assay, quantitative flow cytometric Ki-67 analysis and RCEC pump function measurement demonstrated no significant differences between the cells with or without SPION labeling (P<0.05, for all assays). Results of this study demonstrated successful labeled cultured RCECs with synthetic SPIONs. Labeled cells possessed several important characteristics required to maintain the transparency and refractive parameters of the cornea, including hexagonal cell morphology, higher cell adhesion ability and proliferative potential, cell pump function and the positive expression of several cell markers. PMID:23588968

Bi, Yan-Long; Wu, Ming-Feng; Lu, Li-Xia; Zhou, Qi; Du, Fei; Sun, Xiao-Ting; Tang, Sen-Fei; Xu, Guo-Tong

2013-06-01

200

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

2013-01-01

201

Markedly Enhanced Performance of Dye Sensitized TiO2 Nanoparticle Solar Cells via Rational Surface Treatment  

NASA Astrophysics Data System (ADS)

Dye sensitized solar cell (DSSC) was fabricated with the P-25 TiO2 nanoparticle film sensitized with N719 dye. TiCl4 treatment was found to increase the power conversion efficiency of DSSC. More importantly, subsequent treatment with O2 plasma further enhanced the efficiency, while the O2 plasma processing of an untreated TiO2 photoanode resulted in a lower efficiency. With TiCl4 and O2 plasma treatments, dye sensitized TiO2 nanoparticle solar cell with 21 ?m thick active layer illuminated under 100 mW/cm^2 exhibited a markedly enhanced power conversion efficiency of 8.35% as compared to 3.86% for untreated cells.

Scheiner, Margaret; Xin, Xukai; Lin, Zhiqun

2011-03-01

202

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

203

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

204

Comparative cytotoxicity studies of carbon-encapsulated iron nanoparticles in murine glioma cells.  

PubMed

Carbon-encapsulated iron nanoparticles (CEINs) have recently emerged as a new class of magnetic nanomaterials with a great potential for an increasing number of biomedical applications. To address the current deficient knowledge of cellular responses due to CEIN exposures, we focused on the investigation of internalization profile and resulting cytotoxic effects of CEINs (0.0001-100 ?g/ml) in murine glioma cells (GL261) in vitro. The studied CEIN samples were characterized (TEM, FT-IR, Zeta potential, Boehm titration) and examined as raw and purified nanomaterials with various surface chemistry composition. Of the four type CEINs (the mean diameter 47-56 nm) studied here, the as-synthesized raw nanoparticles (Fe@C/Fe) exhibited high cytotoxic effects on the plasma cell membrane (LDH, Calcein AM/PI) and mitochondria (MTT, JC-1) causing some pro-apoptotic evens (Annexin V/PI) in glioma cells. The effects of the purified (Fe@C) and surface-modified (Fe@C-COOH and Fe@C-(CH2)2COOH) CEINs were found in quite similar patterns; however, most of these cytotoxic events were slightly diminished compared to those induced by Fe@C/Fe. The study showed that the surface-functionalized CEINs affected the cell cycle progression in both S and G2/M phases to a greater extent compared to that of the rest of nanoparticles studied to data. Taken all together, the present results highlight the importance of the rational design of CEINs as their physicochemical features such as morphology, hydrodynamic size, impurity profiles, and especially surface characteristics are critical determinants of different cytotoxic responses. PMID:24632386

Grudzinski, Ireneusz P; Bystrzejewski, Michal; Cywinska, Monika A; Kosmider, Anita; Poplawska, Magdalena; Cieszanowski, Andrzej; Fijalek, Zbigniew; Ostrowska, Agnieszka

2014-05-01

205

Engineered nanoparticles interacting with cells: size matters.  

PubMed

With the rapid advancement of nanoscience and nanotechnology, detailed knowledge of interactions between engineered nanomaterials and cells, tissues and organisms has become increasingly important, especially in regard to possible hazards to human health. This review intends to give an overview of current research on nano-bio interactions, with a focus on the effects of NP size on their interactions with live cells. We summarize common techniques to characterize NP size, highlight recent work on the impact of NP size on active and passive cellular internalization and intracellular localization. Cytotoxic effects are also discussed. PMID:24491160

Shang, Li; Nienhaus, Karin; Nienhaus, Gerd Ulrich

2014-01-01

206

Human iNKT and MAIT cells exhibit a PLZF-dependent proapoptotic propensity that is counterbalanced by XIAP  

PubMed Central

Invariant natural killer (iNKT) T cells and mucosal-associated invariant T (MAIT) cells represent peculiar T-lymphocyte subpopulations with innate-like properties that differ from conventional T cells. iNKT are reduced in the primary immunodeficiency caused by mutations in the X-linked inhibitor of apoptosis (XIAP). By studying the mechanism of this depletion, we herein report that iNKT cells exhibit a high susceptibility to apoptosis that is not observed with conventional T cells. Elevated expression of caspases 3 and 7 accounts for the proapoptotic phenotype of iNKT cells, which is inhibited by XIAP although it exerts a moderate effect in conventional T cells. Similarly, MAIT cells exhibit a proapoptotic propensity with elevated expression of activated caspases and are decreased in XIAP-deficient individuals. Knockdown of the transcription factor PLZF/ZBTB-16, which is involved in the effector program of iNKT cells, diminishes their proapoptotic phenotype. Conversely, overexpression of PLZF/ZBTB-16 in conventional T cells leads to a proapoptotic phenotype. Our findings identify a previously unknown pathway of regulation of innate-like T-cell homeostasis depending on XIAP and PLZF. The proapoptotic feature of iNKT cells also gives a reliable explanation of their exhaustion observed in different human conditions including the XIAP immunodeficiency.

Gerart, Stephane; Siberil, Sophie; Martin, Emmanuel; Lenoir, Christelle; Aguilar, Claire; Picard, Capucine; Lantz, Olivier; Fischer, Alain; Latour, Sylvain

2013-01-01

207

Human circulating CD14+ monocytes as a source of progenitors that exhibit mesenchymal cell differentiation  

Microsoft Academic Search

Circulating CD14 monocytes are pre- cursors of phagocytes, such as macrophages and dendritic cells. Here we report primitive cells with a fibroblast-like morphology derived from human peripheral blood CD14 monocytes that can dif- ferentiate into several distinct mesenchymal cell lineages. We named this cell population monocyte- derived mesenchymal progenitor (MOMP). MOMPs were obtained in vitro from human peripheral blood mononuclear

Masataka Kuwana; Yuka Okazaki; Hiroaki Kodama; Keisuke Izumi; Hidekata Yasuoka; Yoko Ogawa; Yutaka Kawakami; Yasuo Ikeda

2003-01-01

208

Micro-Raman Spectroscopy of Silver Nanoparticle Induced Stress on Optically-Trapped Stem Cells  

PubMed Central

We report here results of a single-cell Raman spectroscopy study of stress effects induced by silver nanoparticles in human mesenchymal stem cells (hMSCs). A high-sensitivity, high-resolution Raman Tweezers set-up has been used to monitor nanoparticle-induced biochemical changes in optically-trapped single cells. Our micro-Raman spectroscopic study reveals that hMSCs treated with silver nanoparticles undergo oxidative stress at doping levels in excess of 2 µg/ml, with results of a statistical analysis of Raman spectra suggesting that the induced stress becomes more dominant at nanoparticle concentration levels above 3 µg/ml.

Bankapur, Aseefhali; Krishnamurthy, R. Sagar; Zachariah, Elsa; Santhosh, Chidangil; Chougule, Basavaraj; Praveen, Bhavishna; Valiathan, Manna; Mathur, Deepak

2012-01-01

209

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

Microsoft Academic Search

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

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

2011-01-01

210

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

211

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

2013-01-01

212

Biosynthesis of gold nanoparticles using Sargassum swartzii and its cytotoxicity effect on HeLa cells  

NASA Astrophysics Data System (ADS)

In this investigation, biological synthesis of gold nanoparticles (AuNPs) using Sargassum swartzii and its cytotoxicity against human cervical carcinoma (HeLa) cells is reported. The biological synthesis involved the reduction of chloroauric acid led to the formation of AuNPs within 5 min at 60 °C and the formation of AuNPs was confirmed using UV-vis spectrophotometer. The AuNPs were stable; spherical in shape with well-defined dimensions, and the average size of the particle is 35 nm. A zeta potential value of -27.6 mV revealed synthesized AuNPs were highly stable. The synthesized AuNPs exhibited a dose-dependent cytotoxicity against human cervical carcinoma (HeLa) cells. Furthermore, induction of apoptosis was measured by DAPI (4?,6-Diamidino-2-phenylindole dihydrochloride) staining.

Dhas, T. Stalin; Kumar, V. Ganesh; Karthick, V.; Govindaraju, K.; Shankara Narayana, T.

2014-12-01

213

Nanoparticles for Applications as Counter Electrodes of CdS Quantum Dot-Sensitized Solar Cells  

NASA Astrophysics Data System (ADS)

Cu2ZnSnS4 (CZTS) nanoparticles have been synthesized through a one-step solvothermal route, which exhibited a nearly single kesterite structure with a fundamental band gap of ˜1.54 eV. Quantum dots-sensitized solar cells were fabricated based on CZTS counter electrodes and CdS QD-sensitized TiO2 NRs photoelectrodes with various thicknesses of QD sensitization layers. The cells based on a CZTS electrode, compared with other single-layer DSSCs in this study, had the highest conversion efficiency of 0.27% (for CdS layer numbers of 9), which was obviously higher than Pt. The performance improvement was attributed to the better stability, sunlight sensitivity, and the resulting photoelectrocatalytic activity of the CZTS electrodes.

Gu, Xiuquan; Zhang, Shuang; Qiang, Yinghuai; Zhao, Yulong; Zhu, Lei

2014-07-01

214

Biosynthesis of gold nanoparticles using Sargassum swartzii and its cytotoxicity effect on HeLa cells.  

PubMed

In this investigation, biological synthesis of gold nanoparticles (AuNPs) using Sargassum swartzii and its cytotoxicity against human cervical carcinoma (HeLa) cells is reported. The biological synthesis involved the reduction of chloroauric acid led to the formation of AuNPs within 5min at 60°C and the formation of AuNPs was confirmed using UV-vis spectrophotometer. The AuNPs were stable; spherical in shape with well-defined dimensions, and the average size of the particle is 35nm. A zeta potential value of -27.6mV revealed synthesized AuNPs were highly stable. The synthesized AuNPs exhibited a dose-dependent cytotoxicity against human cervical carcinoma (HeLa) cells. Furthermore, induction of apoptosis was measured by DAPI (4',6-Diamidino-2-phenylindole dihydrochloride) staining. PMID:24934968

Dhas, T Stalin; Kumar, V Ganesh; Karthick, V; Govindaraju, K; Shankara Narayana, T

2014-12-10

215

A genetically engineered human pancreatic ? cell line exhibiting glucose-inducible insulin secretion  

PubMed Central

Despite intense efforts over the past 30 years, human pancreatic ? cell lines have not been available. Here, we describe a robust technology for producing a functional human ? cell line using targeted oncogenesis in human fetal tissue. Human fetal pancreatic buds were transduced with a lentiviral vector that expressed SV40LT under the control of the insulin promoter. The transduced buds were then grafted into SCID mice so that they could develop into mature pancreatic tissue. Upon differentiation, the newly formed SV40LT-expressing ? cells proliferated and formed insulinomas. The resulting ? cells were then transduced with human telomerase reverse transcriptase (hTERT), grafted into other SCID mice, and finally expanded in vitro to generate cell lines. One of these cell lines, EndoC-?H1, expressed many ? cell–specific markers without any substantial expression of markers of other pancreatic cell types. The cells secreted insulin when stimulated by glucose or other insulin secretagogues, and cell transplantation reversed chemically induced diabetes in mice. These cells represent a unique tool for large-scale drug discovery and provide a preclinical model for cell replacement therapy in diabetes. This technology could be generalized to generate other human cell lines when the cell type–specific promoter is available.

Ravassard, Philippe; Hazhouz, Yasmine; Pechberty, Severine; Bricout-Neveu, Emilie; Armanet, Mathieu; Czernichow, Paul; Scharfmann, Raphael

2011-01-01

216

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

217

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

218

Cytotoxicity and cell membrane depolarization induced by aluminum oxide nanoparticles in human lung epithelial cells A549  

Microsoft Academic Search

The cytotoxicity of 13 and 22 nm aluminum oxide (Al2O3) nanoparticles was investigated in cultured human bronchoalveolar carcinoma-derived cells (A549) and compared with 20 nm CeO2 and 40 nm TiO2 nanoparticles as positive and negative control, respectively. Exposure to both Al2O3 nanoparticles for 24 h at 10 and 25 µg mL doses significantly decreased cell viability compared with control. However,

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

2008-01-01

219

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

PubMed

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 Lipofectamine(TM) 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. PMID:22457592

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

220

Nanoparticle decorated anodes for enhanced current generation in microbial electrochemical cells  

Microsoft Academic Search

The development of highly efficient anode materials is critical for enhancing the current output of microbial electrochemical cells. In this study, Au and Pd nanoparticle decorated graphite anodes were developed and evaluated in a newly designed multi-anode microbial electrolysis cell (MEC). The anodes decorated with Au nanoparticles produced current densities up to 20-fold higher than plain graphite anodes by Shewanella

Yanzhen Fan; Shoutao Xu; Rebecca Schaller; Jun Jiao; Frank Chaplen; Hong Liu

2011-01-01

221

Modeling of Nanoparticle-Mediated Electric Field Enhancement Inside Biological Cells Exposed to AC Electric Fields  

Microsoft Academic Search

We present in this article the effect of alternating electric field at kilohertz (kHz) and megahertz (MHz) frequencies on the biological cells in presence and absence of nanoparticles. The induced electric field strength distribution in the region around cell membrane and nucleus envelope display different behavior at kHz and MHz frequencies. The attachment of gold nanoparticles (GNPs), especially gold nanowires

Pawan K. Tiwari; Sung Kil Kang; Gon Jun Kim; Jun Choi; A.-A. H. Mohamed; Jae Koo Lee

2009-01-01

222

Optimization of light-trapping in thin-film solar cells enhanced with plasmonic nanoparticles  

Microsoft Academic Search

Recently, thin-film solar cells enhanced with plasmonic nanoparticles have attracted much attention of the scientific community. To improve the performance of such cells, an optimization of the nanoparticle parameters such as size, surface coverage and material is performed. Based on this optimization, the role of surface plasmons is discussed and analyzed with respect to optical absorption of the photoactive layer

Yu. A. Akimov; W. S. Koh

2010-01-01

223

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

224

Differential uptake of nanoparticles by endothelial cells through polyelectrolytes with affinity for caveolae.  

PubMed

Nanoparticles (NPs) constitute an important medium for the targeted delivery of cancer therapeutics. Targeting of NPs to a specific cell type is traditionally achieved through the modification of the NP surface with peptides, aptamers, or other motifs that specifically recognize a cell-surface receptor, leading to internalization of NPs via clathrin and caveolae-mediated endocytosis. We have discovered that modifying the NP surface with anionic polyelectrolytes of varying lipophilicity can regulate the uptake of lipid NPs by endothelial and epithelial cells. Furthermore, we report the finding that synthetic polyelectrolytes composed of an aromatic sulfonic acid backbone exhibit specific affinity for caveolae of endothelial cells. By exploiting the higher expression of caveolae in endothelial cells in comparison with epithelial cells, a purely physiochemical approach to the targeted uptake of lipid NPs to endothelial cells is demonstrated. The ability to confer preferential affinity for NPs to cell surface domains by varying the charge and lipophilic characteristics of an NP surface offers a general means of achieving targeted delivery without the need for receptor-ligand-type targeting strategies. PMID:24516167

Voigt, Julia; Christensen, Jon; Shastri, V Prasad

2014-02-25

225

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

226

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

2013-10-25

227

Ultrasound associated uptake of chitosan nanoparticles in MC3T3-E1 cells  

NASA Astrophysics Data System (ADS)

Chitosan is a natural linear polysaccharide that has been well known for its applications in drug delivery system due to its unique physicochemical and biological properties. However, challenges still remain for it to become a fully realized therapeutic agent. In this study, we investigated the uptake of chitosan nanoparticles (CNP) under the ultrasound stimulation, using a model cell culture system (MC3T3-E1 mouse pre-osteoblasts). The CNP were fabricated by an ionic gelation method and were lyophilized prior to characterization and delivery to cells. Particle size and zeta potential were measured using Dynamic Light Scattering (DLS); the efficiency of chitosan complexation was measured using the ninhydrin assay. Cytotoxicity was examined by neutral red assay within 48 hours after delivery. The effect of ultrasound (US) on the efficiency of nanoparticle delivery to the MC3T3-E1 cells was examined at 1MHz and at either 1 or 2 W/cm2. Fluorescein isothiocyanate (FITC)-conjugated-CNP were used to visualize the internalized particles within the cytosol. The uptake of FITC-CNP exhibits a dose and time dependent effect, a strong FITC fluorescence was detected at the concentration of 500microg/mL under fluorescence microscope. Ultrasound assisted uptake of FITC-CNP performed a significant positive effect at 2W/cm2 with 60s of ultrasound exposure time. CNP displayed a slightly decrease in cell viability from 25microg/mL to 100microg/mL, while higher concentration of CNP facilitates the proliferation of MC3T3-E1 cells. Less than 10% of reduction in cell viability was observed for US at 1W/cm2 and 2W/cm2 with 30s and 60s of exposure time, which suggest a mild effect of US to MC3T3-E1 cell line.

Wu, Junyi

228

Recombinant Nox4 cytosolic domain produced by a cell or cell-free base systems exhibits constitutive diaphorase activity  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer A comparison of two bacterial cell and cell-free protein expression systems is presented. Black-Right-Pointing-Pointer Soluble and active truncated Nox4 proteins are produced. Black-Right-Pointing-Pointer Nox4 has a constitutive diaphorase activity which is independent of cytosolic factors. Black-Right-Pointing-Pointer Isoform Nox4B is unable to initiate the first electronic transfer step. Black-Right-Pointing-Pointer Findings contribute to the understanding of the mechanism of Nox4 oxidase activity. -- Abstract: The membrane protein NADPH (nicotinamide adenine dinucleotide phosphate) oxidase Nox4 constitutively generates reactive oxygen species differing from other NADPH oxidases activity, particularly in Nox2 which needs a stimulus to be active. Although the precise mechanism of production of reactive oxygen species by Nox2 is well characterized, the electronic transfer throughout Nox4 remains unclear. Our study aims to investigate the initial electronic transfer step (diaphorase activity) of the cytosolic tail of Nox4. For this purpose, we developed two different approaches to produce soluble and active truncated Nox4 proteins. We synthesized soluble recombinant proteins either by in vitro translation or by bacteria induction. While proteins obtained by bacteria induction demonstrate an activity of 4.4 {+-} 1.7 nmol/min/nmol when measured against iodonitro tetrazolium chloride and 20.5 {+-} 2.8 nmol/min/nmol with cytochrome c, the soluble proteins produced by cell-free expression system exhibit a diaphorase activity with a turn-over of 26 {+-} 2.6 nmol/min/nmol when measured against iodonitro tetrazolium chloride and 48 {+-} 20.2 nmol/min/nmol with cytochrome c. Furthermore, the activity of the soluble proteins is constitutive and does not need any stimulus. We also show that the cytosolic tail of the isoform Nox4B lacking the first NADPH binding site is unable to demonstrate any diaphorase activity pointing out the importance of this domain.

Nguyen, Minh Vu Chuong, E-mail: mvchuong@yahoo.fr [GREPI AGIM FRE 3405 CNRS-UJF, Universite Joseph Fourier, Grenoble (France); Zhang, Leilei [GREPI AGIM FRE 3405 CNRS-UJF, Universite Joseph Fourier, Grenoble (France)] [GREPI AGIM FRE 3405 CNRS-UJF, Universite Joseph Fourier, Grenoble (France); Lhomme, Stanislas; Mouz, Nicolas [PX'Therapeutics, MINATEC/Batiment de Haute Technologie, Grenoble (France)] [PX'Therapeutics, MINATEC/Batiment de Haute Technologie, Grenoble (France); Lenormand, Jean-Luc [HumProTher Laboratory, TheReX/TIMC-IMAG UMR 5525 CNRS UJF, Universite Joseph Fourier, UFR de Medecine, Domaine de la Merci, 38706 La Tronche (France)] [HumProTher Laboratory, TheReX/TIMC-IMAG UMR 5525 CNRS UJF, Universite Joseph Fourier, UFR de Medecine, Domaine de la Merci, 38706 La Tronche (France); Lardy, Bernard; Morel, Francoise [GREPI AGIM FRE 3405 CNRS-UJF, Universite Joseph Fourier, Grenoble (France)] [GREPI AGIM FRE 3405 CNRS-UJF, Universite Joseph Fourier, Grenoble (France)

2012-03-16

229

Large identified pyramidal cells in macaque motor and premotor cortex exhibit "thin spikes": implications for cell type classification  

PubMed Central

Recent studies have suggested that extracellular recordings of putative cortical interneurons have briefer spikes that those of pyramidal neurons, providing a means of identifying cortical cell types in recordings from awake monkeys. To test this, we investigated the spike duration of antidromically identified pyramidal tract neurons (PTNs) recorded from primary motor (M1) or ventral premotor cortex (F5) in 4 awake macaque monkeys. M1 antidromic latencies (ADLs) were skewed towards short ADLs (151 PTNs; 0.5-5.5 ms, median 1.1 ms) and significantly different from that of F5 ADLs (54 PTNs; 1.0-6.9 ms, median 2.6 ms). The duration of PTN spikes, recorded with a high pass filter of 300 Hz and measured from the negative trough to the positive peak of the spike waveform, ranged from 0.15 to 0.71 ms. Importantly, we found a positive linear correlation between ADL and spike duration in both M1 (R2=0.40, p<0.001) and F5 (R2=0.57, p<0.001). Thus PTNs with the shortest ADL (fastest axons) had the briefest spikes, and since PTN soma size is correlated with axon size and conduction velocity, it is likely that the largest pyramidal neurons (Betz cells in M1) have spikes with short durations (0.15 to 0.45 ms), which overlap heavily with those reported for putative interneurons in previous studies in non-primates. In summary, one class of physiologically identified cortical pyramidal neuron exhibits a wide variety of spike durations and the results suggest that spike duration alone may not be a reliable indicator of cell type.

Vigneswaran, G.; Kraskov, A.; Lemon, R. N.

2011-01-01

230

Mechanodelivery of nanoparticles to the cytoplasm of living cells.  

PubMed

Nanotechnology has opened up the opportunity to probe, sense, and manipulate the chemical environment of biological systems with an unprecedented level of spatiotemporal control. A major obstacle to the full realization of these novel technologies is the lack of a general, robust, and simple method for the delivery of arbitrary nanostructures to the cytoplasm of intact live cells. Here, we identify a new delivery modality, based on mechanical disruption of the plasma membrane, which efficiently mediates the delivery of nanoparticles to the cytoplasm of mammalian cells. We use two distinct execution modes, two adherent cell lines, and three sizes of semiconducting nanocrystals, or quantum dots, to demonstrate its applicability and effectiveness. As the underlying mechanism is purely physical, we anticipate that such "mechanodelivery" can be generalized to other modes of execution as well as to the cytoplasmic introduction of a structurally diverse array of functional nanomaterials. PMID:24664211

Emerson, Nyssa T; Hsia, Chih-Hao; Rafalska-Metcalf, Ilona U; Yang, Haw

2014-05-01

231

Heat shock protein expression in testis and bladder cancer cell lines exhibiting differential sensitivity to heat.  

PubMed Central

Testis cancer cells are more sensitive than bladder and most other cancer cells to chemotherapeutic drugs both in the clinic and in vitro. In this study we show that they are also more sensitive than bladder cancer cells to heat. Since heat and drug sensitivity may be related to the ability of a cell to mount a stress response, constitutive and induced levels of heat shock proteins (HSPs) in three testis and three bladder human cancer cell lines were measured using Western blotting and scanning densitometry. No correlation between constitutive levels of HSP 90 or HSP 73/72 and cellular heat sensitivity was found. However, HSP 27 levels were much lower in the testis tumour cells, suggesting that low HSP 27 expression might contribute to heat sensitivity. Protein synthesis studies using [35S]methionine indicated that, for the same heat shocks, the kinetics of synthesis and decay of HSP 90 and HSP 73/72 in 833K (the most heat sensitive testis cells) was similar to or greater than that in HT1376 (the most heat-resistant bladder cells). Both 833K and HT1376 developed thermotolerance, and this followed an increase in synthesis of HSPs. These results indicate that, although there are differences in the constitutive levels of HSPs between testis and bladder cancer cells, both cell types are capable of mounting an induced heat shock response and can develop a similar degree of thermotolerance. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6

Richards, E. H.; Hickman, J. A.; Masters, J. R.

1995-01-01

232

Fixed endothelial cells exhibit physiologically relevant nanomechanics of the cortical actin web  

NASA Astrophysics Data System (ADS)

It has been unknown whether cells retain their mechanical properties after fixation. Therefore, this study was designed to compare the stiffness properties of the cell cortex (the 50–100 nm thick zone below the plasma membrane) before and after fixation. Atomic force microscopy was used to acquire force indentation curves from which the nanomechanical cell properties were derived. Cells were pretreated with different concentrations of actin destabilizing agent cytochalasin D, which results in a gradual softening of the cell cortex. Then cells were studied ‘alive’ or ‘fixed’. We show that the cortical stiffness of fixed endothelial cells still reports functional properties of the actin web qualitatively comparable to those of living cells. Myosin motor protein activity, tested by blebbistatin inhibition, can only be detected, in terms of cortical mechanics, in living but not in fixed cells. We conclude that fixation interferes with motor proteins while maintaining a functional cortical actin web. Thus, fixation of cells opens up the prospect of differentially studying the actions of cellular myosin and actin.

Bodo Grimm, Kai; Oberleithner, Hans; Fels, Johannes

2014-05-01

233

Fixed endothelial cells exhibit physiologically relevant nanomechanics of the cortical actin web.  

PubMed

It has been unknown whether cells retain their mechanical properties after fixation. Therefore, this study was designed to compare the stiffness properties of the cell cortex (the 50-100 nm thick zone below the plasma membrane) before and after fixation. Atomic force microscopy was used to acquire force indentation curves from which the nanomechanical cell properties were derived. Cells were pretreated with different concentrations of actin destabilizing agent cytochalasin D, which results in a gradual softening of the cell cortex. Then cells were studied 'alive' or 'fixed'. We show that the cortical stiffness of fixed endothelial cells still reports functional properties of the actin web qualitatively comparable to those of living cells. Myosin motor protein activity, tested by blebbistatin inhibition, can only be detected, in terms of cortical mechanics, in living but not in fixed cells. We conclude that fixation interferes with motor proteins while maintaining a functional cortical actin web. Thus, fixation of cells opens up the prospect of differentially studying the actions of cellular myosin and actin. PMID:24786855

Grimm, Kai Bodo; Oberleithner, Hans; Fels, Johannes

2014-05-30

234

CD4+NKG2D+ T Cells Exhibit Enhanced Migratory and Encephalitogenic Properties in Neuroinflammation  

PubMed Central

Migration of encephalitogenic CD4+ T lymphocytes across the blood-brain barrier is an essential step in the pathogenesis of multiple sclerosis (MS). We here demonstrate that expression of the co-stimulatory receptor NKG2D defines a subpopulation of CD4+ T cells with elevated levels of markers for migration, activation, and cytolytic capacity especially when derived from MS patients. Furthermore, CD4+NKG2D+ cells produce high levels of proinflammatory IFN-? and IL-17 upon stimulation. NKG2D promotes the capacity of CD4+NKG2D+ cells to migrate across endothelial cells in an in vitro model of the blood-brain barrier. CD4+NKG2D+ T cells are enriched in the cerebrospinal fluid of MS patients, and a significant number of CD4+ T cells in MS lesions coexpress NKG2D. We further elucidated the role of CD4+NKG2D+ T cells in the mouse system. NKG2D blockade restricted central nervous system migration of T lymphocytes in vivo, leading to a significant decrease in the clinical and pathologic severity of experimental autoimmune encephalomyelitis, an animal model of MS. Blockade of NKG2D reduced killing of cultivated mouse oligodendrocytes by activated CD4+ T cells. Taken together, we identify CD4+NKG2D+ cells as a subpopulation of T helper cells with enhanced migratory, encephalitogenic and cytotoxic properties involved in inflammatory CNS lesion development.

Ruck, Tobias; Bittner, Stefan; Gross, Catharina C.; Breuer, Johanna; Albrecht, Stefanie; Korr, Sabrina; Gobel, Kerstin; Pankratz, Susann; Henschel, Christian M.; Schwab, Nicholas; Staszewski, Ori; Prinz, Marco; Kuhlmann, Tanja

2013-01-01

235

Middle T antigen-transformed endothelial cells exhibit an increased activity of nitric oxide synthase  

PubMed Central

Endothelioma cell lines transformed by polyoma virus middle T antigen (mTa) cause cavernous hemangiomas in syngeneic mice by recruitment of host cells. The production of nitric oxide (NO), as measured by nitrite and citrulline production, was significantly higher in mTa-transformed endothelial cells in comparison with nontransformed control cells. The maximal activity of NO synthase (NOS) was about 200-fold higher in cell lysates from the tEnd.1 endothelioma cell line than in lysates from nontransformed controls, whereas the affinity for arginine did not differ. The biochemical characterization of NOS and the study of mRNA transcripts indicate that tEnd.1 cells express both the inducible and the constitutive isoforms. NOS hyperactivity is not a simple consequence of cell transformation but needs a tissue-specific mTa expression. Since tEnd.1-conditioned medium induces NOS activity in normal endothelial cells, most likely NOS hyperactivity in endothelioma cells is attributable to the release of a soluble factor. This NOS- activating factor, which seems to be an anionic protein, could stimulate tEnd.1 cells to express NOS by an autocrine way. By the same mechanism, tEnd.1 cells could induce NOS in the neighboring endothelial cells, and NO release could play a role in the hemangioma development. Such hypothesis is confirmed by our in vivo experiments, showing that the administration of the NOS inhibitor L-canavanine to endothelioma- bearing mice significantly reduced both the volume and the relapse time of the tumor.

1995-01-01

236

Mammal-derived respiratory lipocalin allergens do not exhibit dendritic cell-activating capacity.  

PubMed

Most mammal-derived respiratory allergens belong to the lipocalin family of proteins. Determinants of their allergenic capacity are still unknown. Innate immune cells, in particular dendritic cells, have been shown to be involved in the allergenicity of some proteins. As recognition by dendritic cells is one of the few plausible mechanisms for the allergenicity of proteins, we wanted to investigate their role in the allergenicity of lipocalin allergens. Therefore, we first incubated human monocyte-derived dendritic cells with immunologically functional recombinant allergens mouse Mus m 1, dog Can f 1 and 2, cow Bos d 2, horse Equ c 1 and natural Bos d 2. Then, the surface marker expression and cytokine production of dendritic cells and their capacity to promote T cell proliferation and Th2 immune deviation in naïve CD4(+) T cells were examined in vitro. We found that near to endotoxin-free lipocalin allergens had no effect on the activation, allostimulatory capacity or cytokine production of dendritic cells. The dendritic cells could not induce immune deviation in naïve CD4(+) T cells. In contrast, lipopolysaccharide activated the dendritic cells efficiently. However, lipocalin allergens were not able to modify the lipopolysaccharide-induced responses. We conclude that an important group of mammal-derived respiratory allergens, lipocalins, appear not to be able to activate dendritic cells, a major component involved in the allergenicity of some proteins. It is conceivable that this incapacity of lipocalin allergens to arouse innate immunity may be associated with their poor capacity to induce a strong T cell response, verified in several studies. PMID:23298316

Parviainen, S; Kinnunen, T; Rytkönen-Nissinen, M; Nieminen, A; Liukko, A; Virtanen, T

2013-03-01

237

Progesterone-inducible cytokeratin 5-positive cells in luminal breast cancer exhibit progenitor properties.  

PubMed

Progestins play a deleterious role in the onset of breast cancer, yet their influence on existing breast cancer and tumor progression is not well understood. In luminal estrogen receptor (ER)- and progesterone receptor (PR)-positive breast cancer, progestins induce a fraction of cells to express cytokeratin 5 (CK5), a marker of basal epithelial and progenitor cells in the normal breast. CK5(+) cells lose expression of ER and PR and are relatively quiescent, increasing their resistance to endocrine and chemotherapy compared to intratumoral CK5(-)ER(+)PR(+) cells. Characterization of live CK5(+) cells has been hampered by a lack of means for their direct isolation. Here, we describe optical (GFP) and bioluminescent (luciferase) reporter models to quantitate and isolate CK5(+) cells in luminal breast cancer cell lines utilizing the human KRT5 gene promoter and a viral vector approach. Using this system, we confirmed that the induction of GFP(+)/CK5(+) cells is specific to progestins, is dependent on PR, can be blocked by antiprogestins, and does not occur with other steroid hormones. Progestin-induced, fluorescence-activated cell sorting-isolated CK5(+) cells had lower ER and PR mRNA, were slower cycling, and were relatively more invasive and sphere forming than their CK5(-) counterparts in vitro. Repeated progestin treatment and selection of GFP(+) cells enriched for a persistent population of CK5(+) cells, suggesting that this transition can be semi-permanent. These data support that in PR(+) breast cancers, progestins induce a subpopulation of CK5(+)ER(-)PR(-) cells with enhanced progenitor properties and have implications for treatment resistance and recurrence in luminal breast cancer. PMID:23184698

Axlund, Sunshine Daddario; Yoo, Byong Hoon; Rosen, Rachel B; Schaack, Jerome; Kabos, Peter; Labarbera, Daniel V; Sartorius, Carol A

2013-02-01

238

Quantum dots incorporated magnetic nanoparticles for imaging colon carcinoma cells  

PubMed Central

Background Engineered multifunctional nanoparticles (NPs) have made a tremendous impact on the biomedical sciences, with advances in imaging, sensing and bioseparation. In particular, the combination of optical and magnetic responses through a single particle system allows us to serve as novel multimodal molecular imaging contrast agents in clinical settings. Despite of essential medical imaging modalities and of significant clinical application, only few nanocomposites have been developed with dual imaging contrast. A new method for preparing quantum dots (QDs) incorporated magnetic nanoparticles (MNPs) based on layer-by-layer (LbL) self-assembly techniques have developed and used for cancer cells imaging. Methods Here, citrate - capped negatively charged Fe3O4 NPs were prepared and coated with positively - charged hexadecyltrimethyl ammonium bromide (CTAB). Then, thiol - capped negatively charged CdTe QDs were electrostatically bound with CTAB. Morphological, optical and magnetic properties of the fluorescent magnetic nanoparticles (FMNPs) were characterized. Prepared FMNPs were additionally conjugated with hCC49 antibodies fragment antigen binding (Fab) having binding affinity to sialylated sugar chain of TAG-72 region of LS174T cancer cells, which was prepared silkworm expression system, and then were used for imaging colon carcinoma cells. Results The prepared nanocomposites were magnetically responsive and fluorescent, simultaneously that are useful for efficient cellular imaging, optical sensing and magnetic separation. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) revealed that the particle size is around 50 nm in diameter with inner magnetic core and outer CdTe QDs core-shell structure. Cytotoxicity test of prepared FMNPs indicates high viability in Vero cells. NPs conjugated with anti cancer antibodies were successfully labeled on colon carcinoma cells (LS174) in vitro and showed significant specificity to target cells. Conclusion The present report demonstrates a simple synthesis of CdTe QDs-Fe3O4 NPs. The surface of the prepared FMNPs was enabled simple conjugation to monoclonal antibodies by electrostatic interaction. This property further extended their in vitro applications as cellular imaging contrast agents. Such labeling of cells with new fluorescent-magneto nanoprobes for living detection is of interest to various biomedical applications and has demonstrated the potential for future medical use.

2013-01-01

239

Infrared light-absorbing gold/gold sulfide nanoparticles induce cell death in esophageal adenocarcinoma.  

PubMed

Gold nanoparticles and near infrared-absorbing light are each innocuous to tissue but when combined can destroy malignant tissue while leaving healthy tissue unharmed. This study investigated the feasibility of photothermal ablation therapy for esophageal adenocarcinoma using chitosan-coated gold/gold sulfide (CS-GGS) nanoparticles. A rat esophagoduodenal anastomosis model was used for the in vivo ablation study, and three human esophageal cell lines were used to study the response of cancer cells and benign cells to near infrared light after treatment with CS-GGS. The results indicate that both cancerous tissue and cancer cells took up more gold nanoparticles and were completely ablated after exposure to near infrared light. The benign tissue and noncancerous cells showed less uptake of these nanoparticles, and remained viable after exposure to near infrared light. CS-GGS nanoparticles could provide an optimal endoluminal therapeutic option for near infrared light ablation of esophageal cancer. PMID:23818775

Li, Yan; Gobin, Andre M; Dryden, Gerald W; Kang, Xinqin; Xiao, Deyi; Li, Su Ping; Zhang, Guandong; Martin, Robert C G

2013-01-01

240

Infrared light-absorbing gold/gold sulfide nanoparticles induce cell death in esophageal adenocarcinoma  

PubMed Central

Gold nanoparticles and near infrared-absorbing light are each innocuous to tissue but when combined can destroy malignant tissue while leaving healthy tissue unharmed. This study investigated the feasibility of photothermal ablation therapy for esophageal adenocarcinoma using chitosan-coated gold/gold sulfide (CS-GGS) nanoparticles. A rat esophagoduodenal anastomosis model was used for the in vivo ablation study, and three human esophageal cell lines were used to study the response of cancer cells and benign cells to near infrared light after treatment with CS-GGS. The results indicate that both cancerous tissue and cancer cells took up more gold nanoparticles and were completely ablated after exposure to near infrared light. The benign tissue and noncancerous cells showed less uptake of these nanoparticles, and remained viable after exposure to near infrared light. CS-GGS nanoparticles could provide an optimal endoluminal therapeutic option for near infrared light ablation of esophageal cancer.

Li, Yan; Gobin, Andre M; Dryden, Gerald W; Kang, Xinqin; Xiao, Deyi; Li, Su Ping; Zhang, Guandong; Martin, Robert CG

2013-01-01

241

CMTM5 exhibits tumor suppressor activity through promoter methylation in oral squamous cell carcinoma.  

PubMed

Oral squamous cell carcinoma (OSCC) is one of the most common types of malignancies in the head and neck region. CKLF-like MARVEL transmembrane domain-containing member 5 (CMTM5) has been recently implicated as a tumor suppressor gene in several cancer types. Herein, we examined the expression and function of CMTM5 in oral squamous cell carcinoma. CMTM5 was down-regulated in oral squamous cell lines and tumor samples from patients with promoter methylation. Treatment with the demethylating agent 5-aza-2'-deoxycytidine restored CMTM5 expression. In the OSCC cell lines CAL27 and GNM, the ectopic expression of CMTM5-v1 strongly inhibited cell proliferation and migration and induced apoptosis. In addition, CMTM5-v1 inhibited tumor formation in vivo. Therefore, CMTM5 might act as a putative tumor suppressor gene through promoter methylation in oral squamous cell carcinoma. PMID:24721428

Zhang, Heyu; Nan, Xu; Li, Xuefen; Chen, Yan; Zhang, Jianyun; Sun, Lisha; Han, Wenlin; Li, Tiejun

2014-05-01

242

Manganese-impregnated mesoporous silica nanoparticles for signal enhancement in MRI cell labelling studies.  

PubMed

Mesoporous silica nanoparticles (MSNs) are used in drug delivery and cell tracking applications. As Mn(2+) is already implemented as a "positive" cell contrast agent in preclinical imaging procedures (in the form of MnCl2 for neurological studies), the introduction of Mn in the porous network of MSNs would allow labelling cells and tracking them using MRI. These particles are in general internalized in endosomes, an acidic environment with high saline concentration. In addition, the available MSN porosity could also serve as a carrier to deliver medical/therapeutic substances through the labelled cells. In the present study, manganese oxide was introduced in the porous network of MCM-48 silica nanoparticles (Mn-M48SNs). The particles exhibit a narrow size distribution (~140 nm diam.) and high porosity (~60% vol.), which was validated after insertion of Mn. The resulting Mn-M48SNs were characterized by TEM, N2 physisorption, and XRD. Evidence was found with H2-TPR, and XPS characterization, that Mn(II) is the main oxidation state of the paramagnetic species after suspension in water, most probably in the form of Mn-OOH. The colloidal stability as a function of time was confirmed by DLS in water, acetate buffer and cell culture medium. In NMR data, no significant evidence of Mn(2+) leaching was found in Mn-M48SNs in acidic water (pH 6), up to 96 hours after suspension. High longitudinal relaxivity values of r1 = 8.4 mM(-1) s(-1) were measured at 60 MHz and 37 °C, with the lowest relaxometric ratios (r2/r1 = 2) reported to date for a Mn-MSN system. Leukaemia cells (P388) were labelled with Mn-M48SNs and nanoparticle cell internalization was confirmed by TEM. Finally, MRI contrast enhancement provided by cell labelling with escalated incubation concentrations of Mn-M48SNs was quantified at 1 T. This study confirmed the possibility of efficiently confining Mn into M48SNs using incipient wetness, while maintaining an open porosity and relatively high pore volume. Because these Mn-labelled M48SNs express strong "positive" contrast media properties at low concentrations, they are potentially applicable for cell tracking and drug delivery methodologies. PMID:24178890

Guillet-Nicolas, Rémy; Laprise-Pelletier, Myriam; Nair, Mahesh M; Chevallier, Pascale; Lagueux, Jean; Gossuin, Yves; Laurent, Sophie; Kleitz, Freddy; Fortin, Marc-André

2013-12-01

243

Resolving Sub-Diffraction Limit Encounters in Nanoparticle Tracking Using Live Cell Plasmon Coupling Microscopy  

PubMed Central

We use plasmon coupling between individual gold nanoparticle labels to monitor sub-diffraction limit distances in live cell nanoparticle tracking experiments. While the resolving power of our optical microscope is limited to ~500 nm, we improve this by more than an order of magnitude by detecting plasmon coupling between individual gold nanoparticle labels using a ratiometric detection scheme. We apply this plasmon coupling microscopy to resolve the interparticle separations during individual encounters of gold nanoparticle labeled fibronectin-integrin complexes in living HeLa cells.

Rong, Guoxin; Wang, Hongyun; Skewis, Lynell R.; Reinhard, Bjorn M.

2009-01-01

244

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

245

Selective Cell Targeting with Light-Absorbing Microparticles and Nanoparticles  

PubMed Central

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 mechanism of light-particle interaction was investigated by nanosecond time-resolved microscopy and by thermal modeling. The extent of light-induced damage was investigated by cell lethality, by cell membrane permeability, and by protein inactivation. Strong particle size dependence was found for these interactions. A technique based on light to target endogenous particles is already being exploited to treat pigmented cells in dermatology and ophthalmology. With exogenous particles, phamacokinetics and biodistribution studies are needed before the method can be evaluated against photodynamic therapy for cancer treatment. However, particles are unique, unlike photosensitizers, in that they can remain stable and inert in cells for extended periods. Thus they may be particularly useful for prelabeling cells in engineered tissue before implantation. Subsequent irradiation with laser pulses will allow control of the implanted cells (inactivation or modulation) in a noninvasive manner.

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

2003-01-01

246

Antioxidant activity of Vaccinium stamineum: exhibition of anticancer capability in human lung and leukemia cells.  

PubMed

Fruit of deerberry [Vaccinium stamineum L.] were evaluated for their antioxidant capacity and anticancer properties in JB6 P (+) mouse epidermal cells, human lung and leukemia cells. Deerberries contain potent free radical scavenging activities. Pretreatment of JB6 P (+) mouse epidermal cells with deerberry fruit extracts produced an inhibition on the activation of activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) induced by either 12- O-tetradecanoylphorbol 13-acetate (TPA) or ultraviolet-B (UVB). Deerberry fruit extracts also blocked TPA- or UVB-induced phosphorylation of ERKs and MEK 1/2, two upstream regulators of AP-1 and inhibited proliferation of human leukemia HL-60 cancer cells and human lung epithelial cancer A549 cells and induced apoptosis of HL-60 cells. These results suggest that the inhibition of TPA- or UVB-induced AP-1 and NF-kappaB activity, inhibition of HL-60 cells and cancer A549 cells proliferation and induction of apoptotic in human leukemia HL-60 cancer cells may be mediated through the ERKs and MEK 1/2 signal pathway. PMID:17394101

Wang, Shiow Y; Feng, Rentian; Bowman, Linda; Lu, Yongju; Ballington, James R; Ding, Min

2007-05-01

247

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

248

Developmental factor IRF6 exhibits tumor suppressor activity in squamous cell carcinomas  

PubMed Central

The transcription factor interferon regulatory factor 6 (IRF6) regulates craniofacial development and epidermal proliferation. We recently showed that IRF6 is a component of a regulatory feedback loop that controls the proliferative potential of epidermal cells. IRF6 is transcriptionally activated by p63 and induces its proteasome-mediated down-regulation, thereby limiting keratinocyte proliferative potential. We hypothesized that IRF6 may also be involved in skin carcinogenesis. Hence, we analyzed IRF6 expression in a large series of squamous cell carcinomas (SCCs) and found a strong down-regulation of IRF6 that correlated with tumor invasive and differentiation status. IRF6 down-regulation in SCC cell lines and primary tumors correlates with methylation on a CpG dinucleotide island located in its promoter region. To identify the molecular mechanisms regulating IRF6 potential tumor suppressive activity, we performed a genome-wide analysis by combining ChIP sequencing for IRF6 binding sites and gene expression profiling in primary human keratinocytes after siRNA-mediated IRF6 depletion. We observed dysregulation of cell cycle-related genes and genes involved in differentiation, cell adhesion, and cell–cell contact. Many of these genes were direct IRF6 targets. We also performed in vitro invasion assays showing that IRF6 down-regulation promotes invasive behavior and that reintroduction of IRF6 into SCC cells strongly inhibits cell growth. These results indicate a function for IRF6 in suppression of tumorigenesis in stratified epithelia.

Botti, Elisabetta; Spallone, Giulia; Moretti, Francesca; Marinari, Barbara; Pinetti, Valentina; Galanti, Sergio; De Meo, Paolo D'Onorio; De Nicola, Francesca; Ganci, Federica; Castrignano, Tiziana; Pesole, Graziano; Chimenti, Sergio; Guerrini, Luisa; Fanciulli, Maurizio; Blandino, Giovanni; Karin, Michael; Costanzo, Antonio

2011-01-01

249

Bridged polysilsesquioxanes: Hybrid organic-inorganic materials as fuel cell polyelectrolyte membranes and functional nanoparticles  

NASA Astrophysics Data System (ADS)

This dissertation describes the design, fabrication, and characterization of organic-inorganic hybrid materials. Several classes of bridged polysilsesquioxanes are presented. The first class is a membrane material suitable for fuel cell technology as a proton conducting polyelectrolyte. The second class includes hybrid nanoparticles for display device applications and chromatographic media. Chapter 1 is an introduction to hybrid organic-inorganic materials. Sol-gel chemistry is discussed, followed by a survey of prominent examples of silica hybrids. Examples of physical organic-silica blends and covalent organo-silicas, including ORMOCERSRTM, polyhedral oligomeric silsesquioxanes, and bridged polysilsesquioxanes are discussed. Bridged polysilsesquioxanes are described in great detail. Monomer synthesis, sol-gel chemistry, processing, characterization, and physical properties are included. Chapter 2 describes the design of polyelectrolyte bridged polysilsesquioxane membranes. The materials contain covalently bound sulfonic acid groups originating from the corresponding disulfides. These organic-inorganic hybrid materials integrate a network supporting component which is systematically changed to fine-tune their physical properties. The membranes are characterized as PEM fuel cell electrolytes, where proton conductivities of 4-6 mS cm-1 were measured. In Chapter 3 techniques for the preparation of bridged polysilsesquioxane nanoparticles are described. An inverse water-in-oil microemulsion polymerization method is developed to prepare cationic nanoparticles, including viologen-bridged materials with applications in electrochromic display devices. An aqueous ammonia system is used to prepare neutral nanoparticles containing hydrocarbon bridging groups, which have potential applications as chromatographic media. Chapter 4 describes electrochromic devices developed in collaboration with the Heflin group of Virginia Tech, which incorporate viologen bridged nanoparticles described in Chapter 3. The devices are prepared via the layer-by-layer deposition technique and characterized by voltammetry and transmission spectroscopy. Contrast ratios between yellow and violet states were 45-50% with switching times of 3-3.5 seconds. Finally, Appendix I describes the resolution of racemic 3,3.3',3'-Tetramethyl-1,1"-spirobisindane-5,5',6,6'-tetrol by diastereomeric complex formation with (8S,9R)-(-)-N-benzylcinchonidinium chloride. Enantiomerically pure bisspirocatechol is used to prepare a chiral polymer, which exhibits differences in solid state packing from polymer made with the racemic monomer. Preliminary results on the use of the chiral polymer in enantioselective membrane separations technology are described.

Khiterer, Mariya

250

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

251

Morphological effect of oscillating magnetic nanoparticles in killing tumor cells  

PubMed Central

Forced oscillation of spherical and rod-shaped iron oxide magnetic nanoparticles (MNPs) via low-power and low-frequency alternating magnetic field (AMF) was firstly used to kill cancer cells in vitro. After being loaded by human cervical cancer cells line (HeLa) and then exposed to a 35-kHz AMF, MNPs mechanically damaged cell membranes and cytoplasm, decreasing the cell viability. It was found that the concentration and morphology of the MNPs significantly influenced the cell-killing efficiency of oscillating MNPs. In this preliminary study, when HeLa cells were pre-incubated with 100 ?g/mL rod-shaped MNPs (rMNP, length of 200?±?50 nm and diameter of 50 to 120 nm) for 20 h, MTT assay proved that the cell viability decreased by 30.9% after being exposed to AMF for 2 h, while the cell viability decreased by 11.7% if spherical MNPs (sMNP, diameter of 200?±?50 nm) were used for investigation. Furthermore, the morphological effect of MNPs on cell viability was confirmed by trypan blue assay: 39.5% rMNP-loaded cells and 15.1% sMNP-loaded cells were stained after being exposed to AMF for 2 h. It was also interesting to find that killing tumor cells at either higher (500 ?g/mL) or lower (20 ?g/mL) concentration of MNPs was less efficient than that achieved at 100 ?g/mL concentration. In conclusion, the relatively asymmetric morphological rod-shaped MNPs can kill cancer cells more effectively than spherical MNPs when being exposed to AMF by virtue of their mechanical oscillations.

2014-01-01

252

Morphological effect of oscillating magnetic nanoparticles in killing tumor cells  

NASA Astrophysics Data System (ADS)

Forced oscillation of spherical and rod-shaped iron oxide magnetic nanoparticles (MNPs) via low-power and low-frequency alternating magnetic field (AMF) was firstly used to kill cancer cells in vitro. After being loaded by human cervical cancer cells line (HeLa) and then exposed to a 35-kHz AMF, MNPs mechanically damaged cell membranes and cytoplasm, decreasing the cell viability. It was found that the concentration and morphology of the MNPs significantly influenced the cell-killing efficiency of oscillating MNPs. In this preliminary study, when HeLa cells were pre-incubated with 100 ?g/mL rod-shaped MNPs (rMNP, length of 200 ± 50 nm and diameter of 50 to 120 nm) for 20 h, MTT assay proved that the cell viability decreased by 30.9% after being exposed to AMF for 2 h, while the cell viability decreased by 11.7% if spherical MNPs (sMNP, diameter of 200 ± 50 nm) were used for investigation. Furthermore, the morphological effect of MNPs on cell viability was confirmed by trypan blue assay: 39.5% rMNP-loaded cells and 15.1% sMNP-loaded cells were stained after being exposed to AMF for 2 h. It was also interesting to find that killing tumor cells at either higher (500 ?g/mL) or lower (20 ?g/mL) concentration of MNPs was less efficient than that achieved at 100 ?g/mL concentration. In conclusion, the relatively asymmetric morphological rod-shaped MNPs can kill cancer cells more effectively than spherical MNPs when being exposed to AMF by virtue of their mechanical oscillations.

Cheng, Dengfeng; Li, Xiao; Zhang, Guoxin; Shi, Hongcheng

2014-04-01

253

Molecular detection of biomarkers and cells using magnetic nanoparticles and diagnostic magnetic resonance.  

PubMed

The rapid and sensitive detection of molecular targets such as proteins, cells, and pathogens in biological specimens is a major focus of ongoing medical research, as it could promote early disease diagnoses and the development of tailored therapeutic strategies. Magnetic nanoparticles (MNP) are attractive candidates for molecular biosensing applications because most biological samples exhibit negligible magnetic susceptibility, and thus the background against which measurements are made is extremely low. Numerous magnetic detection methods exist, but sensing based on magnetic resonance effects has successfully been developed into a general detection platform termed diagnostic magnetic resonance (DMR). DMR technology encompasses numerous assay configurations and sensing principles, and to date magnetic nanoparticle biosensors have been designed to detect a wide range of targets including DNA/mRNA, proteins, enzymes, drugs, pathogens, and tumor cells with exquisite sensitivity. The core principle behind DMR is the use of MNP as proximity sensors that modulate the transverse relaxation time of neighboring water molecules. This signal can be quantified using MR imagers or NMR relaxometers, including miniaturized NMR detector chips that are capable of performing highly sensitive measurements on microliter sample volumes and in a multiplexed format. The speed, sensitivity, and simplicity of the DMR principle, coupled with further advances in NMR biosensor technology should provide a high-throughput, low-cost, and portable platform for large-scale parallel sensing in clinical and point-of-care settings. PMID:21424441

Haun, Jered B; Yoon, Tae-Jong; Lee, Hakho; Weissleder, Ralph

2011-01-01

254

The Interstitial Interface within the Renal Stem/Progenitor Cell Niche Exhibits an Unique Microheterogeneous Composition  

PubMed Central

Repair of parenchyma by stem/progenitor cells is seen as a possible alternative to cure acute and chronic renal failure in future. To learn about this therapeutic purpose, the formation of nephrons during organ growth is under focus of present research. This process is triggered by numerous morphogenetic interactions between epithelial and mesenchymal cells within the renal stem/progenitor cell niche. Recent data demonstrate that an astonishingly wide interstitial interface separates both types of stem/progenitor cells probably controlling coordinated cell-to-cell communication. Since conventional fixation by glutaraldehyde (GA) does not declare in transmission electron microscopy the spatial separation, improved contrasting procedures were applied. As a consequence, the embryonic cortex of neonatal rabbit kidneys was fixed in solutions containing glutaraldehyde in combination with cupromeronic blue, ruthenium red or tannic acid. To obtain a comparable view to the renal stem/progenitor cell niche, the specimens had to be orientated along the cortico-medullary axis of lining collecting ducts. Analysis of tissue samples fixed with GA, in combination with cupromeronic blue, demonstrates demasked extracellular matrix. Numerous braces of proteoglycans cover, as well, the basal lamina of epithelial stem/progenitor cells as projections of mesenchymal stem/progenitor cells crossing the interstitial interface. Fixation with GA containing ruthenium red or tannic acid illustrates strands of extracellular matrix that originate from the basal lamina of epithelial stem/progenitor cells and line through the interstitial interface. Thus, for the first time, improved contrasting techniques make it possible to analyze in detail a microheterogeneous composition of the interstitial interface within the renal stem/progenitor cell niche.

Minuth, Will W.; Denk, Lucia

2013-01-01

255

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

256

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

257

Bacterial exopolysaccharide based magnetic nanoparticles: a versatile nanotool for cancer cell imaging, targeted drug delivery and synergistic effect of drug and hyperthermia mediated cancer therapy.  

PubMed

Microbial exopolysaccharides (EPSs) are highly heterogeneous polymers produced by fungi and bacteria that have garnered considerable attention and have remarkable potential in various fields, including biomedical research. The necessity of biocompatible materials to coat and stabilize nanoparticles is highly recommended for successful application of the same in biomedical regime. In our study we have coated magnetic nanoparticles (MNPs) with two bacterial EPS-mauran (MR) and gellan gum (GG). The biocompatibility of EPS coated MNPs was enhanced and we have made it multifunctional by attaching targeting moiety, folate and with encapsulation of a potent anticancerous drug, 5FU. We have conjugated an imaging moiety along with nanocomposite to study the effective uptake of nanoparticles. It was also observed that the dye labeled folate targeted nanoparticles could effectively enter into cancer cells and the fate of nanoparticles was tracked with Lysotracker. The biocompatibility of EPS coated MNPs and synergistic effect of magnetic hyperthermia and drug for enhanced antiproliferation of cancer cells was also evaluated. More than 80% of cancer cells was killed within a period of 60 min when magnetic hyperthermia (MHT) was applied along with drug loaded EPS coated MNPs, thus signifying the combined effect of drug loaded MNPs and MHT. Our results suggests that MR and GG coated MNPs exhibited excellent biocompatibility with low cell cytotoxicity, high therapeutic potential, and superparamagnetic behavior that can be employed as prospective candidates for bacterial EPS based targeted drug delivery, cancer cell imaging and for MHT for killing cancer cells within short period of time. PMID:24749386

Sivakumar, Balasubramanian; Aswathy, Ravindran Girija; Sreejith, Raveendran; Nagaoka, Yutaka; Iwai, Seiki; Suzuki, Masashi; Fukuda, Takahiro; Hasumura, Takashi; Yoshida, Yasuhiko; Maekawa, Toru; Sakthikumar, Dasappan Nair

2014-06-01

258

Isolation from a human MDR lung cell line of multiple clonal subpopulations which exhibit significantly different drug resistance.  

PubMed

The heterogeneous nature of an adriamycin-selected human MDR squamous lung cell line, DLKP-A, was investigated by isolating and characterising 9 of its clonal subpopulations. The DLKP-A cell line exhibits resistance to the classical MDR drugs, overexpresses P-glycoprotein and displays reduced topoisomerase II amounts. The clonal cell lines exhibit a wide range of resistance extents, with the most resistant clone displaying 9 times the extent of adriamycin resistance observed in the least resistant clone. A number of clones exhibit sensitivity to the concentration of adriamycin in which the parental cell line was selected, possibly indicating cooperation between the more and less resistant cells. Detailed analysis of 4 of the clonal subpopulations revealed broadly similar drug resistance mechanisms. Alterations in expression of the MDR-associated genes MDR1 and Topo IIalpha were observed, with no detectable changes in the expression of MDR3, MRP, GSTpi, Topo IIbeta, Topo I and CYP1A1 noted. However, each clonal cell line displayed a distinct extent of expression of MDR1 and Topo IIalpha and further characterisation of the clones indicated that other modes of drug resistance may exist in at least one of the cell lines. In particular, 2 of the clones (DLKPA6B and DLKPA11B) which have almost identical drug resistance profiles appear to have quite different mechanisms of resistance. The clonal subpopulations possess individual growth rates, amounts of adriamycin accumulation and susceptibility to toxicity-enhancement by MDR-modulating agents. It was possible to generate a cell line with a drug toxicity profile similar to DLKP-A by mixing some of the clonal subpopulations. Our results provide evidence of heterogeneity within an MDR human cell population with respect to resistance and expression of MDR-associated genes. PMID:9180164

Heenan, M; O'Driscoll, L; Cleary, I; Connolly, L; Clynes, M

1997-05-29

259

Carbon nanoparticles for gene transfection in eukaryotic cell lines.  

PubMed

For the first time, oxygen terminated cellulose carbon nanoparticles (CCN) was synthesised and applied in gene transfection of pIRES plasmid. The CCN was prepared from catalytic of polyaniline by chemical vapour deposition techniques. This plasmid contains one gene that encodes the green fluorescent protein (GFP) in eukaryotic cells, making them fluorescent. This new nanomaterial and pIRES plasmid formed ?-stacking when dispersed in water by magnetic stirring. The frequencies shift in zeta potential confirmed the plasmid strongly connects to the nanomaterial. In vitro tests found that this conjugation was phagocytised by NG97, NIH-3T3 and A549 cell lines making them fluorescent, which was visualised by fluorescent microscopy. Before the transfection test, we studied CCN in cell viability. Both MTT and Neutral Red uptake tests were carried out using NG97, NIH-3T3 and A549 cell lines. Further, we use metabolomics to verify if small amounts of nanomaterial would be enough to cause some cellular damage in NG97 cells. We showed two mechanisms of action by CCN-DNA complex, producing an exogenous protein by the transfected cell and metabolomic changes that contributed by better understanding of glioblastoma, being the major finding of this work. Our results suggested that this nanomaterial has great potential as a gene carrier agent in non-viral based therapy, with low cytotoxicity, good transfection efficiency, and low cell damage in small amounts of nanomaterials in metabolomic tests. PMID:24863237

Zanin, H; Hollanda, L M; Ceragioli, H J; Ferreira, M S; Machado, D; Lancellotti, M; Catharino, R R; Baranauskas, V; Lobo, A O

2014-06-01

260

Influences of Au nanoparticle density on the performance of GaAs solar cells  

NASA Astrophysics Data System (ADS)

The influence of the Au nanoparticle density on the performance of single-junction GaAs solar cells has been investigated. The single-junction GaAs solar cells are grown on (100) GaAs substrates by using a low-pressure metalorganic chemical vapor deposition (MOCVD) system. Au nanoparticles are dispersed on the surfaces of the cells by micro-pipetted casting and the density of the dispersed nanoparticles varies from 4.7 × 109 to 4.3 × 1010 cm-2. The conversion efficiencies of the GaAs solar cells are observed to depend strongly on the Au nanoparticle densities. For Au nanoparticle densities lower than 2.8 × 1010 cm-2, the conversion efficiency improvement of the GaAs solar cells mainly originates from the antireflection coating effect. In contrast, for the sample with a Au nanoparticle density of 2.8 × 1010 cm-2, the antireflection effect decreases due to the shadow effect and the local field enhancement effect due to the Au nanoparticles starts to be effective. The GaAs solar cell with a Au nanoparticle density of 1.9 × 1010 cm-2 shows a maximum conversion enhancement compared to that of the reference sample.

Lam, Nguyen Dinh; Kim, Youngjo; Kim, Kangho; Lee, Jaejin

2014-03-01

261

Galactosylated chitosan oligosaccharide nanoparticles for hepatocellular carcinoma cell-targeted delivery of adenosine triphosphate.  

PubMed

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. PMID:23899789

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

2013-01-01

262

Enhancing light trapping properties of thin film solar cells by plasmonic effect of silver nanoparticles.  

PubMed

The preparation of thin film silicon solar cells containing Ag nanoparticles is reported in this article. Ag nanoparticles were deposited on fluorine doped tin oxide coated glass substrates by the evaporation and condensation method. a-Si:H solar cells were deposited on these substrates by cluster type plasma enhanced chemical vapor deposition. We discuss the double textured surface effect with respect to both the surface morphology of the substrate and the plasmonic effect of the Ag nanoparticles. Ag nanoparticles of various sizes from 10 to 100 nm were deposited. The haze values of the Ag embedded samples increased with increasing particle size whereas the optical transmittance decreased at the same conditions. The solar cell with the 30 nm size Ag nanoparticles showed a short circuit current density of 12.97 mA/cm2, which is 0.53 mA/cm2 higher than that of the reference solar cell without Ag nanoparticles, and the highest quantum efficiency for wavelengths from 550 to 800 nm. When 30 nm size nanoparticles were employed, the conversion efficiency of the solar cell was increased from 6.195% to 6.696%. This study reports the application of the scattering effect of Ag nanoparticles for the improvement of the conversion efficiency of amorphous silicon solar cells. PMID:24266153

Jung, Junhee; Ha, Kyungyeon; Cho, Jaehyun; Ahn, Shihyun; Park, Hyeongsik; Hussain, Shahzada Qamar; Choi, Mansoo; Yi, Junsin

2013-12-01

263

Cytotoxicity of nickel zinc ferrite nanoparticles on cancer cells of epithelial origin  

PubMed Central

In this study, in vitro cytotoxicity of nickel zinc (NiZn) ferrite nanoparticles against human colon cancer HT29, breast cancer MCF7, and liver cancer HepG2 cells was examined. The morphology, homogeneity, and elemental composition of NiZn ferrite nanoparticles were investigated by scanning electron microscopy, transmission electron microscopy, and energy dispersive X-ray spectroscopy, respectively. The exposure of cancer cells to NiZn ferrite nanoparticles (15.6–1,000 ?g/mL; 72 hours) has resulted in a dose-dependent inhibition of cell growth determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The quantification of caspase-3 and -9 activities and DNA fragmentation to assess the cell death pathway of the treated cells showed that both were stimulated when exposed to NiZn ferrite nanoparticles. Light microscopy examination of the cells exposed to NiZn ferrite nanoparticles demonstrated significant changes in cellular morphology. The HepG2 cells were most prone to apoptosis among the three cells lines examined, as the result of treatment with NiZn nanoparticles. In conclusion, NiZn ferrite nanoparticles are suggested to have potential cytotoxicity against cancer cells.

Al-Qubaisi, Mothanna Sadiq; Rasedee, Abdullah; Flaifel, Moayad Husein; Ahmad, Sahrim HJ; Hussein-Al-Ali, Samer; Hussein, Mohd Zobir; Eid, Eltayeb EM; Zainal, Zulkarnain; Saeed, Mohd; Ilowefah, Muna; Fakurazi, Sharida; Isa, Norhaszalina Mohd; Zowalaty, Mohamed Ezzat El

2013-01-01

264

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

PubMed

The present work demonstrates that Cy5.5 conjugated Fe(3)O(4)/SiO(2) 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. PMID:22575830

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

2012-08-01

265

Effects of titanium dioxide nanoparticles in human gastric epithelial cells in vitro.  

PubMed

Manufacturing or using nanomaterials may result in exposure of workers to nanoparticles. Potential routes of exposure include skin, lung and gastrointestinal tract. The lack of health-based standards for nanomaterials combined with their increasing use in many different workplaces and products emphasize the need for a reliable temporary risk assessment tool. Therefore, the aim of this work was to explore the effects of different doses of titanium dioxide nanoparticles on human gastric epithelial cells in vitro. We analyzed proliferation by MTT assay, apoptosis by Tunel, migration by injury assay, oxidative stress by determining GSH/GSSG ratio and DNA damage by Comet assay on nanoparticle-treated AGS human gastric epithelial cell line in comparison to controls. We show and discuss the tumor-like phenotypes of nanoparticles-exposed AGS cells in vitro, as increased proliferation and decreased apoptosis. Our results demonstrate for the first time that nanoparticles induce tumor-like phenotypes in human gastric epithelial cells. PMID:24051123

Botelho, Monica Catarina; Costa, Carla; Silva, Susana; Costa, Solange; Dhawan, Alok; Oliveira, Paula A; Teixeira, João P

2014-02-01

266

Active targeting of cancer cells using folic acid-conjugated platinum nanoparticles  

NASA Astrophysics Data System (ADS)

Interaction of nanoparticles with human cells is an interesting topic for understanding toxicity and developing potential drug candidates. Water soluble platinum nanoparticles were synthesized via reduction of hexachloroplatinic acid using sodium borohydride in the presence of capping agents. The bioactivity of folic acid and poly(vinyl pyrrolidone) capped platinum nanoparticles (Pt-nps) has been investigated using commercially available cell lines. In the cell viability experiments, PVP-capped nanoparticles were found to be less toxic (>80% viability), whereas, folic acid-capped platinum nanoparticles showed a reduced viability down to 24% after 72 h of exposure at a concentration of 100 ?g ml-1 for MCF7 breast cancer cells. Such toxicity, combined with the possibility to incorporate functional organic molecules as capping agents, can be used for developing new drug candidates.

Teow, Yiwei; Valiyaveettil, Suresh

2010-12-01

267

Gold nanoparticles explore cells: Cellular uptake and their use as intracellular probes.  

PubMed

Understanding uptake of nanomaterials by cells and their use for intracellular sensing is important for studying their interaction and toxicology as well as for obtaining new biological insight. Here, we investigate cellular uptake and intracellular dynamics of gold nanoparticles and demonstrate their use in reporting chemical information from the endocytotic pathway and cytoplasm. The intracellular gold nanoparticles serve as probes for surface-enhanced Raman spectroscopy (SERS) allowing for biochemical characterisation of their local environment. In particular, in this work we compare intracellular SERS using non-functionalised and functionalised nanoparticles in their ability to segregate different but closely related cell phenotypes. The results indicate that functionalised gold nanoparticles are more efficient in distinguishing between different types of cells. Our studies pave the way for understanding the uptake of gold nanoparticles and their utilisation for SERS to give rise to a greater biochemical understanding in cell-based therapies. PMID:24583117

Huefner, Anna; Septiadi, Dedy; Wilts, Bodo D; Patel, Imran I; Kuan, Wei-Li; Fragniere, Alexandra; Barker, Roger A; Mahajan, Sumeet

2014-07-01

268

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

2013-04-01

269

Tumor necrosis factor negative bone marrow-derived dendritic cells exhibit deficient IL10 expression  

Microsoft Academic Search

The effective maturation of dendritic cells (DC) is complex and highly regulated and requires the presence of a variety of signals. Tumor necrosis factor (TNF) and its receptors or innate pattern recognition receptors such as the toll-like receptors have been shown to contribute to this process. DC derived from bone marrow cells in the presence of granulocyte\\/macrophage colony-stimulating factor can

Alicia Roomberg; Jessica Kling; Phillip Fromm; Heinrich Körner

2010-01-01

270

Microvascular Endothelial Cells Exhibit Optimal Aspect Ratio for Minimizing Flow Resistance  

Microsoft Academic Search

A recent analytical solution of the three-dimensional Stokes flow through a bumpy tube predicts that for a given bump area,\\u000a there exists an optimal circumferential wavenumber which minimizes flow resistance. This study uses measurements of microvessel\\u000a endothelial cell morphology to test whether this prediction holds in the microvasculature. Endothelial cell (EC) morphology\\u000a was measured in blood perfused in situ microvessels

Ronen Sumagin; Carl W. Brown; Ingrid H. Sarelius; Michael R. King

2008-01-01

271

The natural products parthenolide and andrographolide exhibit anti-cancer stem cell activity in multiple myeloma.  

PubMed

Multiple myeloma (MM) is an incurable plasma cell malignancy where nearly all patients succumb to a relapse. The current preclinical models of MM target the plasma cells, constituting the bulk of the tumor, leaving the cancer stem cells to trigger a relapse. Utilizing a three-dimensional tissue culture system where cells were grown in extracellular matrix designed to reconstruct human bone marrow, we tested the anti-multiple myeloma cancer stem cell (MM-CSC) potential of two natural product inhibitors of nuclear factor ?B (NF?B). Here we show that parthenolide and andrographolide are potent anti-MM-CSC agents. Both natural products demonstrated preferential toxicity toward MM-CSCs over non-tumorigenic MM cells. Addition of the bone marrow stromal compartment abrogated andrographolide activity while having no effect on parthenolide cytoxicity. This is the first report of a natural product with anti-CSC activity in myeloma, suggesting that it has the potential to improve the survival of patients with MM by eliminating the relapse-causing MM-CSCs. PMID:21417826

Gunn, Ellen J; Williams, John T; Huynh, Daniel T; Iannotti, Michael J; Han, Changho; Barrios, Francis J; Kendall, Stephen; Glackin, Carlotta A; Colby, David A; Kirshner, Julia

2011-06-01

272

Folate conjugated fluorescent silica nanoparticles for labeling neoplastic cells.  

PubMed

We describe a novel technique of using fluorescent silica nanoparticles (FSNPs) to detect over-expressed folate receptors, as typical for certain malignancies (metastatic adenocarcinoma, pituitary adenoma and others). Using Stöber's method with some modification, 135 nm size FSNPs were synthesized by a hydrolysis and co-condensation reaction of tetraethylorthosilicate (TEOS), fluorescein labeled (3-aminopropyl)triethoxysilane (APTS) and a water-dispersible silane reagent, (3-trihydroxysilyl)propyl methylphosphonate (THPMP) in the presence of ammonium hydroxide catalyst. Folic acid (folate) was covalently attached to the amine modified FSNPs by a carbodiimide coupling reaction. The characterization of folate-FSNPs was performed using a variety of spectroscopic (UV-VIS and fluorescence), microscopic (transmission electron microscopy, TEM) and light scattering techniques. Folate conjugated FSNPs were then targeted to human squamous cancer cells (SCC-9). Laser scanning confocal images successfully demonstrated the labeling of SCC-9 cells and the efficacy of FSNP based detection system. PMID:16060150

Santra, Swadeshmukul; Liesenfeld, Bernd; Dutta, Debamitra; Chatel, David; Batich, Christopher D; Tan, Weihong; Moudgil, Brij M; Mericle, Robert A

2005-06-01

273

Monascus-fermented red mold rice exhibits cytotoxic effect and induces apoptosis on human breast cancer cells.  

PubMed

Red mold rice (RMR) is a traditional food and folk medicine to Asian people and has recently become a popular health supplement. RMR has been shown to have some anticancer activities, although the mechanism for inducing cell death of human breast cancer cells is still not fully understood. In this study, bioactive extracts of RMR fermented by Monascus purpureus NTU 803 were analyzed for effects on apoptosis induction in human breast cancer cells. The RMR ethanol extract and ethyl acetate extract contain monacolin K, total phenols, and flavonoids, the three components that have been reported to have anticancer activity. Red mold rice extracts (RMRE) exhibited selective cytotoxic effect on MCF-7 cells. RMRE treatment induced apoptosis and cell cycle arrest at G2/M phase. Apoptosis was confirmed by annexin V-fluorescein isothiocyanate (FITC)/propidium iodide staining, the observation of characteristic chromatin condensation, nuclear DNA fragmentation, and poly(ADP-ribose) polymerase cleavage. Furthermore, the RMRE-induced apoptosis in MCF-7 cells may occur through a mitochondria-dependent pathway while triggering an appropriate balance of bax/bcl-2 and activation of caspase-9 and caspase-3 in a time-dependent manner. To conclude, RMRE exhibits direct cytotoxic and proapoptotic effects on MCF-7 cells and could be considered as a potential functional food for breast cancer prevention. PMID:22814414

Lee, Chu-I; Lee, Chun-Lin; Hwang, Jyi-Faa; Lee, Yi-Hsin; Wang, Jyh-Jye

2013-02-01

274

Interaction of lipid nanoparticles with human epidermis and an organotypic cell culture model.  

PubMed

Various lipid nanoparticle formulations were investigated with respect to (trans)dermal drug delivery with special regard to the mechanism of their effects on human and an organotypic cell culture epidermis. Potential alterations of stratum corneum lipid domains were studied using fluorescence assays with labeled liposomes and thermal analysis of isolated stratum corneum. Influences on the permeation of corticosterone were investigated and the occlusive properties of the nanoparticles were determined by measurements of the transepidermal water loss (TEWL). The penetration of a fluorescence dye was visualized by fluorescence microscopy of cross sections of human epidermis after incubation with cubic and solid lipid nanoparticles. Corticosterone permeation was limited when applied in matrix-type lipid nanoparticles (fat emulsion, smectic and solid lipid nanoparticles). An adhesion of solid lipid nanoparticles was clearly observed in thermal analysis as reflected by additional phase transitions probably caused by the nanoparticle matrix lipid. However, as for the other matrix-type nanoparticles, no distinct alterations of the phase transitions of the stratum corneum lipids were observed. Cubic nanoparticles led to the most predominant effect on skin permeation where the surface-active matrix lipid may act as penetration enhancer. An alteration of the stratum corneum lipids' thermal behavior as well as an interaction with fluorescence labeled liposomes was observed. Differences observed in permeation studies and thermal analysis of human and cell culture epidermis indicate that surface lipids, which are not present to the same extent in the cell culture model than in human epidermis, seem to play an important role. PMID:17920216

Kuntsche, Judith; Bunjes, Heike; Fahr, Alfred; Pappinen, Sari; Rönkkö, Seppo; Suhonen, Marjukka; Urtti, Arto

2008-04-16

275

Hybrid nanocatalysts containing enzymes and metallic nanoparticles for ethanol/O2 biofuel cell  

NASA Astrophysics Data System (ADS)

We report the preparation of hybrid nanostructured bioanodes containing the enzyme alcohol dehydrogenase (ADH) with either Au, Pt, or Pt0.75Sn0.25 nanoparticles for use in ethanol/O2 hybrid biofuel cells. We describe two different methodologies for the preparation of the bioanodes: in a first case, multi walled carbon nanotubes (MWCNTs) were employed as a support for the metallic nanoparticles and TBAB-modified Nafion® aided enzyme immobilization. In the second case, we immobilized the enzymes using dendrimers-encapsulated nanoparticles as the agent for enzyme anchoring. The biofuel cell tests showed that the addition of metallic nanoparticles to the bioanode structure enhanced the overall biofuel cell performance. The bioelectrode containing Au nanoparticles displaying the best performance, with an open circuit potential of 0.61 ± 0.05 V and a maximum power density of 155 ± 11 ?W cm-2. NADH cyclic voltammetric experiments indicated that Au nanoparticles behaved as a catalyst toward NADH oxidation. Comparing the two protocols we used to synthetized nanoparticles, the sample containing the Au nanoparticles supported on MWCNTs furnished fourfold higher values. Therefore, from the satisfactory results obtained, it can be inferred that the combination of small amounts of metallic nanoparticles with enzymes improve bioanode performance.

Aquino Neto, S.; Almeida, T. S.; Palma, L. M.; Minteer, S. D.; de Andrade, A. R.

276

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

277

Cell uptake and oral absorption of titanium dioxide nanoparticles.  

PubMed

Large efforts are invested on the development of in vitro tests to evaluate nanomaterial (NM) toxicity. In order to assess the relevance of the adverse effects identified in in vitro toxicity tests a thorough understanding of the biokinetics of NMs is critical. We used different in vitro and in vivo test methods to evaluate cell uptake and oral absorption of titanium dioxide nanoparticles (TiO2 NPs). These NPs were readily uptaken by A549 cells (carcinomic human alveolar basal epithelial cells) in vitro. Such rapid uptake contrasted with a very low oral absorption in a differentiated Caco-2 monolayer system (human epithelial colorectal adenocarcinoma cells) and after oral gavage administration to rats. In this oral study, no significant increase in the levels of titanium was recorded by ICP-MS in any of the tissues evaluated (including among other: small intestine, Peyer's patches, mesenteric lymph nodes, liver, and spleen). No NPs were observed by TEM in sections of the small intestine, except for several particles in the cytoplasm of a cell from a Peyer's Patch area. The observation of NPs in Peyer's Patch suggests that the Caco-2 monolayer system is likely to underestimate the potential for oral absorption of NPs and that the model could be improved by including M-cells in co-culture. PMID:24793716

Janer, G; Mas Del Molino, E; Fernández-Rosas, E; Fernández, A; Vázquez-Campos, S

2014-07-15

278

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

279

Comparative toxicity of 24 manufactured nanoparticles in human alveolar epithelial and macrophage cell lines  

PubMed Central

Background A critical issue with nanomaterials is the clear understanding of their potential toxicity. We evaluated the toxic effect of 24 nanoparticles of similar equivalent spherical diameter and various elemental compositions on 2 human pulmonary cell lines: A549 and THP-1. A secondary aim was to elaborate a generic experimental set-up that would allow the rapid screening of cytotoxic effect of nanoparticles. We therefore compared 2 cytotoxicity assays (MTT and Neutral Red) and analyzed 2 time points (3 and 24 hours) for each cell type and nanoparticle. When possible, TC50 (Toxic Concentration 50 i.e. nanoparticle concentration inducing 50% cell mortality) was calculated. Results The use of MTT assay on THP-1 cells exposed for 24 hours appears to be the most sensitive experimental design to assess the cytotoxic effect of one nanoparticle. With this experimental set-up, Copper- and Zinc-based nanoparticles appear to be the most toxic. Titania, Alumina, Ceria and Zirconia-based nanoparticles show moderate toxicity, and no toxicity was observed for Tungsten Carbide. No correlation between cytotoxicity and equivalent spherical diameter or specific surface area was found. Conclusion Our study clearly highlights the difference of sensitivity between cell types and cytotoxicity assays that has to be carefully taken into account when assessing nanoparticles toxicity.

Lanone, Sophie; Rogerieux, Francoise; Geys, Jorina; Dupont, Aurelie; Maillot-Marechal, Emmanuelle; Boczkowski, Jorge; Lacroix, Ghislaine; Hoet, Peter

2009-01-01

280

In vitro cytotoxicity of transparent yellow iron oxide nanoparticles on human glioma cells.  

PubMed

With rapid development of nanotechnology, concerns about the possible adverse health effects on human beings by using nanomaterials have been raised. Transparent yellow iron oxide (alpha-FeOOH) nanoparticles have been widely used in paints, plastic, rubber, building materials, papermaking, food products and pharmaceutical industry, thus the potential health implications by the exposure should be considered. The purpose of this study is to assess the cytotoxicity of transparent yellow iron oxide nanoparticles on U251 human glioma cells. The alpha-FeOOH nanoparticles are in clubbed shapes with 9 nm in diameter and 43 nm long. The specific surface area is 115.3 m2/g. After physicochemical characterization of the nanoparticles, U251 cells were exposed to a-FeOOH at the doses of 0, 3.75, 15, 60 and 120 microg/mL. The results showed that the alpha-FeOOH nanoparticles reduced the cell viability and induced necrosis and apoptosis in U251 cells. In addition, nanoparticle exposure significantly increased the levels of superoxide anion and nitric oxide in a dose-dependent fashion in the cells. Our results suggest that exposure to alpha-FeOOH nanoparticles induce significant free radical formation and cytotoxic effects. The large surface area that induced high surface reactivity may play an important role in the cytotoxic effect of alpha-FeOOH nanoparticles. PMID:21121365

Wang, Yun; Zhu, Mo-Tao; Wang, Bing; Wang, Meng; Wang, Hua-Jian; OuYang, Hong; Feng, Wei-Yue

2010-12-01

281

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

282

Effect of poly(ethylene glycol)-block-polylactide nanoparticles on hepatic cells of mouse: Low cytotoxicity, but efflux of the nanoparticles by ATP-binding cassette transporters  

Microsoft Academic Search

The objective of this paper is to study the effects of poly(ethylene glycol)-block-polylactide (PLA–PEG) nanoparticles on hepatic cells of mouse. Blank PLA–PEG nanoparticles have been successfully prepared and MTT assay suggested that the nanoparticles with HepG2 cell co-culture model did not cause significant changes in membrane integrity in controlled concentration range (0.001–0.1mg\\/ml). Immunohistochemical analysis demonstrated that large dose of PLA–PEG

Yangde Zhang; Zhiyuan Hu; Maoying Ye; Yifeng Pan; Jiji Chen; Yulin Luo; Yanqiong Zhang; Lianxiang He; Jiwei Wang

2007-01-01

283

Reduced optical loss in mechanically stacked multi-junction organic solar cells exhibiting complementary absorptions.  

PubMed

This paper describes a promising approach toward preparing effective electrical and optical interconnections for tandem organic photovoltaic devices (OPVs). The first subcell featured a semi-transparent electrode, which allowed a portion of the solar irradiation to pass through and to enter the second subcell exhibiting complementary absorption behavior. The resulting multi-junction OPV had multiple contacts such that the subcells could be easily connected either in series or in parallel. More importantly, we used UV-curable epoxy to "mechanically" stack the two subcells and to eliminate the air gap between them, thereby reducing the optical loss induced by mismatches of refractive indices. Therefore, an improved power conversion efficiency of approximately 6.5% has been achieved. PMID:24922257

Lin, Yen-Tseng; Chou, Chu-Hsien; Chen, Fang-Chung; Chu, Chih-Wei; Hsu, Chain-Shu

2014-03-10

284

Cell Attachment Behavior on Solid and Fluid Substrates Exhibiting Spatial Patterns of Physical Properties  

PubMed Central

The ability to direct proliferation and growth of living cells using chemically and topologically textured surfaces is finding many niche applications, both in fundamental biophysical investigations of cell-surface attachment as well as in developing design principles for many tissue engineering applications. Here we address cellular adhesion behavior on solid patterns of differing wettability (a static substrate) and fluid patterns of membrane topology (a dynamic substrate). We find striking differences in the cellular adhesion characteristics of lipid mono- and bilayers, despite their essentially identical surface chemical and structural character. These differences point to the importance of subtle variations in the physical properties of the lipid mono- and bilayers (e.g., membrane tension and out-of-plane undulations). Furthermore, we find that introducing phosphatidylserine into the patterned lipidic substrates causes a loss of cell-patterning capability. Implications of this finding for the mechanism by which phosphatidylserine promotes cellular adhesion are discussed.

Oliver, Ann E.; Ngassam, Viviane; Dang, Phuong; Sanii, Babak; Wu, Huawen; Yee, Chanel K.; Yeh, Yin; Parikh, Atul N.

2009-01-01

285

CSMD1 exhibits antitumor activity in A375 melanoma cells through activation of the Smad pathway.  

PubMed

In this work, we studied the effects of CUB and Sushi multiple domains 1 gene (CSMD1) expression in A375 melanoma cells in vivo and in vitro. CSDM1 expression decreased proliferation and migration, and increased apoptosis and G(1) arrest in A375 cells in vitro. Expression of CSDM1 in established xenografted tumors decreased tumor size and weight, and decreased the density of intratumor microvessels. The survival rate of mice with tumors expressing CSMD1 was significantly higher than mice with tumors that did not express CSDM1. These results confirm the role of CSDM1 as a tumor suppressor gene in melanoma cells. Furthermore, we found that CSMD1 can interact with Smad3, activate Smad1, Smad2, and Smad3, and increase the expression of Smad4. These results might prove helpful for the development of novel therapies for melanoma treatment. PMID:22538441

Tang, Ming-Rui; Wang, Yu-Xin; Guo, Shu; Han, Si-Yuan; Wang, Di

2012-09-01

286

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

2012-05-01

287

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.

288

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

289

Three fluorescent protein voltage sensors exhibit low plasma membrane expression in mammalian cells.  

PubMed

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 HEK 293 cells and in dissociated hippocampal neurons. We were unable to detect a signal in response to changes in membrane potential after averaging16 trials with any of the three constructs. Using the hydrophobic voltage sensitive dye, di8-ANEPPS, as a surface marker, confocal analyses demonstrated poor plasma membrane expression for Flare, SPARC and VSFP-1 in both HEK 293 cells and dissociated hippocampal neurons. Almost all of the expressed FP-voltage sensors reside in internal membranes in both cell types. This internal expression generates a background fluorescence that increases the noise in the optical measurement. PMID:17126911

Baker, B J; Lee, H; Pieribone, V A; Cohen, L B; Isacoff, E Y; Knopfel, T; Kosmidis, E K

2007-03-30

290

Proliferating mesodermal cells in murine embryos exhibiting macrophage and lymphendothelial characteristics  

PubMed Central

Background The data on the embryonic origin of lymphatic endothelial cells (LECs) from either deep embryonic veins or mesenchymal (or circulating) lymphangioblasts presently available remain inconsistent. In various vertebrates, markers for LECs are first expressed in specific segments of embryonic veins arguing for a venous origin of lymph vessels. Very recently, studies on the mouse have strongly supported this view. However, in the chick, we have observed a dual origin of LECs from veins and from mesodermal lymphangioblasts. Additionally, in murine embryos we have detected mesenchymal cells that co-express LEC markers and the pan-leukocyte marker CD45. Here, we have characterized the mesoderm of murine embryos with LEC markers Prox1, Lyve-1 and LA102 in combination with macrophage markers CD11b and F4/80. Results We observed cells co-expressing both types of markers (e.g. Prox1 – Lyve-1 – F4/80 triple-positive) located in the mesoderm, immediately adjacent to, and within lymph vessels. Our proliferation studies with Ki-67 antibodies showed high proliferative capacities of both the Lyve-1-positive LECs of lymph sacs/lymphatic sprouts and the Lyve-1-positive mesenchymal cells. Conclusion Our data argue for a dual origin of LECs in the mouse, although the primary source of embryonic LECs may reside in specific embryonic veins and mesenchymal lymphangioblasts integrated secondarily into lymph vessels. The impact of a dual source of LECs for ontogenetic, phylogenetic and pathological lymphangiogenesis is discussed.

Buttler, Kerstin; Ezaki, Taichi; Wilting, Jorg

2008-01-01

291

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

PubMed Central

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 (ECCM) or UM (ECUM) and confirmed the identity of the cells before analysis. Upon TNF stimulation in vitro, ECCM 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 ECUM. 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 ECCM than in ECUM. 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.

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

2011-01-01

292

Honokiol induces paraptosis and apoptosis and exhibits schedule-dependent synergy in combination with imatinib in human leukemia cells.  

PubMed

Honokiol, an active component isolated and purified from Chinese traditional herb magnolia, has been shown to inhibit growth and induce apoptosis in different cancer cell lines. This study shows that honokiol can induce a cell death distinct from apoptosis at lower concentrations. The death was characterized by cytoplasmic vacuolization with the endoplasmic reticulum swelling and accompanied by apoptosis at higher concentrations in NB4 and K562 cells. The two death processes may be in sequence at lower concentrations and in parallel with the increase of honokiol concentration. Membrane-associated cytotoxicity was involved in honokiol-induced paraptosis and apoptosis. Furthermore, honokiol inhibited concentration-dependent cell adhesion to extracellular matrix for NB4 cells. In addition, the cytotoxicity of honokiol combined treatment with imatinib was schedule- and concentration-dependent and the sequential administration of honokiol before imatinib appeared to be more beneficial in K562 cells. Taken together, the data suggest that honokiol induced a novel cell death pathway and there was cross-talk between apoptotic and non-apoptotic programmed cell death caused by honokiol in leukemia cells. Moreover, honikiol exhibited schedule-dependent synergy in combination with imatinib and sequential administration of imatinib followed by honokiol could be the optimal sequence to combine these two drugs in K562 cells. PMID:20374036

Wang, Yao; Yang, Zehong; Zhao, Xiaojun

2010-06-01

293

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

2013-10-01

294

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

PubMed Central

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.

Passantino, Lisa; Munoz, Alexandra B.

2014-01-01

295

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

296

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

297

Endocytosis of Titanium Dioxide Nanoparticles in Prostate Cancer PC-3M Cells  

PubMed Central

Nanotechnology has introduced many exciting new tools for the treatment of human diseases. One of the obstacles in its application to that end is the lack of a fundamental understanding of the interaction that occurs between nanoparticles and living cells. This report describes the quantitative analysis of the kinetics and endocytic pathways involved in the uptake of anatase titanium dioxide (TiO2) nanoparticles into prostate cancer PC-3M cells. The experiments were performed with TiO2 nanoconjugates—6 nm nanoparticles with surface conjugated fluorescent Alizarin Red S (ARS). Results obtained by flow cytometry, fluorescence microscopy, and inductively-coupled plasma mass spectrometry confirmed a complex nanoparticle-cell interaction involving a variety of endocytic mechanisms. The results demonstrated that a temperature, concentration, and time-dependent internalization of the TiO2 nanoparticles and nanoconjugates occurred via clathrin-mediated endocytosis, caveolin-mediated endocytosis, and macropinocytosis.

Thurn, Kenneth T.; Arora, Hans; Paunesku, Tatjana; Wu, Aiguo; Brown, Eric M.B.; Doty, Caroline; Kremer, Jeff; Woloschak, Gayle

2011-01-01

298

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

299

Magnetic Carbon nanoparticles enabled efficient photothermal alteration of mammalian cells  

NASA Astrophysics Data System (ADS)

While cw near-infrared (NIR) laser beams have been finding widespread application in photothermal therapy of cancer and pulsed NIR laser microbeams are recently being used for optoporation of exogeneous impermeable materials into cells. Since, carbon nanomaterials are very good in photothermal conversion, we utilized carbon nanoparticles (CNP) doped with Fe, so that they can be localized in a defined area by two fold selectivity, (i) external magnetic field for retention of the CNP in targeted area and (ii) surface functionalization for binding the targeted cells. Here, we report efficient photothermal therapy as well as poration of cells using magnetic CNPs with very low power continuous wave laser beam. Localization of CNPs on cell membrane under application of magnetic field was confirmed by scanning electron microscopy. At different power levels, cells could be damaged or microinjected with fluorescence protein-encoding plasmids or impermeable dyes. Monte Carlo simulation showed that the dose of NIR laser beam is sufficient to elicit response for magnetic CNP based photothermal treatment at significant depth. The results of our study suggest that magnetic CNP based photothermal alteration is a viable approach to remotely guide treatments offering high efficiency with significantly reduced cytotoxicity.

Gu, L.; Vardarajan, V.; Kanneganti, A.; Koymen, A.; Mohanty, S. K.

2011-03-01

300

CTAB capped silver nanoparticles for plasmonic dye-sensitized solar cell  

NASA Astrophysics Data System (ADS)

To improve the light harvesting efficiency of Dye-sensitized solar cell (DSSC), we have explored the surface plasmon property of metal nanoparticles in this paper. Cetyl trimethylammonium bromide (CTAB) capped silver nanoparticles have been synthesized by wet chemical method and studied for spectroscopic and structural investigations. FTIR confirms the capping of CTAB on silver nanoparticles occurs via their head group. Williamson Hall plot revealed the presence of tensile strain. Finally, these particles have been incorporated in DSSC to study the plasmonic effect of nanoparticles on performance of DSSC.

Tanvi, Mahajan, Aman; Bedi, R. K.; Kumar, Subodh

2014-04-01

301

Interaction of cancer cells with magnetic nanoparticles modified by methacrylamido-folic acid  

PubMed Central

Background: Magnetic nanoparticles show great promise for use as tools in a wide variety of biomedical applications. The purpose of this study was to investigate the potential effects of methacrylamido-folic acid (Ma-Fol)-modified magnetic nanoparticles on 5RP7 (H-ras-transformed rat embryonic fibroblasts) and NIH/3T3 (normal mouse embryonic fibroblasts). Methods: The cytotoxicity and viability of 5RP7 and NIH/3T3 cells were detected. The percentage of cells undergoing apoptosis was analyzed by flow cytometry using Annexin V-fluorescein isothiocyanate staining. Nanoparticle internalization into 5RP7 and NIH/3T3 cells was visualized by transmission electron microscopy. Conclusion: In this study, folic acid coupled to the surface of iron oxide for selective binding to cancer cells and immobilized the surfaces of magnetic nanoparticles. This complex improves cell internalization and targeting of cancer cells. We detected increased apoptosis using flow cytometry and transmission electron microscopy. Results: Folic acid modification of magnetic nanoparticles could be used to facilitate uptake to specific cancer cells for cancer therapy and diagnosis. Our results showed that the uptake of folic-acid modified nanoparticles by 5RP7 cancer cells was also much higher than that of 3T3 cells. This modification can be used for successful targeting of cancer cells expressing the folate receptor.

Saltan, Nagehan; Kutlu, H Mehtap; Hur, Deniz; Iscan, Arzu; Say, R?dvan

2011-01-01

302

CdTe Nanoparticles Display Tropism to Core Histones and Histone-Rich Cell Organelles  

Microsoft Academic Search

The disclosure of the mechanisms of nanoparticle interaction with specific intracellular targets represents one of the key tasks in nanobiology. Unmodified luminescent semiconductor nanoparticles, or quantum dots (QDs), are capable of a strikingly rapid accumulation in the nuclei and nucleoli of living human cells, driven by processes of yet unknown nature. Here, it is hypothesized that such a strong tropism

Jennifer Conroy; Stephen J. Byrne; Yurii K. Gun'ko; Yury P. Rakovich; John F. Donegan; Anthony Davies; Dermot Kelleher; Yuri Volkov

2008-01-01

303

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

304

Improved light absorption in thin-film silicon solar cells by integration of silver nanoparticles  

Microsoft Academic Search

Silver nanoparticles, produced by thermal evaporation and a subsequent annealing treatment, were integrated at the back side of thin-film silicon solar cells. Metallic nanoparticles can lead to (i) a strong enhancement of the electric field in their surrounding when they are irradiated by light and (ii) significant scattering of the light when they have the proper diameter (>100nm). In this

E. Moulin; J. Sukmanowski; P. Luo; R. Carius; F. X. Royer; H. Stiebig

2008-01-01

305

Mast cells in the rat liver are phenotypically heterogeneous and exhibit features of immaturity  

Microsoft Academic Search

Gastrointestinal hypersensitivity to food allergens is a significant but relatively poorly understood allergic disease. Recent evidence from a rat model of IgE-mediated gastrointestinal hypersensitivity has suggested that hepatic mast cells (HMC) may play an important role in such reactions. The present study was undertaken to better define their phenotype. Livers from Australian albino Wistar (AaW), Brown Norway (BN) and PVG\\/c

Antonio Chan; Margaret A Cooley; Andrew M Collins

2001-01-01

306

Hepatitis B virus X protein mutants exhibit distinct biological activities in hepatoma Huh7 cells  

Microsoft Academic Search

The role of the hepatitis B virus X protein (HBx) in hepatocarcinogenesis remains controversial. To investigate the biological impact of hepatitis B virus x gene (HBx) mutation on hepatoma cells, plasmids expressing the full-length HBx or HBx deletion mutants were constructed. The biological activities in these transfectants were analyzed by a series of assays. Results showed that HBx3?-20 and HBx3?-40

Xiaohong Liu; Shuhui Zhang; Jing Lin; Shunmin Zhang; Mark A. Feitelson; Hengjun Gao; Minghua Zhu

2008-01-01

307

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

308

VMP1-deficient Chlamydomonas exhibits severely aberrant cell morphology and disrupted cytokinesis  

PubMed Central

Background The versatile Vacuole Membrane Protein 1 (VMP1) has been previously investigated in six species. It has been shown to be essential in macroautophagy, where it takes part in autophagy initiation. In addition, VMP1 has been implicated in organellar biogenesis; endo-, exo- and phagocytosis, and protein secretion; apoptosis; and cell adhesion. These roles underly its proven involvement in pancreatitis, diabetes and cancer in humans. Results In this study we analyzed a VMP1 homologue from the green alga Chlamydomonas reinhardtii. CrVMP1 knockdown lines showed severe phenotypes, mainly affecting cell division as well as the morphology of cells and organelles. We also provide several pieces of evidence for its involvement in macroautophagy. Conclusion Our study adds a novel role to VMP1's repertoire, namely the regulation of cytokinesis. Though the directness of the observed effects and the mechanisms underlying them remain to be defined, the protein's involvement in macroautophagy in Chlamydomonas, as found by us, suggests that CrVMP1 shares molecular characteristics with its animal and protist counterparts.

2014-01-01

309

Tammar wallaby mammary cathelicidins are differentially expressed during lactation and exhibit antimicrobial and cell proliferative activity.  

PubMed

Cathelicidins secreted in milk may be central to autocrine feedback in the mammary gland for optimal development in addition to conferring innate immunity to both the mammary gland and the neonate. This study exploits the unique reproductive strategy of the tammar wallaby (Macropus eugenii) model to analyse differential splicing of cathelicidin genes and to evaluate the bactericidal activity and effect of the protein on mammary epithelial cell proliferation. Two linear peptides, Con73 and Con218, derived from the heterogeneous carboxyl end of cathelicidin transcripts, MaeuCath1 and MaeuCath7 respectively, were evaluated for antimicrobial activity. Both Con73 and Con218 significantly inhibited the growth of Staphylococcus aureus, Pseudomonas aureginosa, Enterococcus faecalis and Salmonella enterica. In addition both MaeuCath1 and MaeuCath7 stimulated proliferation of primary tammar wallaby mammary epithelial cells (WallMEC). Lactation-phase specific alternate spliced transcripts were determined for MaeuCath1 showing utilisation of both antimicrobial and proliferative functions are required by the mammary gland and the suckled young. The study has shown for the first time that temporal regulation of milk cathelicidins may be crucial in antimicrobial protection of the mammary gland and suckled young and mammary cell proliferation. PMID:21824524

Wanyonyi, Stephen S; Sharp, Julie A; Khalil, Elie; Lefevre, Christophe; Nicholas, Kevin R

2011-11-01

310

Mechanodelivery of nanoparticles to the cytoplasm of living cells  

NASA Astrophysics Data System (ADS)

Nanotechnology has opened up the opportunity to probe, sense, and manipulate the chemical environment of biological systems with an unprecedented level of spatiotemporal control. A major obstacle to the full realization of these novel technologies is the lack of a general, robust, and simple method for the delivery of arbitrary nanostructures to the cytoplasm of intact live cells. Here, we identify a new delivery modality, based on mechanical disruption of the plasma membrane, which efficiently mediates the delivery of nanoparticles to the cytoplasm of mammalian cells. We use two distinct execution modes, two adherent cell lines, and three sizes of semiconducting nanocrystals, or quantum dots, to demonstrate its applicability and effectiveness. As the underlying mechanism is purely physical, we anticipate that such ``mechanodelivery'' can be generalized to other modes of execution as well as to the cytoplasmic introduction of a structurally diverse array of functional nanomaterials.Nanotechnology has opened up the opportunity to probe, sense, and manipulate the chemical environment of biological systems with an unprecedented level of spatiotemporal control. A major obstacle to the full realization of these novel technologies is the lack of a general, robust, and simple method for the delivery of arbitrary nanostructures to the cytoplasm of intact live cells. Here, we identify a new delivery modality, based on mechanical disruption of the plasma membrane, which efficiently mediates the delivery of nanoparticles to the cytoplasm of mammalian cells. We use two distinct execution modes, two adherent cell lines, and three sizes of semiconducting nanocrystals, or quantum dots, to demonstrate its applicability and effectiveness. As the underlying mechanism is purely physical, we anticipate that such ``mechanodelivery'' can be generalized to other modes of execution as well as to the cytoplasmic introduction of a structurally diverse array of functional nanomaterials. Electronic supplementary information (ESI) available: Characterization of the QD diameter, passivation of QDs, electroporation protocol, flow cytometric data analysis, and additional epifluorescence images of QD labeled cells, including Table S1 and Fig. S1-S15. See DOI: 10.1039/c3nr06468a

Emerson, Nyssa T.; Hsia, Chih-Hao; Rafalska-Metcalf, Ilona U.; Yang, Haw

2014-04-01

311

Virtual Exhibitions  

Microsoft Academic Search

This case study is designed to provide readers with an overview of the format of a virtual event and the variety of options available to exhibitors. It focuses specifically on the Virtual GITEX 2001 event, which adopted a 3-dimensional virtual reality approach. On October 7, 2001, the virtual component of the Dubai World Trade Centre's largest and most successful exhibition,

Janice Edgar

2002-01-01

312

Exhibiting Lives  

ERIC Educational Resources Information Center

This paper examines some of the dilemmas that accompany the emergence of the personal voice in scholarly work, by taking a close, grounded look at the way in which these unfolded in a specific academic course. As part of the course, entitled "A cultural approach to the life cycle", students were asked to participate in a group exhibition in which…

Golden, Deborah; Elbaz-Luwisch, Freema

2007-01-01

313

Graduation Exhibitions.  

ERIC Educational Resources Information Center

Describes the graduation exhibitions--a student-centered culminating project that each graduating student at the Greenwood Laboratory School in Springfield, Missouri, presented to an audience for review. Notes that the graduation requirement is intended to hold graduates accountable for their learning. (SR)

Fisk, Candace; Dunlop, Vicki; Sills-Briegel, Toni

1997-01-01

314

Radiosensitization of paclitaxel, etanidazole and paclitaxel+etanidazole nanoparticles on hypoxic human tumor cells in vitro  

Microsoft Academic Search

Paclitaxel and etanidazole are hypoxic radiosensitizers that exhibit cytotoxic action at different mechanisms. The poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles containing paclitaxel, etanidazole and paclitaxel+etanidazole were prepared by o\\/w and w\\/o\\/w emulsification-solvent evaporation method. The morphology of the nanoparticles was investigated by scanning electron microscope (SEM). The drug encapsulation efficiency (EE) and release profile in vitro were measured by high-performance liquid chromatography (HPLC).

Cheng Jin; Ling Bai; Hong Wu; Furong Tian; Guozhen Guo

2007-01-01

315

Human Primary Adipocytes Exhibit Immune Cell Function: Adipocytes Prime Inflammation Independent of Macrophages  

PubMed Central

Background Obesity promotes inflammation in adipose tissue (AT) and this is implicated in pathophysiological complications such as insulin resistance, type 2 diabetes and cardiovascular disease. Although based on the classical hypothesis, necrotic AT adipocytes (ATA) in obese state activate AT macrophages (ATM) that then lead to a sustained chronic inflammation in AT, the link between human adipocytes and the source of inflammation in AT has not been in-depth and systematically studied. So we decided as a new hypothesis to investigate human primary adipocytes alone to see whether they are able to prime inflammation in AT. Methods and Results Using mRNA expression, human preadipocytes and adipocytes express the cytokines/chemokines and their receptors, MHC II molecule genes and 14 acute phase reactants including C-reactive protein. Using multiplex ELISA revealed the expression of 50 cytokine/chemokine proteins by human adipocytes. Upon lipopolysaccharide stimulation, most of these adipocyte-associated cytokines/chemokines and immune cell modulating receptors were up-regulated and a few down-regulated such as (ICAM-1, VCAM-1, MCP-1, IP-10, IL-6, IL-8, TNF-? and TNF-? highly up-regulated and IL-2, IL-7, IL-10, IL-13 and VEGF down-regulated. In migration assay, human adipocyte-derived chemokines attracted significantly more CD4+ T cells than controls and the number of migrated CD4+ cells was doubled after treating the adipocytes with LPS. Neutralizing MCP-1 effect produced by adipocytes reduced CD4+ migration by approximately 30%. Conclusion Human adipocytes express many cytokines/chemokines that are biologically functional. They are able to induce inflammation and activate CD4+ cells independent of macrophages. This suggests that the primary event in the sequence leading to chronic inflammation in AT is metabolic dysfunction in adipocytes, followed by production of immunological mediators by these adipocytes, which is then exacerbated by activated ATM, activation and recruitment of immune cells. This study provides novel knowledge about the prime of inflammation in human obese adipose tissue, opening a new avenue of investigations towards obesity-associated type 2 diabetes.

Meijer, Kees; de Vries, Marcel; Al-Lahham, Saad; Bruinenberg, Marcel; Weening, Desiree; Dijkstra, Martijn; Kloosterhuis, Niels; van der Leij, Roelof Jan; van der Want, Han; Kroesen, Bart-Jan; Vonk, Roel; Rezaee, Farhad

2011-01-01

316

Interaction of nanoparticles and cell-penetrating peptides with skin for transdermal drug delivery  

PubMed Central

Topical or transdermal drug delivery is challenging because the skin acts as a natural and protective barrier. Therefore, several methods have been examined to increase the permeation of therapeutic molecules into and through the skin. One approach is to use the nanoparticulate delivery system. Starting with liposomes and other vesicular systems, several other types of nanosized drug carriers have been developed such as solid lipid nanoparticles, nanostructured lipid carriers, polymer-based nanoparticles and magnetic nanoparticles for dermatological applications. This review article discusses how different particulate systems can interact and penetrate into the skin barrier. In this review, the effectiveness of nanoparticles, as well as possible mode of actions of nanoparticles, is presented. In addition to nanoparticles, cell-penetrating peptide (CPP)-mediated drug delivery into the skin and the possible mechanism of CPP-derived delivery into the skin is discussed. Lastly, the effectiveness and possible mechanism of CPP-modified nanocarriers into the skin are addressed.

Desai, Pinaki; Patlolla, Ram R.; Singh, Mandip

2011-01-01

317

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

PubMed

Although endohedral metallofullerenol [Gd@C(82)(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@C(82)(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@C(82)(OH)(22)](n) nanoparticle treatment. Mechanistically, the effect of [Gd@C(82)(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@C(82)(OH)(22)](n) nanoparticles effectively improved bone density and prevented osteoporosis. PMID:23299786

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

2013-02-01

318

Biofunctionalized nanoparticles with pH-responsive and cell penetrating blocks for gene delivery  

NASA Astrophysics Data System (ADS)

Bridging the gap between nanoparticulate delivery systems and translational gene therapy is a long sought after requirement in nanomedicine-based applications. However, recent developments regarding nanoparticle functionalization have brought forward the ability to synthesize materials with biofunctional moieties that mimic the evolved features of viral particles. Herein we report the versatile conjugation of both cell penetrating arginine and pH-responsive histidine moieties into the chitosan polymeric backbone, to improve the physicochemical characteristics of the native material. Amino acid coupling was confirmed by 2D TOCSY NMR and Fourier transform infrared spectroscopy. The synthesized chitosan-histidine-arginine (CH-H-R) polymer complexed plasmid DNA biopharmaceuticals, and spontaneously assembled into stable 105 nm nanoparticles with spherical morphology and positive surface charge. The functionalized delivery systems were efficiently internalized into the intracellular compartment, and exhibited remarkably higher transfection efficiency than unmodified chitosan without causing any cytotoxic effect. Additional findings regarding intracellular trafficking events reveal their preferential escape from degradative lysosomal pathways and nuclear localization. Overall, this assembly of nanocarriers with bioinspired moieties provides the foundations for the design of efficient and customizable materials for cancer gene therapy.

Gaspar, V. M.; Marques, J. G.; Sousa, F.; Louro, R. O.; Queiroz, J. A.; Correia, I. J.

2013-07-01

319

Magnetic resonance tracking of nanoparticle labelled neural stem cells in a rat's spinal cord  

Microsoft Academic Search

Neural stem cells isolated from an adult rat's spinal cord were loaded with superparamagnetic gold-coated monocrystalline iron oxide nanoparticles (Au-MION) intended for use as contrast enhancers in magnetic resonance imaging (MRI). A dose-dependent attenuation of MRI signals was observed for Au-MION down to 0.001 µg Fe\\/µl and for nanoparticle-loaded clusters of only 20 cells. The labelled cells were infused into

F. H. Wang; I. H. Lee; N. Holmström; T. Yoshitake; D. K. Kim; M. Muhammed; J. Frisén; L. Olson; C. Spenger; J. Kehr

2006-01-01

320

Lectin-tagged fluorescent polymeric nanoparticles for targeting of sialic Acid on living cells.  

PubMed

In this study, we fabricated lectin-tagged fluorescent polymeric nanoparticles approximately 35 nm in diameter using biocompatible polymers conjugated with lectins for the purpose of detecting sialic acid on a living cell surface, which is one of the most important biomarkers for cancer diagnosis. Through cellular experiments, we successfully detected sialic acid overexpression on cancerous cells with high specificity. These fluorescent polymeric nanoparticles can be useful as a potential bioimaging probe for detecting diseased cells. PMID:24761752

Cho, Jaebum; Kushiro, Keiichiro; Teramura, Yuji; Takai, Madoka

2014-06-01

321

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

322

Manganese-impregnated mesoporous silica nanoparticles for signal enhancement in MRI cell labelling studies  

NASA Astrophysics Data System (ADS)

Mesoporous silica nanoparticles (MSNs) are used in drug delivery and cell tracking applications. As Mn2+ is already implemented as a ``positive'' cell contrast agent in preclinical imaging procedures (in the form of MnCl2 for neurological studies), the introduction of Mn in the porous network of MSNs would allow labelling cells and tracking them using MRI. These particles are in general internalized in endosomes, an acidic environment with high saline concentration. In addition, the available MSN porosity could also serve as a carrier to deliver medical/therapeutic substances through the labelled cells. In the present study, manganese oxide was introduced in the porous network of MCM-48 silica nanoparticles (Mn-M48SNs). The particles exhibit a narrow size distribution (~140 nm diam.) and high porosity (~60% vol.), which was validated after insertion of Mn. The resulting Mn-M48SNs were characterized by TEM, N2 physisorption, and XRD. Evidence was found with H2-TPR, and XPS characterization, that Mn(ii) is the main oxidation state of the paramagnetic species after suspension in water, most probably in the form of Mn-OOH. The colloidal stability as a function of time was confirmed by DLS in water, acetate buffer and cell culture medium. In NMR data, no significant evidence of Mn2+ leaching was found in Mn-M48SNs in acidic water (pH 6), up to 96 hours after suspension. High longitudinal relaxivity values of r1 = 8.4 mM-1 s-1 were measured at 60 MHz and 37 °C, with the lowest relaxometric ratios (r2/r1 = 2) reported to date for a Mn-MSN system. Leukaemia cells (P388) were labelled with Mn-M48SNs and nanoparticle cell internalization was confirmed by TEM. Finally, MRI contrast enhancement provided by cell labelling with escalated incubation concentrations of Mn-M48SNs was quantified at 1 T. This study confirmed the possibility of efficiently confining Mn into M48SNs using incipient wetness, while maintaining an open porosity and relatively high pore volume. Because these Mn-labelled M48SNs express strong ``positive'' contrast media properties at low concentrations, they are potentially applicable for cell tracking and drug delivery methodologies.Mesoporous silica nanoparticles (MSNs) are used in drug delivery and cell tracking applications. As Mn2+ is already implemented as a ``positive'' cell contrast agent in preclinical imaging procedures (in the form of MnCl2 for neurological studies), the introduction of Mn in the porous network of MSNs would allow labelling cells and tracking them using MRI. These particles are in general internalized in endosomes, an acidic environment with high saline concentration. In addition, the available MSN porosity could also serve as a carrier to deliver medical/therapeutic substances through the labelled cells. In the present study, manganese oxide was introduced in the porous network of MCM-48 silica nanoparticles (Mn-M48SNs). The particles exhibit a narrow size distribution (~140 nm diam.) and high porosity (~60% vol.), which was validated after insertion of Mn. The resulting Mn-M48SNs were characterized by TEM, N2 physisorption, and XRD. Evidence was found with H2-TPR, and XPS characterization, that Mn(ii) is the main oxidation state of the paramagnetic species after suspension in water, most probably in the form of Mn-OOH. The colloidal stability as a function of time was confirmed by DLS in water, acetate buffer and cell culture medium. In NMR data, no significant evidence of Mn2+ leaching was found in Mn-M48SNs in acidic water (pH 6), up to 96 hours after suspension. High longitudinal relaxivity values of r1 = 8.4 mM-1 s-1 were measured at 60 MHz and 37 °C, with the lowest relaxometric ratios (r2/r1 = 2) reported to date for a Mn-MSN system. Leukaemia cells (P388) were labelled with Mn-M48SNs and nanoparticle cell internalization was confirmed by TEM. Finally, MRI contrast enhancement provided by cell labelling with escalated incubation concentrations of Mn-M48SNs was quantified at 1 T. This study confirmed the possibility of efficiently confining Mn into M48SNs using incipient wetness

Guillet-Nicolas, Rémy; Laprise-Pelletier, Myriam; Nair, Mahesh M.; Chevallier, Pascale; Lagueux, Jean; Gossuin, Yves; Laurent, Sophie; Kleitz, Freddy; Fortin, Marc-André

2013-11-01

323

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

NASA Astrophysics Data System (ADS)

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.

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

2012-12-01

324

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

325

Development of biofuel cells based on gold nanoparticle decorated multi-walled carbon nanotubes.  

PubMed

This study focused on developing the synthesis of Au nanoparticle-decorated functionalized multi-walled carbon nanotubes (Au-NPs/f-MWCNTs) for monosaccharide (bio-fuel) oxidation reactions and practical application in air-biofuel cells. We developed a scalable and straightforward method to synthesize Au-NPs/f-MWCNTs which allow us to control the loading and size of the Au-NPs. The Au-NPs/f-MWCNTs exhibited better catalytic activities and stability than the Au sheet and subsequently resulted in a threefold increase in the power density of the air-glucose fuel cell with an exceptionally high open circuit voltage (~1.3 V). The catalytic efficiency was confirmed by high performance liquid chromatography with the superior of the Au-NPs/f-MWCNTs over a bare gold electrode. In addition, the application of this advanced catalyst to other monosaccharide oxidation reactions figured out that the configuration of -OH groups at C(2) and C(3) of the reactants plays an important role in the initial adsorption process, and thus, affects the required activation energy for further oxidation. The different monosaccharides lead to significantly different fuel cell performances in terms of power density, which coherently corresponds to the difference in the configuration of C(2) and C(3). Because two small air-glucose fuel cells using Au-NPs/f-MWCNTs can run a LED lamp, further applications of other monosaccharides as fuel in biofuel cells for equivalent required power devices may be possible. PMID:21983243

Naruse, Junichi; Hoa, Le Quynh; Sugano, Yasuhito; Ikeuchi, Tomohiko; Yoshikawa, Hiroyuki; Saito, Masato; Tamiya, Eiichi

2011-12-15

326

Chromium(III) oxide nanoparticles induced remarkable oxidative stress and apoptosis on culture cells.  

PubMed

Chromium(III) oxide (Cr(2)O(3)) is used for industrial applications such as catalysts and pigments. In the classical form, namely the fine particle, Cr(2)O(3) is insoluble and chemically stable. It is classified as a low-toxicity chromium compound. Recently, industrial application of nanoparticles (a new form composed of small particles with a diameter of ?100 nm, in at least one dimension) has been increasing. Cellular effects induced by Cr(2)O(3) nanoparticles are not known. To shed light upon this, the release of soluble chromium from Cr(2)O(3) nano- and fine-particles in culture medium was compared. Fine Cr(2)O(3) particles were insoluble in the culture medium; on the contrary, Cr(2)O(3) nanoparticles released soluble hexavalent chromium into the culture medium. Cr(2)O(3) nanoparticles showed severe cytotoxicity. The effect of Cr(2)O(3) nanoparticles on cell viability was higher than that of fine particles. Cr(2)O(3) nanoparticles showed cytotoxicity equal to that of hexavalent chromium (K(2)Cr(2)O(7)). Human lung carcinoma A549 cells and human keratinocyte HaCaT cells showed an increase in intracellular reactive oxygen species (ROS) level and activation of antioxidant defense systems on exposure to Cr(2)O(3) nanoparticles. Exposure of Cr(2)O(3) nanoparticles led to caspase-3 activation, showing that the decrease in cell viability by exposure to Cr(2)O(3) nanoparticles was caused by apoptosis. Cellular responses were stronger in the Cr(2)O(3) nanoparticles-exposed cells than in fine Cr(2)O(3) - and CrCl(3) -exposed cells. Cellular uptake of Cr(2)O(3) particles were observed in nano- and fine-particles. The cellular influence of the extracellular soluble trivalent chromium was lower than that of Cr(2)O(3) nanoparticles. Cr(2)O(3) nanoparticles showed cytotoxicity by hexavalent chromium released at outside and inside of cells. The cellular influences of Cr(2)O(3) nanoparticles matched those of hexavalent chromium. In conclusion, Cr(2)O(3) nanoparticles have a high cytotoxic potential. PMID:21384495

Horie, Masanori; Nishio, Keiko; Endoh, Shigehisa; Kato, Haruhisa; Fujita, Katsuhide; Miyauchi, Arisa; Nakamura, Ayako; Kinugasa, Shinichi; Yamamoto, Kazuhiro; Niki, Etsuo; Yoshida, Yasukazu; Iwahashi, Hitoshi

2013-02-01

327

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

328

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

329

The antibacterial substance taurolidine exhibits anti-neoplastic action based on a mixed type of programmed cell death.  

PubMed

The antibacterial amino-acid derivative taurolidine (TAU) has been recently shown to exhibit anti-neoplastic activity based on a mechanism, which is still unknown in detail. Cytotoxicity and clonogenic assays were performed and the impact of apoptosis modulators, a radical scavenger, autophagy inhibitors, silencing of apoptosis inducing actor (AIF) and cytochrome-c (Cyt-C) by siRNA, and knockdown of autophagy related genes were evaluated in vitro. The intracellular ATP-content, release of AIF and Cyt-C, and DNA-laddering were investigated. This study could demonstrate cell killing, inhibition of proliferation, and inhibition or prevention of colony formation in human glioma cell lines and ex vivo glioblastoma cells after incubation with TAU. This effect is based on the induction of a mixed type of programmed cell death with the main preference of autophagy, and involvement of senescence, necroptosis and necrosis. This mechanism of action may open a new approach for therapeutic intervention. PMID:19066471

Stendel, Ruediger; Biefer, Hector Rodriguez Cetina; Dékány, Gabriela Marta; Kubota, Hisashi; Münz, Christian; Wang, Sheng; Mohler, Hanns; Yonekawa, Yasuhiro; Frei, Karl

2009-02-01

330

Patients with sepsis exhibit increased mitochondrial respiratory capacity in peripheral blood immune cells  

PubMed Central

Introduction In sepsis, mitochondria have been associated with both initial dysfunction and subsequent upregulation (biogenesis). However, the evolvement of mitochondrial function in sepsis over time is largely unknown, and we therefore investigated mitochondrial respiration in peripheral blood immune cells (PBICs) in sepsis patients during the first week after admission to the intensive care unit (ICU). Methods PBICs from 20 patients with severe sepsis or septic shock were analyzed with high-resolution respirometry 3 times after admission to the ICU (within 48 hours, days 3 to 4 and days 6 to 7). Mitochondrial DNA (mtDNA), cytochrome c (Cyt c), and citrate synthase (CS) were measured as indicators of cellular mitochondrial content. Results In intact PBICs with endogenous substrates, a gradual increase in cellular respiration reached 173% of controls after 1 week (P = 0.001). In permeabilized cells, respiration using substrates of complex I, II, and IV were significantly increased days 1 to 2, reaching 137%, 130%, and 173% of controls, respectively. In parallel, higher levels of CS activity, mtDNA, and Cyt c content in PBICs (211%, 243%, and 331% of controls for the respective indicators were found at days 6 to 7; P < 0.0001). No differences in respiratory capacities were noted between survivors and nonsurvivors at any of the time points measured. Conclusions PBICs from patients with sepsis displayed higher mitochondrial respiratory capacities compared with controls, due to an increased mitochondrial content, as indicated by increased mitochondrial DNA, protein content, and enzyme activity. The results argue against mitochondrial respiratory dysfunction in this type of cells in sepsis.

2013-01-01

331

Clinical and environmental isolates of Burkholderia cepacia exhibit differential cytotoxicity towards macrophages and mast cells.  

PubMed

Burkholderia cepacia is an emerging opportunistic pathogen that causes fatal infections in patients suffering from cystic fibrosis (CF) and chronic granulomatous disease. Various environmental isolates of B. cepacia are, however, capable of degrading environmental pollutants, such as trichloroethylene, 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), etc., and are also highly effective in controlling plant diseases caused by nematodes and fungi. Such strains have therefore been proposed for environmental release to clean up toxic dump sites or as biopesticides. Various efforts to distinguish between clinical and environmental isolates of B. cepacia with regard to their virulence characteristics have produced ambiguous results, suggesting that newer methods are needed to test for the presence or absence of pathogenic potential in B. cepacia strains proposed for environmental release. We now report that several clinical strains of B. cepacia secrete cytotoxic factors that allow macrophage and mast cell death in the presence of external ATP. Several environmental strains had reduced activity in this regard. We also demonstrate that, while all the strains secrete enzymes that have nucleoside diphosphate kinase (Ndk), adenylate kinase (Ak) and 5'-nucleotidase activity, the level of secretion of the 5'-nucleotidase (and/or ATPase/phosphatase) appears to be lower in the environmental strains than in the clinical strains. The secretion of these enzymes is specifically activated in the presence of eukaryotic proteins such as alpha2-macroglobulin. As macrophage-or mast cell surface-associated P2Z receptors promote their cell death in the presence of mM concentrations of ATP, and as the secreted ATP-using enzymes generate various phosphorylated or non-phosphorylated adenine nucleotides that may even be better agonists than ATP in activating the P2Z receptors or may act through the activation of additional purinergic receptors, such enzymes may play an important role in allowing B. cepacia to evade host defence. PMID:10931297

Melnikov, A; Zaborina, O; Dhiman, N; Prabhakar, B S; Chakrabarty, A M; Hendrickson, W

2000-06-01

332

Hepatitis C virus proteins exhibit conflicting effects on the interferon system in human hepatocyte cells  

Microsoft Academic Search

We previously found that hepatitis C virus (HCV) core protein (Core) activated the interferon (IFN)-inducible 40\\/46kDa 2?-5?-oligoadenylate synthetase (2?-5?-OAS) gene through an IFN-stimulated response element (ISRE) in non-neoplastic human hepatocyte PH5CH8 cells. Here, we found that Core and NS5B synergistically enhanced the 2?-5?-OAS gene promoter activity through ISRE. Further analysis revealed that amino acid positions 12 and\\/or 13 of Core

Hiromichi Dansako; Kazuhito Naka; Masanori Ikeda; Nobuyuki Kato

2005-01-01

333

Bendamustine, but not fludarabine, exhibits a low stem cell toxicity in vitro  

Microsoft Academic Search

Purpose  We investigated the in vitro toxicity of bendamustine and fludarabine to hematopoietic progenitors and stem cells from healthy\\u000a donors.\\u000a \\u000a \\u000a \\u000a Methods  Clonogenic agar colony assays, non-clonogenic long-term liquid cultures (LTC) and apoptosis assays were used to assess the\\u000a cytotoxicity of both the agents.\\u000a \\u000a \\u000a \\u000a Results  Total colony-forming units (CFU) were more sensitive to fludarabine than to bendamustine in agar colony assays (IC50 0.7 ?M\\/L and

M. Schmidt-Hieber; A. Busse; B. Reufi; W. Knauf; E. Thiel; I. W. Blau

2009-01-01

334

Bright single-chain conjugated polymer dots embedded nanoparticles for long-term cell tracing and imaging.  

PubMed

Single-chain conjugated polymer (CP) dots embedded nanoparticles (NPs) bearing cell penetration peptide (TAT) as surface ligands are synthesized for long term cancer cell tracing applications. The CPNPs are fabricated by matrix-encapsulation method and the embedded CPs can be modulated into spherical dots with different size upon alteration of feed concentrations. Single-chain CP dots are formed upon decreasing feed concentration to 0.2 mg/mL, where CPNPs exhibit highest fluorescence quantum yield of 32%. Maleimide is introduced as the new NP surface functional group, which favors easy conjugation with cell penetration peptide via click chemistry to preserve its biofunctions. The obtained CPNPs show high brightness and good biocompatibility, which allow cell tracing for over 9 generations, superior to commercial cell tracker Qtracker 585. PMID:24339178

Feng, Guangxue; Li, Kai; Liu, Jie; Ding, Dan; Liu, Bin

2014-03-26

335

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

336

Pegylated siRNA-loaded calcium phosphate nanoparticle-driven amplification of cancer cell internalization in vivo  

PubMed Central

The cell membrane is a critical barrier to effective delivery for many therapeutics, including those which are nanoparticle-based. Improving nanoparticle transport across the cell membrane remains a fundamental challenge. Cancer cells preferentially internalized pegylated calcium phosphate nanoparticles over normal epithelial cells. Furthermore, non-cytotoxic levels of doxorubicin markedly amplified this difference by increasing free unbound caveolin-1 and resulted in enhanced caveolin-mediated nanoparticle endocytosis in cancer cells. Engineered pegylated siRNA-loaded triple-shell calcium phosphate nanoconstructs incorporating ultra-low levels of doxorubicin recapitulated these effects and delivered increased numbers of siRNA into cancer cells with target-specific results. Systemic administration of nanoparticles in vivo demonstrated highly preferential entry into tumors, little bystander organ biodistribution, and significant tumor growth arrest. In conclusion, siRNA-loaded calcium phosphate nanoparticles incorporating non-cytotoxic amounts of doxorubicin markedly enhances nanoparticle internalization and results in increased payload delivery with concomitant on-target effects.

Tobin, Lisa A.; Xie, Yili; Tsokos, Maria; Chung, Su I.; Merz, Allison A.; Arnold, Michael A.; Li, Guang; Malech, Harry L.; Kwong, King F.

2013-01-01

337

CEBPG Exhibits Allele-Specific Expression in Human Bronchial Epithelial Cells  

PubMed Central

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.

Blomquist, Thomas M.; Brown, Ronald D.; Crawford, Erin L.; de la Serna, Ivana; Williams, Kandace; Yoon, Youngsook; Hernandez, Dawn-Alita; Willey, James C.

2013-01-01

338

Human blood dendritic cell subsets exhibit discriminative pattern recognition receptor profiles.  

PubMed

Dendritic cells (DCs) operate as the link between innate and adaptive immunity. Their expression of pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and C-type lectin receptors (CLRs), enables antigen recognition and mediates appropriate immune responses. Distinct subsets of human DCs have been identified; however their expression of PRRs is not fully clarified. Expressions of CLRs by DC subpopulations, in particular, remain elusive. This study aimed to identify and compare PRR expressions on human blood DC subsets, including CD1c(+) , CD141(+) and CD16(+) myeloid DCs and CD123(+) plasmacytoid DCs, in order to understand their capacity to recognize different antigens as well as their responsiveness to PRR-directed targeting. Whole blood was obtained from 13 allergic and six non-allergic individuals. Mononuclear cells were purified and multi-colour flow cytometry was used to assess the expression of 10 CLRs and two TLRs on distinct DC subsets. PRR expression levels were shown to differ between DC subsets for each PRR assessed. Furthermore, principal component analysis and random forest test demonstrated that the PRR profiles were discriminative between DC subsets. Interestingly, CLEC9A was expressed at lower levels by CD141(+) DCs from allergic compared with non-allergic donors. The subset-specific PRR expression profiles suggests individual responsiveness to PRR-targeting and supports functional specialization. PMID:24444310

Lundberg, Kristina; Rydnert, Frida; Greiff, Lennart; Lindstedt, Malin

2014-06-01

339

Toxicity study of cerium oxide nanoparticles in human neuroblastoma cells.  

PubMed

The present study consisted of cytotoxic, genotoxic, and oxidative stress responses of human neuroblastoma cell line (IMR32) following exposure to different doses of cerium oxide nanoparticles (CeO2 NPs; nanoceria) and its microparticles (MPs) for 24 hours. Cytotoxicity was evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase assays whereas genotoxicity was assessed using the cytokinesis-block micronucleus and comet assays. A battery of assays including lipid peroxidation, reactive oxygen species (ROS), hydrogen peroxide, reduced glutathione, nitric oxide, glutathione reductase, glutathione peroxidase, superoxide dismutase, catalase, and glutathione S-transferase were performed to test the hypothesis that ROS was responsible for the toxicity of nanoceria. The results showed that nanosized CeO2 was more toxic than cerium oxide MPs. Hence, further study on safety evaluation of CeO2 NPs on other models is recommended. PMID:24510415

Kumari, Monika; Singh, Shailendra Pratap; Chinde, Srinivas; Rahman, Mohammed Fazlur; Mahboob, Mohammed; Grover, Paramjit

2014-01-01

340

One-Step Bulk Synthesis of Stable, Near Unit-Cell Sized Oxide Nanoparticles and Nanoparticle Blends Using KO2.  

PubMed

Presented here is a novel one-step synthesis of oxide or hydroxide nanoparticles using, for the first time, potassium superoxide (KO2). This work demonstrates that the reaction of KO2 with different salt solutions produces grams of stable, near unit-cell sized nanoparticles. This new synthetic technique is applied to representative elements from across the periodic table to rapidly produce nanometer sized oxides or hydroxides of Mg, Al, Y, Ti, Mn, Fe, Co, Ni, Cu, Zn, Sn, Tl, Pb, and Ce. This technique is also used to produce blends of nanoparticles, demonstrating the ability to prepare complex materials such as nanoparticulate blends of a lithium cathode material (LiCoO2), the multiferroic compound (BiMnO3+?), and the superconducting YBa2Cu3O7-?. PMID:24724979

Sutto, Thomas E

2014-05-01

341

Nanoparticle mediated ablation of breast cancer cells using a nanosecond pulsed electric field  

NASA Astrophysics Data System (ADS)

In the past, both nanomaterials and various heating modalities have been researched as means for treating cancers. However, many of the current methodologies have the flaws of inconsistent tumor ablation and significant destruction of healthy cells. Based on research performed using constant radiofrequency electric fields and metallic nanoparticles (where cell necrosis is induced by the heating of these nanoparticles) we have developed a modality that simlarly uses functionalized metallic nanoparticles, specific for the T47D breast cancer cell line, and nanosecond pulsed electric fields as the hyperthermic inducer. Using both iron oxide and gold nanoparticles the results of our pilot studies indicated that up to 90% of the cancer cells were ablated given the optimal treatment parameters. These quantities of ablated cells were achieved using a cumulative exposure time 6 orders of magnitude less than most in vitro radiofrequency electric field studies.

Burford, Christopher

342

Study of gold nanoparticles and live cells interactions by using planar evanescent wave excitation  

NASA Astrophysics Data System (ADS)

We present a planar evanescent wave (PEW) technique combined with phase contrast optical microscopy to study the interactions between cells and gold nanoparticles (AuNPs). The PEW method employs a dual-fiber-line guide to couple light into a thin glass slide. It produces a uniform and long evanescent wave near the glass surface, as verified by the optical near-field measurement. High-contrast AuNP images are obtained by the PEW illumination. At the same time, cells are observed only by using the phase contrast microscopy. The nanoparticles and cell images indicated that unmodified AuNPs had no interactions with cells, possibly due to the negative surface charges on both cells and nanoparticles. The electrostatic concept was further verified by coating AuNPs with positively charged poly (L-lysine). DNA aptamers for surface mucin glycoprotein were coated on AuNPs to demonstrate the application for single nanoparticle tracking.

Lee, Chia-Wei; Lin, En-Hong; Cheng, Ji-Yen; Wei, Pei-Kuen

2009-03-01

343

Substituted titanocenes induce caspase-dependent apoptosis in human epidermoid carcinoma cells in vitro and exhibit antitumour activity in vivo  

PubMed Central

Titanocene compounds are a novel series of agents that exhibit cytotoxic effects in a variety of human cancer cells in vitro and in vivo. In this study, the antiproliferative activity of two titanocenes (Titanocenes X and Y) was evaluated in human epidermoid cancer cells in vitro. Titanocenes X and Y induce apoptotic cell death in epidermoid cancer cells, with IC50 values that are comparable to cisplatin. Characterisation of the cell death pathway induced by titanocene compounds in A431 cells revealed that apoptosis is preceded by cell cycle arrest and the inhibition of cell proliferation. The induction of apoptosis is dependent on the activation of caspase-3 and -7 but not caspase-8. Furthermore, the antitumour activity of Titanocene Y was tested in an A431 xenograft model of epidermoid cancer. Results indicate that Titanocene Y significantly reduced the growth of A431 xenografts with an antitumour effect similar to cisplatin. These results suggest that titanocenes represent a novel series of promising antitumour agents.

Bannon, J H; Fichtner, I; O'Neill, A; Pampillon, C; Sweeney, N J; Strohfeldt, K; Watson, R W; Tacke, M; Mc Gee, M M

2007-01-01

344

Novel curcumin analogue IHCH exhibits potent anti?proliferative effects by inducing autophagy in A549 lung cancer cells.  

PubMed

Curcumin is a natural polyphenolic compound that exhibits strong antioxidant and anticancer activities; however, low bioavailability has restricted its application in chemotherapeutic trials. The present study aimed to investigate the anticancer effect of the novel curcumin derivative 2E,6E?2?(1H?indol?3?yl) methylene)?6?(4?hydroxy?3?methoxy benzylidene)?cyclohexanone (IHCH) on A549 lung cancer cells. Cells were treated with IHCH at different concentrations (1?40 µM) for different time periods (1?36 h). Microscopic analysis revealed that IHCH inhibited A549 cell growth and induced the formation of characteristic autophagolysosomes in a dose? and time?dependent manner. Furthermore, the inhibitory rate of IHCH (40 µM) on A549 cell viability was 77.34% after 36 h of treatment. Acridine orange staining revealed an increase in autophagic vacuoles in the IHCH?treated A549 cells. Monodansylcadaverine staining was used to analyze autophagy rate. Immunocytochemistry revealed an increase in light chain (LC) 3 protein expression in the IHCH?treated cells and western blot analysis detected the conversion of LC3?I to LC3?II, as well as the recruitment of LC3 to autophagosomes in the cytoplasmatic compartment, suggesting the occurrence of autophagy. These findings show that IHCH induced autophagy in A549 cells, which is a novel cell death mechanism induced by curcumin derivatives. PMID:24788478

Zhou, Guang-Zhou; Xu, Su-Li; Sun, Gang-Chun; Chen, Xiao-Bing

2014-07-01

345

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

2013-01-01

346

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

347

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

348

Translocation of Cell Penetrating Peptide Engrafted Nanoparticles Across Skin Layers  

PubMed Central

The objective of the current study was to evaluate the ability of cell penetrating peptides (CPP) to translocate the lipid payload into the skin layers. Fluorescent dye (DID-oil) encapsulated nano lipid crystal nanoparticles (FNLCN) were prepared using Compritol, Miglyol and DOGS-NTA-Ni lipids by hot melt homogenization technique. The FNLCN surface was coated with TAT peptide (FNLCNT) or control YKA peptide (FNLCNY) and in vitro rat skin permeation studies were performed using Franz diffusion cells. Observation of lateral skin sections obtained using cryotome with a confocal microscope demonstrated that skin permeation of FNLCNT was time dependent and after 24 h, fluorescence was observed upto a depth of 120 µm which was localized in the hair follicles and epidermis. In case of FNLCN and FNLCNY formulations fluorescence was mainly observed in the hair follicles. This observation was further supported by confocal Raman spectroscopy where higher fluorescence signal intensity was observed at 80 and 120 µm depth with FNLCNT treated skin and intensity of fluorescence peaks was in the ratio of 2:1:1 and 5:3:1 for FNLCNT, FNLCN, and FNLCNY treated skin sections, respectively. Furthermore, replacement of DID-oil with celecoxib (Cxb), a model lipophilic drug showed similar results and after 24 h, the CXBNT formulation increased the Cxb concentration in SC by 3 and 6 fold and in epidermis by 2 and 3 fold as compared to CXBN and CXBNY formulations respectively. Our results strongly suggest that CPP can translocate nanoparticles with their payloads into deeper skin layers.

Patlolla, Ram R; Desai, Pinaki; Belay, Kalayu; Singh, Mandip

2010-01-01

349

Museum Exhibit  

NASA Technical Reports Server (NTRS)

A TSP from NASA Tech Briefs provided the solution to an electrical problem at a Florida museum. When a model train would not start without a jerk, a Marshall Space Flight Center development called pulse width control was adapted. The new circuit enables the train to start smoothly and reduces construction and maintenance costs. The same technology is also used in another hands-on exhibit. Applications of other TSPs are anticipated.

1991-01-01

350

Retinal cone and rod photoreceptor cells exhibit differential susceptibility to light-induced damage  

PubMed Central

All-trans-retinal and its condensation-products can cause retinal degeneration in a light–dependent manner and contribute to the pathogenesis of human macular diseases such as Stargardt’s disease and age–related macular degeneration (AMD). Although these toxic retinoid by–products originate from rod and cone photoreceptor cells, the contribution of each cell type to light–induced retinal degeneration is unknown. Here the primary objective was to learn whether rods or cones are more susceptible to light–induced, all–trans–retinal–mediated damage. Previously, we reported that mice lacking enzymes that clear all–trans–retinal from the retina, ATP–binding cassette transporter 4 (ABCA4) and retinol dehydrogenase 8 (RDH8), manifested light-induced retinal dystrophy. We first examined early-stage-AMD patients and found retinal degenerative changes in rod-rich rather than cone-rich regions of the macula. We then evaluated transgenic mice with rod–only and cone–like–only retinas in addition to progenies of such mice inbred with Rdh8?/? Abca4?/? mice. Of all these strains, Rdh8?/? Abca4?/? mice with a mixed rod–cone population showed the most severe retinal degeneration under regular cyclic light conditions. Intense light exposure induced acute retinal damage in Rdh8?/? Abca4?/? and rod–only mice but not cone–like–only mice. These findings suggest that progression of retinal degeneration in Rdh8-/- Abca4-/- mice is affected by differential vulnerability of rods and cones to light.

Okano, Kiichiro; Maeda, Akiko; Chen, Yu; Chauhan, Vishal; Tang, Johnny; Palczewska, Grazyna; Sakai, Tsutomu; Tsuneoka, Hiroshi; Palczewski, Krzysztof; Maeda, Tadao

2012-01-01

351

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

352

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

353

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,