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1

Carboplatin loaded protein nanoparticles exhibit improve anti-proliferative activity in retinoblastoma cells.  

PubMed

Retinoblastoma, a common neoplasm of eye in children accounts about 9-10% of all paediatric cancer. Carboplatin (carbo) is preferred chemotherapeutic regimen. In this study the prospective of carboplatin loaded apotranferrin (Apo-nano-carbo) and lactoferrin (Lacto-nano-carbo) nanoparticles have been demonstrated for the treatment of retinoblastoma. Apo-nano-carbo and Lacto-nano-carbo were prepared by sol-oil method (as a patented formula) with size of 82-92 nm and 68-81 nm, hydrodynamic size were 142±15 nm and 263±20 nm, encapsulation efficiency were 50%±2.3 and 52%±3.9 respectively. Results of pH dependent-drug release and receptor-blocking assay showed that nanoparticles may deliver drug through receptor mediated endocytosis. The carboplatin loaded nanoparticles shows greater intracellular uptake, sustained retention and thus, high anti-proliferative activity (Apo-nano-carbo IC50=4.31 ?g ml(-1), Lacto-nano-carbo IC50=4.16 ?g ml(-1), Sol-carbo IC50=13.498 ?g ml(-1)) into the retinoblastoma cells compared to their soluble counterpart. PMID:25088498

Ahmed, Farhan; Ali, Mohammad Javed; Kondapi, Anand K

2014-09-01

2

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. PMID:25045260

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

2014-01-01

3

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

PubMed

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

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

2013-01-01

4

Cell tracking using nanoparticles.  

PubMed

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

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

2008-09-01

5

Implications and consequences of ferromagnetism universally exhibited by inorganic nanoparticles  

NASA Astrophysics Data System (ADS)

The occurrence of surface ferromagnetism in inorganic nanoparticles as a universal property not only explains many of the unusual magnetic features of oxidic thin films, but also suggests its possible use in creating new materials, as exemplified by multiferroic BaTiO 3 nanoparticles. While the use of Mn-doped ZnO and such materials in spintronics appears doubtful, it is possible to have materials exhibiting the coexistence of (bulk) superconductivity and (surface) ferromagnetism.

Sundaresan, A.; Rao, C. N. R.

2009-08-01

6

Functional nanoparticles in cells  

NASA Astrophysics Data System (ADS)

In this paper we present an overview of our recent studies regarding the interactions of functional nanoparticles with the human umbilical endothelial cells (HUVECs). Cellular uptake, cytotoxicity and laser hyperthermia of cells loaded with gold nanoparticles are discussed. Particles with different shape, size and charge are compared and evaluated to conclude at the most appropriate types for specific biomedical applications (i.e. drug delivery, laser hyperthermia).

Bartczak, Dorota; Muskens, Otto L.; Nitti, Simone; Sanchez-Elsner, Tilman; Millar, Timothy M.; Kanaras, Antonios G.

2012-03-01

7

Lipid-coated Cisplatin nanoparticles induce neighboring effect and exhibit enhanced anticancer efficacy.  

PubMed

Encapsulation of cisplatin (CDDP) into nanoparticles (NPs) with high drug loading and encapsulation efficiency has been difficult due to the poor solubility of CDDP. However, this barrier has been overcome with a reverse microemulsion method appropriating CDDP's poor solubility to our advantage promoting the synthesis of a pure cisplatin nanoparticle with a high drug loading capacity (approximately 80.8 wt %). Actively targeted CDDP NPs exhibited significant accumulation in human A375M melanoma tumor cells in vivo. In addition, CDDP NPs achieved potent antitumor efficacy through the neighboring effect at a dose of 1 mg/kg when injected weekly via iv without inducing nephrotoxicity. The neighboring effect regards an observation made in vivo when the tumor cells that took up CDDP NPs released active drug following apoptosis. Via diffusion, surrounding cells that were previously unaffected showed intake of the released drug and their apoptosis soon followed. This observation was also made in vitro when A375M melanoma tumor cells incubated with CDDP NPs exhibited release of active drug and induced apoptosis on untreated neighboring cells. However, the neighboring effect was unique to rapidly proliferating tumor cells. Liver functional parameters and H&E staining of liver tissue in vivo failed to detect any difference between CDDP NP treated and control groups in terms of tissue health. By simultaneously promoting an increase in cytotoxicity and a lesser degree of side effects over free CDDP, CDDP NPs show great therapeutic potential with lower doses of drug while enhancing anticancer effectiveness. PMID:24083505

Guo, Shutao; Wang, Yuhua; Miao, Lei; Xu, Zhenghong; Lin, C Michael; Zhang, Yuan; Huang, Leaf

2013-11-26

8

SDF-1? in Glycan Nanoparticles Exhibits Full Activity and Reduces Pulmonary Hypertension in Rats  

PubMed Central

In order to establish a homing signal in the lung to recruit circulating stem cells for tissue repair, we formulated a nanoparticle, SDF-1? NP, by complexing SDF-1? with dextran sulfate and chitosan. The data show that SDF-1? was barely released from the nanoparticles over an extended period of time in vitro (3% in 7 days at 37°C); however, incorporated SDF-1? exhibited full chemotactic activity and receptor activation compared to its free form. The nanoparticles were not endocytosed after incubation with Jurkat cells. When aerosolized into the lungs of rats, SDF-1? NP displayed a greater retention time compared to free SDF-1? (64% vs. 2% remaining at 16 hr). In a rat model of monocrotaline-induced lung injury, SDF-1? NP, but not free form SDF-1?, was found to reduce pulmonary hypertension. These data suggest that the nanoparticle formulation protected SDF-1? from rapid clearance in the lung and sustained its biological function in vivo. PMID:24059347

Yin, Tao; Bader, Andrew R.; Hou, Tim K.; Maron, Bradley A.; Kao, Derrick D.; Qian, Ray; Kohane, Daniel S.; Handy, Diane E.; Loscalzo, Joseph; Zhang, Ying-Yi

2013-01-01

9

Conjugated polymer nanoparticles for cell membrane imaging.  

PubMed

The outstanding optical properties and biocompatibility of fluorescent conjugated polymer nanoparticles (CPNs) make them favorable for bioimaging application. However, few CPNs could achieve stable cell membrane labeling due to cell endocytosis. In this work, conjugated polymer nanoparticles (PFPNP-PLE) encapsulated with PFP and PLGA-PEG-N3 in the matrix and functionalized with the small-molecule drug plerixafor (PLE) on the surface were prepared by a mini-emulsion method. PFPNP-PLE exhibits excellent photophysical properties, low cytotoxicity, and specific cytomembrane location, which makes it a potential cell membrane labeling reagent with blue fluorescence emission, an important component for multilabel/multicolor bioimaging. PMID:25200372

Li, Meng; Nie, Chenyao; Feng, Liheng; Yuan, Huanxiang; Liu, Libing; Lv, Fengting; Wang, Shu

2014-11-01

10

Exhibits  

Microsoft Academic Search

With more than 40 sessions covering the hottest topics in today's industry, ASLRRA's Annual Convention is widely regarded as the premier educational event for employees of small railroads. But don't overlook the excellent learning opportunities housed in the only Exhibit Hall specifically geared toward the short line industry and featuring the latest and greatest products and services for your operation.

M. Derryberry

1941-01-01

11

Zinc oxide nanoparticles as selective killers of proliferating cells  

PubMed Central

Background: It has recently been demonstrated that zinc oxide nanoparticles (ZnO NPs) induce death of cancerous cells whilst having no cytotoxic effect on normal cells. However, there are several issues which need to be resolved before translation of zinc oxide nanoparticles into medical use, including lack of suitable biocompatible dispersion protocols and a better understanding being needed of the mechanism of their selective cytotoxic action. Methods: Nanoparticle dose affecting cell viability was evaluated in a model of proliferating cells both experimentally and mathematically. The key issue of selective toxicity of ZnO NPs toward proliferating cells was addressed by experiments using a biological model of noncancerous cells, ie, mesenchymal stem cells before and after cell differentiation to the osteogenic lineage. Results: In this paper, we report a biocompatible protocol for preparation of stable aqueous solutions of monodispersed zinc oxide nanoparticles. We found that the threshold of intracellular ZnO NP concentration required to induce cell death in proliferating cells is 0.4 ± 0.02 mM. Finally, flow cytometry analysis revealed that the threshold dose of zinc oxide nanoparticles was lethal to proliferating pluripotent mesenchymal stem cells but exhibited negligible cytotoxic effects to osteogenically differentiated mesenchymal stem cells. Conclusion: Results confirm the ZnO NP selective cytotoxic action on rapidly proliferating cells, whether benign or malignant. PMID:21698081

Taccola, Liuba; Raffa, Vittoria; Riggio, Cristina; Vittorio, Orazio; Iorio, Maria Carla; Vanacore, Renato; Pietrabissa, Andrea; Cuschieri, Alfred

2011-01-01

12

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. PMID:19653303

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

2009-01-01

13

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

NASA Astrophysics Data System (ADS)

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

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

2008-07-01

14

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

15

Anticancer activity of cisplatin-loaded PLGA-mPEG nanoparticles on LNCaP prostate cancer cells  

Microsoft Academic Search

The in vitro anticancer activity of cisplatin-loaded PLGA-mPEG nanoparticles on human prostate cancer LNCaP cells was investigated. The uptake of the PLGA-mPEG nanoparticles by the LNCaP cells was also studied. Blank PLGA-mPEG nanoparticles exhibited low cytotoxicity, which increased with increasing PLGA\\/PEG ratio in the PLGA-mPEG copolymer used to prepare the nanoparticles, possibly due to the increased cell uptake observed with

Evangelos C. Gryparis; Maria Hatziapostolou; Evangelia Papadimitriou; Konstantinos Avgoustakis

2007-01-01

16

Cisplatin-tethered gold nanoparticles that exhibit enhanced reproducibility, drug loading, and stability: a step closer to pharmaceutical approval?  

PubMed

Gold nanoparticles (AuNPs) can be used as delivery vehicles for platinum anticancer drugs, improving their targeting and uptake into cells. Here, we examine the appropriateness of different-sized AuNPs as components of platinum-based drug-delivery systems, investigating their controlled synthesis, reproducibility, consistency of drug loading, and stability. The active component of cisplatin was tethered to 25, 55, and 90 nm AuNPs, with the nanoparticles being almost spherical in nature and demonstrating good batch-to-batch reproducibility (24.37 ± 0.62, 55.2 ± 1.75, and 89.1 ± 2.32 nm). The size distribution of 25 nm AuNPs has been significantly improved, compared with a previous method that produces polydispersed nanoparticles. Attachment of platinum to the AuNP surface through a poly(ethylene glycol) (PEG) linker exhibits an increase in the drug loading with increasing particle size: 25 nm (815 ± 106 drug molecules per AuNP), 55 nm (14216 ± 880), and 90 nm (54487 ± 15996). The stability of the naked, PEGylated, and platinum-conjugated nanoparticles has been examined over time under various conditions. When stored at 4 °C, there is minimal variation in the diameter for all three AuNP sizes; variation after 28 days for the 25 nm AuNPs was 2.4%; 55 nm, 3.3%; and 90 nm, 3.6%. The 25 nm AuNPs also demonstrate minimal changes in UV-visible absorbance over the same time period. PMID:22390791

Craig, Gemma E; Brown, Sarah D; Lamprou, Dimitrios A; Graham, Duncan; Wheate, Nial J

2012-03-19

17

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

18

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. PMID:23638335

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

2013-01-01

19

Gold nanoparticles for in vivo cell tracking.  

PubMed

Cell-based therapy offers a promising solution for the treatment of diseases and injuries that conventional medicines and therapies cannot cure effectively, and thus comprises an encouraging arena for future medical breakthroughs. The development of an accurate and quantitative noninvasive cell tracking technique is a highly challenging task that could help in evaluating the effectiveness of treatments. Moreover, cell tracking could provide essential knowledge regarding the fundamental trafficking patterns and poorly understood mechanisms underlying the success or failure of cell therapy. This article focuses on gold nanoparticles, which provide cells with 'visibility' in a variety of imaging modalities for stem cell therapy, immune cell therapy and cancer treatment. Current challenges and future prospects relating to the use of gold nanoparticles in such roles are discussed. PMID:25343353

Meir, Rinat; Motiei, Menachem; Popovtzer, Rachela

2014-09-01

20

Nanoparticle Solar Cell Final Technical Report  

SciTech Connect

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

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

2008-06-17

21

Layer-by-layer deposited multilayer films of water soluble polythiophene derivative and gold nanoparticles exhibiting photoresponsive properties  

Microsoft Academic Search

Multilayer films of poly(3,4-(3?,3?-dithienyloxy) propyltrimethylammonium bromide) (P34TOPA) and 11-mercaptoundecanonate (MUA) capped gold nanoparticles (GNPs) have been fabricated by layer-by-layer (LBL) deposition. These films exhibit enhanced photoresponsive properties in comparison with those of a monolayer of P34TOPA and MUA capped GNPs. The photocurrent densities increased linearly with the bilayer number (1–10) of the multilayer films, indicating a sufficient charge separation and

Shibin Wang; Chun Li; Feng’en Chen; Gaoquan Shi

2007-01-01

22

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. PMID:22101191

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

2012-01-01

23

Nanoparticle-based monitoring of cell therapy  

NASA Astrophysics Data System (ADS)

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

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

2011-12-01

24

Acentrosomal Drosophila epithelial cells exhibit abnormal cell division, leading to cell death and compensatory proliferation.  

PubMed

Mitotic spindles are critical for accurate chromosome segregation. Centrosomes, the primary microtubule nucleating centers of animal cells, play key roles in forming and orienting mitotic spindles. However, the survival of Drosophila without centrosomes suggested they are dispensable in somatic cells, challenging the canonical view. We used fly wing disc epithelia as a model to resolve these conflicting hypotheses, revealing that centrosomes play vital roles in spindle assembly, function, and orientation. Many acentrosomal cells exhibit prolonged spindle assembly, chromosome missegregation, DNA damage, misoriented divisions, and eventual apoptosis. We found that multiple mechanisms buffer the effects of centrosome loss, including alternative microtubule nucleation pathways and the spindle assembly checkpoint. Apoptosis of acentrosomal cells is mediated by JNK signaling, which also drives compensatory proliferation to maintain tissue integrity and viability. These data reveal the importance of centrosomes in fly epithelia and demonstrate the robust compensatory mechanisms at the cellular and organismal level. PMID:25241934

Poulton, John S; Cuningham, John C; Peifer, Mark

2014-09-29

25

Biocompatibility of cerium dioxide and silicon dioxide nanoparticles with endothelial cells  

PubMed Central

Summary Cerium dioxide (CeO2) and silicon dioxide (SiO2) nanoparticles are of widespread use in modern life. This means that human beings are markedly exposed to them in their everyday life. Once passing biological barriers, these nanoparticles are expected to interact with endothelial cells, leading to systemic alterations with distinct influences on human health. In the present study we observed the metabolic impact of differently sized CeO2 (8 nm; 35 nm) and SiO2 nanoparticles (117 nm; 315 nm) on immortalized human microvascular (HMEC-1) and primary macrovascular endothelial cells (HUVEC), with particular focus on the CeO2 nanoparticles. The characterization of the CeO2 nanoparticles in cell culture media with varying serum content indicated a steric stabilization of nanoparticles due to interaction with proteins. After cellular uptake, the CeO2 nanoparticles were localized around the nucleus in a ring-shaped manner. The nanoparticles revealed concentration and time, but no size-dependent effects on the cellular adenosine triphosphate levels. HUVEC reacted more sensitively to CeO2 nanoparticle exposure than HMEC-1. This effect was also observed in relation to cytokine release after nanoparticle treatment. The CeO2 nanoparticles exhibited a specific impact on the release of diverse proteins. Namely, a slight trend towards pro-inflammatory effects, a slight pro-thrombotic impact, and an increase of reactive oxygen species after nanoparticle exposure were observed with increasing incubation time. For SiO2 nanoparticles, concentration- and time-dependent effects on the metabolic activity as well as pro-inflammatory reactions were detectable. In general, the effects of the investigated nanoparticles on endothelial cells were rather insignificant, since the alterations on the metabolic cell activity became visible at a nanoparticle concentration that is by far higher than those expected to occur in the in vivo situation (CeO2 nanoparticles: 100 µg/mL; SiO2 nanoparticles: 10 µg/mL). PMID:25383291

Strobel, Claudia; Forster, Martin

2014-01-01

26

Lunar soil simulant and synthesized nanoparticles of magnetite exhibit diverse neurotoxic potential  

NASA Astrophysics Data System (ADS)

Lunar soli simulant can be deleterious to human physiology and the components of lunar soil may be internalized by lung epithelium and may overcome the blood-brain barrier. Nanoparticles of ferric oxide are one of the components of Lunar soil simulants. Neurotoxic potential of lunar soil simulant and synthesized nanoparticles of magnetite was analyzed. The size of particles, their effects on membrane potential, acidification of synaptic vesicles, uptake and ambient level of glutamate, which is the major excitatory neurotransmitter in the CNS, were studied in isolated rat brain nerve terminals (synaptosomes) using photon correlation spectroscopy, spectrofluorimetry, radiolabeled assay, respectively. No significant effect of Lunar soil simulant and synthesized nanoparticles of magnetite on acidification of synaptic vesicles were found in synaptosomes. Also, nanoparticles did not influence the potential of the plasma membrane of synaptosomes. Unspecific binding of L-[14C]glutamate to synaptosomes was not altered by nanoparticles of magnetite, whereas in the presence of Lunar soil simulant this parameter was changed. Thus, it was suggested that Lunar soil simulant might disturb glutamate homeostasis in the mammalian CNS.

Borisova, Tatiana; Krisanova, Natalia; Sivko, Roman; Nazarova, Anastasiya; Borysov, Arseniy

27

Magnetic nanoparticles coated with carboxymethylated polysaccharide shells—Interaction with human cells  

NASA Astrophysics Data System (ADS)

The interaction of magnetic core shell nanoparticles with living cells depends on the structure of the shell. In this paper we demonstrate a strong difference in the cell-nanoparticle interaction depending on the backbone of carboxymethylated polysaccharides used as shell material. Carboxymethyl cellulose with its ?-1?4 linked structure and the carboxymethylated pullulan [?-1?6 linked maltotriose with ?-1?4 linkages] show a constant interaction rate with both, tumor cells and leukocytes. In contrast, carboxymethyl dextran with a ?-1?6 linked backbone exhibits a rapid interaction kinetic with tumor cells that is reduced with leukocytes as target.

Wotschadlo, Jana; Liebert, Tim; Heinze, Thomas; Wagner, Kerstin; Schnabelrauch, Matthias; Dutz, Silvio; Müller, Robert; Steiniger, Frank; Schwalbe, Manuela; Kroll, Torsten C.; Höffken, Klaus; Buske, Norbert; Clement, Joachim H.

2009-05-01

28

Photosensitive Pt(IV)-azide prodrug-loaded nanoparticles exhibit controlled drug release and enhanced efficacy in vivo.  

PubMed

Cisplatin has long been the first line of treatment for a variety of solid tumors. However, poor pharmacokinetics and high incidences of resistance in the clinic have motivated the production of numerous alternative Pt-based anticancer species. Recently, photosensitive Pt(IV) complexes have garnered much interest because they offer a method of selective induction of active Pt(II) at the tumor site by UVA irradiation. Here, we report the first synthesis, in vitro and in vivo characterization of a novel series of photosensitive Pt(IV)–azide prodrugs and micellar nanoparticle formulations thereof. Upon mild UVA irradiation, both free Pt(IV) complexes and micellar nanoparticles rapidly released biologically active Pt(II), capable of binding to 5?-GMP,while remaining extremely stable in the dark. In vitro, uptake of photosensitive Pt(IV) prodrugs by ovarian cancer SKOV-3 cells was greatly enhanced with the micellar nanoparticles compared to their free prodrug analogs, as well as cisplatin and oxaliplatin. Increased cytotoxicity was observed upon UVA treatment, with up to a 13-fold enhancement over oxaliplatin for the micellar nanoparticles. In vivo bioavailability of micellar nanoparticles was enhanced ~10 fold over free Pt(IV) prodrugs. Importantly, micellar nanoparticles demonstrated significantly improved efficacy against H22 murine hepatocarcinoma, showing decreased systemic toxicity and increased tumor growth inhibition relative to small molecule drugs. These findings establish that photosensitive Pt(IV) complexes, specifically when formulated into micellar nanoparticles, have the potential to offer a robust platform for the controlled delivery and selective activation of Pt-based anticancer therapeutics. PMID:24511610

Xiao, Haihua; Noble, Gavin T; Stefanick, Jared F; Qi, Ruogu; Kiziltepe, Tanyel; Jing, Xiabin; Bilgicer, Basar

2014-01-10

29

Nanoparticle labeling identifies slow cycling human endometrial stromal cells  

PubMed Central

Introduction Evidence suggests that the human endometrium contains stem or progenitor cells that are responsible for its remarkable regenerative capability. A common property of somatic stem cells is their quiescent state. It remains unclear whether slow-cycling cells exist in the human endometrium. We hypothesized that the human endometrium contains a subset of slow-cycling cells with somatic stem cell properties. Here, we established an in vitro stem cell assay to isolate human endometrial-derived mesenchymal stem-like cells (eMSC). Methods Single-cell stromal cultures were initially labeled with fluorescent nanoparticles and a small population of fluorescent persistent cells (FPC) remained after culture of 21 days. Two populations of stromal cells, namely FPC and non-FPC were sorted. Results Quantitative analysis of functional assays demonstrated that the FPC had higher colony forming ability, underwent more rounds of self-renewal and had greater enrichment of phenotypically defined prospective eMSC markers: CD146+/CD140b+ and W5C5+ than the non-FPC. They also differentiate into multiple mesenchymal lineages and the expression of lineage specific markers was lower than that of non-FPC. The FPC exhibit low proliferation activities. A proliferation dynamics study revealed that more FPC had a prolonged G1 phase. Conclusions With this study we present an efficient method to label and isolate slow-proliferating cells obtained from human endometrial stromal cultures without genetic modifications. The FPC population could be easily maintained in vitro and are of interest for tissue-repair and engineering perspectives. In summary, nanoparticle labeling is a promising tool for the identification of putative somatic stem or progenitor cells when their surface markers are undefined. PMID:24996487

2014-01-01

30

Cell-mediated delivery of nanoparticles: taking advantage of circulatory cells to target nanoparticles.  

PubMed

Cellular hitchhiking leverages the use of circulatory cells to enhance the biological outcome of nanoparticle drug delivery systems, which often suffer from poor circulation time and limited targeting. Cellular hitchhiking utilizes the natural abilities of circulatory cells to: (i) navigate the vasculature while avoiding immune system clearance, (ii) remain relatively inert until needed and (iii) perform specific functions, including nutrient delivery to tissues, clearance of pathogens, and immune system surveillance. A variety of synthetic nanoparticles attempt to mimic these functional attributes of circulatory cells for drug delivery purposes. By combining the advantages of circulatory cells and synthetic nanoparticles, many advanced drug delivery systems have been developed that adopt the concept of cellular hitchhiking. Here, we review the development and specific applications of cellular hitchhiking-based drug delivery systems. PMID:24747161

Anselmo, Aaron C; Mitragotri, Samir

2014-09-28

31

Hepatoma SK Hep-1 Cells Exhibit Characteristics of Oncogenic Mesenchymal Stem Cells with Highly Metastatic Capacity  

PubMed Central

Background SK Hep-1 cells (SK cells) derived from a patient with liver adenocarcinoma have been considered a human hepatoma cell line with mesenchymal origin characteristics, however, SK cells do not express liver genes and exhibit liver function, thus, we hypothesized whether mesenchymal cells might contribute to human liver primary cancers. Here, we characterized SK cells and its tumourigenicity. Methods and Principal Findings We found that classical mesenchymal stem cell (MSC) markers were presented on SK cells, but endothelial marker CD31, hematopoietic markers CD34 and CD45 were negative. SK cells are capable of differentiate into adipocytes and osteoblasts as adipose-derived MSC (Ad-MSC) and bone marrow-derived MSC (BM-MSC) do. Importantly, a single SK cell exhibited a substantial tumourigenicity and metastatic capacity in immunodefficient mice. Metastasis not only occurred in circulating organs such as lung, liver, and kidneys, but also in muscle, outer abdomen, and skin. SK cells presented greater in vitro invasive capacity than those of Ad-MSC and BM-MSC. The xenograft cells from subcutaneous and metastatic tumors exhibited a similar tumourigenicity and metastatic capacity, and showed the same relatively homogenous population with MSC characteristics when compared to parental SK cells. SK cells could unlimitedly expand in vitro without losing MSC characteristics, its tumuorigenicity and metastatic capacity, indicating that SK cells are oncogenic MSC with enhanced self-renewal capacity. We believe that this is the first report that human MSC appear to be transformed into cancer stem cells (CSC), and that their derivatives also function as CSCs. Conclusion Our findings demonstrate that SK cells represent a transformation mechanism of normal MSC into an enhanced self-renewal CSC with metastasis capacity, SK cells and their xenografts represent a same relative homogeneity of CSC with substantial metastatic capacity. Thus, it represents a novel mechanism of tumor initiation, development and metastasis by CSCs of non-epithelial and endothelia origin. PMID:25338121

Zhang, Yanling; Zhang, Yanhong; Tschudy-Seney, Benjamin; Ramsamooj, Rajen; Wan, Yu-Jui Yvonne; Theise, Neil D.; Zern, Mark A.; Duan, Yuyou

2014-01-01

32

Cytotoxicity of monodispersed chitosan nanoparticles against the Caco-2 cells.  

PubMed

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. PMID:22609640

Loh, Jing Wen; Saunders, Martin; Lim, Lee-Yong

2012-08-01

33

Regenerated hair cells exhibit a transient resistance to aminoglycoside toxicity  

Microsoft Academic Search

Recent studies have demonstrated that sensory hair cells in the avian inner ear are reproduced by cell proliferation in response to the death of the original hair cell population. The regenerated hair cells appear to construct functional synaptic contacts, thereby transmitting acoustic signals to the peripheral nervous system. One of the most extraordinary, but overlooked characteristics of these regenerated hair

Eri Hashino; Richard J. Salvi

1996-01-01

34

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

35

Simple monitoring of cancer cells using nanoparticles.  

PubMed

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

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

2012-08-01

36

Rabeprazole exhibits antiproliferative effects on human gastric cancer cell lines  

PubMed Central

Intracellular proton extrusion in gastric cancer cells has been reported to promote cancer cell survival under acidic conditions via hydrogen/potassium adenosine triphosphatase (H+/K+-ATPase). Rabeprazole is a frequently used second-generation proton pump inhibitor (PPI) that irreversibly inactivates gastric H+/K+-ATPase. Therefore, we hypothesized that rabeprazole could reduce the viability of gastric cancer cells. In the present study, four human gastric cancer cell lines and one non-cancer gastric cell line were cultured. Cell viability, the ?- and ?-subunits of H+/K+-ATPase and cellular apoptosis were analyzed by dye exclusion assay, reverse transcription-polymerase chain reaction and annexin V-fluorescein isothiocyanate/propidium iodide staining, respectively. The expression level of total extracellular signal-regulated protein kinase 1/2 (ERK 1/2) and phosphorylated-ERK protein was detected by western blot analysis. Gastric cancer cell lines were more tolerant of the acidic culture media than non-cancer cells. Administration of rabeprazole led to a marked decrease in the viability of MKN-28 cells. Exposure to rabeprazole induced significant apoptosis in AGS cells. Rabeprazole completely inhibited the phosphorylation of ERK 1/2 in the MKN-28 cells, whereas the same effect was not observed in either the KATO III or MKN-45 cells. The ERK 1/2 inhibitor, PD98059, attenuated the viability of the AGS cells. A similar antiproliferative effect was observed in the rabeprazole treatment group. In addition, PD98059 and rabeprazole were able to efficaciously inhibit the phosphorylation of ERK 1/2 in the gastric cancer cells. Therefore, it was concluded that rabeprazole can attenuate the cell viability of human gastric cancer cells through inactivation of the ERK1/2 signaling pathway. The results of the present study demonstrate that rabeprazole inhibits the viability of gastric cancer cells in vitro and may serve as a novel antineoplastic agent.

GU, MENGLI; ZHANG, YAN; ZHOU, XINXIN; MA, HAN; YAO, HANGPING; JI, FENG

2014-01-01

37

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

38

A family of metal-organic frameworks exhibiting size-selective catalysis with encapsulated noble-metal nanoparticles.  

PubMed

The encapsulation of noble-metal nanoparticles (NPs) in metal-organic frameworks (MOFs) with carboxylic acid ligands, the most extensive branch of the MOF family, gives NP/MOF composites that exhibit excellent shape-selective catalytic performance in olefin hydrogenation, aqueous reaction in the reduction of 4-nitrophenol, and faster molecular diffusion in CO oxidation. The strategy of using functionalized cavities of MOFs as hosts for different metal NPs looks promising for the development of high-performance heterogeneous catalysts. PMID:24710716

Zhang, Weina; Lu, Guang; Cui, Chenlong; Liu, Yayuan; Li, Shaozhou; Yan, Wenjin; Xing, Chong; Chi, Yonggui Robin; Yang, Yanhui; Huo, Fengwei

2014-06-25

39

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

40

Modified bleomycin disaccharides exhibiting improved tumor cell targeting.  

PubMed

The bleomycins (BLMs) are a family of antitumor antibiotics used clinically for anticancer chemotherapy. Their antitumor selectivity derives at least in part from their ability to target tumor cells, a property that resides in the carbohydrate moiety of the antitumor agent. In earlier studies, we have demonstrated that the tumor cell selectivity resides in the mannose carbamoyl moiety of the BLM saccharide and that both the BLM disaccharide and monosaccharide containing the carbamoyl moiety were capable of the delivery/uptake of a conjugated cyanine dye into cultured cancer cell lines. Presently, the nature of the participation of the carbamoyl moiety has been explored further to provide compounds of utility for defining the nature of the mechanism of tumor cell recognition and uptake by BLM saccharides and in the hope that more efficient compounds could be identified. A library of seven disaccharide-Cy5** dye conjugates was prepared that are structural analogues of the BLM disaccharide. These differed from the natural BLM disaccharide in the position, orientation, and substitution of the carbamoyl group. Studies of these compounds in four matched sets of tumor and normal cell lines revealed a few that were both tumor cell selective and internalized 2-4-fold more efficiently than the natural BLM disaccharide. PMID:25272367

Madathil, Manikandadas M; Bhattacharya, Chandrabali; Yu, Zhiqiang; Paul, Rakesh; Rishel, Michael J; Hecht, Sidney M

2014-11-01

41

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

PubMed

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

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

2013-03-01

42

Stem cell tracking using iron oxide nanoparticles  

PubMed Central

Superparamagnetic iron oxide nanoparticles (SPIONs) are an exciting advancement in the field of nanotechnology. They expand the possibilities of noninvasive analysis and have many useful properties, making them potential candidates for numerous novel applications. Notably, they have been shown that they can be tracked by magnetic resonance imaging (MRI) and are capable of conjugation with various cell types, including stem cells. In-depth research has been undertaken to establish these benefits, so that a deeper level of understanding of stem cell migratory pathways and differentiation, tumor migration, and improved drug delivery can be achieved. Stem cells have the ability to treat and cure many debilitating diseases with limited side effects, but a main problem that arises is in the noninvasive tracking and analysis of these stem cells. Recently, researchers have acknowledged the use of SPIONs for this purpose and have set out to establish suitable protocols for coating and attachment, so as to bring MRI tracking of SPION-labeled stem cells into common practice. This review paper explains the manner in which SPIONs are produced, conjugated, and tracked using MRI, as well as a discussion on their limitations. A concise summary of recently researched magnetic particle coatings is provided, and the effects of SPIONs on stem cells are evaluated, while animal and human studies investigating the role of SPIONs in stem cell tracking will be explored. PMID:24729700

Bull, Elizabeth; Madani, Seyed Yazdan; Sheth, Roosey; Seifalian, Amelia; Green, Mark; Seifalian, Alexander M

2014-01-01

43

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. PMID:24638208

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

2014-01-01

44

Trypsinization-dependent cell labeling with fluorescent nanoparticles  

PubMed Central

Trypsin is often used to detach adhered cell subculture from a substrate. However, the proteolytic activity of trypsin may harm cells by cleaving the cell membrane proteins. The present study shows that cellular uptake of fluorescent nanoparticles is remarkably increased within 24 h after trypsinization. These results highlight the trypsin-induced protein digestion, provoking leaky cell plasma membrane which leads to the strongly enhanced cellular uptake of the nanoparticles. To prevent this effect, one should expose cells to the nanoparticle (NP)-based fluorescent labels at least 48 h after trypsinization. PMID:25328505

2014-01-01

45

Transport across the cell-membrane dictates nanoparticle fate and toxicity: a new paradigm in nanotoxicology.  

PubMed

The toxicity of metallic nanoparticles (MNPs) has been fully ascertained, but the mechanisms underlying their cytotoxicity remain still largely unclear. Here we demonstrate that the cytotoxicity of MNPs is strictly reliant on the pathway of cellular internalization. In particular, if otherwise toxic gold, silver, and iron oxide NPs are forced through the cell membrane bypassing any form of active mechanism (e.g., endocytosis), no significant cytotoxic effect is registered. Pneumatically driven NPs across the cell membrane show a different distribution within the cytosol compared to NPs entering the cell by active endocytosis. Specifically, they exhibit free random Brownian motions within the cytosol and do not accumulate in lysosomes. Results suggest that intracellular accumulation of metallic nanoparticles into endo-lysosomal compartments is the leading cause of nanotoxicity, due to consequent nanoparticle degradation and in situ release of metal ions. PMID:25061814

Guarnieri, Daniela; Sabella, Stefania; Muscetti, Ornella; Belli, Valentina; Malvindi, Maria Ada; Fusco, Sabato; De Luca, Elisa; Pompa, Pier Paolo; Netti, Paolo A

2014-09-01

46

Targeting nanoparticles to dendritic cells for immunotherapy.  

PubMed

Dendritic cells (DCs) are key players in the initiation of adaptive immune responses and are currently exploited in immunotherapy for treatment of cancer and infectious diseases. Development of targeted nanodelivery systems carrying vaccine components, including antigens and adjuvants, to DCs in vivo represents a promising strategy to enhance immune responses. Delivering particulate vaccines specifically to DCs and preventing nonspecific uptake by other endocytotic cells are challenging. Size represents a critical parameter determining whether particulate vaccines can penetrate lymph nodes and reach resident DCs. Specific delivery is further enhanced by actively targeting DC-specific receptors. This chapter discusses the rationale for the use of particle-based vaccines and provides an overview of antigen-delivery vehicles currently under investigation. In addition, we discuss how vaccine delivery systems may be developed, focusing on liposomes, PLGA polymers, and gold nanoparticles, to obtain safe and efficacious vaccines. PMID:22568905

Cruz, Luis J; Tacken, Paul J; Rueda, Felix; Domingo, Joan Carles; Albericio, Fernando; Figdor, Carl G

2012-01-01

47

nanoparticles  

NASA Astrophysics Data System (ADS)

In this paper, we report the observation of intrinsic room temperature ferromagnetism in pure La2O3 nanoparticles. Magnetism measurement indicates that all of the samples exhibit room temperature ferromagnetism and the saturation magnetization for the samples decreases with the increase in annealing temperature from 700 to 1,000 °C. X-ray photoelectron spectroscopy identifies the presence of oxygen vacancies in the La2O3 nanoparticles. The fitting results of the O 1 s spectrum indicate that the variation of the oxygen vacancy concentration is in complete agreement with the change of the saturation magnetization. It is also found that the saturation magnetization of the La2O3 nanoparticles can be tuned by post-annealing in argon or oxygen atmosphere. These results suggest that the oxygen vacancies are largely responsible for the room temperature ferromagnetism in pure La2O3 nanoparticles.

Xu, Qiang; Gao, Daqiang; Zhang, Jing; Yang, Zhaolong; Zhang, Zhipeng; Rao, Jinwei; Xue, Desheng

2014-09-01

48

Detecting and Tracking Nonfluorescent Nanoparticles Probes in Live Cells  

SciTech Connect

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

Wang, Gufeng; Fang, Ning

2012-01-17

49

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. PMID:24872703

Oh, Nuri; Park, Ji-Ho

2014-01-01

50

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

PubMed

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

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

2012-03-12

51

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

52

The side population of ovarian cancer cells defines a heterogeneous compartment exhibiting stem cell characteristics  

PubMed Central

Cancer stem cells (CSC) are believed to be involved in tumor evasion of classical antitumor therapies and have thus become an attractive target for further improvement of anticancer strategies. However, the existence and identity of CSC are still a matter of controversy. In a systematic screen of 13 ovarian cancer cell lines we show that cells with stem cell properties are reliably detectable as a minor population, characterized by ABC transporter expression resulting in the side population (SP) phenotype. In different cell lines, either ABCG2 or ABCB1 was found to be responsible for this effect. Purified SP cells featured virtually all characteristics of bona fide CSC, including clonogenicity, asymmetric division and high tumorigenicity in vivo. Using in-depth phenotyping by multicolor flow cytometry, we found that among the investigated ovarian cancer cell lines the SP compartment exhibits tremendous heterogeneity and is composed of multiple phenotypically distinct subpopulations. Thus, our study confirms previous results showing that CSC are contained within the SP. However, the exact identity of the CSC-containing is still disguised by the high complexity of the CSC containing compartment. Further functional studies are needed to determine whether a single cellular subset can unambiguously be defined as CSC or whether multiple stem cell-like cells with different properties coexist. Moreover, the observed heterogeneity may reflect a high level of plasticity and likely influences tumor progression, escape from immune-surveillance and development of resistance to anticancer therapies and should therefore be considered in the development of new treatment strategies. PMID:25216521

Boesch, Maximilian; Zeimet, Alain G.; Reimer, Daniel; Schmidt, Stefan; Gastl, Guenther; Parson, Walther; Spoeck, Franziska; Hatina, Jiri

2014-01-01

53

The side population of ovarian cancer cells defines a heterogeneous compartment exhibiting stem cell characteristics.  

PubMed

Cancer stem cells (CSC) are believed to be involved in tumor evasion of classical antitumor therapies and have thus become an attractive target for further improvement of anticancer strategies. However, the existence and identity of CSC are still a matter of controversy. In a systematic screen of 13 ovarian cancer cell lines we show that cells with stem cell properties are reliably detectable as a minor population, characterized by ABC transporter expression resulting in the side population (SP) phenotype. In different cell lines, either ABCG2 or ABCB1 was found to be responsible for this effect. Purified SP cells featured virtually all characteristics of bona fide CSC, including clonogenicity, asymmetric division and high tumorigenicity in vivo. Using in-depth phenotyping by multicolor flow cytometry, we found that among the investigated ovarian cancer cell lines the SP compartment exhibits tremendous heterogeneity and is composed of multiple phenotypically distinct subpopulations. Thus, our study confirms previous results showing that CSC are contained within the SP. However, the exact identity of the CSC-containing is still disguised by the high complexity of the CSC containing compartment. Further functional studies are needed to determine whether a single cellular subset can unambiguously be defined as CSC or whether multiple stem cell-like cells with different properties coexist. Moreover, the observed heterogeneity may reflect a high level of plasticity and likely influences tumor progression, escape from immune-surveillance and development of resistance to anticancer therapies and should therefore be considered in the development of new treatment strategies. PMID:25216521

Boesch, Maximilian; Zeimet, Alain G; Reimer, Daniel; Schmidt, Stefan; Gastl, Guenther; Parson, Walther; Spoeck, Franziska; Hatina, Jiri; Wolf, Dominik; Sopper, Sieghart

2014-08-30

54

Shape-controlled synthesis of Pt–Pd core–shell nanoparticles exhibiting polyhedral morphologies by modified polyol method  

Microsoft Academic Search

Pt–Pd core–shell nanoparticles were synthesized by a simple synthetic method. First, Pt nanoparticles were synthesized in a controlled manner via the reduction of chloroplantinic acid hexahydrate in ethylene glycol (EG) at 160°C in the presence of silver nitrate and the stabilization of polyvinylpyrrolidon. AgNO3 used acts as a structure-modifying agent to the morphology of the Pt nanoparticles. These Pt nanoparticles

Nguyen Viet Long; Toru Asaka; Takashi Matsubara; Masayuki Nogami

2011-01-01

55

Tracking nanoparticles optically to study their interaction with cells  

Microsoft Academic Search

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

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

56

Detection of circulating cancer cells using electrocatalytic gold nanoparticles.  

PubMed

A rapid cancer cell detection and quantification assay, based on the electrocatalytic properties of gold nanoparticles towards the hydrogen evolution reaction, is described. The selective labeling of cancer cells is performed in suspension, allowing a fast interaction between the gold nanoparticle labels and the target proteins expressed at the cell membrane. The subsequent electrochemical detection is accomplished with small volumes of sample and user-friendly equipment through a simple electrochemical method that generates a fast electrochemical response used for the quantification of nanoparticle-labeled cancer cells. The system establishes a selective cell-detection assay capable of detecting 4 × 10(3) cancer cells in suspension that can be extended to several other cells detection scenarios. PMID:22893274

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

2012-12-01

57

Quantification of Nanoparticle Dose and Vesicular Inheritance in Proliferating Cells  

PubMed Central

Assessing dose in nanoparticle–cell interactions is inherently difficult due to a complex multiplicity of possible mechanisms and metrics controlling particle uptake. The fundamental unit of nanoparticle dose is the number of particles internalized per cell; we show that this can be obtained for large cell populations that internalize fluorescent nanoparticles by endocytosis, through calibration of cytometry measurements to transmission electron microscopy data. Low-throughput, high-resolution electron imaging of quantum dots in U-2 OS cells is quantified and correlated with high-throughput, low-resolution optical imaging of the nanoparticle-loaded cells. From the correlated data, we obtain probability distribution functions of vesicles per cell and nanoparticles per vesicle. Sampling of these distributions and comparison to fluorescence intensity histograms from flow cytometry provide the calibration factor required to transform the cytometry metric to total particle dose per cell, the mean value of which is 2.4 million. Use of the probability distribution functions to analyze particle partitioning during cell division indicates that, while vesicle inheritance is near symmetric, highly variable vesicle loading leads to a highly asymmetric particle dose within the daughter cells. PMID:23773085

2013-01-01

58

Polystyrene nanoparticles activate ion transport in human airway epithelial cells  

PubMed Central

Background Over the last decade, nanotechnology has provided researchers with new nanometer materials, such as nanoparticles, which have the potential to provide new therapies for many lung diseases. In this study, we investigated the acute effects of polystyrene nanoparticles on epithelial ion channel function. Methods Human submucosal Calu-3 cells that express cystic fibrosis transmembrane conductance regulator (CFTR) and baby hamster kidney cells engineered to express the wild-type CFTR gene were used to investigate the actions of negatively charged 20 nm polystyrene nanoparticles on short-circuit current in Calu-3 cells by Ussing chamber and single CFTR Clchannels alone and in the presence of known CFTR channel activators by using baby hamster kidney cell patches. Results Polystyrene nanoparticles caused sustained, repeatable, and concentration-dependent increases in short-circuit current. In turn, these short-circuit current responses were found to be biphasic in nature, ie, an initial peak followed by a plateau. EC50 values for peak and plateau short-circuit current responses were 1457 and 315.5 ng/mL, respectively. Short-circuit current was inhibited by diphenylamine-2-carboxylate, a CFTR Cl? channel blocker. Polystyrene nanoparticles activated basolateral K+ channels and affected Cl? and HCO3 ? secretion. The mechanism of short-circuit current activation by polystyrene nanoparticles was found to be largely dependent on calcium-dependent and cyclic nucleotide-dependent phosphorylation of CFTR Cl? channels. Recordings from isolated inside-out patches using baby hamster kidney cells confirmed the direct activation of CFTR Cl? channels by the nanoparticles. Conclusion This is the first study to identify the activation of ion channels in airway cells after exposure to polystyrene-based nanomaterials. Thus, polystyrene nanoparticles cannot be considered as a simple neutral vehicle for drug delivery for the treatment of lung diseases, due to the fact that they may have the ability to affect epithelial cell function and physiological processes on their own. PMID:21760729

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

2011-01-01

59

Synthesis and characterization of jacalin-gold nanoparticles conjugates as specific markers for cancer cells.  

PubMed

New nanobiocomposites that combine nanoparticles and biomolecules have been shown very relevant for medical applications. Recently, cancer diagnostics and treatment have benefited from the development of nanobiocomposites, in which metallic or magnetic nanoparticles are conjugated with specific biomolecules for selective cell uptake. Despite recent advances in this area, the biomedical applications of these materials are still limited by the low efficiency of functionalization, low stability, among other factors. In this study, we report the synthesis of jacalin-conjugated gold nanoparticles, a nanoconjugate with potential application in medical areas, especially for cancer diagnosis. Jacalin is a lectin protein and it was employed due to its ability to recognize the Gal?1-3GalNAc disaccharide, which is highly expressed in tumor cells. Gold nanoparticles (AuNPs) were synthesized in the presence of generation 4 polyamidoamine dendrimer (PAMAM G4) and conjugated with fluorescein isothiocyanate (FITC)-labeled jacalin. The AuNPs/jacalin nanoconjugates were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and vibrational spectroscopy (FTIR). We also performed an investigation using isothermal titration calorimetry (ITC) and fluorescence quenching measurements to understand the interactions occurring between the AuNPs and jacalin, which revealed that the nanoconjugate formation is driven by an entropic process with good affinity. Furthermore, in vitro tests revealed that the AuNPs/jacalin-FITC nanoconjugates exhibited higher affinity for leukemic K562 cells than for healthy mononuclear blood cells, which could be useful for biomedical applications, including cancer cells imaging. PMID:24028851

Marangoni, Valeria S; Paino, Ieda M; Zucolotto, Valtencir

2013-12-01

60

Aneuploid yeast strains exhibit defects in cell growth and passage through START  

PubMed Central

Aneuploidy, a chromosome content that is not a multiple of the haploid karyotype, is associated with reduced fitness in all organisms analyzed to date. In budding yeast aneuploidy causes cell proliferation defects, with many different aneuploid strains exhibiting a delay in G1, a cell cycle stage governed by extracellular cues, growth rate, and cell cycle events. Here we characterize this G1 delay. We show that 10 of 14 aneuploid yeast strains exhibit a growth defect during G1. Furthermore, 10 of 14 aneuploid strains display a cell cycle entry delay that correlates with the size of the additional chromosome. This cell cycle entry delay is due to a delayed accumulation of G1 cyclins that can be suppressed by supplying cells with high levels of a G1 cyclin. Our results indicate that aneuploidy frequently interferes with the ability of cells to grow and, as with many other cellular stresses, entry into the cell cycle. PMID:23468524

Thorburn, Rebecca R.; Gonzalez, Christian; Brar, Gloria A.; Christen, Stefan; Carlile, Thomas M.; Ingolia, Nicholas T.; Sauer, Uwe; Weissman, Jonathan S.; Amon, Angelika

2013-01-01

61

Immobilization of gold nanoparticles on cell culture surfaces for safe and enhanced gold nanoparticle-mediated laser transfection  

NASA Astrophysics Data System (ADS)

In comparison to standard transfection methods, gold nanoparticle-mediated laser transfection has proven to be a versatile alternative. This is based on its minor influence on cell viability and its high efficiency, especially for the delivery of small molecules like small interfering RNA. However, in order to transfer it to routine usage, a safety aspect is of major concern: The avoidance of nanoparticle uptake by the cells is desired. The immobilization of the gold nanoparticles on cell culture surfaces can address this issue. In this study, we achieved this by silanization of the appropriate surfaces and the binding of gold nanoparticles to them. Comparable perforation efficiencies to the previous approaches of gold nanoparticle-mediated laser transfection with free gold nanoparticles are demonstrated. The uptake of the immobilized particles by the cells is unlikely. Consequently, these investigations offer the possibility of bringing gold nanoparticle-mediated laser transfection closer to routine usage.

Kalies, Stefan; Heinemann, Dag; Schomaker, Markus; Gentemann, Lara; Meyer, Heiko; Ripken, Tammo

2014-07-01

62

Nanoparticle facilitated extracellular electron transfer in microbial fuel cells.  

PubMed

Microbial fuel cells (MFCs) have been the focus of substantial research interest due to their potential for long-term, renewable electrical power generation via the metabolism of a broad spectrum of organic substrates, although the low power densities have limited their applications to date. Here, we demonstrate the potential to improve the power extraction by exploiting biogenic inorganic nanoparticles to facilitate extracellular electron transfer in MFCs. Simultaneous short-circuit current recording and optical imaging on a nanotechnology-enabled platform showed substantial current increase from Shewanella PV-4 after the formation of cell/iron sulfide nanoparticle aggregates. Detailed characterization of the structure and composition of the cell/nanoparticle interface revealed crystalline iron sulfide nanoparticles in intimate contact with and uniformly coating the cell membrane. In addition, studies designed to address the fundamental mechanisms of charge transport in this hybrid system showed that charge transport only occurred in the presence of live Shewanella, and moreover demonstrated that the enhanced current output can be attributed to improved electron transfer at cell/electrode interface and through the cellular-networks. Our approach of interconnecting and electrically contacting bacterial cells through biogenic nanoparticles represents a unique and promising direction in MFC research and has the potential to not only advance our fundamental knowledge about electron transfer processes in these biological systems but also overcome a key limitation in MFCs by constructing an electrically connected, three-dimensional cell network from the bottom-up. PMID:25310721

Jiang, Xiaocheng; Hu, Jinsong; Lieber, Alexander M; Jackan, Charles S; Biffinger, Justin C; Fitzgerald, Lisa A; Ringeisen, Bradley R; Lieber, Charles M

2014-11-12

63

Laser-targeted photofabrication of gold nanoparticles inside cells  

NASA Astrophysics Data System (ADS)

Nanoparticle manipulation is of increasing interest, since they can report single molecule-level measurements of the cellular environment. Until now, however, intracellular nanoparticle locations have been essentially uncontrollable. Here we show that by infusing a gold ion solution, focused laser light-induced photoreduction allows in situ fabrication of gold nanoparticles at precise locations. The resulting particles are pure gold nanocrystals, distributed throughout the laser focus at sizes ranging from 2 to 20?nm, and remain in place even after removing the gold solution. We demonstrate the spatial control by scanning a laser beam to write characters in gold inside a cell. Plasmonically enhanced molecular signals could be detected from nanoparticles, allowing their use as nano-chemical probes at targeted locations inside the cell, with intracellular molecular feedback. Such light-based control of the intracellular particle generation reaction also offers avenues for in situ plasmonic device creation in organic targets, and may eventually link optical and electron microscopy.

Smith, Nicholas I.; Mochizuki, Kentaro; Niioka, Hirohiko; Ichikawa, Satoshi; Pavillon, Nicolas; Hobro, Alison J.; Ando, Jun; Fujita, Katsumasa; Kumagai, Yutaro

2014-10-01

64

Laser-targeted photofabrication of gold nanoparticles inside cells.  

PubMed

Nanoparticle manipulation is of increasing interest, since they can report single molecule-level measurements of the cellular environment. Until now, however, intracellular nanoparticle locations have been essentially uncontrollable. Here we show that by infusing a gold ion solution, focused laser light-induced photoreduction allows in situ fabrication of gold nanoparticles at precise locations. The resulting particles are pure gold nanocrystals, distributed throughout the laser focus at sizes ranging from 2 to 20?nm, and remain in place even after removing the gold solution. We demonstrate the spatial control by scanning a laser beam to write characters in gold inside a cell. Plasmonically enhanced molecular signals could be detected from nanoparticles, allowing their use as nano-chemical probes at targeted locations inside the cell, with intracellular molecular feedback. Such light-based control of the intracellular particle generation reaction also offers avenues for in situ plasmonic device creation in organic targets, and may eventually link optical and electron microscopy. PMID:25298313

Smith, Nicholas I; Mochizuki, Kentaro; Niioka, Hirohiko; Ichikawa, Satoshi; Pavillon, Nicolas; Hobro, Alison J; Ando, Jun; Fujita, Katsumasa; Kumagai, Yutaro

2014-01-01

65

In Vitro Cytotoxicity of Nanoparticles in Mammalian Germline Stem Cells  

PubMed Central

Gametogenesis is a complex biological process that is particularly sensitive to environmental insults such as chemicals. Many chemicals have a negative impact on the germline, either by directly affecting the germ cells, or indirectly through their action on the somatic nursing cells. Ultimately, these effects can inhibit fertility, and they may have negative consequences for the development of the offspring. Recently, nanomaterials such as nanotubes, nanowires, fullerene derivatives (buckyballs), and quantum dots have received enormous national attention in the creation of new types of analytical tools for biotechnology and the life sciences. Despite the wide application of nanomaterials, there is a serious lack of information concerning their impact on human health and the environment. Thus, there are limited studies available on toxicity of nanoparticles for risk assessment of nanomaterials. The purpose of this study was to assess the suitability of a mouse spermatogonial stem cell line as a model to assess nanotoxicity in the male germline in vitro. The effects of different types of nanoparticles on these cells were evaluated by light microscopy, and by cell proliferation and standard cytotoxicity assays. Our results demonstrate a concentration-dependent toxicity for all types of particles tested, whereas the corresponding soluble salts had no significant effect. Silver nanoparticles were the most toxic while molybdenum trioxide (MoO3) nanoparticles were the least toxic. Our results suggest that this cell line provides a valuable model with which to assess the cytotoxicity of nanoparticles in the germ line in vitro. PMID:16014736

Braydich-Stolle, Laura; Hussain, Saber; Schlager, John J.; Hofmann, Marie-Claude

2010-01-01

66

Rat alveolar type I cells proliferate, express OCT-4, and exhibit phenotypic plasticity in vitro  

PubMed Central

Alveolar type I (TI) cells are large, squamous cells that cover 95–99% of the internal surface area of the lung. Although TI cells are believed to be terminally differentiated, incapable of either proliferation or phenotypic plasticity, TI cells in vitro both proliferate and express phenotypic markers of other differentiated cell types. Rat TI cells isolated in purities of >99% proliferate in culture, with a sixfold increase in cell number before the cells reach confluence; >50% of the cultured TI cells are Ki67+. At cell densities of 1–2 cells/well, ?50% of the cells had the capacity to form colonies. Under the same conditions, type II cells do not proliferate. Cultured TI cells express RTI40 and aquaporin 5, phenotypic markers of the TI cell phenotype. By immunofluorescence, Western blotting, and Q-PCR, TI cells express OCT-4A (POU5F1), a transcription factor associated with maintenance of the pluripotent state in stem cells. Based on the expression patterns of various marker proteins, TI cells are distinct from either of two recently described putative pulmonary multipotent cell populations, the bronchoalveolar stem cell or the OCT-4+ stem/progenitor cell. Although TI cells in adult rat lung tissue do not express either surfactant protein C (SP-C) or CC10, respective markers of the TII and Clara cell phenotypes, in culture TI cells can be induced to express both SP-C and CC10. Together, the findings that TI cells proliferate and exhibit phenotypic plasticity in vitro raise the possibility that TI cells may have similar properties in vivo. PMID:19717550

Gonzalez, Robert F.; Allen, Lennell

2009-01-01

67

Toxicity of Cerium Oxide Nanoparticles in Human Lung Cancer Cells  

SciTech Connect

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

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

2006-12-31

68

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

69

nanoparticles  

NASA Astrophysics Data System (ADS)

Undoped and Zn-doped TiO2 nanoparticles were synthesized by the sol gel method. The dopant (Zn) was taken at 0.1, 0.2, 0.5, 0.7, and 1.0 mol%. The initial precursors were titanium tetraisopropoxide and zinc acetate. The samples were characterized by X-ray powder diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, and UV-vis diffuse reflectance. The photocatalytic activity of the prepared nanoparticles was studied by observing their role in degradation of two azo dyes, i.e., Eriochrome Black T and Methyl Red under UV-visible light. The results revealed that Zn-doped TiO2 nanoparticles exhibited better degradation as compared to undoped TiO2 nanoparticles. In this study, 0.7 mol% Zn-doped TiO2 showed highest photocatalytic activity. Doping of Zn allowed better separation of electron-hole pairs which results in increased oxidation and reduction reactions.

Singla, Pooja; Sharma, Manoj; Pandey, O. P.; Singh, K.

2014-07-01

70

Rapid coating of surfaces with functionalized nanoparticles for regulation of cell behavior.  

PubMed

A robust monolayer of nanoparticles is formed via dip-coating of cell culture plates. These surfaces provide cell type-specific modulation of growth behavior without the uptake of nanoparticles. PMID:24677290

Tang, Rui; Moyano, Daniel F; Subramani, Chandramouleeswaran; Yan, Bo; Jeoung, Eunhee; Tonga, Gülen Yesilbag; Duncan, Bradley; Yeh, Yi-Cheun; Jiang, Ziwen; Kim, Chaekyu; Rotello, Vincent M

2014-05-28

71

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

72

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

PubMed Central

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

2011-01-01

73

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

74

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

PubMed Central

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

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

2013-01-01

75

Cell uptake enhancement of folate targeted polymer coated magnetic nanoparticles.  

PubMed

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

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

2013-06-01

76

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

77

Recent thymic emigrants and mature naive T cells exhibit differential DNA methylation at key cytokine loci.  

PubMed

Recent thymic emigrants (RTEs) are the youngest T cells in the lymphoid periphery and exhibit phenotypic and functional characteristics distinct from those of their more mature counterparts in the naive peripheral T cell pool. We show in this study that the Il2 and Il4 promoter regions of naive CD4(+) RTEs are characterized by site-specific hypermethylation compared with those of both mature naive (MN) T cells and the thymocyte precursors of RTEs. Thus, RTEs do not merely occupy a midpoint between the thymus and the mature T cell pool, but represent a distinct transitional T cell population. Furthermore, RTEs and MN T cells exhibit distinct CpG DNA methylation patterns both before and after activation. Compared with MN T cells, RTEs express higher levels of several enzymes that modify DNA methylation, and inhibiting methylation during culture allows RTEs to reach MN T cell levels of cytokine production. Collectively, these data suggest that the functional differences that distinguish RTEs from MN T cells are influenced by epigenetic mechanisms and provide clues to a mechanistic basis for postthymic maturation. PMID:23686491

Berkley, Amy M; Hendricks, Deborah W; Simmons, Kalynn B; Fink, Pamela J

2013-06-15

78

Nanoparticles blast cancerous cells with killer drugs | KurzweilAI http://www.kurzweilai.net/nanoparticles-blast-cancerous-cells-with-killer-drugs[5/2/2011 12:14:51 PM  

E-print Network

Nanoparticles blast cancerous cells with killer drugs | KurzweilAI http://www.kurzweilai.net/nanoparticles-blast-cancerous-cells-with-killer-drugs[5/2/2011 12:14:51 PM] You are here: Home News Nanoparticles blast cancerous cells with killer drugs News ALL NEWS Confirm Like You like Nanoparticles blast cancerous cells with killer drugs | Kurzweil

Brinker, C. Jeffrey

79

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. PMID:20098636

Smith, Ron

2009-01-01

80

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

81

Circulating tumor cells exhibit a biologically aggressive cancer phenotype accompanied by selective resistance to chemotherapy.  

PubMed

With prostate cancer (PCa), circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) portend a poor clinical prognosis. Their unknown biology precludes rational therapeutic design. We demonstrate that CTC and DTC cell lines, established from mice bearing human PCa orthotopic implants, exhibit increased cellular invasion in vitro, increased metastasis in mice, and express increased epithelial to mesenchymal transition biomarkers. Further, they are selectively resistant to growth inhibition by mitoxantrone-like agents. These findings demonstrate that CTC formation is accompanied by phenotypic progression without obligate reversion. Their increased metastatic potential, selective therapeutic resistance, and differential expression of potential therapeutic targets provide a rational basis to test further interventions. PMID:25016063

Pavese, Janet M; Bergan, Raymond C

2014-10-01

82

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

83

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. PMID:24886333

2014-01-01

84

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

85

Oxidized silicon nanoparticles for radiosensitization of cancer and tissue cells.  

PubMed

The applicability of ultrasmall uncapped and aminosilanized oxidized silicon nanoparticles (SiNPs and NH2-SiNPs) as radiosensitizer was studied by internalizing these nanoparticles into human breast cancer (MCF-7) and mouse fibroblast cells (3T3) that were exposed to X-rays at a single dose of 3 Gy. While SiNPs did not increase the production of reactive oxygen species (ROS) in X-ray treated cells, the NH2-SiNPs significantly enhanced the ROS formation. This is due to the amino functionality as providing positive surface charges in aqueous environment. The NH2-SiNPs were observed to penetrate into the mitochondrial membrane, wherein these nanoparticles provoked oxidative stress. The NH2-SiNPs induced mitochondrial ROS production was confirmed by the determination of an increased malondialdehyde level as representing a gauge for the extent of membrane lipid peroxidation. X-ray exposure of NH2-SiNPs incubated MCF-7 and 3T3 cells increased the ROS concentration for 180%, and 120%, respectively. Complementary cytotoxicity studies demonstrate that these silicon nanoparticles are more cytotoxic for MCF-7 than for 3T3 cells. PMID:23535374

Klein, Stefanie; Dell'Arciprete, Maria L; Wegmann, Marc; Distel, Luitpold V R; Neuhuber, Winfried; Gonzalez, Mónica C; Kryschi, Carola

2013-05-01

86

Cancer-initiating cells derived from established cervical cell lines exhibit stem-cell markers and increased radioresistance  

PubMed Central

Background Cancer-initiating cells (CICs) are proposed to be responsible for the generation of metastasis and resistance to therapy. Accumulating evidences indicates CICs are found among different human cancers and cell lines derived from them. Few studies address the characteristics of CICs in cervical cancer. We identify biological features of CICs from four of the best-know human cell lines from uterine cervix tumors. (HeLa, SiHa, Ca Ski, C-4 I). Methods Cells were cultured as spheres under stem-cell conditions. Flow cytometry was used to detect expression of CD34, CD49f and CD133 antigens and Hoechst 33342 staining to identify side population (SP). Magnetic and fluorescence-activated cell sorting was applied to enrich and purify populations used to evaluate tumorigenicity in nude mice. cDNA microarray analysis and in vitro radioresistance assay were carried out under standard conditions. Results CICs, enriched as spheroids, were capable to generate reproducible tumor phenotypes in nu-nu mice and serial propagation. Injection of 1 × 103 dissociated spheroid cells induced tumors in the majority of animals, whereas injection of 1 × 105 monolayer cells remained nontumorigenic. Sphere-derived CICs expressed CD49f surface marker. Gene profiling analysis of HeLa and SiHa spheroid cells showed up-regulation of CICs markers characteristic of the female reproductive system. Importantly, epithelial to mesenchymal (EMT) transition-associated markers were found highly expressed in spheroid cells. More importantly, gene expression analysis indicated that genes required for radioresistance were also up-regulated, including components of the double-strand break (DSB) DNA repair machinery and the metabolism of reactive oxygen species (ROS). Dose-dependent radiation assay indicated indeed that CICs-enriched populations exhibit an increased resistance to ionizing radiation (IR). Conclusions We characterized a self-renewing subpopulation of CICs found among four well known human cancer-derived cell lines (HeLa, SiHa, Ca Ski and C-4 I) and found that they express characteristic markers of stem cell, EMT and radioresistance. The fact that CICs demonstrated a higher degree of resistance to radiation than differentiated cells suggests that specific detection and targeting of CICs could be highly valuable for the therapy of tumors from the uterine cervix. PMID:22284662

2012-01-01

87

BTLA exhibits immune memory for ?? T cells in patients with active pulmonary tuberculosis  

PubMed Central

Despite past extensive studies, the role of B and T lymphocyte attenuator (BTLA) in ?? T cells in patients with active pulmonary tuberculosis (ATB) remains poorly understood. Here we demonstrate that BTLA expression on ?? T cells is decreased in patients with M. tuberculosis (Mtb) infection. Particularly, BTLA expression levels are likely critical for ?? T cells to manifest and maintain an active central memory phenotype with high capacity for secretion of IFN-? and perforin, which are important for immune memory against TB infection. BTLAhigh ?? T cells also exhibited higher capacity in response to Mtb peptide stimulation. In contrast to the role of BTLA played for negative regulation of immune responses, our data in the current studies suggest that BTLA expression on ?? T cells is likely associated with protective immune memory against Mtb infection in the setting of patients with active pulmonary tuberculosis. This previous unappreciated role for BTLA may have implications for prevention and treatment of patients with Mtb infection.

Zeng, Jin-Cheng; Lin, Dong-Zi; Yi, Lai-Long; Liu, Gan-Bin; Zhang, Hui; Wang, Wan-Dang; Zhang, Jun-Ai; Wu, Xian-Jing; Xiang, Wen-Yu; Kong, Bin; Chen, Zheng W; Wang, Cong-Yi; Xu, Jun-Fa

2014-01-01

88

Mammalian cells transfected with the listeriolysin gene exhibit enhanced proliferation and focus formation.  

PubMed Central

Mouse 3T6 and 3T3 fibroblasts and rat epithelial L2 cells were transfected with recombinant plasmids containing the listeriolysin gene (hly) of Listeria monocytogenes. This bacterial gene (with and without the 5' signal sequence) was cloned under the control of a murine metallothionein promoter, resulting in elevated transcription of both forms of the hly gene after induction with ZnSO4. However, the gene product could be observed only when the listeriolysin gene lacking the 5' signal sequence was used. Intact listeriolysin could not be detected in the cytoplasm or in the supernatant of the hly-transfected cells. 3T6 and L2 cells transfected with the intact hly gene exhibited significantly increased cell proliferation and increased formation of actin microfilaments upon induction of hly expression with ZnSO4. Both cell types are not contact inhibited and formed large piles of spherical cells after transfection with hly. In contrast, contact-inhibited 3T3 cells transfected with the hly gene showed increased proliferation but no formation of such cell aggregates. When 3T6 fibroblasts were transfected with the hly gene without the 5' signal sequence, inhibition of growth, lack of cell layer confluency, and altered (spherical) cell morphology were observed. Images PMID:7927793

Demuth, A; Chakraborty, T; Krohne, G; Goebel, W

1994-01-01

89

In ViWo Tumor Cell Targeting with "Click" Nanoparticles Geoffrey von Maltzahn,,  

E-print Network

In ViWo Tumor Cell Targeting with "Click" Nanoparticles Geoffrey von Maltzahn,, Yin Ren,, Ji of inorganic nanoparticles to tumors. We find that "click" chemistry allows cyclic LyP-1 targeting peptides to be specifically linked to azido-nanoparticles and to direct their binding to p32-expressing tumor cells in Vitro

Bhatia, Sangeeta

90

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

PubMed

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

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

2013-01-01

91

Basis of differential cytotoxicity exhibited by rhodamine 123 for certain carcinoma cell types  

SciTech Connect

The authors have previously demonstrated the inhibitory effect of rhodamine 123 (Rh123) on mitochondrial bioenergetic function and established mitochondrial F/sub 1/-F/sub 0/ ATPase as the primary target site for Rh123 toxicity. Further, they found that the amount of Rh123 taken up by isolated rat liver mitochondria is a linear function of mitochondrial membrane potential. Here they investigated the possibility that the differential cytotoxicity exhibited by Rh123 for certain carcinoma cell types might be a function of an increased mitochondrial membrane potential. Membrane potential in mitochondria isolated from cultured cells was measured by equilibrium distribution of /sup 86/Rb. Mitochondria from CX-1, a Rh123-sensitive carcinoma cell type, had a higher membrane potential (163 +/- 7mV) than did mitochondria from CV-1, a Rh123-insensitive, normal epithelial cell type (104 +/- 9mV). In addition polarographic determination of respiratory activity of mitochondria isolated from these cells showed that CX-1 mitochondria were more sensitive than CV-1 mitochondria to inhibition by Rh123. Finally, there was no evidence of differential sensitivity of F/sub 1/-F/sub 0/ ATPase activity to Rh123 in CX-1 vs. CV-1 mitochondria. These data strongly suggest that inherent differences in mitochondrial membrane potential contribute to the differential cytotoxicity exhibited by Rh123 for certain carcinoma cell types.

Modica-Napolitano, J.S.; Aprille, J.R.

1986-05-01

92

Toxicity of Cerium Oxide Nanoparticles in Human Lung Cancer Cells  

Microsoft Academic Search

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

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

2006-01-01

93

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

94

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

PubMed Central

When clonal populations of human cells are exposed to apoptosis-inducing agents, some cells die and others survive. This fractional killing arises not from mutation but from preexisting, stochastic differences in the levels and activities of proteins regulating apoptosis. Here we examine the properties of cells that survive treatment with agonists of two distinct death receptors, tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) and anti-FasR antibodies. We find that “survivor” cells are highly resistant to a second ligand dose applied 1 d later. Resistance is reversible, resetting after several days of culture in the absence of death ligand. “Reset” cells appear identical to drug-naive cells with respect to death ligand sensitivity and gene expression profiles. TRAIL survivors are cross-resistant to activators of FasR and vice versa and exhibit an NF-?B–dependent inflammatory phenotype. Remarkably, reversible resistance is induced in the absence of cell death when caspase inhibitors are present and can be sustained for 1 wk or more, also without cell death, by periodic ligand exposure. Thus stochastic differences in cell state can have sustained consequences for sen­sitivity to prodeath ligands and acquisition of proinflammatory phenotypes. The important role played by periodicity in TRAIL exposure for induction of opposing apoptosis and survival mechanisms has implications for the design of optimal therapeutic agents and protocols. PMID:23699397

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

2013-01-01

95

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. PMID:23312348

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

2013-01-01

96

Nanoparticles Based Stem Cell Tracking in Regenerative Medicine  

PubMed Central

Stem cell therapies offer great potentials in the treatment for a wide range of diseases and conditions. With so many stem cell replacement therapies going through clinical trials currently, there is a great need to understand the mechanisms behind a successful therapy, and one of the critical points of discovering them is to track stem cell migration, proliferation and differentiation in vivo. To be of most use tracking methods should ideally be non-invasive, high resolution and allow tracking in three dimensions. Magnetic resonance imaging (MRI) is one of the ideal methods, but requires a suitable contrast agent to be loaded to the cells to be tracked, and one of the most wide-spread in stem cell tracking is a group of agents known as magnetic nanoparticles. This review will explore the current use of magnetic nanoparticles in developing and performing stem cell therapies, and will investigate their potential limitations and the future directions magnetic nanoparticle tracking is heading in. PMID:23946823

Edmundson, Matthew; Thanh, Nguyen TK; Song, Bing

2013-01-01

97

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

98

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

PubMed

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

Yordanov, Georgi; Evangelatov, Alexander; Skrobanska, Ralica

2013-07-01

99

Two-photon excited fluorescence of silica nanoparticles loaded with a fluorene-based monomer and its cross-conjugated polymer: their application to cell imaging  

NASA Astrophysics Data System (ADS)

In this work the two-photon activity of nanoparticles obtained from a fluorene monomer (M1) and its cross-conjugated polymer (P1) is reported. Aqueous suspensions of M1 and P1 nanoparticles prepared through the reprecipitation method exhibited maximum two-photon absorption (TPA) cross-sections of 84 and 9860 GM (1 GM = 10-50 cm4 s) at 740 nm, respectively, and a fluorescence quantum yield of ~1. Such a two-photon activity was practically equal with respect to that for molecular solutions of M1 and P1. These materials were then successfully encapsulated into silica nanoparticles to provide bio-compatibly. A lung cancer cell line (A549) and a human cervical cancer cell line (HeLa cells) were incubated with our fluorescent silica nanoparticles to carry out two-photon imaging. By means of these studies we demonstrate that optimized nonlinear optical polymers loaded in silica nanoparticles can be used as efficient probes with low cytotoxicity and good photostability for two-photon fluorescence microscopy. To the best of our knowledge, studies concerning polymer-doped silica nanoparticles exhibiting large two-photon activity have not been reported in the literature.In this work the two-photon activity of nanoparticles obtained from a fluorene monomer (M1) and its cross-conjugated polymer (P1) is reported. Aqueous suspensions of M1 and P1 nanoparticles prepared through the reprecipitation method exhibited maximum two-photon absorption (TPA) cross-sections of 84 and 9860 GM (1 GM = 10-50 cm4 s) at 740 nm, respectively, and a fluorescence quantum yield of ~1. Such a two-photon activity was practically equal with respect to that for molecular solutions of M1 and P1. These materials were then successfully encapsulated into silica nanoparticles to provide bio-compatibly. A lung cancer cell line (A549) and a human cervical cancer cell line (HeLa cells) were incubated with our fluorescent silica nanoparticles to carry out two-photon imaging. By means of these studies we demonstrate that optimized nonlinear optical polymers loaded in silica nanoparticles can be used as efficient probes with low cytotoxicity and good photostability for two-photon fluorescence microscopy. To the best of our knowledge, studies concerning polymer-doped silica nanoparticles exhibiting large two-photon activity have not been reported in the literature. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr31925j

Aparicio-Ixta, Laura; Ramos-Ortiz, Gabriel; Pichardo-Molina, Juan L.; Maldonado, José Luis; Rodríguez, Mario; Tellez-Lopez, Víctor M.; Martinez-Fong, Daniel; Zolotukhin, Mikhail G.; Fomine, Serguei; Meneses-Nava, Marco. A.; Barbosa-García, Oracio

2012-11-01

100

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

101

Sensitization of ovarian cancer cells to cisplatin by gold nanoparticles  

PubMed Central

Recently we reported that gold nanoparticles (AuNPs) inhibit ovarian tumor growth and metastasis in mice by reversing epithelial-mesenchymal transition (EMT). Since EMT is known to confer drug resistance to cancer cells, we wanted to investigate whether anti-EMT property of AuNP could be utilized to sensitize ovarian cancer cells to cisplatin. Herein, we report that AuNPs prevent cisplatin-induced acquired chemoresistance and stemness in ovarian cancer cells and sensitize them to cisplatin. AuNPs inhibit cisplatin induced EMT, decrease the side population cells and key stem cell markers such as ALDH1, CD44, CD133, Sox2, MDR1 and ABCG2 in ovarian cancer cells. Mechanistically, AuNPs prevent cisplatin-induced activation of Akt and NF-?B signaling axis in ovarian cancer cells that are critical for EMT, stem cell maintenance and drug resistance. In vivo, AuNPs sensitize orthotopically implanted ovarian tumor to a low dose of cisplatin and significantly inhibit tumor growth via facilitated delivery of both AuNP and cisplatin. These findings suggest that by depleting stem cell pools and inhibiting key molecular pathways gold nanoparticles sensitize ovarian cancer cells to cisplatin and may be used in combination to inhibit tumor growth and metastasis in ovarian cancer. PMID:25071019

Saha, Sounik; Robertson, David J.; McMeekin, Scott; Bhattacharya, Resham; Mukherjee, Priyabrata

2014-01-01

102

Influence of surface-modified maghemite nanoparticles on in vitro survival of human stem cells  

PubMed Central

Summary Surface-modified maghemite (?-Fe2O3) nanoparticles were obtained by using a conventional precipitation method and coated with D-mannose and poly(N,N-dimethylacrylamide). Both the initial and the modified particles were characterized by transmission electron microscopy and dynamic light scattering with regard to morphology, particle size and polydispersity. In vitro survival of human stem cells was then investigated by using the methyl thiazolyl tetrazolium (MTT) assay, which showed that D-mannose- and poly(N,N-dimethylacrylamide)-coated ?-Fe2O3 particles exhibit much lower level of cytotoxicity than the non-coated ?-Fe2O3. PMID:25383284

Babic, Michal; Lukash, Lyubov L; Ruban, Tetiana A; Kolomiets, Yurii N; Shpylova, Svitlana P; Grypych, Oksana A

2014-01-01

103

Anionic polymers and 10 nm Fe?O?@UA wound dressings support human foetal stem cells normal development and exhibit great antimicrobial properties.  

PubMed

The aims of this study were the development, characterization and bioevaluation of a novel biocompatible, resorbable and bio-active wound dressing prototype, based on anionic polymers (sodium alginate--AlgNa, carboximethylcellulose--CMC) and magnetic nanoparticles loaded with usnic acid (Fe?O?@UA). The antimicrobial activity was tested against Staphylococcus aureus grown in biofilms. The biocompatibility testing model included an endothelial cell line from human umbilical vein and human foetal progenitor cells derived from the amniotic fluid, that express a wide spectrum of surface molecules involved in different vascular functions and inflammatory response, and may be used as skin regenerative support. The obtained results demonstrated that CMC/Fe?O?@UA and AlgNa/Fe?O?@UA are exhibiting structural and functional properties that recommend them for further applications in the biomedical field. They could be used alone or coated with different bio-active compounds, such as Fe?O?@UA, for the development of novel, multifunctional porous materials used in tissues regeneration, as antimicrobial substances releasing devices, providing also a mechanical support for the eukaryotic cells adhesion, and exhibiting the advantage of low cytotoxicity on human progenitor cells. The great antimicrobial properties exhibited by the newly synthesized nano-bioactive coatings are recommending them as successful candidates for improving the implanted devices surfaces used in regenerative medicine. PMID:23994366

Grumezescu, Alexandru Mihai; Holban, Alina Maria; Andronescu, Ecaterina; Mogo?anu, George Dan; Vasile, Bogdan Stefan; Chifiriuc, Mariana Carmen; Lazar, Veronica; Andrei, Eugen; Constantinescu, Andrei; Maniu, Horia

2014-03-25

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

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. PMID:20969773

2010-01-01

106

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

107

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

PubMed Central

To assess effects of carbon nanoparticle (CNP) exposure on renal epithelial cells, fullerenes (C60), single-walled carbon nanotubes (SWNT), and multi-walled carbon nanotubes (MWNT) were incubated with a confluent renal epithelial line for 48 h. At low concentrations, CNP-treated cells exhibited significant decreases in transepithelial electrical resistance (TEER) but no changes in hormone-stimulated ion transport or CNP-induced toxicity or stress responses as measured by lactate dehydrogenase or cytokine release. The changes in TEER, manifested as an inverse relationship with CNP concentration, were mirrored by an inverse correlation between dose and changes in protein expression. Lower, more physiologically relevant, concentrations of CNP have the most profound effects on barrier cell function and protein expression. These results indicate an impact of CNPs on renal epithelial cells at concentrations lower than have been previously studied and suggest caution with regard to increasing CNP levels entering the food chain due to increasing environmental pollution. PMID:21067278

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

2011-01-01

108

Nanoparticle vesicle encoding for imaging and tracking cell populations.  

PubMed

For phenotypic behavior to be understood in the context of cell lineage and local environment, properties of individual cells must be measured relative to population-wide traits. However, the inability to accurately identify, track and measure thousands of single cells via high-throughput microscopy has impeded dynamic studies of cell populations. We demonstrate unique labeling of cells, driven by the heterogeneous random uptake of fluorescent nanoparticles of different emission colors. By sequentially exposing a cell population to different particles, we generated a large number of unique digital codes, which corresponded to the cell-specific number of nanoparticle-loaded vesicles and were visible within a given fluorescence channel. When three colors are used, the assay can self-generate over 17,000 individual codes identifiable using a typical fluorescence microscope. The color-codes provided immediate visualization of cell identity and allowed us to track human cells with a success rate of 78% across image frames separated by 8 h. PMID:25218182

Rees, Paul; Wills, John W; Brown, M Rowan; Tonkin, James; Holton, Mark D; Hondow, Nicole; Brown, Andrew P; Brydson, Rik; Millar, Val; Carpenter, Anne E; Summers, Huw D

2014-11-01

109

Establishment of tendon-derived cell lines exhibiting pluripotent mesenchymal stem cell-like property  

Microsoft Academic Search

Development of the musculoskeletal system requires coordinated formation of distinct types of tissues, including bone, cartilage, muscle, and tendon. Compared to muscle, cartilage, and bone, cellular and molecular bases of tendon development have not been well understood due to the lack of tendon cell lines. The purpose of this study was to establish and characterize tendon cell lines. Three clonal

R Salingcarnboriboon; H Yoshitake; K Tsuji; M Obinata; T Amagasa; A Nifuji; M Noda

2003-01-01

110

Human cervical and foreskin epithelial cells immortalized by human papillomavirus DNAs exhibit dysplastic differentiation in vivo.  

PubMed

Human papillomavirus (HPV) DNAs are detected in approximately 90% of anogenital carcinomas. To assess directly the effect of HPV on squamous differentiation, normal human cervical and foreskin epithelial cells and cells immortalized by recombinant HPV DNAs were transplanted beneath a skin-muscle flap in athymic mice. Xenografts containing normal cells formed well-differentiated stratified squamous epithelia 2 to 3 weeks after transplantation, but cell lines immortalized by four HPV types (HPV16, HPV18, HPV31, and HPV33) detected in anogenital cancer exhibited dysplastic morphology and molecular alterations in gene expression characteristic of intraepithelial neoplasia. Morphological alterations were accompanied by delayed commitment to terminal differentiation, alterations in the pattern of involucrin expression, and reductions in levels of involucrin and keratin 1 RNAs. HPV18-immortalized cells developed dysplastic changes more rapidly than cells immortalized by HPV16 DNA. These results show that human genital epithelial cells immortalized by HPV DNAs detected in genital cancers undergo dysplastic differentiation in vivo. PMID:1692766

Woodworth, C D; Waggoner, S; Barnes, W; Stoler, M H; DiPaolo, J A

1990-06-15

111

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

PubMed Central

Summary Not much is known about the molecular and functional features of pluripotent stem cells (PSCs) in rabbits. To address this, we derived and characterized 2 types of rabbit PSCs from the same breed of New Zealand White rabbits: 4 lines of embryonic stem cells (rbESCs), and 3 lines of induced PSCs (rbiPSCs) that were obtained by reprogramming adult skin fibroblasts. All cell lines required fibroblast growth factor 2 for their growth and proliferation. All rbESC lines showed molecular and functional properties typically associated with primed pluripotency. The cell cycle of rbESCs had a prolonged G1 phase and a DNA damage checkpoint before entry into the S phase, which are the 2 features typically associated with the somatic cell cycle. In contrast, the rbiPSC lines exhibited some characteristics of naïve pluripotency, including resistance to single-cell dissociation by trypsin, robust activity of the distal enhancer of the mouse Oct4 gene, and expression of naïve pluripotency-specific genes, as defined in rodents. According to gene expression profiles, rbiPSCs were closer to the rabbit inner cell mass (ICM) than rbESCs. Furthermore, rbiPSCs were capable of colonizing the ICM after aggregation with morulas. Therefore, we propose that rbiPSCs self-renew in an intermediate state between naïve and primed pluripotency, which represents a key step toward the generation of bona fide naïve PSC lines in rabbits. PMID:23789112

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

2013-01-01

112

Nanoparticles Targeting Dendritic Cell Surface Molecules Effectively Block T cell Conjugation and Shift Response  

PubMed Central

Dendritic cells (DCs) are potent professional antigen presenting cells (APC) that activate naïve T cells. Interaction of ICAM-1 and LFA-1 molecules on each cell is required for T cell conjugation to DCs which leads to naïve CD4+ T cell activation and proliferation. Nanoparticles capable of blocking LFA-1/ICAM-1 interaction were studied as inhibitors of T cell conjugation to DCs. Primary DCs were primed with ovalbumin, then treated with a peptide that binds ICAM-1 (LABL), a peptide that binds LFA-1 (cIBR) or the same peptides covalently linked to the surface of poly(dl-lactic-co-glycolic acid) nanoparticles (NPs). LABL-NPs and cIBR-NPs rapidly bound to DCs and inhibited T cell conjugation to DCs to a greater extent than the free peptides, unconjugated nanoparticles (NPs), anti-ICAM-1 antibodies and anti-LFA-1 antibodies. In addition, DCs treated with NPs or with cIBR-NPs stimulated the proliferation of T cells, but DCs treated with LABL-NPs did not stimulate T cell proliferation. Nanoparticles targeting ICAM-1 or LFA-1 also altered cytokine production by DC cocultured with T cells when compared to free ligands suggesting these NPs may offer a unique tool for shaping T cell response. PMID:21375342

Chittasupho, Chuda; Shannon, Laura; Siahaan, Teruna J.; Vines, Charlotte M.; Berkland, Cory

2014-01-01

113

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

NASA Astrophysics Data System (ADS)

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

Mizuno, Hidenori; Makita, Kikuo; Matsubara, Koji

2012-11-01

114

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

115

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

NASA Astrophysics Data System (ADS)

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

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

2011-07-01

116

Dendritic Cells Transduced with SOCS1 Gene Exhibit Regulatory DC Properties and Prolong Allograft Survival  

PubMed Central

SOCS1 is a key regulator of cytokine signaling and is important for maintaining balance in the immune system. It is thought to participate in negative feedback loops in cytokine signaling and may be an important signal for the regulation of dendritic cell (DC) maturation. However, it remains unclear whether DCs transduced with SOCS1 exhibit characteristics of regulatory DCs and induce allogeneic T-cell hyporesponsiveness. In this study, we constructed adenoviral vector coding SOCS1 (Ad-SOCS1) that can efficiently increase SOCS1 gene expression in bone marrow-derived dendritic cells. DCs transduced with Ad-SOCS1 (DC-SOCS1) expressed low levels of costimulatory and MHC molecules, were resistant to maturation and activation stimulation, induced allogeneic T-cell hyporesponsiveness, and promoted the generation of regulatory-like T cells in vitro. DC-SOCS1 pretreatment significantly prolonged the survival of allografts and led to a substantial increase in the generation of regulatory T cells. Our data suggest that SOCS1 inhibits DC maturation and induces regulatory DC generation, therefore possessing therapeutic potential to prevent rejection in organ transplantation. PMID:19403057

Fu, Hong; Song, Shaohua; Liu, Fang; Ni, Zhijia; Tang, Yi; Shen, Xiaoyun; Xiao, Liang; Ding, Guoshan; Wang, Quanxing

2009-01-01

117

Inorganic molecular-scale MoSI nanowire-gold nanoparticle networks exhibit self-organized critical self-assembly.  

PubMed

We investigate for the first time the topological characteristics of large molecular-scale inorganic networks self-assembled in solution using the unique sulfur-bonding chemistry of conducting MoSI molecular wires and gold nanoparticles (GNPs). The network self-assembly is shown to display power-law distribution of graph edges, indicating an intrinsic tendency to self-organize into scale-invariant critical state, without any external control parameter. We discuss the electronic transport properties of such networks particularly with regard to the possibility of data processing. PMID:19199756

Strle, Jure; Vengust, Damjan; Mihailovic, Dragan

2009-03-01

118

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

119

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. PMID:23403634

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

120

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

121

In vitro self-assembly of gold nanoparticle-coated poly(3-hydroxybutyrate) granules exhibiting plasmon-induced thermo-optical enhancements.  

PubMed

Polyhydroxyalkanoate (PHA) synthase attached to gold nanoparticles (AuNP) produce poly(3-hydroxybutyrate) (PHB) upon the addition of 3-hydroxybutyrate-CoA, and then coalesce to form micrometer-sized AuNP-coated PHB granules. These AuNP-coated PHB granules are potential theranostic agents that have enhanced imaging capabilities and are capable of heating upon near-infrared laser irradiation. The AuNP-coated PHB exhibited 11-fold enhancement in surface-enhanced Raman scattering over particles prior polymerization. Stained AuNP-coated PHB exhibited a 6-fold enhancement in fluorescence intensity as well as a 1.3-fold decrease in photobleaching rate compared to PHB granules alone. The granules were also shown to emit heat when illuminated at 808 nm with a 3.9-fold increase in heating rate compared to particles alone. PMID:20565131

Rey, Diego A; Strickland, Aaron D; Kirui, Dickson; Niamsiri, Nuttawee; Batt, Carl A

2010-07-01

122

Amyloid fibrils enhance transport of metal nanoparticles in living cells and induced cytotoxicity.  

PubMed

Amyloid protein fibrils occur in vivo as pathological agents, in the case of neurodegenerative diseases, or as functional amyloids, when playing biologically vital roles. Here we show how amyloid fibrils generated from a food protein, ?-lactoglobulin, can be used as nanoreactors for the synthesis of metal nanoparticles and demonstrate that the resulting hybrids can play a central role in the internalization of nanoparticles into living cells, with up to 3-fold-enhanced transport properties over pristine nanoparticles. We conjugate gold, silver, and palladium nanoparticles onto amyloid fibrils by chemical reduction, and we study their effect on dendritic and MCF7 breast cancer cells. Transmission electron microscopy indicates localization of nanoparticles inside vesicles of the cells. Flow cytometry reveals that silver nanoparticle-amyloid hybrids are cytotoxic, while gold and palladium nanoparticle-amyloid hybrids produce no notable effect on cell viability and activation status. PMID:24941321

Bolisetty, Sreenath; Boddupalli, Chandra Sekhar; Handschin, Stephan; Chaitanya, Krishna; Adamcik, Jozef; Saito, Yasuyuki; Manz, Markus G; Mezzenga, Raffaele

2014-07-14

123

Mice lacking TrkB in parvalbumin-positive cells exhibit sexually dimorphic behavioral phenotypes.  

PubMed

Activity-dependent brain-derived neurotrophic factor (BDNF) signaling through receptor tyrosine kinase B (TrkB) is required for cued fear memory consolidation and extinction. Although BDNF is primarily secreted from glutamatergic neurons, TrkB is expressed by other genetically defined cells whose contributions to the behavioral effects of BDNF remain poorly understood. Parvalbumin (PV)-positive interneurons, which are highly enriched in TrkB, are emerging as key regulators of fear memory expression. We therefore hypothesized that activity-dependent BDNF signaling in PV-interneurons may modulate emotional learning. To test this hypothesis, we utilized the LoxP/Cre system for conditional deletion of TrkB in PV-positive cells to examine the impact of cell-autonomous BDNF signaling on Pavlovian fear conditioning and extinction. However, behavioral abnormalities indicative of vestibular dysfunction precluded the use of homozygous conditional knockouts in tests of higher cognitive functioning. While vestibular dysfunction was apparent in both sexes, female conditional knockouts exhibited an exacerbated phenotype, including extreme motor hyperactivity and circling behavior, compared to their male littermates. Heterozygous conditional knockouts were spared of vestibular dysfunction. While fear memory consolidation was unaffected in heterozygotes of both sexes, males exhibited impaired extinction consolidation compared to their littermate controls. Our findings complement evidence from human and rodent studies suggesting that BDNF signaling promotes consolidation of extinction and point to PV-positive neurons as a discrete population that mediates these effects in a sex-specific manner. PMID:25127683

Lucas, Elizabeth K; Jegarl, Anita; Clem, Roger L

2014-11-01

124

Multinucleated giant cell formation exhibits features of phagocytosis with participation of the endoplasmic reticulum.  

PubMed

Macrophage fusion leading to formation of multinucleated giant cells during chronic inflammation is poorly understood in mechanism and physiological significance. To address this, we developed a system of human macrophage fusion that utilizes IL-4, IL-13, or alpha-tocopherol to generate large foreign body-type giant cells (FBGC). Extending our previously demonstrated requirements for F-actin and mannose receptor (MR) activity, we find that macrophage fusion exhibits further features of a phagocytic process. Pharmacological inhibition of IL-4-induced FBGC formation indicates critical roles for vacuolar-type ATPase, microtubules, the endoplasmic reticulum (ER), and calcium-independent phospholipase A(2) (iPLA(2)), but not calcium-dependent PLA(2) (cPLA(2)), secretory PLA(2) (sPLA(2)), cyclooxygenase, or lipoxygenase. Immunocytochemistry confirms iPLA(2) expression and absence of cPLA(2) or sPLA(2) expression in macrophages/FBGC. As markers of ER-mediated phagocytosis, calnexin and calregulin are detectable on non-permeabilized fusing macrophages and also concentrated at fusion interfaces where they co-localize with actin in permeabilized macrophages/FBGC. Furthermore, ER markers co-localize with concanavalin A reactivity on non-permeabilized fusing macrophages, suggesting that the ER may present MR ligand during fusion events. These data demonstrate for the first time that the mechanism of macrophage fusion leading to formation of multinucleated giant cells exhibits multiple features of phagocytosis with potential participation of the ER. PMID:16109404

McNally, Amy K; Anderson, James M

2005-10-01

125

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

PubMed

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

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

2012-11-30

126

Combination of SNX-2112 with 5-FU exhibits antagonistic effect in esophageal cancer cells.  

PubMed

The low efficacy of single-drug chemotherapy forms the basis for combination therapy in esophageal squamous cell carcinoma. SNX-2112, a selective heat shock protein 90 (Hsp90) inhibitor, was recently reported as being effective in combination with cisplatin and paclitaxel. In this study, we investigated the effect of SNX-2112 in combination with 5-fluorouracil (5-FU), another first-line anticancer drug, in esophageal cancer. Unexpectedly, tetrazolium assay revealed that the combination of SNX-2112 with 5-FU exhibited antagonistic effect. Flow cytometry revealed that the SNX-2112 and 5-FU combination greatly decreased the number of G2/M cells compared to SNX-2112-only treatment in Eca?109 cells. This effect might be related to the altered mRNA level of cyclin-related genes including cyclin D1, Chk2 and Cdk4. Further, 5-FU attenuated SNX-2112-induced apoptosis by decreasing poly(ADP-ribose) polymerase (PARP) cleavage and inactivating caspase-3, -8 and -9. Additionally, 5-FU suppressed the SNX-2112-induced decrease of mitochondrial membrane potential. Moreover, 5-FU partly recovered Hsp90 client proteins, including Akt, p-Akt, inhibitor of ?B kinase (IKK)?, extracellular signal-regulated kinase (ERK)1/2, and glycogen synthase kinase (GSK)-3?, which SNX-2112 had downregulated. Taken together, this is the first report that the combination of SNX-2112 with 5-FU exhibited antagonistic effect in esophageal cancer cells by affecting growth inhibition, cell cycle, apoptosis, and Hsp90 client proteins, suggesting that care is required in the clinical application of combined SNX-2112 and 5-FU. PMID:25333998

Liu, Yuting; Wang, Xiao; Wang, Ying; Zhang, Yi; Zheng, Kai; Yan, Haizhao; Zhang, Li; Chen, Wenbo; Wang, Xiaoyan; Liu, Qiuying; Wang, Shaoxiang; Wang, Yifei

2015-01-01

127

Preparation of ZnO nanoparticles and characteristics of dye-sensitized solar cells based on nanoparticles film  

NASA Astrophysics Data System (ADS)

ZnO nanoparticles were synthesized by hydrolization method and the effects of zinc nitrate concentration and reaction temperature on the resulted particle properties were studied. The transmission of the as-prepared and calcined films and their optical band gaps are measured and calculated respectively. Furthermore, as an application of the ZnO nanoparticles film, dye-sensitized solar cells based on it were successfully fabricated and the cell performances were characterized. The short circuit current for ZnO nanoparticles film DSSCs is 1.35 mA cm -2, which indicates good value of the prepared film using this technique.

Liu, Zhifeng; Liu, Chengcheng; Ya, Jing; E, Lei

2010-01-01

128

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

2007-02-01

129

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

130

Amorphous silica nanoparticles enhance cross-presentation in murine dendritic cells  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer Silica nanoparticles enhanced cross-presentation. Black-Right-Pointing-Pointer Silica nanoparticles induced endosomal release of exogenous antigens. Black-Right-Pointing-Pointer Silica nanoparticle-induced cross-presentation was mediated by scavenger receptors. Black-Right-Pointing-Pointer Surface-modification may enable the manufacture of safer silica nanoparticles. -- Abstract: Nanomaterials (NMs) exhibit unique physicochemical properties and innovative functions, and they are increasingly being used in a wide variety of fields. Ensuring the safety of NMs is now an urgent task. Recently, we reported that amorphous silica nanoparticles (nSPs), one of the most widely used NMs, enhance antigen-specific cellular immune responses and may therefore aggravate immune diseases. Thus, to ensure the design of safer nSPs, investigations into the effect of nSPs on antigen presentation in dendritic cells, which are central orchestrators of the adaptive immune response, are now needed. Here, we show that nSPs with diameters of 70 and 100 nm enhanced exogenous antigen entry into the cytosol from endosomes and induced cross-presentation, whereas submicron-sized silica particles (>100 nm) did not. Furthermore, we show that surface modification of nSPs suppressed cross-presentation. Although further studies are required to investigate whether surface-modified nSPs suppress immune-modulating effects in vivo, the current results indicate that appropriate regulation of the characteristics of nSPs, such as size and surface properties, will be critical for the design of safer nSPs.

Hirai, Toshiro [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan)] [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Yoshioka, Yasuo, E-mail: yasuo@phs.osaka-u.ac.jp [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan)] [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Takahashi, Hideki; Ichihashi, Ko-ichi; Yoshida, Tokuyuki; Tochigi, Saeko [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan)] [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Nagano, Kazuya [Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saitoasagi, Ibaraki, Osaka 567-0085 (Japan)] [Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saitoasagi, Ibaraki, Osaka 567-0085 (Japan); Abe, Yasuhiro [Cancer Biology Research Center, Sanford Research/USD, 2301 E. 60th Street N, Sioux Falls, SD 57104 (United States)] [Cancer Biology Research Center, Sanford Research/USD, 2301 E. 60th Street N, Sioux Falls, SD 57104 (United States); Kamada, Haruhiko; Tsunoda, Shin-ichi [Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saitoasagi, Ibaraki, Osaka 567-0085 (Japan) [Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saitoasagi, Ibaraki, Osaka 567-0085 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Nabeshi, Hiromi [Division of Foods, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan)] [Division of Foods, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan); Yoshikawa, Tomoaki [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan)] [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Tsutsumi, Yasuo, E-mail: ytsutsumi@phs.osaka-u.ac.jp [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan) [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saitoasagi, Ibaraki, Osaka 567-0085 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan)

2012-10-26

131

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

132

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

133

Selective cytotoxic effect of ZnO nanoparticles on glioma cells  

Microsoft Academic Search

In this study we examined the cytotoxic effect of ZnO nanoparticles on various human cancer and normal cells. We found that\\u000a the ZnO nanoparticles exerted a cytotoxic effect on the human glioma cell lines A172, U87, LNZ308, LN18, and LN229, whereas\\u000a no cytotoxic effect was observed on normal human astrocytes. Similarly, the ZnO nanoparticles induced cell death in breast\\u000a and

Stella Ostrovsky; Gila Kazimirsky; Aharon Gedanken; Chaya Brodie

2009-01-01

134

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

Microsoft Academic Search

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

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

2009-01-01

135

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

136

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

Microsoft Academic Search

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

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

2009-01-01

137

Vasopressin cell groups exhibit strongly divergent responses to copulation and male-male interactions in mice  

PubMed Central

Arginine vasopressin (AVP) and its nonmammalian homolog arginine vasotocin influence social behaviors ranging from affiliation to resident–intruder aggression. Although numerous sites of action have been established for these behavioral effects, the involvement of specific AVP cell groups in the brain is poorly understood, and socially elicited Fos responses have not been quantified for many of the AVP cell groups found in rodents. Surprisingly, this includes the AVP population in the posterior part of the medial bed nucleus of the stria terminalis (BSTMP), which has been extensively implicated, albeit indirectly, in various aspects of affiliation and other social behaviors. We examined the Fos responses of eight hypothalamic and three extra-hypothalamic AVP-immunoreactive (-ir) cell groups to copulation, nonaggressive male–male interaction, and aggressive male–male interaction in both dominant and subordinate C57BL/6J mice. The BSTMP cells exhibited a response profile that was unlike all other cell groups: from a control baseline of ~5% of AVP-ir neurons colocalizing with Fos, colocalization increased significantly to ~12% following nonaggressive male–male interaction, and to ~70% following copulation. Aggressive interactions did not increase colocalization beyond the level observed in nonaggressive male mice. These results suggest that BSTMP neurons in mice may increase AVP-Fos colocalization selectively in response to affiliation-related stimuli, similar to findings in finches. In contrast, virtually all other cell groups were responsive to negative aspects of interaction, either through elevated AVP-Fos colocalization in subordinate animals, positive correlations of AVP-Fos colocalization with bites received, and/or negative correlations of AVP-Fos colocalization with dominance. These findings greatly expand what is known of the contributions of specific brain AVP cell groups to social behavior. PMID:20382147

Ho, Jacqueline M.; Murray, John H.; Demas, Gregory E.; Goodson, James L.

2014-01-01

138

Vasopressin cell groups exhibit strongly divergent responses to copulation and male-male interactions in mice.  

PubMed

Arginine vasopressin (AVP) and its nonmammalian homolog arginine vasotocin influence social behaviors ranging from affiliation to resident-intruder aggression. Although numerous sites of action have been established for these behavioral effects, the involvement of specific AVP cell groups in the brain is poorly understood, and socially elicited Fos responses have not been quantified for many of the AVP cell groups found in rodents. Surprisingly, this includes the AVP population in the posterior part of the medial bed nucleus of the stria terminalis (BSTMP), which has been extensively implicated, albeit indirectly, in various aspects of affiliation and other social behaviors. We examined the Fos responses of eight hypothalamic and three extra-hypothalamic AVP-immunoreactive (-ir) cell groups to copulation, nonaggressive male-male interaction, and aggressive male-male interaction in both dominant and subordinate C57BL/6J mice. The BSTMP cells exhibited a response profile that was unlike all other cell groups: from a control baseline of approximately 5% of AVP-ir neurons colocalizing with Fos, colocalization increased significantly to approximately 12% following nonaggressive male-male interaction, and to approximately 70% following copulation. Aggressive interactions did not increase colocalization beyond the level observed in nonaggressive male mice. These results suggest that BSTMP neurons in mice may increase AVP-Fos colocalization selectively in response to affiliation-related stimuli, similar to findings in finches. In contrast, virtually all other cell groups were responsive to negative aspects of interaction, either through elevated AVP-Fos colocalization in subordinate animals, positive correlations of AVP-Fos colocalization with bites received, and/or negative correlations of AVP-Fos colocalization with dominance. These findings greatly expand what is known of the contributions of specific brain AVP cell groups to social behavior. PMID:20382147

Ho, Jacqueline M; Murray, John H; Demas, Gregory E; Goodson, James L

2010-08-01

139

Toxicity evaluations of superparamagnetic iron oxide nanoparticles: cell "vision" versus physicochemical properties of nanoparticles.  

PubMed

In the last few decades, nanoparticles (NPs) have been recognized as promising candidates for starting a new revolution in science and technology due to their unusual properties, attracting the attention of physicists, chemists, biologists, and engineers. The aim of this study is to evaluate the toxicities (at both cellular and molecular levels) of three forms of superparamagnetic iron oxide nanoparticles (SPIONs) of various surface chemistries (COOH, plain, and NH(2)) through the comparison with gene expression patterns of three cell types (i.e., human heart, brain, and kidney). For this purpose, both an MTT assay and a DNA microarray analysis were applied in three human cell lines--HCM (heart), BE-2-C (brain), and 293T (kidney)--under the exposure to SPIONs-COOH, SPIONs-NH(2), and bare SPIONs. The specific gene alteration and hierarchical clustering revealed that SPIONs-COOH altered genes associated with cell proliferative responses due to their reactive oxygen species (ROS) properties. It was also found that the cell type can have quite a significant role in the definition of suitable pathways for detoxification of NPs, which has deep implications for the safe and high yield design of NPs for biomedical applications and will require serious consideration in the future. PMID:21838310

Mahmoudi, Morteza; Laurent, Sophie; Shokrgozar, Mohammad A; Hosseinkhani, Mohsen

2011-09-27

140

Glial cells, but not neurons, exhibit a controllable response to a localized inflammatory microenvironment in vitro  

PubMed Central

The ability to design long-lasting intracortical implants hinges on understanding the factors leading to the loss of neuronal density and the formation of the glial scar. In this study, we modify a common in vitro mixed cortical culture model using lipopolysaccharide (LPS) to examine the responses of microglia, astrocytes, and neurons to microwire segments. We also use dip-coated polyethylene glycol (PEG), which we have previously shown can modulate impedance changes to neural microelectrodes, to control the cellular responses. We find that microglia, as expected, exhibit an elevated response to LPS-coated microwire for distances of up to 150 ?m, and that this elevated response can be mitigated by co-depositing PEG with LPS. Astrocytes exhibit a more complex, distance-dependent response, whereas neurons do not appear to be affected by the type or magnitude of glial response within this in vitro model. The discrepancy between our in vitro responses and typically observed in vivo responses suggest the importance of using a systems approach to understand the responses of the various brain cell types in a chronic in vivo setting, as well as the necessity of studying the roles of cell types not native to the brain. Our results further indicate that the loss of neuronal density observed in vivo is not a necessary consequence of elevated glial activation.

Sommakia, Salah; Rickus, Jenna L.; Otto, Kevin J.

2014-01-01

141

Eco-Friendly Fabrication of 4% Efficient Organic Solar Cells from Surfactant-Free P3HT:ICBA Nanoparticle Dispersions.  

PubMed

Photo-active layers from non-stabilized P3HT:ICBA nanoparticles enable the fabrication of inverted organic solar cells from eco-friendly, alcoholic dispersions. Exhibiting power conversion efficiencies (PCEs) ?4%, the devices are competitive to state-of-the-art P3HT:ICBA solar cells from chlorinated solvents. Upon thermal annealing, the short circuit current density and consequently the PCE of the inverted solar cells improve radically due to a more intimate contact of the nanoparticles and hence an enhanced charge carrier extraction. PMID:25186115

Gärtner, Stefan; Christmann, Marco; Sankaran, Sivaramakrishnan; Röhm, Holger; Prinz, Eva-Marie; Penth, Felix; Pütz, Andreas; Türeli, Akif Emre; Penth, Bernd; Baumstümmler, Bernd; Colsmann, Alexander

2014-10-01

142

Nanoparticle assisted photothermal deformation of individual neuronal organelles and cells  

PubMed Central

Stimulation of the localized surface plasmon of metallic nanoparticles has been shown to be an effective mechanism to induce photothermal damage in biological tissues. However, few studies have focused on single cell or subcellular ablation. Our results show that, upon incubation, gold nanostars are internalized by neurons of acute mouse cerebellar brain slices, clustering inside or close to the nucleus. By stimulating the nanostars’ surface plasmon using a femtosecond laser, we show deformation of single nuclei and single cells. Given its precision and extremely localized effect, this is a promising technique for photothermal therapy in areas sensitive to collateral thermal damage such as the nervous system.

Romero, V. H.; Kereselidze, Z.; Egido, W.; Michaelides, E. A.; Santamaria, F.; Peralta, X. G.

2014-01-01

143

Commercial Nanoparticles for Stem Cell Labeling and Tracking  

PubMed Central

Stem cell therapy provides promising solutions for diseases and injuries that conventional medicines and therapies cannot effectively treat. To achieve its full therapeutic potentials, the homing process, survival, differentiation, and engraftment of stem cells post transplantation must be clearly understood. To address this need, non-invasive imaging technologies based on nanoparticles (NPs) have been developed to track transplanted stem cells. Here we summarize existing commercial NPs which can act as contrast agents of three commonly used imaging modalities, including fluorescence imaging, magnetic resonance imaging and photoacoustic imaging, for stem cell labeling and tracking. Specifically, we go through their technologies, industry distributors, applications and existing concerns in stem cell research. Finally, we provide an industry perspective on the potential challenges and future for the development of new NP products. PMID:23946821

Wang, Yaqi; Xu, Chenjie; Ow, Hooisweng

2013-01-01

144

Commercial nanoparticles for stem cell labeling and tracking.  

PubMed

Stem cell therapy provides promising solutions for diseases and injuries that conventional medicines and therapies cannot effectively treat. To achieve its full therapeutic potentials, the homing process, survival, differentiation, and engraftment of stem cells post transplantation must be clearly understood. To address this need, non-invasive imaging technologies based on nanoparticles (NPs) have been developed to track transplanted stem cells. Here we summarize existing commercial NPs which can act as contrast agents of three commonly used imaging modalities, including fluorescence imaging, magnetic resonance imaging and photoacoustic imaging, for stem cell labeling and tracking. Specifically, we go through their technologies, industry distributors, applications and existing concerns in stem cell research. Finally, we provide an industry perspective on the potential challenges and future for the development of new NP products. PMID:23946821

Wang, Yaqi; Xu, Chenjie; Ow, Hooisweng

2013-01-01

145

Berbamine exhibits potent antitumor effects on imatinib-resistant CML cells in vitro and in vivo  

PubMed Central

Aim: The aim of this study was to explore the effects and mechanism of berbamine on imatinib-resistant BCR-ABL-positive human leukemia K562 (K562-r) cells in vitro and in vivo. Methods: Cell viability was measured by MTT assay, and apoptotic morphology changes were detected by fluorescence microscopy. The apoptosis rate was measured by flow cytometric assay. mdr-1 mRNA levels were determined by RT-PCR. Bcl-2 family proteins, cytochrome c(cyt C), poly (ADP-ribose) polymerase (PARP), and P-glycoprotein were detected by Western blot. BALB/c nu/nu mice were injected with K562-r cells subcutaneously. Tumor-bearing mice were treated intravenously with berbamine. Results: MTT tests revealed that berbamine significantly inhibited K562-r cell proliferation and increased the chemo-sensitivity of K562-r cells to imatinib. The apoptosis rate was significantly increased following treatment with 21.2 ?mol/L berbamine; formation of typical apoptotic blebs was apparent, as observed by fluorescence microscopy. Expression levels of mdr-1 mRNA and P-gp protein were high in untreated K562-r cells and significantly down-regulated by berbamine treatment. Berbamine-treated K562-r cells also exhibited down-regulated expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, up-regulated expression of the apoptotic proteins Bax and cytoplasmic cyt C, and stimulated proteolytic cleavage of PARP. In addition, berbamine also suppressed the growth of K562-r xenotransplanted tumors in vivo. Conclusion: Berbamine inhibited proliferation of K562-r cells both in vitro and in vivo. Berbamine-induced apoptosis in K562-r cells appeared to occur through a mechanism involving Bcl-2 family proteins, as well as mdr-1 mRNA and P-gp protein. Berbamine in combination with imatinib restored the chemo-sensitivity of K562-r cells to imatinib. Our findings suggest that berbamine may be useful in treating imatinib-resistant CML patients. PMID:19270722

Wei, Yan-lin; Xu, Lei; Liang, Yun; Xu, Xiao-hua; Zhao, Xiao-ying

2009-01-01

146

Novel cell lines isolated from mouse embryonic stem cells exhibiting de novo methylation of the e-cadherin promoter.  

PubMed

Mouse embryonic stem cells (mESCs) and epiblast stem cells represent the naïve and primed pluripotent states, respectively. These cells self-renew via distinct signaling pathways and can transition between the two states in the presence of appropriate growth factors. Manipulation of signaling pathways has therefore allowed the isolation of novel pluripotent cell types such as Fibroblast growth factor, Activin and BIO-derived stem cells and IESCs. However, the effect of cell seeding density on pluripotency remains unexplored. In this study, we have examined whether mESCs can epigenetically regulate E-cadherin to enter a primed-like state in response to low cell seeding density. We show that low density seeding in the absence of leukaemia inhibitory factor (LIF) induces decreased apoptosis and maintenance of pluripotency via Activin/Nodal, concomitant with loss of E-cadherin, Signal transducer and activator of transcription phosphorylation, and chimera-forming ability. These cells, E-cadherin negative proliferating stem cells (ENPSCs) can be reverted to a naïve phenotype by addition of LIF or forced E-cadherin expression. However, prolonged culture of ENPSCs without LIF leads to methylation of the E-cadherin promoter (ENPSC(M) ), which cannot be reversed by LIF supplementation, and increased histone H3K27 and decreased H3K4 trimethylation. Transcript analysis of ENPSC(M) revealed a primed-like phenotype and their differentiation leads to enrichment of neuroectoderm cells. The generation of ENPSCs is similar to tumorigenesis as ENPSCs exhibit transcript alterations associated with neoplasia, hyperplasia, carcinoma, and metastasis. We therefore describe a novel cell model to elucidate the role of E-cadherin in pluripotency and to investigate epigenetic regulation of this gene during mESC differentiation and tumor metastasis. Stem Cells 2014;32:2869-2879. PMID:25074424

Hawkins, Kate; Keramari, Maria; Soncin, Francesca; Segal, Joe M; Mohamet, Lisa; Miazga, Natalie; Ritson, Sarah; Bobola, Nicoletta; Merry, Catherine L R; Ward, Christopher M

2014-11-01

147

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

PubMed

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. PMID:24710127

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

2014-05-21

148

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 PMID:7659523

Bertoncini, C R; Meneghini, R

1995-01-01

149

Congenital amegakaryocytic thrombocytopenia iPS cells exhibit defective MPL-mediated signaling  

PubMed Central

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

2013-01-01

150

Pulmonary large cell neuroendocrine carcinoma exhibiting extensive pagetoid spread in the bronchial epithelium: A case report  

PubMed Central

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive malignant tumor, which was proposed as a novel type of neuroendocrine tumor in 1991. Although it is categorized as a non-small cell lung carcinoma, the precise pathological condition is unknown due to its rare occurrence. The present study outlines the case of a patient presenting with an LCNEC that exhibited pagetoid spread from the region of the primary tumor to the bronchial epithelium (distance, >30 mm). The pagetoid spread was unconfirmed preoperatively, however, was identified by intraoperative rapid diagnosis. This caused us to suffer the perioperative decision of additional resection and resulted in an incomplete resection, as suture of the bronchus was not possible. Pagetoid spread, which is often apparent in the breast, presents as a rare pattern of infiltration of cancer cells when a massive carcinoma is identified beneath the intraepithelial spread. Although preoperative diagnosis of pagetoid spread is difficult due to its rarity and undefined clinical features, it is important for surgeons and pathologists treating lung cancer patients to be aware of potential pagetoid spread in the thoracic region. PMID:25364438

OGAWA, HIROYUKI; TANAKA, YUGO; KOMA, YU-ICHIRO; HOKKA, DAISUKE; TANE, SHINYA; TAUCHI, SHUNSUKE; UCHINO, KAZUYA; YOSHIMURA, MASAHIRO; MANIWA, YOSHIMASA

2014-01-01

151

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. PMID:19883077

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

2009-01-01

152

Cytotoxic and genotoxic effects of silver nanoparticles in testicular cells.  

PubMed

Serious concerns have been expressed about potential risks of engineered nanoparticles. Regulatory health risk assessment of such particles has become mandatory for the safe use of nanomaterials in consumer products and medicines; including the potential effects on reproduction and fertility, are relevant for this risk evaluation. In this study, we examined effects of silver particles of nano- (20nm) and submicron- (200nm) size, and titanium dioxide nanoparticles (TiO(2)-NPs; 21nm), with emphasis on reproductive cellular- and genotoxicity. Ntera2 (NT2, human testicular embryonic carcinoma cell line), and primary testicular cells from C57BL6 mice of wild type (WT) and 8-oxoguanine DNA glycosylase knock-out (KO, mOgg1(-/-)) genotype were exposed to the particles. The latter mimics the repair status of human testicular cells vs oxidative damage and is thus a suitable model for human male reproductive toxicity studies. The results suggest that silver nano- and submicron-particles (AgNPs) are more cytotoxic and cytostatic compared to TiO(2)-NPs, causing apoptosis, necrosis and decreased proliferation in a concentration- and time-dependent manner. The 200nm AgNPs in particular appeared to cause a concentration-dependent increase in DNA-strand breaks in NT2 cells, whereas the latter response did not seem to occur with respect to oxidative purine base damage analysed with any of the particles tested. PMID:22085606

Asare, Nana; Instanes, Christine; Sandberg, Wiggo J; Refsnes, Magne; Schwarze, Per; Kruszewski, Marcin; Brunborg, Gunnar

2012-01-27

153

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. PMID:22514708

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

2012-01-01

154

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

155

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

156

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

157

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

158

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

PubMed Central

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

2014-01-01

159

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

160

Detection of fluorescent nanoparticle interactions with primary immune cell subpopulations by flow cytometry.  

PubMed

Engineered nanoparticles are endowed with very promising properties for therapeutic and diagnostic purposes. This work describes a fast and reliable method of analysis by flow cytometry to study nanoparticle interaction with immune cells. Primary immune cells can be easily purified from human or mouse tissues by antibody-mediated magnetic isolation. In the first instance, the different cell populations running in a flow cytometer can be distinguished by the forward-scattered light (FSC), which is proportional to cell size, and the side-scattered light (SSC), related to cell internal complexity. Furthermore, fluorescently labeled antibodies against specific cell surface receptors permit the identification of several subpopulations within the same sample. Often, all these features vary when cells are boosted by external stimuli that change their physiological and morphological state. Here, 50 nm FITC-SiO2 nanoparticles are used as a model to identify the internalization of nanostructured materials in human blood immune cells. The cell fluorescence and side-scattered light increase after incubation with nanoparticles allowed us to define time and concentration dependence of nanoparticle-cell interaction. Moreover, such protocol can be extended to investigate Rhodamine-SiO2 nanoparticle interaction with primary microglia, the central nervous system resident immune cells, isolated from mutant mice that specifically express the Green Fluorescent Protein (GFP) in the monocyte/macrophage lineage. Finally, flow cytometry data related to nanoparticle internalization into the cells have been confirmed by confocal microscopy. PMID:24747480

Gamucci, Olimpia; Bertero, Alice; Malvindi, Maria Ada; Sabella, Stefania; Pompa, Pier Paolo; Mazzolai, Barbara; Bardi, Giuseppe

2014-01-01

161

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

162

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

163

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

164

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

PubMed

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

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

2010-11-01

165

Role of sustained antigen release from nanoparticle vaccines in shaping the T cell memory phenotype  

E-print Network

Role of sustained antigen release from nanoparticle vaccines in shaping the T cell memory phenotype PLGA Nanoparticle Persistence Vaccine Memory T cells a b s t r a c t Particulate vaccines are emerging, are two of the most ubiquitous platforms in vaccine delivery studies. Here we directly compared

Fahmy, Tarek

166

ZnO nanoparticles and nanowire array hybrid photoanodes for dye-sensitized solar cells  

E-print Network

ZnO nanoparticles and nanowire array hybrid photoanodes for dye-sensitized solar cells Supan for dye-sensitized solar cell DSC with NW arrays to serve as a direct pathway for fast electron transport January 2010; published online 19 February 2010 ZnO nanoparticle-nanowire NP-NW array hybrid photoanodes

Cao, Guozhong

167

Structure and dynamics of ferroelectric liquid crystal cells exhibiting thresholdless switching.  

PubMed

Surface-stabilized ferroelectric liquid crystal cells are usually bistable, with the spontaneous polarization either up or down, perpendicular to the plane of the cell. In materials with high spontaneous polarization the polarization charge self-interaction leads to a monostable structure that exhibits a thresholdless, "V-shaped" switching of the optical response to an applied voltage. With a model that includes the electrostatic self-energy of the spontaneous polarization, we examine the transition from bistablity to monostability as a function of the polar and nonpolar anchoring energies, the liquid crystal elasticity, and the thickness of the alignment layers. Two bistable and one monostable structures are possible. The bistable state is only obtained when the thickness of the insulating alignment layer and the polar anchoring energy are small, or when the spontaneous polarization is small. From linear stability analysis we get analytical expressions for the limits of stability of the structures. Numerical calculations show that in some ranges of the parameters two structures can coexist. We also present the calculation of the polarization fluctuation modes. The lowest one becomes soft at the continuous transitions among the structures and at the limits of stability. PMID:11863546

Copic, Martin; Maclennan, Joseph E; Clark, Noel A

2002-02-01

168

GABAergic striatal neurons exhibit caspase-independent, mitochondrially mediated programmed cell death.  

PubMed

GABAergic striatal neurons are compromised in basal ganglia pathologies and we analysed how insult nature determined their patterns of injury and recruitment of the intrinsic mitochondrial pathway during programmed cell death (PCD). Stressors affecting targets implicated in striatal neurodegeneration [3-morpholinylsydnoneimine (SIN-1), 3-nitropropionic acid (3-NP), NMDA, 3,5-dihydroxyphenylglycine (DHPG), and staurosporine (STS)] were compared in cultured GABAergic neurons from murine striatum by analyzing the progression of injury and its correlation with mitochondrial involvement, the redistribution of intermembrane space (IMS) proteins, and patterns of protease activation. Stressors produced PCD exhibiting slow-onset kinetics with time-dependent annexin-V labeling and eventual DNA fragmentation. IMS proteins including cytochrome c were differentially distributed, although stressors except STS produced early redistribution of apoptosis-inducing factor and Omi, suggestive of early recruitment of both caspase-dependent and caspase-independent signaling. In general, Bax mobilization to mitochondria appeared to promote IMS protein redistribution. Caspase 3 activation was prominent after STS, whereas NMDA and SIN-1 produced mainly calpain activation, and 3-NP and DHPG elicited a mixed profile of protease activation. PCD and redistribution of IMS proteins in striatal GABAergic neurons were canonical and insult-dependent, reflecting differential interplay between the caspase cascade and alternate cell death pathways. PMID:19393028

Diwakarla, Shanti; Mercer, Linda D; Kardashsyan, Liubov; Chu, Percy W Y; Shin, Yea Seul; Lau, Chew L; Hughes, Maria L R; Nagley, Phillip; Beart, Philip M

2009-05-01

169

Antiproliferative effect of ASC-J9 delivered by PLGA nanoparticles against estrogen-dependent breast cancer cells.  

PubMed

Among polymeric nanoparticles designed for cancer therapy, PLGA nanoparticles have become one of the most popular polymeric devices for chemotherapeutic-based nanoformulations against several kinds of malignant diseases. Promising properties, including long-circulation time, enhanced tumor localization, interference with "multidrug" resistance effects, and environmental biodegradability, often result in an improvement of the drug bioavailability and effectiveness. In the present work, we have synthesized 1,7-bis(3,4-dimethoxyphenyl)-5-hydroxyhepta-1,4,6-trien-3-one (ASC-J9) and developed uniform ASC-J9-loaded PLGA nanoparticles of about 120 nm, which have been prepared by a single-emulsion process. Structural and morphological features of the nanoformulation were analyzed, followed by an accurate evaluation of the in vitro drug release kinetics, which exhibited Fickian law diffusion over 10 days. The intracellular degradation of ASC-J9-bearing nanoparticles within estrogen-dependent MCF-7 breast cancer cells was correlated to a time- and dose-dependent activity of the released drug. A cellular growth inhibition associated with a specific cell cycle G2/M blocking effect caused by ASC-J9 release inside the cytosol allowed us to put forward a hypothesis on the action mechanism of this nanosystem, which led to the final cell apoptosis. Our study was accomplished using Annexin V-based cell death analysis, MTT assessment of proliferation, radical scavenging activity, and intracellular ROS evaluation. Moreover, the intracellular localization of nanoformulated ASC-J9 was confirmed by a Raman optical imaging experiment designed ad hoc. PLGA nanoparticles and ASC-J9 proved also to be safe for a healthy embryo fibroblast cell line (3T3-L1), suggesting a possible clinical translation of this potential nanochemotherapeutic to expand the inherently poor bioavailability of hydrophobic ASC-J9 that could be proposed for the treatment of malignant breast cancer. PMID:24945469

Verderio, Paolo; Pandolfi, Laura; Mazzucchelli, Serena; Marinozzi, Maria Rosaria; Vanna, Renzo; Gramatica, Furio; Corsi, Fabio; Colombo, Miriam; Morasso, Carlo; Prosperi, Davide

2014-08-01

170

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

PubMed Central

Background Tungsten carbide nanoparticles are being explored for their use in the manufacture of hard metals. To develop nanoparticles for broad applications, potential risks to human health and the environment should be evaluated and taken into consideration. Objective We aimed to assess the toxicity of well-characterized tungsten carbide (WC) and cobaltdoped tungsten carbide (WC-Co) nanoparticle suspensions in an array of mammalian cells. Methods We examined acute toxicity of WC and of WC-Co (10% weight content Co) nanoparticles in different human cell lines (lung, skin, and colon) as well as in rat neuronal and glial cells (i.e., primary neuronal and astroglial cultures and the oligodendro cyte precursor cell line OLN-93). Furthermore, using electron microscopy, we assessed whether nanoparticles can be taken up by living cells. We chose these in vitro systems in order to evaluate for potential toxicity of the nanoparticles in different mammalian organs (i.e., lung, skin, intestine, and brain). Results Chemical–physical characterization confirmed that WC as well as WC-Co nanoparticles with a mean particle size of 145 nm form stable suspensions in serum-containing cell culture media. WC nanoparticles were not acutely toxic to the studied cell lines. However, cytotoxicity became apparent when particles were doped with Co. The most sensitive were astrocytes and colon epithelial cells. Cytotoxicity of WC-Co nanoparticles was higher than expected based on the ionic Co content of the particles. Analysis by electron microscopy demonstrated presence of WC nanoparticles within mammalian cells. Conclusions Our findings demonstrate that doping of WC nanoparticles with Co markedly increases their cytotoxic effect and that the presence of WC-Co in particulate form is essential to elicit this combinatorial effect. PMID:19440490

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

2009-01-01

171

Interfacial phenomena in droplet evaporation and nanoparticle-cell systems  

NASA Astrophysics Data System (ADS)

The factors affecting droplet evaporation are discussed. It is found that the droplet morphology at a specific temperature is controlled by the physical properties of the liquid itself, such as the molecular weight, density, diffusion coefficient in air, and heat of vaporization. Two processes are included in droplet evaporation: (1) diffusion of liquid molecules into the air (diffusion part) and (2) flow of the liquid molecules from inside the droplet to the free outer shell liquid layer within the liquid-vapor interface (energy part). The diffusion part remains steady during drying and was not sensitive to the variation of temperature. The energy part, however, was an active factor and determined the differences in drop evaporation behaviors. A model is developed to measure the solubility parameters of the solvents via droplet evaporation. Droplets were deposited on Octadecyltrichlorosilane (OTS) covered silicon surfaces and the contact angle and overall drop morphology are observed using a KSV contact angle goniometer as a function of time. OTS is considered a non-absorbing surface for the solvents examined and does not affect the accuracy of the measured results. This method allows determination of the attraction forces between solvent molecules in the condensed phases. The solubility parameter values of droplets containing pure water, methanol, ethanol and butanol are measured. The test results are independent of the droplet size. The evaporation kinetics of droplets containing DNA is studied. Simultaneously, the DNA re-distribution and adsorption kinetics are measured by confocal microscopy. The DNA droplets are stained with ethidium bromide solution and deposited on OTS covered silicon surfaces. The results showed that the drying behavior depended on the DNA concentration. During drying, DNA relocation inside of the drop affects the internal forces of the liquid. A ring is formed at the air/solid/liquid interface. The absorbed amount of DNA was obtained by measuring the intensity on the ring using the confocal microscope. The interactions of citrate/gold nanoparticles with Caucasian female Human Dermal Fibroblasts are also investigated at different nanoparticle concentrations and exposure times. The presence of nanoparticles in the cell culture media destroys actin stress fibers, inducing major adverse effects for cell viability. Thus, properties such as cell spreading, adhesion, and growth are altered dramatically. Nanoparticles are found to enter the cell membrane within 30 minutes of loading into the media via endocytosis pathways. In vivo, the particles end up in lysosomes. Possible mechanisms are discussed.

Fang, Xiaohua

172

Variable Nanoparticle-Cell Adhesion Strength Regulates Cellular Uptake  

NASA Astrophysics Data System (ADS)

In receptor-mediated endocytosis, cells exercise biochemical control over the mechanics of adhesion to engulf foreign particles, featuring a variable adhesion strength. Here we present a thermodynamic model with which we elucidate that the variable adhesion strength critically governs the cellular uptake, yielding an uptake phase diagram in the space of ligand density and particle size. We identify from the diagram an endocytosed phase with markedly high uptake, encompassed by a lower and an upper phase boundary that are set, respectively, by the enthalpic and entropic limits of the adhesion strength. The phase diagram may provide useful guidance to the rational design of nanoparticle-based therapeutic and diagnostic agents.

Yuan, Hongyan; Li, Ju; Bao, Gang; Zhang, Sulin

2010-09-01

173

Morphological effect of oscillating magnetic nanoparticles in killing tumor cells.  

PubMed

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. PMID:24872797

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

2014-01-01

174

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. PMID:24872797

2014-01-01

175

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

176

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

177

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

178

Field emission scanning electron microscopy (FE-SEM) as an approach for nanoparticle detection inside cells.  

PubMed

When developing new nanoparticles for bio-applications, it is important to fully characterize the nanoparticle's behavior in biological systems. The most common techniques employed for mapping nanoparticles inside cells include transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM). These techniques entail passing an electron beam through a thin specimen. STEM or TEM imaging is often used for the detection of nanoparticles inside cellular organelles. However, lengthy sample preparation is required (i.e., fixation, dehydration, drying, resin embedding, and cutting). In the present work, a new matrix (FTO glass) for biological samples was used and characterized by field emission scanning electron microscopy (FE-SEM) to generate images comparable to those obtained by TEM. Using FE-SEM, nanoparticle images were acquired inside endo/lysosomes without disruption of the cellular shape. Furthermore, the initial steps of nanoparticle incorporation into the cells were captured. In addition, the conductive FTO glass endowed the sample with high stability under the required accelerating voltage. Owing to these features of the sample, further analyses could be performed (material contrast and energy-dispersive X-ray spectroscopy (EDS)), which confirmed the presence of nanoparticles inside the cells. The results showed that FE-SEM can enable detailed characterization of nanoparticles in endosomes without the need for contrast staining or metal coating of the sample. Images showing the intracellular distribution of nanoparticles together with cellular morphology can give important information on the biocompatibility and demonstrate the potential of nanoparticle utilization in medicine. PMID:25173605

Havrdova, M; Polakova, K; Skopalik, J; Vujtek, M; Mokdad, A; Homolkova, M; Tucek, J; Nebesarova, J; Zboril, R

2014-12-01

179

Augmented cellular uptake of nanoparticles using tea catechins: effect of surface modification on nanoparticle-cell interaction.  

PubMed

Nanoparticles may serve as carriers in targeted therapeutics; interaction of the nanoparticles with a biological system may determine their targeting effects and therapeutic efficacy. Epigallocatechin-3-gallate (EGCG), a major component of tea catechins, has been conjugated with nanoparticles and tested as an anticancer agent. We investigated whether EGCG may enhance nanoparticle uptake by tumor cells. Cellular uptake of a dextran-coated magnetic nanoparticle (MNP) was determined by confocal microscopy, flow cytometry or a potassium thiocyanate colorimetric method. We demonstrated that EGCG greatly enhanced interaction and/or internalization of MNPs (with or without polyethylene glycol) by glioma cells, but not vascular endothelial cells. The enhancing effects are both time- and concentration-dependent. Such effects may be induced by a simple mix of MNPs with EGCG at a concentration as low as 1-3 ?M, which increased MNP uptake 2- to 7-fold. In addition, application of magnetic force further potentiated MNP uptake, suggesting a synergetic effect of EGCG and magnetic force. Because the effects of EGCG were preserved at 4 °C, but not when EGCG was removed from the culture medium prior to addition of MNPs, a direct interaction of EGCG and MNPs was implicated. Use of an MNP-EGCG composite produced by adsorption of EGCG and magnetic separation also led to an enhanced uptake. The results reveal a novel interaction of a food component and nanocarrier system, which may be potentially amenable to magnetofection, cell labeling/tracing, and targeted therapeutics. PMID:25069428

Lu, Yi-Ching; Luo, Pei-Chun; Huang, Chun-Wan; Leu, Yann-Lii; Wang, Tzu-Hao; Wei, Kuo-Chen; Wang, Hsin-Ell; Ma, Yunn-Hwa

2014-09-01

180

Different cell responses induced by exposure to maghemite nanoparticles.  

PubMed

Recent advances in nanotechnology have permitted the development of a wide repertoire of inorganic magnetic nanoparticles (NPs) with extensive promise for biomedical applications. Despite this remarkable potential, many questions still arise concerning the biocompatible nature of NPs when in contact with biological systems. Herein, we have investigated how controlled changes in the physicochemical properties of iron oxide NPs at their surface (i.e., surface charge and hydrodynamic size) affect, first, their interaction with cell media components and, subsequently, cell responses to NP exposure. For that purpose, we have prepared iron oxide NPs with three different coatings (i.e., dimercaptosuccinic acid - DMSA, (3-aminopropyl)triethoxysilane - APS and dextran) and explored the response of two different cell types, murine L929 fibroblasts and human Saos-2 osteoblasts, to their exposure. Interestingly, different cell responses were found depending on the NP concentration, surface charge and cell type. In this sense, neutral NPs, as those coated with dextran, induced negligible cell damage, as their cellular internalization was significantly reduced. In contrast, surface-charged NPs (i.e., those coated with DMSA and APS) caused significant cellular changes in viability, morphology and cell cycle under certain culture conditions, as a result of a more active cellular internalization. These results also revealed a particular cellular ability to detect and remember the original physicochemical properties of the NPs, despite the formation of a protein corona when incubated in culture media. Overall, conclusions from these studies are of crucial interest for future biomedical applications of iron oxide NPs. PMID:23963338

Luengo, Yurena; Nardecchia, Stefania; Morales, María Puerto; Serrano, M Concepción

2013-12-01

181

Mechanisms of gold nanoparticle mediated ultrashort laser cell membrane perforation  

NASA Astrophysics Data System (ADS)

The gold nanoparticle (AuNP) mediated ultrashort laser cell membrane perforation has been proven as an efficient delivery method to bring membrane impermeable molecules into the cytoplasm. Nevertheless, the underlying mechanisms have not been fully determined yet. Different effects may occur when irradiating a AuNP with ultrashort laser pulses and finally enable the molecule to transfer. Depending on the parameters (pulse length, laser fluence and wavelength, particle size and shape, etc.) light absorption or an enhanced near field scattering can lead to perforation of the cell membrane when the particle is in close vicinity. Here we present our experimental results to clarify the perforation initiating mechanisms. The generation of cavitation and gas bubbles due to the laser induced effects were observed via time resolved imaging. Additionally, pump-probe experiments for bubble detection was performed. Furthermore, in our patch clamp studies a depolarization of the membrane potential and the current through the membrane of AuNP loaded cell during laser treatment was detected. This indicates an exchange of extra- and intra cellular ions trough the perforated cell membrane for some milliseconds. Additionally investigations by ESEM imaging were applied to study the interaction of cells and AuNP after co incubation. The images show an attachment of AuNP at the cell membrane after several hours of incubation. Moreover, images of irradiated and AuNP loaded cells were taken to visualize the laser induced effects.

Schomaker, M.; Baumgart, J.; Motekaitis, D.; Heinemann, D.; Krawinkel, J.; Pangalos, M.; Bintig, W.; Boulais, E.; Lachaine, R.; St.-Louis Lalonde, B.; Ngezahayo, A.; Meunier, M.; Heisterkamp, A.

2011-03-01

182

Targeting polymeric fluorescent nanodiamond-gold/silver multi-functional nanoparticles as a light-transforming hyperthermia reagent for cancer cells  

NASA Astrophysics Data System (ADS)

This work demonstrates a simple route for synthesizing multi-functional fluorescent nanodiamond-gold/silver nanoparticles. The fluorescent nanodiamond is formed by the surface passivation of poly(ethylene glycol) bis(3-aminopropyl) terminated. Urchin-like gold/silver nanoparticles can be obtained via one-pot synthesis, and combined with each other via further thiolation of nanodiamond. The morphology of the nanodiamond-gold/silver nanoparticles thus formed was identified herein by high-resolution transmission electron microscopy, and clarified using diffraction patterns. Fourier transform infrared spectroscopy clearly revealed the surface functionalization of the nanoparticles. The fluorescence of the materials with high photo stability was examined by high power laser irradiation and long-term storage at room temperature. To develop the bio-recognition of fluorescent nanodiamond-gold/silver nanoparticles, pre-modified transferrin was conjugated with the gold/silver nanoparticles, and the specificity and activity were confirmed in vitro using human hepatoma cell line (J5). The cellular uptake analysis that was conducted using flow cytometry and inductively coupled plasma mass spectrometry exhibited that twice as many transferrin-modified nanoparticles as bare nanoparticles were engulfed, revealing the targeting and ease of internalization of the human hepatoma cell. Additionally, the in situ monitoring of photothermal therapeutic behavior reveals that the nanodiamond-gold/silver nanoparticles conjugated with transferrin was more therapeutic than the bare nanodiamond-gold/silver materials, even when exposed to a less energetic laser source. Ultimately, this multi-functional material has great potential for application in simple synthesis. It is non-cytotoxic, supports long-term tracing and can be used in highly efficient photothermal therapy against cancer cells.This work demonstrates a simple route for synthesizing multi-functional fluorescent nanodiamond-gold/silver nanoparticles. The fluorescent nanodiamond is formed by the surface passivation of poly(ethylene glycol) bis(3-aminopropyl) terminated. Urchin-like gold/silver nanoparticles can be obtained via one-pot synthesis, and combined with each other via further thiolation of nanodiamond. The morphology of the nanodiamond-gold/silver nanoparticles thus formed was identified herein by high-resolution transmission electron microscopy, and clarified using diffraction patterns. Fourier transform infrared spectroscopy clearly revealed the surface functionalization of the nanoparticles. The fluorescence of the materials with high photo stability was examined by high power laser irradiation and long-term storage at room temperature. To develop the bio-recognition of fluorescent nanodiamond-gold/silver nanoparticles, pre-modified transferrin was conjugated with the gold/silver nanoparticles, and the specificity and activity were confirmed in vitro using human hepatoma cell line (J5). The cellular uptake analysis that was conducted using flow cytometry and inductively coupled plasma mass spectrometry exhibited that twice as many transferrin-modified nanoparticles as bare nanoparticles were engulfed, revealing the targeting and ease of internalization of the human hepatoma cell. Additionally, the in situ monitoring of photothermal therapeutic behavior reveals that the nanodiamond-gold/silver nanoparticles conjugated with transferrin was more therapeutic than the bare nanodiamond-gold/silver materials, even when exposed to a less energetic laser source. Ultimately, this multi-functional material has great potential for application in simple synthesis. It is non-cytotoxic, supports long-term tracing and can be used in highly efficient photothermal therapy against cancer cells. Electronic supplementary information (ESI) available: The TEM images of ND and FND-Au/Ag. The photo-stability of FND which is exposures at 561 nm laser for 3 h and stores at room temperature for 1 month. See DOI: 10.1039/c3nr34091k

Cheng, Liang-Chien; Chen, Hao Ming; Lai, Tsung-Ching; Chan, Yung-Chieh; Liu, Ru-Shi; Sung, James C.; Hsiao, Michael; Chen, Chung-Hsuan; Her, Li-Jane; Tsai, Din Ping

2013-04-01

183

Anticancer studies of the synthesized gold nanoparticles against MCF 7 breast cancer cell lines  

NASA Astrophysics Data System (ADS)

It has been previously stated that gold nanoparticles have been successfully synthesized using various green extracts of plants. The synthesized gold nanoparticles were characterized under scanning electron microscopy and EDX to identify the size of the nanoparticles. It was found that the nanoparticles were around 30 nm in size, which is a commendable nano dimension achieved through a plant mediated synthesis. The nanoparticles were further studied for their various applications. In the current study, we have made attempts to exploit the anticancer ability of the gold nano particles. The nanoparticles were studied against MCF 7 breast cancer cell lines. The results obtained from the studies of anticancer activity showed that gold nanoparticles gave an equivalent good results, in par with the standard drugs against cancer. The AuNP's proved to be efficient even from the minimum concentrations of 2 ?g/ml, and as the concentration increased the anticancer efficacy as well increased.

Kamala Priya, M. R.; Iyer, Priya R.

2014-09-01

184

Use of titanium dioxide nanoparticles biosynthesized by Bacillus mycoides in quantum dot sensitized solar cells  

PubMed Central

Background One of the major challenges of nanotechnology during the last decade has been the development of new procedures to synthesize nanoparticles. In this context, biosynthetic methods have taken hold since they are simple, safe and eco-friendly. Results In this study, we report the biosynthesis of TiO2 nanoparticles by an environmental isolate of Bacillus mycoides, a poorly described Gram-positive bacterium able to form colonies with novel morphologies. This isolate was able to produce TiO2 nanoparticles at 37°C in the presence of titanyl hydroxide. Biosynthesized nanoparticles have anatase polymorphic structure, spherical morphology, polydisperse size (40–60 nm) and an organic shell as determined by UV–vis spectroscopy, TEM, DLS and FTIR, respectively. Also, conversely to chemically produced nanoparticles, biosynthesized TiO2 do not display phototoxicity. In order to design less expensive and greener solar cells, biosynthesized nanoparticles were evaluated in Quantum Dot Sensitized Solar Cells (QDSSCs) and compared with chemically produced TiO2 nanoparticles. Solar cell parameters such as short circuit current density (ISC) and open circuit voltage (VOC) revealed that biosynthesized TiO2 nanoparticles can mobilize electrons in QDSSCs similarly than chemically produced TiO2. Conclusions Our results indicate that bacterial extracellular production of TiO2 nanoparticles at low temperatures represents a novel alternative for the construction of green solar cells. PMID:25027643

2014-01-01

185

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

NASA Astrophysics Data System (ADS)

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

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

2013-09-01

186

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

187

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

PubMed Central

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

188

Surface engineering of macrophages with nanoparticles to generate a cell-nanoparticle hybrid vehicle for hypoxia-targeted drug delivery.  

PubMed

Tumors frequently contain hypoxic regions that result from a shortage of oxygen due to poorly organized tumor vasculature. Cancer cells in these areas are resistant to radiation- and chemotherapy, limiting the treatment efficacy. Macrophages have inherent hypoxia-targeting ability and hold great advantages for targeted delivery of anticancer therapeutics to cancer cells in hypoxic areas. However, most anticancer drugs cannot be directly loaded into macrophages because of their toxicity. In this work, we designed a novel drug delivery vehicle by hybridizing macrophages with nanoparticles through cell surface modification. Nanoparticles immobilized on the cell surface provide numerous new sites for anticancer drug loading, hence potentially minimizing the toxic effect of anticancer drugs on the viability and hypoxia-targeting ability of the macrophage vehicles. In particular, quantum dots and 5-(aminoacetamido) fluorescein-labeled polyamidoamine dendrimer G4.5, both of which were coated with amine-derivatized polyethylene glycol, were immobilized to the sodium periodate-treated surface of RAW264.7 macrophages through a transient Schiff base linkage. Further, a reducing agent, sodium cyanoborohydride, was applied to reduce Schiff bases to stable secondary amine linkages. The distribution of nanoparticles on the cell surface was confirmed by fluorescence imaging, and it was found to be dependent on the stability of the linkages coupling nanoparticles to the cell surface. PMID:20161985

Holden, Christopher A; Yuan, Quan; Yeudall, W Andrew; Lebman, Deborah A; Yang, Hu

2010-01-01

189

IsomiR expression profiles in human lymphoblastoid cell lines exhibit population and gender dependencies  

PubMed Central

For many years it was believed that each mature microRNA (miRNA) existed as a single entity with fixed endpoints and a ‘static’ and unchangeable primary sequence. However, recent evidence suggests that mature miRNAs are more ‘dynamic’ and that each miRNA precursor arm gives rise to multiple isoforms, the isomiRs. Here we report on our identification of numerous and abundant isomiRs in the lymphoblastoid cell lines (LCLs) of 452 men and women from five different population groups. Unexpectedly, we find that these isomiRs exhibit an expression profile that is population-dependent and gender-dependent. This is important as it indicates that the LCLs of each gender/population combination have their own unique collection of mature miRNA transcripts. Moreover, each identified isomiR has its own characteristic abundance that remains consistent across biological replicates indicating that these are not degradation products. The primary sequences of identified isomiRs differ from the known miRBase miRNA either at their 5´-endpoint (leads to a different ‘seed’ sequence and suggests a different targetome), their 3´-endpoint, or both simultaneously. Our analysis of Argonaute PAR-CLIP data from LCLs supports the association of many of these newly identified isomiRs with the Argonaute silencing complex and thus their functional roles through participation in the RNA interference pathway. PMID:25229428

Loher, Phillipe; Londin, Eric R.; Rigoutsos, Isidore

2014-01-01

190

Nup50 is required for cell differentiation and exhibits transcription-dependent dynamics.  

PubMed

The nuclear pore complex (NPC) plays a critical role in gene expression by mediating import of transcription regulators into the nucleus and export of RNA transcripts to the cytoplasm. Emerging evidence suggests that in addition to mediating transport, a subset of nucleoporins (Nups) engage in transcriptional activation and elongation at genomic loci that are not associated with NPCs. The underlying mechanism and regulation of Nup mobility on and off nuclear pores remain unclear. Here we show that Nup50 is a mobile Nup with a pronounced presence both at the NPC and in the nucleoplasm that can move between these different localizations. Strikingly, the dynamic behavior of Nup50 in both locations is dependent on active transcription by RNA polymerase II and requires the N-terminal half of the protein, which contains importin ?- and Nup153-binding domains. However, Nup50 dynamics are independent of importin ?, Nup153, and Nup98, even though the latter two proteins also exhibit transcription-dependent mobility. Of interest, depletion of Nup50 from C2C12 myoblasts does not affect cell proliferation but inhibits differentiation into myotubes. Taken together, our results suggest a transport-independent role for Nup50 in chromatin biology that occurs away from the NPC. PMID:24943837

Buchwalter, Abigail L; Liang, Yun; Hetzer, Martin W

2014-08-15

191

Nup50 is required for cell differentiation and exhibits transcription-dependent dynamics  

PubMed Central

The nuclear pore complex (NPC) plays a critical role in gene expression by mediating import of transcription regulators into the nucleus and export of RNA transcripts to the cytoplasm. Emerging evidence suggests that in addition to mediating transport, a subset of nucleoporins (Nups) engage in transcriptional activation and elongation at genomic loci that are not associated with NPCs. The underlying mechanism and regulation of Nup mobility on and off nuclear pores remain unclear. Here we show that Nup50 is a mobile Nup with a pronounced presence both at the NPC and in the nucleoplasm that can move between these different localizations. Strikingly, the dynamic behavior of Nup50 in both locations is dependent on active transcription by RNA polymerase II and requires the N-terminal half of the protein, which contains importin ?– and Nup153-binding domains. However, Nup50 dynamics are independent of importin ?, Nup153, and Nup98, even though the latter two proteins also exhibit transcription-dependent mobility. Of interest, depletion of Nup50 from C2C12 myoblasts does not affect cell proliferation but inhibits differentiation into myotubes. Taken together, our results suggest a transport-independent role for Nup50 in chromatin biology that occurs away from the NPC. PMID:24943837

Buchwalter, Abigail L.; Liang, Yun; Hetzer, Martin W.

2014-01-01

192

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

193

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

194

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

195

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. PMID:21303616

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

2010-01-01

196

Oxidative stress mediated cytotoxicity of biologically synthesized silver nanoparticles in human lung epithelial adenocarcinoma cell line  

NASA Astrophysics Data System (ADS)

The goal of the present study was to investigate the toxicity of biologically prepared small size of silver nanoparticles in human lung epithelial adenocarcinoma cells A549. Herein, we describe a facile method for the synthesis of silver nanoparticles by treating the supernatant from a culture of Escherichia coli with silver nitrate . The formation of silver nanoparticles was characterized using various analytical techniques. The results from UV-visible (UV-vis) spectroscopy and X-ray diffraction analysis show a characteristic strong resonance centered at 420 nm and a single crystalline nature, respectively. Fourier transform infrared spectroscopy confirmed the possible bio-molecules responsible for the reduction of silver from silver nitrate into nanoparticles. The particle size analyzer and transmission electron microscopy results suggest that silver nanoparticles are spherical in shape with an average diameter of 15 nm. The results derived from in vitro studies showed a concentration-dependent decrease in cell viability when A549 cells were exposed to silver nanoparticles. This decrease in cell viability corresponded to increased leakage of lactate dehydrogenase (LDH), increased intracellular reactive oxygen species generation (ROS), and decreased mitochondrial transmembrane potential (MTP). Furthermore, uptake and intracellular localization of silver nanoparticles were observed and were accompanied by accumulation of autophagosomes and autolysosomes in A549 cells. The results indicate that silver nanoparticles play a significant role in apoptosis. Interestingly, biologically synthesized silver nanoparticles showed more potent cytotoxicity at the concentrations tested compared to that shown by chemically synthesized silver nanoparticles. Therefore, our results demonstrated that human lung epithelial A549 cells could provide a valuable model to assess the cytotoxicity of silver nanoparticles.

Han, Jae Woong; Gurunathan, Sangiliyandi; Jeong, Jae-Kyo; Choi, Yun-Jung; Kwon, Deug-Nam; Park, Jin-Ki; Kim, Jin-Hoi

2014-09-01

197

Efficient gene transfer into rat mesenchymal stem cells with cationized Lycium barbarum polysaccharides nanoparticles  

Microsoft Academic Search

A new gene vector, cationized Lycium barbarum polysaccharides (cLBP) nanoparticles, prepared with different amine compounds for non-viral delivery of plasmid DNA encoding for transforming growth factor beta 1 (TGF?-1) was developed and the efficiency of these nanoparticles to transfect rat mesenchymal stem cells in vitro was determined. The spherical cLBP-plasmid TGF?-1 nanoparticles were 160–330nm in diameter and can retard the

Miao Wang; Wenwen Deng; Min Fu; Xia Cao; Yan Yang; Weiyan Su; Jiangnan Yu; Ximing Xu

2011-01-01

198

Targeting cancer cells using PLGA nanoparticles surface modified with monoclonal antibody  

Microsoft Academic Search

Targeting drugs to their sites of action is still a major challenge in pharmaceutical research. In this study, polylactic-co-glycolic acid (PLGA) immuno-nanoparticles were prepared for targeting invasive epithelial breast tumour cells. Monoclonal antibody (mAb) was used as a homing ligand and was attached to the nanoparticle surface either covalently or non-covalently. The presence of mAb on the nanoparticle surface, its

Petra Kocbek; Nataša Obermajer; Mateja Cegnar; Janko Kos; Julijana Kristl

2007-01-01

199

The effect of poloxamer 188 on nanoparticle morphology, size, cancer cell uptake, and cytotoxicity  

Microsoft Academic Search

The aim of this work was to investigate the effect of triblock copolymer poloxamer 188 on nanoparticle morphology, size, cancer cell uptake, and cytotoxicity. Docetaxel-loaded nanoparticles were prepared by oil-in-water emulsion\\/solvent evaporation technique using biodegradable poly(lactic-co-glycolic acid) (PLGA) with or without addition of poloxamer 188, respectively. The resulting nanoparticles were found to be spherical with a rough and porous surface.

Fei Yan; Chao Zhang; Yi Zheng; Lin Mei; Lina Tang; Cunxian Song; Hongfan Sun; Laiqiang Huang

2010-01-01

200

Quantitative analysis of nanoparticle internalization in mammalian cells by high resolution X-ray microscopy  

PubMed Central

Background Quantitative analysis of nanoparticle uptake at the cellular level is critical to nanomedicine procedures. In particular, it is required for a realistic evaluation of their effects. Unfortunately, quantitative measurements of nanoparticle uptake still pose a formidable technical challenge. We present here a method to tackle this problem and analyze the number of metal nanoparticles present in different types of cells. The method relies on high-lateral-resolution (better than 30 nm) transmission x-ray microimages with both absorption contrast and phase contrast -- including two-dimensional (2D) projection images and three-dimensional (3D) tomographic reconstructions that directly show the nanoparticles. Results Practical tests were successfully conducted on bare and polyethylene glycol (PEG) coated gold nanoparticles obtained by x-ray irradiation. Using two different cell lines, EMT and HeLa, we obtained the number of nanoparticle clusters uptaken by each cell and the cluster size. Furthermore, the analysis revealed interesting differences between 2D and 3D cultured cells as well as between 2D and 3D data for the same 3D specimen. Conclusions We demonstrated the feasibility and effectiveness of our method, proving that it is accurate enough to measure the nanoparticle uptake differences between cells as well as the sizes of the formed nanoparticle clusters. The differences between 2D and 3D cultures and 2D and 3D images stress the importance of the 3D analysis which is made possible by our approach. PMID:21477355

2011-01-01

201

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

202

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

Microsoft Academic Search

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

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

2002-01-01

203

Oxidative stress mediated apoptosis induced by nickel ferrite nanoparticles in cultured A549 cells.  

PubMed

Due to the interesting magnetic and electrical properties with good chemical and thermal stabilities, nickel ferrite nanoparticles are being utilized in many applications including magnetic resonance imaging, drug delivery and hyperthermia. Recent studies have shown that nickel ferrite nanoparticles produce cytotoxicity in mammalian cells. However, there is very limited information concerning the toxicity of nickel ferrite nanoparticles at the cellular and molecular level. The aim of this study was to investigate the cytotoxicity, oxidative stress and apoptosis induction by well-characterized nickel ferrite nanoparticles (size 26 nm) in human lung epithelial (A549) cells. Nickel ferrite nanoparticles induced dose-dependent cytotoxicity in A549 cells demonstrated by MTT, NRU and LDH assays. Nickel ferrite nanoparticles were also found to induce oxidative stress evidenced by generation of reactive oxygen species (ROS) and depletion of antioxidant glutathione (GSH). Further, co-treatment with the antioxidant L-ascorbic acid mitigated the ROS generation and GSH depletion due to nickel ferrite nanoparticles suggesting the potential mechanism of oxidative stress. Quantitative real-time PCR analysis demonstrated that following the exposure of A549 cells to nickel ferrite nanoparticles, the level of mRNA expressions of cell cycle checkpoint protein p53 and apoptotic proteins (bax, caspase-3 and caspase-9) were significantly up-regulated, whereas the expression of anti-apoptotic proteins (survivin and bcl-2) were down-regulated. Moreover, activities of caspase-3 and caspase-9 enzymes were also significantly higher in nickel ferrite nanoparticles exposed cells. To the best of our knowledge this is the first report showing that nickel ferrite nanoparticles induced apoptosis in A549 cells through ROS generation and oxidative stress via p53, survivin, bax/bcl-2 and caspase pathways. PMID:21382431

Ahamed, Maqusood; Akhtar, Mohd Javed; Siddiqui, Maqsood A; Ahmad, Javed; Musarrat, Javed; Al-Khedhairy, Abdulaziz A; AlSalhi, Mohamad S; Alrokayan, Salman A

2011-05-10

204

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

205

The Effect of Titanium Dioxide Nanoparticles on Keratinocyte Cell (KC) and Squamous Cell Carcinoma (SCC-13)  

NASA Astrophysics Data System (ADS)

We have studied the effects of TiO2 nanoparticles on cell keratinocyte and SCC (Squamous Cell Carcinoma) cells. We found that the concentration of particles required to adversely affect the cells was many times higher for keratinocyte than SCC cells. Confocal microscope shows that the particles in keratinocyte culture are sequestered in membranes between the cell colonies. The particles penetrated into the cells in the case of the SCC cells. TEM images revealed very few particles in the keratinocyte, many more particles were observed sequestered in vacuole of the SCC cells. These results indicate that the keratinocyte layer behaves very different from the fibroblast layers which are much more sensate to TiO2 nanoparticle damage and may suggest a protection mechanism of the dermal tissue. The effect of UV exposure in the presence of DNA was also investigated. We found that adsorbed proteins, as well as grafted polymer provided a measure of protection against free radical formation. The effects of low level UV exposure when the particles are near in-vitro cell culture will be presented.

Lin, Chienhsiu; Simon, Marcia; Jurukovski, Vladimir; Lee, Wilson; Rafailovich, Miriam

2009-03-01

206

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

207

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

PubMed Central

Hydroxyapatite nanoparticles (nano-HAPs) have been reported to exhibit antitumor effects on various human cancers, but the effects of nano-HAPs on human glioma cells remain unclear. The aim of this study was to explore the inhibitory effect of nano-HAPs on the growth of human glioma U251 and SHG44 cells in vitro and in vivo. Nano-HAPs could inhibit the growth of U251 and SHG44 cells in a dose- and time-dependent manner, according to methyl thiazoletetrazolium assay and flow cytometry. Treated with 120 mg/L and 240 mg/L nano-HAPs for 48 hours, typical apoptotic morphological changes were noted under Hoechst staining and transmission electron microscopy. The tumor growth of cells was inhibited after the injection in vivo, and the related side effects significantly decreased in the nano-HAP-and-drug combination group. Because of the function of nano-HAPs, the expression of c-Met, SATB1, Ki-67, and bcl-2 protein decreased, and the expression of SLC22A18 and caspase-3 protein decreased noticeably. The findings indicate that nano-HAPs have an evident inhibitory action and induce apoptosis of human glioma cells in vitro and in vivo. In a drug combination, they can significantly reduce the adverse reaction related to the chemotherapeutic drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). PMID:22888225

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

2012-01-01

208

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

PubMed

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

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

2013-01-01

209

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

210

Fabrication, performance and atmospheric stability of inverted ZnO nanoparticle/polymer solar cell  

NASA Astrophysics Data System (ADS)

Zinc oxide (ZnO) nanoparticles (NPs, ~5 nm) were first synthesized by a simple wet chemical method. A mixture of poly(3-hexylthiophene-2,5-diyl):(6,6)-phenyl C61 butyric acid methyl ester (P3HT:PCBM) was used as the photoactive layer, and an inverted solar cell with a structure of ITO/ZnO NPs/P3HT:PCBM/MoO3/Ag was fabricated. Its performance and stability in the ambient atmosphere were investigated in detail. The results showed that the fabricated solar cell under 100 mW/cm2 AM1.5 illumination exhibited a power conversion efficiency (PCE) of 0.28 %. In addition, illumination intensity had significant effect on open circuit voltage (V oc), short circuit current (J sc), fill factor (FF), and PCE of the fabricated solar cell. The dark storability (darkness, room temperature, and 50-60 % relative humidity) was shown to exceed 4,416 h without notable loss in PCE. The fabricated solar cell with excellent long-term stability was achieved in an ambient atmosphere; also, the stable mechanism of the solar cell in the ambient atmosphere was illuminated.

Yuan, Zhaolin

2014-08-01

211

Influence of nanoparticle shape on charge transport and recombination in polymer/nanocrystal solar cells.  

PubMed

A key consideration for the efficient operation of hybrid solar cells based upon conjugated polymers and inorganic semiconductor nanocrystals is charge transport in the nanocrystal phase. Here we report the results of a study into the charge transport kinetics of polymer/nanocrystal solar cells based on blends poly(3-hexylthiophene) (P3HT) with either CdSe nano-dots or CdSe nano-tetrapods. Transient photocurrent measurements reveal significant differences in the charge transport kinetics of nano-dot and nano-tetrapod hybrid cells, with the charge collection of the P3HT/CdSe nano-dot device severely limited by charge trapping. In comparison the nano-tetrapod cell exhibits significantly reduced charge trapping compared to the nano-dot cell accounting for the improved fill-factor and overall device efficiency. Transient photovoltage measurements have also been employed that demonstrate slower recombination rates in the P3HT/CdSe tetrapod device compared to the P3HT/CdSe dot device. These observations directly identify nanoparticle shape as a critical factor influencing the charge transport and hence recombination in this benchmark hybrid system, confirming the hypothesis that the use of tetrapods improves device performance through an improvement in electron transport in the nanocrystal phase. PMID:24781139

Li, Zhe; Wang, Weiyuan; Greenham, Neil C; McNeill, Christopher R

2014-12-21

212

Mice deficient of glutamatergic signaling from intrinsically photosensitive retinal ganglion cells exhibit abnormal circadian photoentrainment.  

PubMed

Several aspects of behavior and physiology, such as sleep and wakefulness, blood pressure, body temperature, and hormone secretion exhibit daily oscillations known as circadian rhythms. These circadian rhythms are orchestrated by an intrinsic biological clock in the suprachiasmatic nuclei (SCN) of the hypothalamus which is adjusted to the daily environmental cycles of day and night by the process of photoentrainment. In mammals, the neuronal signal for photoentrainment arises from a small subset of intrinsically photosensitive retinal ganglion cells (ipRGCs) that send a direct projection to the SCN. ipRGCs also mediate other non-image-forming (NIF) visual responses such as negative masking of locomotor activity by light, and the pupillary light reflex (PLR) via co-release of neurotransmitters glutamate and pituitary adenylate cyclase-activating peptide (PACAP) from their synaptic terminals. The relative contribution of each neurotransmitter system for the circadian photoentrainment and other NIF visual responses is still unresolved. We investigated the role of glutamatergic neurotransmission for circadian photoentrainment and NIF behaviors by selective ablation of ipRGC glutamatergic synaptic transmission in mice. Mutant mice displayed delayed re-entrainment to a 6 h phase shift (advance or delay) in the light cycle and incomplete photoentrainment in a symmetrical skeleton photoperiod regimen (1 h light pulses between 11 h dark periods). Circadian rhythmicity in constant darkness also was reduced in some mutant mice. Other NIF responses such as the PLR and negative masking responses to light were also partially attenuated. Overall, these results suggest that glutamate from ipRGCs drives circadian photoentrainment and negative masking responses to light. PMID:25357191

Purrier, Nicole; Engeland, William C; Kofuji, Paulo

2014-01-01

213

Mice Deficient of Glutamatergic Signaling from Intrinsically Photosensitive Retinal Ganglion Cells Exhibit Abnormal Circadian Photoentrainment  

PubMed Central

Several aspects of behavior and physiology, such as sleep and wakefulness, blood pressure, body temperature, and hormone secretion exhibit daily oscillations known as circadian rhythms. These circadian rhythms are orchestrated by an intrinsic biological clock in the suprachiasmatic nuclei (SCN) of the hypothalamus which is adjusted to the daily environmental cycles of day and night by the process of photoentrainment. In mammals, the neuronal signal for photoentrainment arises from a small subset of intrinsically photosensitive retinal ganglion cells (ipRGCs) that send a direct projection to the SCN. ipRGCs also mediate other non-image-forming (NIF) visual responses such as negative masking of locomotor activity by light, and the pupillary light reflex (PLR) via co-release of neurotransmitters glutamate and pituitary adenylate cyclase-activating peptide (PACAP) from their synaptic terminals. The relative contribution of each neurotransmitter system for the circadian photoentrainment and other NIF visual responses is still unresolved. We investigated the role of glutamatergic neurotransmission for circadian photoentrainment and NIF behaviors by selective ablation of ipRGC glutamatergic synaptic transmission in mice. Mutant mice displayed delayed re-entrainment to a 6 h phase shift (advance or delay) in the light cycle and incomplete photoentrainment in a symmetrical skeleton photoperiod regimen (1 h light pulses between 11 h dark periods). Circadian rhythmicity in constant darkness also was reduced in some mutant mice. Other NIF responses such as the PLR and negative masking responses to light were also partially attenuated. Overall, these results suggest that glutamate from ipRGCs drives circadian photoentrainment and negative masking responses to light. PMID:25357191

Purrier, Nicole; Engeland, William C.; Kofuji, Paulo

2014-01-01

214

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

PubMed

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

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

2013-01-01

215

Cooperative plasmonic effect of Ag and Au nanoparticles on enhancing performance of polymer solar cells.  

PubMed

This article describes a cooperative plasmonic effect on improving the performance of polymer bulk heterojunction solar cells. When mixed Ag and Au nanoparticles are incorporated into the anode buffer layer, dual nanoparticles show superior behavior on enhancing light absorption in comparison with single nanoparticles, which led to the realization of a polymer solar cell with a power conversion efficiency of 8.67%, accounting for a 20% enhancement. The cooperative plasmonic effect aroused from dual resonance enhancement of two different nanoparticles. The idea was further unraveled by comparing Au nanorods with Au nanoparticles for solar cell application. Detailed studies shed light into the influence of plasmonic nanostructures on exciton generation, dissociation, and charge recombination and transport inside thin film devices. PMID:23237567

Lu, Luyao; Luo, Zhiqiang; Xu, Tao; Yu, Luping

2013-01-01

216

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. PMID:20887814

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

2011-01-01

217

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

SciTech Connect

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

Polf, Jerimy C.; Gillin, Michael [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Bronk, Lawrence F. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); David H. Koch Center, University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Driessen, Wouter H. P.; Arap, Wadih; Pasqualini, Renata [David H. Koch Center, University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States)

2011-05-09

218

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

Microsoft Academic Search

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

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

2008-01-01

219

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

Microsoft Academic Search

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

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

2011-01-01

220

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

221

Mouse lymphatic endothelial cell targeted probes: anti-LYVE-1 antibody-based magnetic nanoparticles  

PubMed Central

Purpose To investigate the specific targeting property of lymphatic vessel endothelial hyaluronan receptor-1 binding polyethylene glycol-coated ultrasmall superparamagnetic iron oxide (LYVE-1-PEG-USPIO) nanoparticles to mouse lymphatic endothelial cells (MLECs). Methods A ligand specific target to lymphatic vessels was selected by immunohistochemical staining on the sections of a Lewis subcutaneous transplanted tumor. The z-average hydrodynamic diameter (HD), zeta potential, and the relaxivity of PEG-USPIO and LYVE-1-PEG-USPIO nanoparticles were determined with a laser particle analyzer and magnetic resonance T2 spin echo sequence, respectively. Prussian blue staining and transmission electron microscopy (TEM) of nanoparticle labeled cells were performed to determine the nanoparticles’ binding form. Magnetic resonance imaging (MRI) was performed in vitro to evaluate the signal enhancement on the T2 spin echo sequence of the nanoparticle labeled cells. The iron content of the labeled cells after the Prussian blue staining and MRI scanning was determined by atomic absorption spectroscopy (AAS). Results The anti-LYVE-1 antibody was used as the specific ligand to synthesize the target probe to the MLECs. The mean z-average HDs of the LYVE-1-PEG-USPIO and PEG-USPIO nanoparticles were 57.42 ± 0.31 nm and 47.91 ± 0.73 nm, respectively, and the mean zeta potentials of the LYVE-1-PEG-USPIO and PEG-USPIO nanoparticles were 12.38 ± 4.87 mV and 2.57 ± 0.83 m V, respectively. The relaxivities of the LYVE-1-PEG-USPIO and PEG-USPIO nanoparticles were 185.48 mM?1s?1 and 608.32 mM?1s?1. Cells binding nanoparticles were visualized as blue granules in the Prussian blue staining. The TEM results of the labeled cells showed the specific localization of nanoparticles. The AAS results of labeled cells after the Prussian blue staining and MRI scanning showed that the LYVE-1-PEG-USPIO nanoparticles had good binding selectivity for MLECs. MRI results indicated that the PEG-USPIO and LYVE-1-PEG-USPIO nanoparticles could generate contrast on T2-weighted imaging, and the correlation between R2 and the iron content of the labeled cells was significantly positive. Conclusion This study demonstrated that LYVE-1-PEG-USPIO nanoparticles might potentially be used as an MRI contrast agent for targeting MLECs, and the magnetic properties of LYVE-1-PEG-USPIO nanoparticles were suitable for MRI. PMID:23818783

Guo, Qiu; Liu, Yi; Xu, Ke; Ren, Ke; Sun, WenGe

2013-01-01

222

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

PubMed

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

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

2010-05-31

223

Hyperthermia HeLa cell treatment with silica coated manganese oxide nanoparticles  

E-print Network

HeLa tumour cells incubated with ferromagnetic nanoparticles of manganese oxide perovskite La0.56(SrCa)0.22MnO3 were treated with a high frequency alternating magnetic field. The particles were previously coated with silica to improve their biocompatibility. The control assays made with HeLa tumour cells showed that cell survival and growth rate were not affected by the particle internalization in cells, or by the electromagnetic field on cells without nanoparticles. The application of an alternating electromagnetic field to cells incubated with this silica coated manganese oxide induced a significant cellular damage that finally lead to cell death by an apoptotic mechanism.

Villanueva, A; Alonso, JM; Rueda, T; Martínez, A; Crespo, P; Morales, MP; Fernandez, MA Gonzalez; Valdes, J; Rivero, G

2009-01-01

224

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

E-print Network

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 ...

Bauer, Michael

225

Cytogenetic and genotoxic effects of zinc oxide nanoparticles on root cells of Allium cepa  

Microsoft Academic Search

Increasing use of zinc oxide nanoparticles (ZnO NP) in consumer products may enhance its release into the environment. Phytotoxicity study is important to understand its possible environmental impact. Allium cepa (Onion bulb) is the best model organism to study genetic toxicology of nanoparticles. Here we have reported cytogenetic and genotoxic effects of ZnO NPs on the root cells of A.

Mamta Kumari; S. Sudheer Khan; Sunandan Pakrashi; Amitava Mukherjee; Natarajan Chandrasekaran

2011-01-01

226

Different cell responses induced by exposure to maghemite nanoparticles  

NASA Astrophysics Data System (ADS)

Recent advances in nanotechnology have permitted the development of a wide repertoire of inorganic magnetic nanoparticles (NPs) with extensive promise for biomedical applications. Despite this remarkable potential, many questions still arise concerning the biocompatible nature of NPs when in contact with biological systems. Herein, we have investigated how controlled changes in the physicochemical properties of iron oxide NPs at their surface (i.e., surface charge and hydrodynamic size) affect, first, their interaction with cell media components and, subsequently, cell responses to NP exposure. For that purpose, we have prepared iron oxide NPs with three different coatings (i.e., dimercaptosuccinic acid - DMSA, (3-aminopropyl)triethoxysilane - APS and dextran) and explored the response of two different cell types, murine L929 fibroblasts and human Saos-2 osteoblasts, to their exposure. Interestingly, different cell responses were found depending on the NP concentration, surface charge and cell type. In this sense, neutral NPs, as those coated with dextran, induced negligible cell damage, as their cellular internalization was significantly reduced. In contrast, surface-charged NPs (i.e., those coated with DMSA and APS) caused significant cellular changes in viability, morphology and cell cycle under certain culture conditions, as a result of a more active cellular internalization. These results also revealed a particular cellular ability to detect and remember the original physicochemical properties of the NPs, despite the formation of a protein corona when incubated in culture media. Overall, conclusions from these studies are of crucial interest for future biomedical applications of iron oxide NPs.Recent advances in nanotechnology have permitted the development of a wide repertoire of inorganic magnetic nanoparticles (NPs) with extensive promise for biomedical applications. Despite this remarkable potential, many questions still arise concerning the biocompatible nature of NPs when in contact with biological systems. Herein, we have investigated how controlled changes in the physicochemical properties of iron oxide NPs at their surface (i.e., surface charge and hydrodynamic size) affect, first, their interaction with cell media components and, subsequently, cell responses to NP exposure. For that purpose, we have prepared iron oxide NPs with three different coatings (i.e., dimercaptosuccinic acid - DMSA, (3-aminopropyl)triethoxysilane - APS and dextran) and explored the response of two different cell types, murine L929 fibroblasts and human Saos-2 osteoblasts, to their exposure. Interestingly, different cell responses were found depending on the NP concentration, surface charge and cell type. In this sense, neutral NPs, as those coated with dextran, induced negligible cell damage, as their cellular internalization was significantly reduced. In contrast, surface-charged NPs (i.e., those coated with DMSA and APS) caused significant cellular changes in viability, morphology and cell cycle under certain culture conditions, as a result of a more active cellular internalization. These results also revealed a particular cellular ability to detect and remember the original physicochemical properties of the NPs, despite the formation of a protein corona when incubated in culture media. Overall, conclusions from these studies are of crucial interest for future biomedical applications of iron oxide NPs. Electronic supplementary information (ESI) available: Additional details about NP characterization and viability controls of Saos-2 osteoblasts. See DOI: 10.1039/c3nr02148c

Luengo, Yurena; Nardecchia, Stefania; Morales, María Puerto; Serrano, M. Concepción

2013-11-01

227

Cytotoxicity of Paclitaxel Incorporated in PLGA Nanoparticles on Hypoxic Human Tumor Cells  

Microsoft Academic Search

Purpose  The aim of this work was to prepare paclitaxel-loaded PLGA nanoparticles and determine cytotoxicity of released paclitaxel\\u000a for two hypoxic human tumor cell lines: breast carcinoma (MCF-7) and carcinoma cervicis (HeLa).\\u000a \\u000a \\u000a \\u000a Methods  Poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles containing paclitaxel were prepared by o\\/w emulsification-solvent evaporation\\u000a method. Physicochemical characteristics of nanoparticles were studied. Cellular uptake of nanoparticles was evaluated by transmission\\u000a electronic microscopy and

Cheng Jin; Ling Bai; Hong Wu; Wenjie Song; Guozhen Guo; Kefeng Dou

2009-01-01

228

Nonendocytic Delivery of Functional Engineered Nanoparticles into the Cytoplasm of Live Cells Using a Novel, High-Throughput Microfluidic Device  

E-print Network

The ability to straightforwardly deliver engineered nanoparticles into the cell cytosol with high viability will vastly expand the range of biological applications. Nanoparticles could potentially be used as delivery ...

Lee, Jungmin

229

The Fate of ZnO Nanoparticles Administered to Human Bronchial Epithelial Cells  

PubMed Central

A particular challenge for nanotoxicology is the evaluation of the biological fate and toxicity of nanomaterials that dissolve in aqueous fluids. Zinc oxide nanomaterials are of particular concern because dissolution leads to release of the toxic divalent zinc ion. Although dissolved zinc ions have been implicated in ZnO cytotoxicity, direct identification of the chemical form of zinc taken up by cells exposed to ZnO nanoparticles, and its intracellular fate, has not yet been achieved. We combined high resolution X-ray spectromicroscopy and high elemental sensitivity X-ray microprobe analyses to determine the fate of ZnO and less soluble iron-doped ZnO nanoparticles following exposure to cultures of human bronchial epithelial cells, BEAS-2B. We complemented two-dimensional X-ray imaging methods with atomic force microscopy of cell surfaces to distinguish between nanoparticles that were transported inside the cells from those that adhered to the cell exterior. The data suggest cellular uptake of ZnO nanoparticles is a mechanism of zinc accumulation in cells. Following uptake, ZnO nanoparticles dissolved completely generating intracellular Zn2+ complexed by molecular ligands. These results corroborate a model for ZnO nanoparticle toxicity that is based on nanoparticle uptake followed by intracellular dissolution. PMID:22646753

Gilbert, Benjamin; Fakra, Sirine C.; Xia, Tian; Pokhrel, Suman; Mädler, Lutz; Nel, André E.

2014-01-01

230

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

231

Magnetic nanoparticle effects on the red blood cells  

NASA Astrophysics Data System (ADS)

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

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

2009-05-01

232

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

233

Plasmonic nanoparticles enhanced dye-sensitized solar cells  

NASA Astrophysics Data System (ADS)

Here we present investigations on utilizing two kinds of plasmonic nanoparticles (NPs) to enhance the efficiency of dye sensitized solar cells (DSCs). The Au@PVP NPs is proposed and present the specialty of adhesiveness to dye molecules, which could help to localize additional dye molecules near the plasmonic NPs, hence increasing the optical absorption consequently the power conversion efficiency (PCE) of the DSCs by 30% from 3.3% to 4.3%. Meanwhile, an irregular Au-Ag alloy popcorn-shaped NPs (popcorn NPs) with plenty of fine structures is also proposed and realized to enhance the light absorption of DSC. A pronounced absorption enhancement in a broadband wavelength range is observed due to the excitation of localized surface plasmon at different wavelengths. The PCE is enhanced by 32% from 5.94% to 7.85%.

Xu, Qi; Liu, Fang; Meng, Weisi; Huang, Yidong

2013-12-01

234

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. PMID:21028936

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

2011-01-01

235

Release of magnetic nanoparticles from cell-encapsulating biodegradable nanobiomaterials.  

PubMed

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. PMID:22680777

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

2012-08-28

236

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. PMID:22680777

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

2013-01-01

237

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

238

Effect of hydroxyapatite nanoparticles on osmotic responses of pig iliac endothelial cells.  

PubMed

In order to fully explore the potential applications of nanoparticles in biopreservation, it is necessary to study the effect of nanoparticles on cell membrane permeabilities. The aim of this study is therefore to comparatively evaluate the osmotic responses of pig iliac endothelial cells in the absence and presence of commercially available hydroxyapatite nanoparticles. The results indicate that, after the introduction of 0.01wt% hydroxyapatite nanoparticles, the dependence of cell membrane hydraulic conductivity (Lp) on temperature still obeys the Arrhenius relationship, while the reference value of the hydraulic conductivity of the cell membrane at 273.15K (Lpg) and the activation energy for water transport across cell membrane (ELp) change from 0.77×10(-14)m/Pa/s and 15.65kJ/mol to 0.65×10(-14)m/Pa/s and 26.14kJ/mol. That is to say, the reference value of the hydraulic conductivity of the cell membrane has been slightly decreased while the activation energy for water transport across cell membrane has been greatly enhanced, and thus it implies that the hydraulic conductivity of cell membrane are more sensitive to temperature in the presence of nanoparticles. These findings are of potential significance to the optimization of nanoparticles-aided cryopreservation. PMID:25111088

Yue, Cui; Zhao, Gang; Yi, Jingru; Gao, Cai; Shen, Lingxiao; Zhang, Yuntian; Wang, Zhen; Liu, Wei

2014-10-01

239

Laser-induced cell detachment, patterning, and regrowth on gold nanoparticle functionalized surfaces.  

PubMed

We report on the selective cell detachment from nanoengineered gold nanoparticle (AuNP) surfaces triggered by laser irradiation, which occurs in a nonthermal manner. The gold nanoparticle-based surfaces reveal good adhesion of NIH3T3 fibroblast cells. Patterning is achieved by lithographic microcontact printing, selective gold nanoparticle deposition, and by laser beam profiling. It is shown that the effectiveness of fibroblast cell detachment depends on the cell age, laser power, and AuNP patterning profile. Heat distribution and temperature rise around gold nanoparticle functionalized surfaces is modeled, revealing low heating of nanoparticles by laser illumination. The nonthermal photochemical mechanism of cell detachment due to production of reactive oxygen species under illumination of gold nanoparticles by green laser light is studied. We also demonstrate that cells migrate from unirradiated areas leading to their reattachment and surface recovery which is important for controlled spatial organization of cells in wound healing and tissue engineering. Research presented in this work is targeted at designing biointerfaces for cell cultures. PMID:23066742

Kolesnikova, Tatiana A; Kohler, Dorothee; Skirtach, Andre G; Möhwald, Helmuth

2012-11-27

240

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

241

Paracrine signalling events in embryonic stem cell renewal mediated by affinity targeted nanoparticles  

E-print Network

Paracrine signalling events in embryonic stem cell renewal mediated by affinity targeted: Embryonic stem cell Biodegradable nanoparticles Paracrine delivery Renewal a b s t r a c t Stem cell growth and pluripotency of mouse embryonic stem cells. Leukaemia Inhibitory Factor (LIF) was encapsulated in biodegradable

Fahmy, Tarek

242

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

PubMed

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

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

2013-09-01

243

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

244

Lead sulfide nanoparticles increase cell wall chitin content and induce apoptosis in Saccharomyces cerevisiae.  

PubMed

Although there have been numerous studies on bacterial toxicity, the cytotoxicity of nanoparticles toward fungi remains poorly understood. We investigated the toxicity of various sizes of lead sulfide particles against the important model fungus, Saccharomyces cerevisiae. The smallest particle exerted the highest toxicity, inhibiting cell growth and decreasing cell viability, likely reflecting reduced sedimentation and persistent cell wall attack. In response to cell wall stress, S. cerevisiae showed an increase in the cell wall chitin content and the overexpression of FKS2 and PRM5, two genes of the cell wall integrity signaling pathway. Cell wall stress increased the concentration of intracellular reactive oxygen species, leading to mitochondrial dysfunction and cell apoptosis. The contribution of dissolved lead ions to the overall toxicity was negligible. These findings provide the first demonstration of the physiological protective response of a fungus toward nanoparticles, thereby contributing useful information to the assessment of the environmental impact of metal nanoparticles. PMID:24704549

Sun, Meiqing; Yu, Qilin; Hu, Mengyuan; Hao, Zhenwei; Zhang, Chengdong; Li, Mingchun

2014-05-30

245

Embryos derived from porcine skin-derived stem cells exhibit enhanced preimplantation development.  

PubMed

Ongoing research to identify the most suitable type of donor cell for nuclear transfer (NT) has suggested that less differentiated stem cells may be better donors than other somatic cell types. Recently, we have reported the isolation and characterization of porcine skin-originated sphere (PSOS) stem cells from fetal skin, making it possible to test this hypothesis in a nonrodent animal model. In the present study, we have investigated and compared the feasibility and preimplantation developmental efficiency of using fetal PSOS cells and fibroblasts as nuclear-transfer donors. The majority of fetal PSOS cells are in the G1/ G0 stage of the cell cycle, which is desirable for NT. During long-term in vitro culture, fetal PSOS cells had greater genome stability, with a lower frequency of abnormal karyotypes than fetal fibroblast cells. Embryos cloned from PSOS cells showed enhanced preimplantation development compared with fibroblast cloned embryos, which is indicated by an increased rate of blastocyst development and a higher total cell number in Day 7 blastocysts. The gene expression profile of genes critical for early development from eight-cell-stage PSOS NT embryos more closely resembled the pattern observed from in vivo-produced embryos compared with that of fibroblast-cloned embryos. Cumulatively, our data suggest that fetal PSOS cells may be better donor cells for NT in the pig. PMID:15306555

Zhu, Hai; Craig, Jesse A; Dyce, Paul W; Sunnen, Nicole; Li, Julang

2004-12-01

246

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. PMID:21865645

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

2011-01-01

247

Structural responses of cells to intracellular magnetic force induced by superparamagnetic iron oxide nanoparticles.  

PubMed

In this paper, we study the effects of intracellular force on human umbilical vein endothelial cells. We generated intracellular force on endothelial cells under different magnetic fields using the cell uptake of superparamagnetic iron oxide nanoparticles. Cell responses to intracellular force were observed using fluorescent microscopy. Our results indicated that nanoparticles were taken up by the cell by endocytosis and were deposited in lysosomes. Nanoparticles and lysosomes inside the cell could be relocated by the application of a magnetic force. The intracellular magnetic force could also be used to accelerate cell migration by adjusting the magnetic fields and giving the cell free culture space. No cytotoxicity of nanoparticles was found in our experiments. By comparing intracellular relocalization with migration of the whole cell, we obtained a better understanding of the self-defence mechanisms of cells based on their mechanical properties. Based on the promising mechanical properties and low cytotoxicity of our magnetic nanoparticles, their potential applications in cytomechanics and cell patterning are discussed. PMID:24336693

Shen, Han; Tong, Sheng; Bao, Gang; Wang, Biao

2014-02-01

248

Silica nanoparticles for cell imaging and intracellular sensing  

NASA Astrophysics Data System (ADS)

There is increasing interest in the use of nanoparticles (NPs) for biomedical applications. In particular, nanobiophotonic approaches using fluorescence offers the potential of high sensitivity and selectivity in applications such as cell imaging and intracellular sensing. In this review, we focus primarily on the use of fluorescent silica NPs for these applications and, in so doing, aim to enhance and complement the key recent review articles on these topics. We summarize the main synthetic approaches, namely the Stöber and microemulsion processes, and, in this context, we deal with issues in relation to both covalent and physical incorporation of different types of dyes in the particles. The important issue of NP functionalization for conjugation to biomolecules is discussed and strategies published in the recent literature are highlighted and evaluated. We cite recent examples of the use of fluorescent silica NPs for cell imaging in the areas of cancer, stem cell and infectious disease research, and we review the current literature on the use of silica NPs for intracellular sensing of oxygen, pH and ionic species. We include a short final section which seeks to identify the main challenges and obstacles in relation to the potential widespread use of these particles for in vivo diagnostics and therapeutics.

Korzeniowska, B.; Nooney, R.; Wencel, D.; McDonagh, C.

2013-11-01

249

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 (BiMnO(3+?)), and the superconducting YBa2Cu3O(7-?). PMID:24724979

Sutto, Thomas E

2014-05-01

250

Characterization of actinomycin-D-resistant CHO cell lines exhibiting a multidrug-resistance phenotype and amplified DNA sequences.  

PubMed

Actinomycin D (DACT)-resistant sublines of the Chinese hamster ovary cell line CHO-K1 were selected in vitro. Sublines were derived which expressed 5.2-fold (CHO 15DACT) and 35.8-fold (CHO 100DACT) resistance to DACT. The CHO 100DACT subline displayed marked cross-resistance to bleomycin, adriamycin, daunomycin, vinblastine, vincristine, VP 16 and VM 26. No cross-resistance was found to cisplatin or methotrexate. The resistant cells exhibited enhanced (collateral) sensitivity to prednisolone. Combination of prednisolone with vincristine resulted in a pronounced synergistic effect on sensitive cells, whereas in resistant cells the combined effect of both drugs was merely additive. Resistant cells, viably stained with the DNA-specific dye Hoechst 33342, exhibited decreased fluorescence intensities compared to parental cells. In contrast to sensitive cells the resistant sublines did not accumulate the mitochondria-specific dye rhodamine 123. Co-incubation with verapamil, however, effectively enhanced accumulation of the dye. The potential diagnostic value of these fluorescent compounds as marker dyes for the multidrug-resistance phenotype is discussed. Non-toxic doses of verapamil almost completely reversed the resistance to various drugs in CHO 100DACT cells. Specific DNA sequences were amplified in resistant cells, and the increase in resistance was paralleled by a concomitant increase in the copy number of these sequences, suggesting that the corresponding gene may be functionally linked to the multidrug-resistance phenotype. PMID:2445701

Diddens, H; Gekeler, V; Neumann, M; Niethammer, D

1987-11-15

251

One-pot synthesis of sustained-released doxorubicin silica nanoparticles for aptamer targeted delivery to tumor cells  

NASA Astrophysics Data System (ADS)

Site-specific delivery of drugs can significantly reduce drug toxicity and increase the therapeutic effect. Here, we report a one-pot synthesis of doxorubicin-doped silica nanoparticles (Dox/SiNPs) by using sodium fluoride (NaF) catalyzed hydrolysis of tetraethyl orthosilicate in a water-in-oil microemulsion. Through further surface chemical modification, carboxyl-terminated Dox/SiNPs (COOH-Dox/SiNPs) exhibiting high drug entrapment efficiency, strong fluorescence and long sustained release are obtained. Cell toxicity tests demonstrate that the COOH-Dox/SiNPs kill tumor cells effectively, while pure COOH-SiNPs are nontoxic. An aptamer is further conjugated to the nanoparticles for delivering loaded Dox to target cells. It is demonstrated that Dox/SiNPs modified with the aptamer sgc8c (sgc8c-Dox/SiNPs) could deliver loaded doxorubicin to CCRF-CEM cells with high specificity and excellent efficiency. Furthermore, ex vivo imaging studies show that the COOH-Dox/SiNPs are able to accumulate highly in the tumor areas, thanks to the enhanced permeability and retention (EPR) effects. Our data suggest that the sgc8c-Dox/SiNPs may be a useful new tumor therapy system.Site-specific delivery of drugs can significantly reduce drug toxicity and increase the therapeutic effect. Here, we report a one-pot synthesis of doxorubicin-doped silica nanoparticles (Dox/SiNPs) by using sodium fluoride (NaF) catalyzed hydrolysis of tetraethyl orthosilicate in a water-in-oil microemulsion. Through further surface chemical modification, carboxyl-terminated Dox/SiNPs (COOH-Dox/SiNPs) exhibiting high drug entrapment efficiency, strong fluorescence and long sustained release are obtained. Cell toxicity tests demonstrate that the COOH-Dox/SiNPs kill tumor cells effectively, while pure COOH-SiNPs are nontoxic. An aptamer is further conjugated to the nanoparticles for delivering loaded Dox to target cells. It is demonstrated that Dox/SiNPs modified with the aptamer sgc8c (sgc8c-Dox/SiNPs) could deliver loaded doxorubicin to CCRF-CEM cells with high specificity and excellent efficiency. Furthermore, ex vivo imaging studies show that the COOH-Dox/SiNPs are able to accumulate highly in the tumor areas, thanks to the enhanced permeability and retention (EPR) effects. Our data suggest that the sgc8c-Dox/SiNPs may be a useful new tumor therapy system. Electronic supplementary information (ESI) available: See DOI: 10.1039/c0nr00913j

He, Xiaoxiao; Hai, Luo; Su, Jing; Wang, Kemin; Wu, Xu

2011-07-01

252

Evaluating Cytotoxicity of Hyaluronate Targeted Solid Lipid Nanoparticles of Etoposide on SK-OV-3 Cells  

PubMed Central

The epithelial ovarian carcinoma is one of the most fatal gynecological cancers. Etoposide is used in treating platinum-resistant ovarian cancer. Sodium hyaluronate is a substance that binds to the CD44 receptors overexpressed in SK-OV-3 cells of epithelial ovarian carcinoma. The aim of the present work was to study the cytotoxicity effect of hyaluronate targeted solid lipid nanoparticles (SLNs) of etoposide on SK-OV-3 cells. The cytotoxicity of the targeted and nontargeted SLNs of etoposide was compared to free drug on the SK-OV-3 cells by MTT assay method. The cellular uptake of the targeted and nontargeted nanoparticles containing sodium fluorescein was also studied. The difference of cell vitality between nontargeted nanoparticles and also targeted nanoparticles with free drug was significant. Targeted nanoparticles also caused more toxicity than nontargeted nanoparticles (P < 0.05). After 4 hours of incubating, the fluorescence was remarkably higher in the cells treated by targeted SLNs rather than nontargeted ones, and there was no observable fluorescence in cells incubated with pure sodium fluorescein. Hyaluronate targeted SLNs containing etoposide increased the cytotoxicity of etoposide on SK-OV-3 cells which may be a worthwhile potential method for reducing the prescribed dose and systemic side effects of this drug in epithelial ovarian carcinoma. PMID:24868467

Varshosaz, Jaleh; Sadeghi Aliabadi, Hojatollah

2014-01-01

253

Evaluating Cytotoxicity of Hyaluronate Targeted Solid Lipid Nanoparticles of Etoposide on SK-OV-3 Cells.  

PubMed

The epithelial ovarian carcinoma is one of the most fatal gynecological cancers. Etoposide is used in treating platinum-resistant ovarian cancer. Sodium hyaluronate is a substance that binds to the CD44 receptors overexpressed in SK-OV-3 cells of epithelial ovarian carcinoma. The aim of the present work was to study the cytotoxicity effect of hyaluronate targeted solid lipid nanoparticles (SLNs) of etoposide on SK-OV-3 cells. The cytotoxicity of the targeted and nontargeted SLNs of etoposide was compared to free drug on the SK-OV-3 cells by MTT assay method. The cellular uptake of the targeted and nontargeted nanoparticles containing sodium fluorescein was also studied. The difference of cell vitality between nontargeted nanoparticles and also targeted nanoparticles with free drug was significant. Targeted nanoparticles also caused more toxicity than nontargeted nanoparticles (P < 0.05). After 4 hours of incubating, the fluorescence was remarkably higher in the cells treated by targeted SLNs rather than nontargeted ones, and there was no observable fluorescence in cells incubated with pure sodium fluorescein. Hyaluronate targeted SLNs containing etoposide increased the cytotoxicity of etoposide on SK-OV-3 cells which may be a worthwhile potential method for reducing the prescribed dose and systemic side effects of this drug in epithelial ovarian carcinoma. PMID:24868467

Mohammadi Ghalaei, Parviz; Varshosaz, Jaleh; Sadeghi Aliabadi, Hojatollah

2014-01-01

254

Magnetic nanoparticles sensitize MCF-7 breast cancer cells to doxorubicin-induced apoptosis  

PubMed Central

Background Resistance of breast cancer cells to the available chemotherapeutics is a major obstacle to successful treatment. Recent studies have shown that magnetic nanoparticles might have significant application in different medical fields including cancer treatment. The goal of this study is to verify the ability of magnetic nanoparticles to sensitize cancer cells to the clinically available chemotherapy. Methods The role of iron oxide nanoparticles, static magnetic field, or a combination in the enhancement of the apoptotic potential of doxorubicin against the resistant breast cancer cells, MCF-7 was evaluated using the MTT assay and the propidium iodide method. Results In the present study, results revealed that pre-incubation of MCF-7 cells with iron oxide nanoparticles before the addition of doxorubicin did not enhance doxorubicin-induced growth inhibition. Pre-incubation of MCF-7 cells with iron oxide nanoparticles followed by a static magnetic field exposure significantly (P?cell death. Conclusions These results might point to the importance of combining magnetic nanoparticles with a static magnetic field in treatment of doxorubicin-refractory breast cancer cells. PMID:22533492

2012-01-01

255

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

E-print Network

One of the major challenges in the development of targeted nanoparticles (NPs) for cancer therapy is to discover targeting ligands that allow for differential binding and uptake by the target cancer cells. Using prostate ...

Xiao, Zeyu

256

High-Efficiency 6?? Multicrystalline Black Solar Cells Based on Metal-Nanoparticle-Assisted Chemical Etching  

E-print Network

Multicrystalline silicon (mc-Si) photovoltaic (PV) solar cells with nanoscale surface texturing by metal-nanoparticle-assisted etching are proposed to achieve high power efficiency. The investigation of average nanorod ...

Hsu, W. Chuck

2012-01-01

257

The Characteristics and Mechanisms of Uptake of PLGA Nanoparticles in Rabbit Conjunctival Epithelial Cell Layers  

Microsoft Academic Search

Purpose. To delineate the characteristics and mechanisms of up- take of biodegradable poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles in primary cultured rabbit conjunctival epithelial cells (RCECs).

Mohamed G. Qaddoumi; Hideo Ueda; Johnny Yang; Jasmine Davda; Vinod Labhasetwar; Vincent H. L. Lee

2004-01-01

258

Green Synthesis of Silver Nanoparticles Using Cell Extracts of Anabaena doliolum and Screening of Its Antibacterial and Antitumor Activity.  

PubMed

In the present work, we describe a simple, cheap, and unexplored method for "green" synthesis of silver nanoparticles using cell extracts of the cyanobacterium Anabaena doliolum. An attempt was also made to test the antimicrobial and antitumor activities of the synthesized nanoparticles. Analytical techniques, namely UV-vis spectroscopy, X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), and TEMselected area electron diffraction, were used to elucidate the formation and characterization of silver-cyanobacterial nanoparticles (Ag-CNPs). Results showed that the original color of the cell extract changed from reddish blue to dark brown after addition of silver nitrate solution (1 mM) within 1 h, suggesting the synthesis of Ag-CNPs. That the formation Ag-CNPs indeed occurred was also evident from the spectroscopic analysis of the reaction mixture, wherein a prominent peak at 420 nm was noted. TEM images revealed well-dispersed, spherical Ag- CNPs with a particle size in the range of 10-50 nm. The X-ray diffraction spectrum suggested a crystalline nature of the Ag-CNPs. FTIR analysis indicated the utilization of a hydroxyl (-OH) group in the formation of Ag-CNPs. Ag-CNPs exhibited strong antibacterial activity against three multidrug-resistant bacteria. Additionally, Ag-CNPs strongly affected the survival of Dalton's lymphoma and human carcinoma colo205 cells at a very low concentration. The Ag-CNPs-induced loss of survival of both cell types may be due to the induction of reactive oxygen species generation and DNA fragmentation, resulting in apoptosis. Properties exhibited by the Ag-CNP suggest that it may be used as a potential antibacterial and antitumor agent. PMID:24986675

Singh, Garvita; Babele, Piyoosh K; Shahi, Shailesh K; Sinha, Rajeshwar P; Tyagi, Madhu B; Kumar, Ashok

2014-10-28

259

Polymeric nanoparticles of different sizes overcome the cell membrane barrier.  

PubMed

Polymeric nanoparticles have tremendous potential either as carriers or markers in treatment for diseases or as diagnostics in biomedical applications. Finding the optimal conditions for effective intracellular delivery of the payload to the location of interest is still a big challenge. The particles have to overcome the barrier of the cell membrane. Here, we investigated the uptake in HeLa cells of fluorescent polystyrene particles with different size and surface charge. Particles stabilized with the nonionic surfactant Lutensol AT50® (132 nm, 180 nm, 242 nm, 816 nm, 846 nm diameter) were synthesized via dispersion polymerization. Cationic particles (120 nm, 208 nm, 267 nm, 603 nm diameter) were obtained by a combination of miniemulsion and seed dispersion polymerization using cationic surfactant (cetyltrimethylammonium chloride (CTMA-Cl). The particle uptake into HeLa cells was studied by confocal laser scanning microscopy and flow cytometry. Nonionic particles were - independent of their size - taken up by cells only at a barely detectable level, thus aggravating a quantitative comparison. The uptake of positively charged particles was substantially higher and therefore enabling further investigation keeping constant one of these parameters: either material amount or particles number or total interaction surface area. It was found that the uptake rather depends on the total amount of polymeric material present in the media than on the number of particles. The total particle's surface area does not correlate linearly with the uptake, thus indicating that there is no direct dependency between the total surface area and the cellular endocytotic process to overcome the biobarrier "cell membrane." A potentially novel uptake mechanism is found which can be described as an excavator shovel like mechanism. It is a kind of macropinocytosis dependent on actin filaments as well as dynamin, but is clathrin-independent. PMID:23422734

Lerch, Simone; Dass, Martin; Musyanovych, Anna; Landfester, Katharina; Mailänder, Volker

2013-06-01

260

PEG-detachable lipid-polymer hybrid nanoparticle for delivery of chemotherapy drugs to cancer cells.  

PubMed

The experiment aimed to increase the drug-delivery efficiency of poly-lactic-co-glycolic acid (PLGA) nanoparticles. Lipid-polymer hybrid nanoparticles (LPNs-1) were prepared using PLGA as a hydrophobic core and FA-PEG-hyd-DSPE as an amphiphilic shell. Uniform and spherical nanoparticles with an average size of 185 nm were obtained using the emulsification solvent evaporation method. The results indicated that LPNs-1 showed higher drug loading compared with naked PLGA nanoparticles (NNPs). Drug release from LPNs-1 was faster in an acidic environment than in a neutral environment. LPNs-1 showed higher cytotoxicity on KB cells, A549 cells, MDA-MB-231 cells, and MDA-MB-231/ADR cells compared with free doxorubicin (DOX) and NNPs. The results also showed that, compared with free DOX and NNPs, LPNs-1 delivered more DOX to the nuclear of KB cells and MDA-MB-231/ADR cells. LPNs-1 induced apoptosis in KB cells and MDA-MB-231/ADR cells in a dose-dependent manner. The above data indicated that DOX-loaded LPNs-1 could kill not only normal tumor cells but also drug-resistant tumor cells. These results indicated that modification of PLGA nanoparticles with FA-PEG-hyd-DSPE could considerably increase the drug-delivery efficiency and LPNs-1 had potential in the delivery of chemotherapeutic agents in the treatment of cancer. PMID:24590167

Du, Jiang-bo; Song, Yan-feng; Ye, Wei-liang; Cheng, Ying; Cui, Han; Liu, Dao-zhou; Liu, Miao; Zhang, Bang-le; Zhou, Si-yuan

2014-08-01

261

Managing magnetic nanoparticle aggregation and cellular uptake: a precondition for efficient stem-cell differentiation and MRI tracking.  

PubMed

The labeling of stem cells with iron oxide nanoparticles is increasingly used to enable MRI cell tracking and magnetic cell manipulation, stimulating the fields of tissue engineering and cell therapy. However, the impact of magnetic labeling on stem-cell differentiation is still controversial. One compromising factor for successful differentiation may arise from early interactions of nanoparticles with cells during the labeling procedure. It is hypothesized that the lack of control over nanoparticle colloidal stability in biological media may lead to undesirable nanoparticle localization, overestimation of cellular uptake, misleading MRI cell tracking, and further impairment of differentiation. Herein a method is described for labeling mesenchymal stem cells (MSC), in which the physical state of citrate-coated nanoparticles (dispersed versus aggregated) can be kinetically tuned through electrostatic and magnetic triggers, as monitored by diffusion light scattering in the extracellular medium and by optical and electronic microscopy in cells. A set of statistical cell-by-cell measurements (flow cytometry, single-cell magnetophoresis, and high-resolution MRI cellular detection) is used to independently quantify the nanoparticle cell uptake and the effects of nanoparticle aggregation. Such aggregation confounds MRI cell detection as well as global iron quantification and has adverse effects on chondrogenetic differentiation. Magnetic labeling conditions with perfectly stable nanoparticles-suitable for obtaining differentiation-capable magnetic stem cells for use in cell therapy-are subsequently identified. PMID:23184893

Fayol, Delphine; Luciani, Nathalie; Lartigue, Lenaic; Gazeau, Florence; Wilhelm, Claire

2013-02-01

262

Comprehensive studies on the interactions between chitosan nanoparticles and some live cells  

Microsoft Academic Search

As more and more oral formulations of nanoparticles are used in clinical contexts, a comprehensive study on the mechanisms\\u000a of interaction between polymer nanoparticles and live cells seems merited. Such a study was conducted and the results were\\u000a compared to the polymer itself in order to demonstrate different kinds of effects that are brought into the cell by polymer\\u000a and

Ai-ping Zheng; Hui-xue Liu; Lan Yuan; Meng Meng; Jian-cheng Wang; Xuan Zhang; Qiang Zhang

263

In vitro interaction of colloidal nanoparticles with mammalian cells: What have we learned thus far?  

PubMed Central

Summary The interfacing of colloidal nanoparticles with mammalian cells is now well into its second decade. In this review our goal is to highlight the more generally accepted concepts that we have gleaned from nearly twenty years of research. While details of these complex interactions strongly depend, amongst others, upon the specific properties of the nanoparticles used, the cell type, and their environmental conditions, a number of fundamental principles exist, which are outlined in this review. PMID:25247131

Nazarenus, Moritz; Zhang, Qian; Soliman, Mahmoud G; del Pino, Pablo; Pelaz, Beatriz; Carregal-Romero, Susana; Rejman, Joanna; Rothen-Rutishauser, Barbara; Clift, Martin J D; Zellner, Reinhard; Nienhaus, G Ulrich; Delehanty, James B; Medintz, Igor L

2014-01-01

264

Noninvasive radiofrequency field-induced hyperthermic cytotoxicity in human cancer cells using cetuximab-targeted gold nanoparticles.  

PubMed

Shortwave (MHz range) radiofrequency (RF) energy is nonionizing, penetrates deeply into biologic tissues with no adverse side effects, and heats gold nanoparticles efficiently. Targeted delivery of gold nanoparticles to cancer cells should result in hyperthermic cytotoxicity upon exposure to a focused, noninvasive RF field. In this report we demonstrate 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:19227011

Curley, Steven A; Cherukuri, Paul; Briggs, Katrina; Patra, Chitta Ranjan; Upton, Mark; Dolson, Elisa; Mukherjee, Priyabrata

2008-01-01

265

Defining the Subcellular Interface of Nanoparticles by Live-Cell Imaging  

PubMed Central

Understanding of nanoparticle-bio-interactions within living cells requires knowledge about the dynamic behavior of nanomaterials during their cellular uptake, intracellular traffic and mutual reactions with cell organelles. Here, we introduce a protocol of combined kinetic imaging techniques that enables investigation of exemplary fluorochrome-labelled nanoparticles concerning their intracellular fate. By time-lapse confocal microscopy we observe fast, dynamin-dependent uptake of polystyrene and silica nanoparticles via the cell membrane within seconds. Fluorescence recovery after photobleaching (FRAP) experiments reveal fast and complete exchange of the investigated nanoparticles at mitochondria, cytoplasmic vesicles or the nuclear envelope. Nuclear translocation is observed within minutes by free diffusion and active transport. Fluorescence correlation spectroscopy (FCS) and raster image correlation spectroscopy (RICS) indicate diffusion coefficients of polystyrene and silica nanoparticles in the nucleus and the cytoplasm that are consistent with particle motion in living cells based on diffusion. Determination of the apparent hydrodynamic radii by FCS and RICS shows that nanoparticles exert their cytoplasmic and nuclear effects mainly as mobile, monodisperse entities. Thus, a complete toolkit of fluorescence fluctuation microscopy is presented for the investigation of nanomaterial biophysics in subcellular microenvironments that contributes to develop a framework of intracellular nanoparticle delivery routes. PMID:23637951

Hemmerich, Peter H.; von Mikecz, Anna H.

2013-01-01

266

Magnetic nanoparticle-mediated massively-parallel mechanical modulation of single-cell behavior  

PubMed Central

We report a technique for generating controllable, time-varying and localizable forces on arrays of cells in a massively parallel fashion. To achieve this, we grow magnetic nanoparticle-dosed cells in defined patterns on micro-magnetic substrates. By manipulating and coalescing nanoparticles within cells, we apply localized nanoparticle-mediated forces approaching cellular yield tensions on the cortex of HeLa cells. We observed highly coordinated responses in cellular behavior, including the p21-activated kinase (PAK)-dependent generation of active, leading-edge type filopodia, and biasing of the metaphase plate during mitosis. The large sample size and rapid sample generation inherent to this approach allow the analysis of cells at an unprecedented rate; a single experiment can potentially stimulate tens of thousands of cells for high statistical accuracy in measurements. This technique shows promise as a tool for both cell analysis and control. PMID:23064517

Tseng, Peter; Judy, Jack W.; Di Carlo, Dino

2012-01-01

267

Factors affecting T cell responses induced by fully synthetic glyco-gold-nanoparticles  

NASA Astrophysics Data System (ADS)

We have synthesized and characterized nearly monodisperse and highly pure gold nanoparticles (2 and 5 nm) coated with non-immunoactive mono- and disaccharides, modelled after the capsular polysaccharide of serogroup A of the Neisseria meningitidis bacterium. We have used them to test their ability to induce immune cell responses as a consequence of their multivalency. The results indicate that they are indeed immunoactive and that immunoactivity is strongly dependent on size, and larger, 5 nm nanoparticles perform far better than smaller, 2 nm ones. Immune response (activation of macrophages) initiates with the whole nanoparticle recognition by the surface of antigen-presenting cells, independent of the saccharide oligomerization (or charge) on the nanoparticle surface. The induction of T cell proliferation and the increase of IL-2 levels, a consequence of the expression of MHC II involved in antigen presentation, require the presence of a disaccharide on the nanoparticle, not just a monosaccharide. A possible explanation is that, at this stage, the saccharides are detached from the gold surface. These results may provide leads for designing new saccharide-based, nanoparticle-conjugate vaccines.We have synthesized and characterized nearly monodisperse and highly pure gold nanoparticles (2 and 5 nm) coated with non-immunoactive mono- and disaccharides, modelled after the capsular polysaccharide of serogroup A of the Neisseria meningitidis bacterium. We have used them to test their ability to induce immune cell responses as a consequence of their multivalency. The results indicate that they are indeed immunoactive and that immunoactivity is strongly dependent on size, and larger, 5 nm nanoparticles perform far better than smaller, 2 nm ones. Immune response (activation of macrophages) initiates with the whole nanoparticle recognition by the surface of antigen-presenting cells, independent of the saccharide oligomerization (or charge) on the nanoparticle surface. The induction of T cell proliferation and the increase of IL-2 levels, a consequence of the expression of MHC II involved in antigen presentation, require the presence of a disaccharide on the nanoparticle, not just a monosaccharide. A possible explanation is that, at this stage, the saccharides are detached from the gold surface. These results may provide leads for designing new saccharide-based, nanoparticle-conjugate vaccines. Electronic supplementary information (ESI) available: Fig. S1-S10 mentioned in the text related to the syntheses of nanosystems, nanoparticle characterization, and biological tests. See DOI: 10.1039/c2nr32338a

Fallarini, Silvia; Paoletti, Tiziana; Battaglini, Carolina Orsi; Ronchi, Paolo; Lay, Luigi; Bonomi, Renato; Jha, Satadru; Mancin, Fabrizio; Scrimin, Paolo; Lombardi, Grazia

2012-12-01

268

Immuno Nanoparticles Integrated Electrical Control of Targeted Cancer Cell Development Using Whole Cell Bioelectronic Device  

PubMed Central

Electrical properties of cells determine most of the cellular functions, particularly ones which occur in the cell's membrane. Manipulation of these electrical properties may provide a powerful electrotherapy option for the treatment of cancer as cancerous cells have been shown to be more electronegative than normal proliferating cells. Previously, we used an electrical impedance sensing system (EIS) to explore the responses of cancerous SKOV3 cells and normal HUVEC cells to low intensity (<2 V/cm) AC electric fields, determining that the optimal frequency for SKOV3 proliferation arrest was 200 kHz, without harming the non-cancerous HUVECs. In this study, to determine if these effects are cell type dependant, human breast adenocarcinoma cells (MCF7) were subjected to a range of frequencies (50 kHz-2 MHz) similar to the previously tested SKOV3. For the MCF7, an optimal frequency of 100 kHz was determined using the EIS, indicating a higher sensitivity towards the applied field. Further experiments specifically targeting the two types of cancer cells using HER2 antibody functionalized gold nanoparticles (HER2-AuNPs) were performed to determine if enhanced electric field strength can be induced via the application of nanoparticles, consequently leading to the killing of the cancerous cells without affecting non cancerous HUVECs and MCF10a providing a platform for the development of a non-invasive cancer treatment without any harmful side effects. The EIS was used to monitor the real-time consequences on cellular viability and a noticeable decrease in the growth profile of the MCF7 was observed with the application of the HER2-AuNPs and the electric fields indicating specific inhibitory effects on dividing cells in culture. To further understand the effects of the externally applied field to the cells, an Annexin V/EthD-III assay was performed to determine the cell death mechanism indicating apoptosis. The zeta potential of the SKOV3 and the MCF7 before and after incorporation of the HER2-AuNPs was also obtained indicating a decrease in zeta potential with the incorporation of the nanoparticles. The outcome of this research will improve our fundamental understanding of the behavior of cancer cells and define optimal parameters of electrotherapy for clinical and drug delivery applications. PMID:25057316

Hondroulis, Evangelia; Zhang, Rui; Zhang, Chengxiao; Chen, Chunying; Ino, Kosuke; Matsue, Tomokazu; Li, Chen-Zhong

2014-01-01

269

Comparative in vitro cytotoxicity study of silver nanoparticle on two mammalian cell lines.  

PubMed

In this study the cytotoxic effect of commercially available silver (Ag) nanoparticle was evaluated using human dermal and cervical cancer cell lines. Prior to the cellular studies a full particle size characterisation was carried out using Dynamic Light Scattering (DLS), Transmission Electron Microscopy and Scanning Electron Microscopy in distilled water and cell culture media. The Zeta Potential (ZP) associated with the Ag nanoparticle was also determined in order to assess its stability in the solutions and its possible interaction with the media. The DLS and ZP study have suggested interaction of Ag nanoparticles with the media, which can lead to secondary toxicity. The toxic effects of Ag nanoparticles were then evaluated using different cytotoxic endpoints namely the lysosomal activity, mitochondrial metabolism, basic cellular metabolism, cellular protein content and cellular proliferative capacity. The cytotoxic effect of Ag nanoparticle was dependant on dose, exposure time and on the cell line tested. Further investigation was carried out on HeLa and HaCaT cell lines to elucidate the mechanism of its cytotoxicity. The Ag nanoparticle was noted to induce elevated levels of oxidative stress, glutathione depletion and damage to the cell membrane as found from the adenylate kinase assay and that leads to the apoptosis. Overall, significant differences were observed between the sensitivity of the two cell lines which can be understood in terms of their natural antioxidant levels. PMID:22198051

Mukherjee, Sanchali Gupta; O'Claonadh, Niall; Casey, Alan; Chambers, Gordon

2012-03-01

270

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

271

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. PMID:7528781

1995-01-01

272

High resolution SEM imaging of gold nanoparticles in cells and tissues.  

PubMed

The growing demand of gold nanoparticles in medical applications increases the need for simple and efficient characterization methods of the interaction between the nanoparticles and biological systems. Due to its nanometre resolution, modern scanning electron microscopy (SEM) offers straightforward visualization of metallic nanoparticles down to a few nanometre size, almost without any special preparation step. However, visualization of biological materials in SEM requires complicated preparation procedure, which is typically finished by metal coating needed to decrease charging artefacts and quick radiation damage of biomaterials in the course of SEM imaging. The finest conductive metal coating available is usually composed of a few nanometre size clusters, which are almost identical to the metal nanoparticles employed in medical applications. Therefore, SEM monitoring of metal nanoparticles within cells and tissues is incompatible with the conventional preparation methods. In this work, we show that charging artefacts related to non-conductive biological specimen can be successfully eliminated by placing the uncoated biological sample on a conductive substrate. By growing the cells on glass pre-coated with a chromium layer, we were able to observe the uptake of 10 nm gold nanoparticles inside uncoated and unstained macrophages and keratinocytes cells. Imaging in back scattered electrons allowed observation of gold nanoparticles located inside the cells, while imaging in secondary electron gave information on gold nanoparticles located on the surface of the cells. By mounting a skin cross-section on an improved conductive holder, consisting of a silicon substrate coated with copper, we were able to observe penetration of gold nanoparticles of only 5 nm size through the skin barrier in an uncoated skin tissue. The described method offers a convenient modification in preparation procedure for biological samples to be analyzed in SEM. The method provides high conductivity without application of surface coating and requires less time and a reduced use of toxic chemicals. PMID:25228335

Goldstein, A; Soroka, Y; Fruši?-Zlotkin, M; Popov, I; Kohen, R

2014-12-01

273

Nanoparticles containing allotropes of carbon have genotoxic effects on glioblastoma multiforme cells.  

PubMed

The carbon-based nanomaterial family consists of nanoparticles containing allotropes of carbon, which may have a number of interactions with biological systems. The objective of this study was to evaluate the toxicity of nanoparticles comprised of pristine graphene, reduced graphene oxide, graphene oxide, graphite, and ultradispersed detonation diamond in a U87 cell line. The scope of the work consisted of structural analysis of the nanoparticles using transmission electron microscopy, evaluation of cell morphology, and assessment of cell viability by Trypan blue assay and level of DNA fragmentation of U87 cells after 24 hours of incubation with 50 ?g/mL carbon nanoparticles. DNA fragmentation was studied using single-cell gel electrophoresis. Incubation with nanoparticles containing the allotropes of carbon did not alter the morphology of the U87 cancer cells. However, incubation with pristine graphene and reduced graphene oxide led to a significant decrease in cell viability, whereas incubation with graphene oxide, graphite, and ultradispersed detonation diamond led to a smaller decrease in cell viability. The results of a comet assay demonstrated that pristine graphene, reduced graphene oxide, graphite, and ultradispersed detonation diamond caused DNA damage and were therefore genotoxic in U87 cells, whereas graphene oxide was not. PMID:24876774

Hinzmann, Mateusz; Jaworski, S?awomir; Kutwin, Marta; Jagie??o, Joanna; Kozi?ski, Rafa?; Wierzbicki, Mateusz; Grodzik, Marta; Lipi?ska, Ludwika; Sawosz, Ewa; Chwalibog, Andrè

2014-01-01

274

Analysis of the Influence of Cell Heterogeneity on Nanoparticle Dose Response  

PubMed Central

Understanding the effect of variability in the interaction of individual cells with nanoparticles on the overall response of the cell population to a nanoagent is a fundamental challenge in bionanotechnology. Here, we show that the technique of time-resolved, high-throughput microscopy can be used in this endeavor. Mass measurement with single-cell resolution provides statistically robust assessments of cell heterogeneity, while the addition of a temporal element allows assessment of separate processes leading to deconvolution of the effects of particle supply and biological response. We provide a specific demonstration of the approach, in vitro, through time-resolved measurement of fibroblast cell (HFF-1) death caused by exposure to cationic nanoparticles. The results show that heterogeneity in cell area is the major source of variability with area-dependent nanoparticle capture rates determining the time of cell death and hence the form of the exposure–response characteristic. Moreover, due to the particulate nature of the nanoparticle suspension, there is a reduction in the particle concentration over the course of the experiment, eventually causing saturation in the level of measured biological outcome. A generalized mathematical description of the system is proposed, based on a simple model of particle depletion from a finite supply reservoir. This captures the essential aspects of the nanoparticle–cell interaction dynamics and accurately predicts the population exposure–response curves from individual cell heterogeneity distributions. PMID:24923782

2014-01-01

275

Titanium dioxide nanoparticles increase inflammatory responses in vascular endothelial cells.  

PubMed

Atherosclerosis is a chronic inflammatory disease that remains the leading cause of death in the United States. Numerous risk factors for endothelial cell inflammation and the development of atherosclerosis have been identified, including inhalation of ultrafine particles. Recently, engineered nanoparticles (NPs) such as titanium (TiO2) NPs have attracted much attention due to their wide range of applications. However, there are also great concerns surrounding potential adverse health effects in vascular systems. Although TiO2 NPs are known to induce oxidative stress and inflammation, the associated signaling pathways have not been well studied. The focus of this work, therefore, deals with examination of the cellular signaling pathways responsible for TiO2 NP-induced endothelial oxidative stress and inflammation. In this study, primary vascular endothelial cells were treated with TiO2 NPs for 2-16h at concentrations of 0-50 ?g/mL. TiO2 NP exposure increased cellular oxidative stress and DNA binding of NF-?B. Further, phosphorylation of Akt, ERK, JNK and p38 was increased in cells exposed to TiO2 NPs. TiO2 NPs also significantly increased induction of mRNA and protein levels of vascular cell adhesion molecule-1 (VCAM-1) and mRNA levels of monocyte chemoattractant protein-1 (MCP-1). Pretreatment with inhibitors for NF-?B (pyrrolidine dithiocarbamate), oxidative stress (epigallocatechin gallate and apocynin), Akt (LY294002), ERK (PD98059), JNK (SP600125) and p38 (SB203580) significantly attenuated TiO2 NP-induced MCP-1 and VCAM-1 gene expression. These data indicate that TiO2 NPs can induce endothelial inflammatory responses via redox-sensitive cellular signaling pathways. PMID:23380242

Han, Sung Gu; Newsome, Bradley; Hennig, Bernhard

2013-04-01

276

Aging Hematopoietic Stem Cells Decline in Function and Exhibit Epigenetic Dysregulation  

Microsoft Academic Search

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

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

2007-01-01

277

Toxicity and antibacterial assessment of chitosancoated silver nanoparticles on human pathogens and macrophage cells  

PubMed Central

Background Pathogenic bacteria are able to develop various strategies to counteract the bactericidal action of antibiotics. Silver nanoparticles (AgNPs) have emerged as a potential alternative to conventional antibiotics because of their potent antimicrobial properties. The purpose of this study was to synthesize chitosan-stabilized AgNPs (CS-AgNPs) and test for their cytotoxic, genotoxic, macrophage cell uptake, antibacterial, and antibiofilm activities. Methods AgNPs were synthesized using chitosan as both a stabilizing and a reducing agent. Antibacterial activity was determined by colony-forming unit assay and scanning electron microscopy. Genotoxic and cytotoxic activity were determined by DNA fragmentation, comet, and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays. Cellular uptake and intracellular antibacterial activity were tested on macrophages. Results CS-AgNPs exhibited potent antibacterial activity against different human pathogens and also impeded bacterial biofilm formation. Scanning electron microscopy analysis indicated that CS-AgNPs kill bacteria by disrupting the cell membrane. CS-AgNPs showed no significant cytotoxic or DNA damage effect on macrophages at the bactericidal dose. Propidium iodide staining indicated active endocytosis of CS-AgNPs resulting in reduced intracellular bacterial survival in macrophages. Conclusion The present study concludes that at a specific dose, chitosan-based AgNPs kill bacteria without harming the host cells, thus representing a potential template for the design of antibacterial agents to decrease bacterial colonization and to overcome the problem of drug resistance. PMID:22619529

Jena, Prajna; Mohanty, Soumitra; Mallick, Rojee; Jacob, Biju; Sonawane, Avinash

2012-01-01

278

CD133+CXCR4+ colon cancer cells exhibit metastatic potential and predict poor prognosis of patients  

PubMed Central

Background Colorectal cancer (CRC), which frequently metastasizes to the liver, is one of the three leading causes of cancer-related deaths worldwide. Growing evidence suggests that a subset of cells exists among cancer stem cells. This distinct subpopulation is thought to contribute to liver metastasis; however, it has not been fully explored in CRC yet. Methods Flow cytometry analysis was performed to detect distinct subsets with CD133 and CXCR4 markers in human primary and metastatic CRC tissues. The 'stemness' and metastatic capacities of different subpopulations derived from the colon cancer cell line HCT116 were compared in vitro and in vivo. The roles of epithelial-mesenchymal transition (EMT) and stromal-cell derived factor-1 (SDF-1) in the metastatic process were also investigated. A survival curve was used to explore the correlation between the content of CD133+CXCR4+ cancer cells and patient survival. Results In human specimens, the content of CD133+CXCR4+ cells was higher in liver metastases than in primary colorectal tumors. Clonogenic and tumorigenic cells were restricted to CD133+ cells in the HCT116 cell line, with CXCR4 expression having no impact on the 'stemness' properties. We found that CD133+CXCR4+ cancer cells had a high metastatic capacity in vitro and in vivo. Compared with CD133+CXCR4- cells, CD133+CXCR4+ cancer cells experienced EMT, which contributed partly to their metastatic phenotype. We then determined that SDF-1/CXCL12 treatment could further induce EMT in CD133+CXCR4+ cancer cells and enhance their invasive behavior, while this could not be observed in CD133+CXCR4- cancer cells. Blocking SDF-1/CXCR4 interaction with a CXCR4 antagonist, AMD3100 (1,10-[1,4-phenylenebis(methylene)]bis-1,4,8,11 -tetraazacyclotetradecane octahydrochloride), inhibited metastatic tumor growth in a mouse hepatic metastasis model. Finally, a high percentage of CD133+CXCR4+ cells in human primary CRC was associated with a reduced two-year survival rate. Conclusions Strategies targeting the SDF-1/CXCR4 interaction may have important clinical applications in the suppression of colon cancer metastasis. Further investigations on how high expression of CXCR4 and EMT occur in this identified cancer stem cell subset are warranted to provide insights into our understanding of tumor biology. PMID:22871210

2012-01-01

279

Developmental factor IRF6 exhibits tumor suppressor activity in squamous cell carcinomas.  

PubMed

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. PMID:21807998

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

2011-08-16

280

Functionalized polystyrene nanoparticles trigger human dendritic cell maturation resulting in enhanced CD4+ T cell activation.  

PubMed

Nanoparticles (NP) represent a promising tool for biomedical applications. Here, sulfonate- and phosphonate-functionalized polystyrene NP are analyzed for their interaction with human monocyte-derived dendritic cells (DC). Immature dendritic cells (iDC) display a higher time- and dose-dependent uptake of functionalized polystyrene NP compared to mature dendritic cells (mDC). Notably, NP induce an enhanced maturation of iDC but not of mDC (upregulation of stimulatory molecules and cytokines). NP-triggered maturation results in a significantly enhanced T cell stimulatory capacity (increased CD4(+) T cell proliferation and IFN-? production), indicating a shift to a pronounced Th1 response. Immunomodulatory properties of NP may be a useful strategy for strengthening the efficacy of NP-based approaches in immunotherapy. PMID:23042770

Frick, Stefanie U; Bacher, Nicole; Baier, Grit; Mailänder, Volker; Landfester, Katharina; Steinbrink, Kerstin

2012-12-01

281

Comparative Cytotoxic Evaluation of Free and Sodium Alginate Nanoparticle-Encapsulated ICD-85 on Primary Lamb Kidney Cells  

PubMed Central

Background Current anti-cancer drug therapy results in systemic side effects due to non-specific uptake by normal healthy noncancerous tissues. To alleviate this difficulty, many attempts have been devoted to the development of new delivery systems such as polymeric Nanoparticles (NPs). In this study, we prepared ICD-85 NPs based on sodium alginate and analyzed the cytotoxic activity of ICD-85 NPs relative to free ICD-85 on primary lamb kidney cells. Methods ICD-85 loaded sodium alginate nanoparticles were prepared by ionic gelation method and were characterized by the particle size, size distribution and Fourier Transform Infrared (FT-IR) spectroscopy. The in vitro cytotoxicity was evaluated by MTT assay and membrane integrity was evaluated by measuring Lactate Dehydrogenase (LDH) activity. The morphological alterations of untreated and treated cells were assessed by light inverted microscope. Results MTT assay showed that ICD-85 NPs could significantly decrease the in vitro cytotoxicity on primary lamb kidney cells compared to the free ICD-85. The IC10 value at 72 hours was increased from 9±2.7 ?g/ml for free ICD-85 to 52±4.3 ?g/ml for ICD-85 NPs. LDH assay demonstrated that free ICD-85 had dose-dependent cytotoxicity on primary lamb kidney cells while ICD-85 NPs exhibited significantly decreased cytotoxicity at equivalent concentrations. Moreover, morphological analysis showed no significant difference between control and treated cells with ICD-85 NPs. Conclusion Based on the results obtained in the present study it can be concluded that encapsulation of ICD-85 with sodium alginate nanoparticles can reduce its necrotic effect on primary lamb kidney cells.

Zare Mirakabadi, Abbas; Moradhaseli, Saeed

2013-01-01

282

Invasive breast carcinoma cells from patients exhibit MenaINV- and macrophage-dependent transendothelial migration.  

PubMed

Metastasis is a complex, multistep process of cancer progression that has few treatment options. A critical event is the invasion of cancer cells into blood vessels (intravasation), through which cancer cells disseminate to distant organs. Breast cancer cells with increased abundance of Mena [an epidermal growth factor (EGF)-responsive cell migration protein] are present with macrophages at sites of intravasation, called TMEM sites (for tumor microenvironment of metastasis), in patient tumor samples. Furthermore, the density of these intravasation sites correlates with metastatic risk in patients. We found that intravasation of breast cancer cells may be prevented by blocking the signaling between cancer cells and macrophages. We obtained invasive breast ductal carcinoma cells of various subtypes by fine-needle aspiration (FNA) biopsies from patients and found that, in an in vitro transendothelial migration assay, cells that migrated through a layer of human endothelial cells were enriched for the transcript encoding Mena(INV), an invasive isoform of Mena. This enhanced transendothelial migration required macrophages and occurred with all of the breast cancer subtypes. Using mouse macrophages and the human cancer cells from the FNAs, we identified paracrine and autocrine activation of colony-stimulating factor-1 receptor (CSF-1R). The paracrine or autocrine nature of the signal depended on the breast cancer cell subtype. Knocking down Mena(INV) or adding an antibody that blocks CSF-1R function prevented transendothelial migration. Our findings indicate that Mena(INV) and TMEM frequency are correlated prognostic markers and CSF-1 and Mena(INV) may be therapeutic targets to prevent metastasis of multiple breast cancer subtypes. PMID:25429076

Pignatelli, Jeanine; Goswami, Sumanta; Jones, Joan G; Rohan, Thomas E; Pieri, Evan; Chen, Xiaoming; Adler, Esther; Cox, Dianne; Maleki, Sara; Bresnick, Anne; Gertler, Frank B; Condeelis, John S; Oktay, Maja H

2014-01-01

283

Human adipose tissue-derived stem cells exhibit proliferation potential and spontaneous rhythmic contraction after fusion with neonatal rat cardiomyocytes  

PubMed Central

Various types of stem cells have been shown to have beneficial effects on cardiac function. It is still debated whether fusion of injected stem cells with local resident cardiomyocytes is one of the mechanisms. To better understand the role of fusion in stem cell-based myocardial regeneration, the present study was designed to investigate the fate of human adipose tissue-derived stem cells (hASCs) fused with neonatal rat cardiomyocytes in vitro. hASCs labeled with the green fluorescent probe Vybrant DiO were cocultured with neonatal rat cardiomyocytes labeled with the red fluorescent probe Vybrant DiI and then treated with fusion-inducing hemagglutinating virus of Japan (HVJ). Cells that incorporated both red and green fluorescent signals were considered to be hASCs that had fused with rat cardiomyocytes. Fusion efficiency was 19.86 ± 4.84% at 5 d after treatment with HVJ. Most fused cells displayed cardiomyocyte-like morphology and exhibited spontaneous rhythmic contraction. Both immunofluorescence staining and lentiviral vector labeling showed that fused cells contained separate rat cardiomyocyte and hASC nuclei. Immunofluorescence staining assays demonstrated that human nuclei in fused cells still expressed the proliferation marker Ki67. In addition, hASCs fused with rat cardiomyocytes were positive for troponin I. Whole-cell voltage-clamp analysis demonstrated action potentials in beating fused cells. RT-PCR analysis using rat- or human-specific myosin heavy chain primers revealed that the myosin heavy-chain expression in fused cells was derived from rat cardiomyocytes. Real-time PCR identified expression of human troponin T in fused cells and the presence of rat cardiomyocytes induced a cardiomyogenic protein expression of troponin T in human ASCs. This study illustrates that hASCs exhibit both stem cell (proliferation) and cardiomyocyte properties (action potential and spontaneous rhythmic beating) after fusion with rat cardiomyocytes, supporting the theory that fusion, even if artificially induced in our study, could indeed be a mechanism for cardiomyocyte renewal in the heart.—Metzele, R., Alt, C., Bai, X., Yan, Y., Zhang, Z., Pan, Z., Coleman, M., Vykoukal, J., Song, Y.-H., Alt, E. Human adipose tissue-derived stem cells exhibit proliferation potential and spontaneous rhythmic contraction after fusion with neonatal rat cardiomyocytes. PMID:21059751

Metzele, Roxana; Alt, Christopher; Bai, Xiaowen; Yan, Yasheng; Zhang, Zhi; Pan, Zhizhong; Coleman, Michael; Vykoukal, Jody; Song, Yao-Hua; Alt, Eckhard

2011-01-01

284

In vitro acoustic molecular imaging of tissue factor expressed by smooth muscle cells with stable liquid perfluorocarbon nanoparticle contrast agents  

Microsoft Academic Search

Liquid perfluorocarbon nanoparticle contrast agents can be used to target specific tissue types through incorporation of appropriate ligands into the nanoparticles' outer lipid monolayer. In this study we sought to characterize the specificity of targeting of perfluorooctyl bromide (PFOB) nanoparticles to tissue factor, a transmembrane glycoprotein expressed by smooth muscle cells as part of inflammatory response after vessel injury (e.g.,

Jon N. Marsh; Kathryn C. Crowder; Michael S. Hughes; Michael J. Scott; Elizabeth K. Lacy; Gregory M. Lanza; Samuel A. Wickline

2004-01-01

285

Highly specific and ultrasensitive graphene-enhanced electrochemical detection of low-abundance tumor cells using silica nanoparticles coated with antibody-conjugated quantum dots.  

PubMed

A dual signal amplification immunosensing strategy that offers high sensitivity and specificity for the detection of low-abundance tumor cells was designed. High sensitivity was achieved by using graphene to modify the immunosensor surface to accelerate electron transfer and quantum dot (QD)-coated silica nanoparticles as tracing tags. High specificity was further obtained by the simultaneous measurement of two disease-specific biomarkers on the cell surface using different QD-coated silica nanoparticle tracers. The immunosensor was constructed by covalently immobilized capture antibodies on a chitosan/electrochemically reduced graphene oxide film-modified glass carbon electrode. Cells were captured with a sandwich-type immunoreaction and the different QD-coated silica nanoparticle tracers were captured on the surface of the cells. Each biorecognition event yields a distinct voltammetric peak, which position and size reflects the corresponding identity and amount of the respective antigen. This strategy was vividly demonstrated by the simultaneous immunoassay of EpCAM and GPC3 antigens on the surface of the human liver cancer cell line Hep3B using anti-EpCAM-CdTe- and anti-GPC3-ZnSe-coated silica nanoparticle tracers. The two tracers gave comparable sensitivity, and the immunosensor exhibited high sensitivity and specificity with excellent stability, reproducibility, and accuracy, indicating its wide range of potential applications in clinical and molecular diagnostics. PMID:23402311

Wu, Yafeng; Xue, Peng; Kang, Yuejun; Hui, Kam M

2013-03-19

286

Targeting of peptide conjugated magnetic nanoparticles to urokinase plasminogen activator receptor (uPAR) expressing cells  

NASA Astrophysics Data System (ADS)

Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific targeting peptide onto polyethylene glycol (PEG) coated USPIO nanoparticles by click chemistry resulted in a five times higher uptake in vitro in a uPAR positive cell line compared to nanoparticles carrying a non-binding control peptide. In accordance with specific receptor-mediated recognition, a low uptake was observed in the presence of an excess of ATF, a natural ligand for uPAR. The uPAR specific magnetic nanoparticles can potentially provide a useful supplement for tumor patient management when combined with MRI and drug delivery.Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific targeting peptide onto polyethylene glycol (PEG) coated USPIO nanoparticles by click chemistry resulted in a five times higher uptake in vitro in a uPAR positive cell line compared to nanoparticles carrying a non-binding control peptide. In accordance with specific receptor-mediated recognition, a low uptake was observed in the presence of an excess of ATF, a natural ligand for uPAR. The uPAR specific magnetic nanoparticles can potentially provide a useful supplement for tumor patient management when combined with MRI and drug delivery. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr32922d

Hansen, Line; Unmack Larsen, Esben Kjær; Nielsen, Erik Holm; Iversen, Frank; Liu, Zhuo; Thomsen, Karen; Pedersen, Michael; Skrydstrup, Troels; Nielsen, Niels Chr.; Ploug, Michael; Kjems, Jørgen

2013-08-01

287

Nanoparticle-Mediated IgE-Receptor Aggregation and Signaling in RBL Mast Cells  

E-print Network

Nanoparticle-Mediated IgE-Receptor Aggregation and Signaling in RBL Mast Cells Yu-Fen Huang by the formation of cross-links among multiple receptor-ligand bonds. The activation of mast cells provides mast cell line is the most widely used and convenient model system for the study of regulated secretion

Tan, Weihong

288

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

NASA Astrophysics Data System (ADS)

The internalization and biocompatibility of iron oxide nanoparticles surface functionalized with four differently charged carbohydrates have been tested in the human cervical carcinoma cell line (HeLa). Neutral, positive, and negative iron oxide nanoparticles were obtained by coating with dextran, aminodextran, heparin, and dimercaptosuccinic acid, resulting in colloidal suspensions stable at pH 7 with similar aggregate size. No intracellular uptake was detected in cells incubated with neutral charged nanoparticles, while negative particles showed different behaviour depending on the nature of the coating. Thus, dimercaptosuccinic-coated nanoparticles showed low cellular uptake with non-toxic effects, while heparin-coated particles showed cellular uptake only at high nanoparticle concentrations and induced abnormal mitotic spindle configurations. Finally, cationic magnetic nanoparticles show excellent properties for possible in vivo biomedical applications such as cell tracking by magnetic resonance imaging (MRI) and cancer treatment by hyperthermia: (i) they enter into cells with high effectiveness, and are localized in endosomes; (ii) they can be easily detected inside cells by optical microscopy, (iii) they are retained for relatively long periods of time, and (iv) they do not induce any cytotoxicity.

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

2009-03-01

289

Effects of titanium nanoparticles on adhesion, migration, proliferation, and differentiation of mesenchymal stem cells  

PubMed Central

Background The purpose of this study was to investigate the influences of nanoscale wear particles derived from titanium/titanium alloy-based implants on integration of bone. Here we report the potential impact of titanium oxide (TiO2) nanoparticles on adhesion, migration, proliferation, and differentiation of mesenchymal stem cells (MSC) from the cellular level to the molecular level in the Wistar rat. Methods A series of TiO2 nanoparticles (14 nm, 108 nm, and 196 nm) were synthesized and characterized by scanning electron microscopy and transmission electron microscopy, respectively. Results The TiO2 nanoparticles had negative effects on cell viability, proliferation, and the cell cycle of MSC in a dose-dependent and size-dependent manner. Confocal laser scanning microscopy was used to investigate the effects of particle internalization on adhesion, spreading, and morphology of MSC. The integrity of the cell membrane, cytoskeleton, and vinculin of MSC were negatively influenced by large TiO2 nanoparticles. Conclusion The Transwell migration assay and a wound healing model suggested that TiO2 nanoparticles had a strong adverse impact on cell migration as particle size increased (P < 0.01). Furthermore, alkaline phosphatase, gene expression of osteocalcin (OC) and osteopontin (OPN), and mineralization measurements indicate that the size of the TiO2 nanoparticles negatively affected osteogenic differentiation of MSC. PMID:24101871

Hou, Yanhua; Cai, Kaiyong; Li, Jinghua; Chen, Xiuyong; Lai, Min; Hu, Yan; Luo, Zhong; Ding, Xingwei; Xu, Dawei

2013-01-01

290

Synthesis, characterization, cell imaging and anti-tumor activity of multifunctional nanoparticles  

NASA Astrophysics Data System (ADS)

Most anticancer complexes are unable to differentiate between diseased and healthy cells, systemic toxicity and undesired side effects can result. In the current study, a PEG and RGD peptides functionalized fluorescent dye Rhodamine B isothiocyanate (RBITC) doped magnetic silica nanoparticle (MnFe3O4@SiO2-PEG-RGD), carrying a anticancer superparamagnetic Mn(II) complex, was synthesized and characterized using spectroscopic methods. The multifunctional nanoparticles (MnFe3O4@SiO2-PEG-RGD) can image HepG-2 cells and differentiate between HepG-2 and WRL-68 cells based on T1 MR imaging technology. The in vitro fluorescence image and inhibition assay on the proliferation of HeLa cells indicate that MnFe3O4@SiO2-PEG-RGD nanoparticles can effectively reach the tumor site, be internalized by endocytosis and then retain in cancer cells due to the retention effect of nanoparticles. This study demonstrated that a PEG and RGD peptides functionalized silica nanoparticle was a good carrier for the anticancer complexes, and the anticancer complexes loaded multifunctional nanoparticles could be developed as special agents in monitoring therapy of cancer.

Chen, Qiu-Yun; Tao, Gen-Ping; Liu, Ying-Qi; Yang, Xia

2012-10-01

291

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

292

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

PubMed Central

Survivin orchestrates intracellular pathways during cell division and apoptosis. Its central function as mitotic regulator and inhibitor of cell death has major implications for tumor cell proliferation. Analyses in early-branching Metazoa so far propose an exclusive role of survivin as a chromosomal passenger protein, whereas only later during evolution a complementary antiapoptotic function might have arisen, concurrent with increased organismal complexity. To lift the veil on the ancestral function(s) of this key regulator, a survivin-like protein (SURVL) of one of the earliest-branching metazoan taxa was identified and functionally characterized. SURVL of the sponge Suberites domuncula shares considerable similarities with its metazoan homologs, ranging from conserved exon/intron structure to presence of protein-interaction domains. Whereas sponge tissue shows a low steady-state level, SURVL expression was significantly upregulated in rapidly proliferating primmorph cells. In addition, challenge of tissue and primmorphs with heavy metal or lipopeptide stimulated SURVL expression, concurrent with the expression of a newly discovered caspase. Complementary functional analyses in transfected HEK-293 cells revealed that heterologous expression of a SURVL–EFGP fusion not only promotes proliferation but also enhances resistance to cadmium-induced cell death. Taken together, these results suggest both a deep evolutionary conserved dual role of survivin and an equally conserved central position in the interconnected pathways of cell cycle and apoptosis. PMID:20651742

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

2011-01-01

293

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

PubMed Central

Although there have been numerous reports describing the isolation of liver progenitor cells from adult liver, their exact origin has not been clearly defined; and the role played by mature hepatocytes as direct contributors to the hepatic progenitor cell pool has remained largely unknown. Here we report strong evidence that mature hepatocytes in culture have the capacity to dedifferentiate into a population of adult liver progenitors without genetic or epigenetic manipulations. By using highly-purified mature hepatocytes, which were obtained from untreated, healthy rat liver and labeled with fluorescent dye PKH2, we found that hepatocytes in culture gave rise to a population of PKH2-positive liver progenitor cells. These cells, Liver Derived Progenitor Cells or LDPCS, which share phenotypic similarities with oval cells, were previously reported to be capable of forming mature hepatocytes both in culture and in animals. Studies done at various time points during the course of dedifferentiation cultures revealed that hepatocytes rapidly transformed into liver progenitors within one week through a transient oval cell-like stage. This finding was supported by lineage-tracing studies involving double-transgenic AlbuminCreXRosa26 mice expressing ?-galactosidase exclusively in hepatocytes. Cultures set up with hepatocytes obtained from these mice resulted in generation of ?-galactosidase-positive liver progenitor cells demonstrating that they were a direct dedifferentiation product of mature hepatocytes. Additionally, these progenitors differentiated into hepatocytes in vivo when transplanted into rats that had undergone retrorsine pretreatment and partial hepatectomy. Conclusion Our studies provide strong evidence for the unexpected plasticity of mature hepatocytes to dedifferentiate into progenitor cells in culture; and this may potentially have a significant impact on the treatment of liver diseases requiring liver or hepatocyte transplantation. PMID:21953633

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

2011-01-01

294

Trisomy 12 chronic lymphocytic leukemia cells exhibit upregulation of integrin signaling that is modulated by NOTCH1 mutations.  

PubMed

The leukocyte adhesion cascade is important in chronic lymphocytic leukemia (CLL), as it controls migration of malignant cells into the pro-survival lymph node microenvironment. Circulating trisomy 12 CLL cells have increased expression of the integrins CD11a and CD49d, as well as CD38, but the tissue expression of these and other molecules, and the functional and clinical sequelae of these changes have not been described. Here, we demonstrate that circulating trisomy 12 CLL cells also have increased expression of the integrins CD11b, CD18, CD29, and ITGB7, and the adhesion molecule CD323. Notably, there was reduced expression of CD11a, CD11b, and CD18 in trisomy 12 cases with NOTCH1 mutations compared with wild type. Trisomy 12 cells also exhibit upregulation of intracellular integrin signaling molecules CALDAG-GEFI, RAP1B, and Ras-related protein ligand, resulting in enhanced very late antigen-4 [VLA-4] directed adhesion and motility. CD38 expression in CLL has prognostic significance, but the increased CD38 expression in trisomy 12 CLL cells must be taken into account in this subgroup, and the threshold of CD38 positivity should be raised to 40% for this marker to retain its prognostic value. In conclusion, trisomy 12 CLL cells exhibit functional upregulation of integrin signaling, with ?2-integrin expression being modulated by NOTCH1 mutation status. PMID:24829201

Riches, John C; O'Donovan, Conor J; Kingdon, Sarah J; McClanahan, Fabienne; Clear, Andrew J; Neuberg, Donna S; Werner, Lillian; Croce, Carlo M; Ramsay, Alan G; Rassenti, Laura Z; Kipps, Thomas J; Gribben, John G

2014-06-26

295

Aneuploid yeast strains exhibit defects in cell growth and passage through START  

E-print Network

Aneuploidy, a chromosome content that is not a multiple of the haploid karyotype, is associated with reduced fitness in all organisms analyzed to date. In budding yeast aneuploidy causes cell proliferation defects, with ...

Thorburn, Rebecca Ruth

296

Detection of circulating tumor cells using targeted surface-enhanced Raman scattering nanoparticles and magnetic enrichment  

NASA Astrophysics Data System (ADS)

While more than 90% of cancer deaths are due to metastases, our ability to detect circulating tumor cells (CTCs) is limited by low numbers of these cells in the blood and factors confounding specificity of detection. We propose a magnetic enrichment and detection technique for detecting CTCs with high specificity. We targeted both magnetic and surface-enhanced Raman scattering (SERS) nanoparticles to cancer cells. Only cells that are dual-labeled with both kinds of nanoparticles demonstrate an increasing SERS signal over time due to magnetic trapping.

Shi, Wei; Paproski, Robert J.; Moore, Ronald; Zemp, Roger

2014-05-01

297

Asymmetric Freedericksz transitions from symmetric liquid crystal cells doped with harvested ferroelectric nanoparticles.  

PubMed

The electrical Freedericksz transition characteristics of planar aligned liquid crystal cells doped with harvested single ferroelectric domain 9 nm nanoparticles of BaTiO(3) have been measured. We demonstrate for the first time that the electrical pre-history of the cells imparts significant polarity sensitivity to the Freedericksz characteristics. The presence of harvested single domain ferroelectric nanoparticles enables cells to be programmably semi-permanently polarized. This reduces or increases the Freedericksz transition threshold by 0.8 V, depending on the polarity of the applied voltage, giving a net 1.6 V Freedericksz threshold asymmetry for 8 mum thick cells filled with TL205 liquid crystal. PMID:20721121

Cook, G; Reshetnyak, V Yu; Ziolo, R F; Basun, S A; Banerjee, P P; Evans, D R

2010-08-01

298

Synthesis of Biomolecule-Modified Mesoporous Silica Nanoparticles for Targeted Hydrophobic Drug Delivery to Cancer Cells  

PubMed Central

Synthetic methodologies integrating hydrophobic drug delivery and biomolecular targeting with mesoporous silica nanoparticles are described. Transferrin and cyclic-RGD peptides are covalently attached to the nanoparticles utilizing different techniques and provide selectivity between primary and metastatic cancer cells. The increase in cellular uptake of the targeted particles is examined using fluorescence microscopy and flow cytometry. Transferrin-modified silica nanoparticles display enhancement in particle uptake by Panc-1 cancer cells over that of normal HFF cells. The endocytotic pathway for these particles is further investigated through plasmid transfection of the transferrin receptor into the normal HFF cell line, which results in an increase in particle endocytosis as compared to unmodified HFF cells. By designing and attaching a synthetic cyclic-RGD, selectivity between primary cancer cells (BT-549) and metastatic cancer cells (MDA-MB 435) is achieved with enhanced particle uptake by the metastatic cancer cell line. Incorporation of the hydrophobic drug Camptothecin into these two types of biomolecular-targeted nanoparticles causes an increase in mortality of the targeted cancer cells compared to that caused by both the free drug and nontargeted particles. These results demonstrate successful biomolecular-targeted hydrophobic drug delivery carriers that selectively target specific cancer cells and result in enhanced drug delivery and cell mortality. PMID:21595023

Ferris, Daniel P.; Lu, Jie; Gothard, Chris; Yanes, Rolando; Thomas, Courtney R.; Olsen, John-Carl; Stoddart, J. Fraser; Tamanoi, Fuyuhiko; Zink, Jeffrey I.

2011-01-01

299

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

300

3D Graphene Oxide-encapsulated Gold Nanoparticles to Detect Neural Stem Cell Differentiation  

PubMed Central

Monitoring of stem cell differentiation and pluripotency is an important step for the practical use of stem cells in the field of regenerative medicine. Hence, a new non-destructive detection tool capable of in situ monitoring of stem cell differentiation is highly needed. In this study, we report a 3D graphene oxide-encapsulated gold nanoparticle that is very effective for the detection of the differentiation potential of neural stem cells (NSCs) based on surface-enhanced Raman spectroscopy (SERS). A new material, 3D GO-encapsulated gold nanoparticle, is developed to induce the double enhancement effect of graphene oxide and gold nanoparticle on SERS signals which is only effective for undifferentiated NSCs. The Raman peaks achieved from undifferentiated NSCs on the graphene oxide (GO)-encapsulated gold nanoparticles were 3.5 times higher than peaks obtained from normal metal structures and were clearly distinguishable from those of differentiated cells. The number of C=C bonds and the raman instensity at 1656cm?1 was found to show a positive correlation, which matches the differentiation state of the NSCs. Moreover, the substrate composed of 3D GO-encapsulated gold nanoparticles was also effective at distinguishing the differentiation state of single NSC by using electrochemical and electrical techniques. Hence, the proposed technique can be used as a powerful non-destructive in situ monitoring tool for the identification of the differentiation potential of various kinds of stem cells (mesenchymal, hematopoietic, and neural stem cells). PMID:23937915

Kim, Tae-Hyung; Lee, Ki-Bum; Choi, Jeong-Woo

2013-01-01

301

Multi-ligand poly(L-lactic-co-glycolic acid) nanoparticles inhibit activation of endothelial cells.  

PubMed

Endothelial cell (EC) activation and inflammation is a key step in the initiation and progression of many cardiovascular diseases. Targeted delivery of therapeutic reagents to inflamed EC using nanoparticles is challenging as nanoparticles do not arrest on EC efficiently under high shear stress. In this study, we developed a novel polymeric platelet-mimicking nanoparticle for strong particle adhesion onto ECs and enhanced particle internalization by ECs. This nanoparticle was encapsulated with dexamethasone as the anti-inflammatory drug, and conjugated with polyethylene glycol, glycoprotein 1b, and trans-activating transcriptional peptide. The multi-ligand nanoparticle showed significantly greater adhesion on P-selectin, von Willebrand Factor, than the unmodified particles, and activated EC in vitro under both static and flow conditions. Treatment of injured rat carotid arteries with these multi-ligand nanoparticles suppressed neointimal stenosis more than unconjugated nanoparticles did. These results indicate that this novel multi-ligand nanoparticle is efficient to target inflamed EC and inhibit inflammation and subsequent stenosis. PMID:23640308

Xu, Hao; Kona, Soujanya; Su, Lee-Chun; Tsai, Yi-Ting; Dong, Jing-Fei; Brilakis, Emmanouil S; Tang, Liping; Banerjee, Subhash; Nguyen, Kytai T

2013-08-01

302

Molecular-scale interface engineering of metal nanoparticles for plasmon-enhanced dye sensitized solar cells.  

PubMed

A molecular surface chemical treatment is introduced into a dye sensitized solar cell (DSSC) incorporating metal nanoparticles to suppress the charge recombination. Dodecanethiol molecules as a surface treatment agent are successfully anchored onto the exposed Au nanoparticle sites of the ZnO nanorods/Au nanoparticles/N719 photoanode. ATR-FTIR and Raman measurements are conducted to understand the adsorptions of different molecules (dodecanethiol, N719) on the ZnO nanorods and Au nanoparticles surface. The effects of the dodecanethiol surface treatment on the performance of the plasmon-enhanced DSSC are investigated by UV-vis absorption, incident photon-to-current conversion efficiency (IPCE) and electrochemical impedance spectroscopy (EIS). The plasmon-enhanced light absorption due to the presence of Au nanoparticles is not affected by the dodecanethiol surface treatment. The charge recombination on the ZnO nanorods-dye-electrolyte interface is substantially retarded by insulating the exposed Au nanoparticle sites from the oxidized form of the electrolyte via dodecanethiol molecules. The strategy of a molecular surface chemical treatment on the photoanode of a DSSC with metal nanoparticles fully exploits the plasmon-enhanced light absorption and explores a simple method to protect the metal nanoparticles for the plasmon-enhanced DSSC. PMID:23407603

Lou, Yanyan; Yuan, Shuai; Zhao, Yin; Hu, Pengfei; Wang, Zhuyi; Zhang, Meihong; Shi, Liyi; Li, Dongdong

2013-04-21

303

Proteomic study of human bronchial epithelial cells exposed to SiC nanoparticles  

NASA Astrophysics Data System (ADS)

The presented work proposes an optimized methodology for the study of cell exposure to nanomaterials at protein level. The study was investigated on proteins extracted from human bronchial epithelial cells exposed and non-exposed to silicon carbide nanoparticles (SiC). The analytical strategy was based on high resolution measurement using Fourier transform mass spectrometer 9.4 T. The methodology proposed succeeds in identifying over 300 proteins; most of the identified proteins are present in both exposed and non exposed cells to SiC nanoparticles. More interestingly, cytokines as Macrophage migration inhibitory factor protein could be identified only in the cells exposed to SiC nanoparticles indicating cell inflammatory response.

Tokarski, Caroline; Hirano, Seishiro; Rolando, Christian

2011-07-01

304

Multifunctional superparamagnetic fe3O4@SiO2 core/shell nanoparticles: design and application for cell imaging.  

PubMed

Highly biocompatible sub-50-nm monodisperse superparamagnetic Fe3O4@SiO2 core/shell nanoparticles with luminescent silica shells were synthesized by a w/o-microemulsion technique. And then these nanoparticles were coated with the covalently bonded biocompatible polymer poly(ethylene glycol) (PEG) and modified with the biological cancer targeting ligand folic acid (FA). After characterized by means of powder X-ray diffraction (XRD), transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transformed infrared spectroscopy (FT-IR), Thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), UV-vis, fluorescence spectroscopy and confocal laser scanning microscopy (CLSM), we confirmed that Fe3O4@SiO2 (FITC)-PEG-FA nanocomposites (SMNPs-FA) could be efficiently taken up by HeLa cancer cells and KB cells which are of over-expression of folate receptors. The multifunctional nanomaterials exhibited superparamagnetic, monodisperse, highly biocompatible, intensively fluorescent and capable of recognizing and binding cells that overexpress folate receptors, which would be useful for targeting cell imaging and provide an excellent platform for further development of an efficient cancer therapy. PMID:24738334

Zhao, Xueling; Zhao, Hongli; Yuan, Huihui; Lan, Minbo

2014-02-01

305

Metabolic profiling reveals disorder of carbohydrate metabolism in mouse fibroblast cells induced by titanium dioxide nanoparticles.  

PubMed

As titanium dioxide (TiO(2)) nanoparticles are widely used commercially, their potential biosafety and metabolic mechanism needs to be fully explained. In this study, the cytotoxicity of homogeneous and weakly aggregated (< 100?nm) TiO(2) nanoparticles was investigated by analyzing the changes in metabolite profiles both in mouse fibroblast (L929) cells and their corresponding culture media using gas chromatograph with a time-of-flight mass spectrometry (GC/TOFMS)-based metabolomic strategy. With multivariate statistics analysis, satisfactory separations were observed in principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models. Based on the variable importance in the OPLS-DA models, a series of differential metabolites were identified by comparison between TiO(2) nanoparticle-treated L929 cells or their corresponding culture media and the control groups. It was found that the major biochemical metabolism (carbohydrate metabolism) was suppressed in TiO(2) nanoparticle-treated L929 cells and their corresponding culture media. These results might account for the serious damage to energy metabolism in mitochondria and the increased cellular oxidation stress in TiO(2) nanoparticle-induced L929 cells. These results also suggest that the metabolomic strategy had a great potential in evaluating the cytotoxicity of TiO(2) nanoparticles and thus was very helpful in understanding its underlying molecular mechanisms. PMID:22996321

Jin, Chengyu; Liu, Yumin; Sun, Limin; Chen, Tianlu; Zhang, Yinan; Zhao, Aihua; Wang, Xiaoyan; Cristau, Melanie; Wang, Kaisheng; Jia, Wei

2013-12-01

306

Visualization of Carbon Nanoparticles Within Cells and Implications for Toxicity  

NASA Astrophysics Data System (ADS)

Carbon nanostructures (CNS), such as C60, single-walled nanotubes (SWNTs) exhibit extraordinary properties and are one of the most commercially relevant class of NS. CNS have already found uses in high-performance sports equipment (nanotubes) and face cream (C60), whilst potential applications include optical and electronic materials and superconductors. Following the huge growth in these nanotechnology-related industries, significant concerns have arisen about their potential toxicity and impact on the environment. A lack in understanding of the interaction of such small structures with cellular material has resulted in concerns over their impact on human health. The potential toxicity of CNS and safety to human health requires an understanding of their interaction with cells and this in turn relies on the measurement of the pathways by which they enter the cell, their spatial distribution within and whether the CNS are transformed by the action of the cell; visualization of intracellular CNS is therefore imperative. However visualizing unlabelled CNS within cells is demanding because it is difficult to distinguish CNS from carbon-rich organelles given their similarity in composition and dimensions. In particular, the challenge lies in translating analytical imaging tools developed for inorganic systems to organic systems. This chapter describes how the state-of-the-art transmission electron microscopy (TEM) techniques, such as low-loss energy-filtered TEM (EFTEM) can be employed to differentiate between unlabelled C60, SWNTs and the cell. Further, we demonstrate how these techniques can be used to trace the uptake of CNS into the cell and to assess their localized effects on cell structure.

Porter, Alexandra; Gass, Mhairi

307

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

NASA Astrophysics Data System (ADS)

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

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

2013-06-01

308

Evaluation of specific delivery of chimeric phi29 pRNA/siRNA nanoparticles to multiple tumor cells  

PubMed Central

The pRNA (packaging RNA) of bacteriophage phi29 DNA packaging motor has been reported to have novel applications in nanotechnology and nanomedicine. The unique ability of pRNA to form dimers, trimers, hexamers and patterned superstructures via the interaction of two reengineered interlocking loops makes it a promising polyvalent vehicle to load siRNA and other therapeutic molecules and be applied as a therapeutic nanoparticle in tumor therapy. In this study, several tumor cell lines were used to evaluate the previously reported pRNA nanotechnology for specific siRNA delivery and for the silencing of targeted genes. It was found that MCF-7 and HeLa cells, out of twenty-five tested tumor cell lines, expressed high levels of folate receptors and exhibited specific binding of the FITC-folate-pRNA nanoparticles, while the others expressed low levels and thus, for these, delivery was not feasible using folate as a targeting agent. Folate receptor positive tumor cells were then incubated with the chimeric pRNA dimer harboring both the folate-pRNA and the chimeric pRNA/siRNA (survivin). Knock down effects of survivin expression in these tumor cells were detected at the mRNA level by real time-PCR and at the protein level by western blot. Apoptosis was detected by flow cytometry analysis with dual staining of annexinV-FITC and PI. The data suggest that the chimeric pRNA nanoparticles containing folate-pRNA and pRNA/siRNA (survivin) could be specifically taken up by tumor cells through folate receptor-mediated endocytosis, resulting in significant inhibition of both transcription and expression of survivin in tumor cells and triggering cell apoptosis. Using such protein-free nanoparticles as therapeutic reagents would not only allow specific gene delivery and extend the in vivo retaining time but also allow long-term administration of therapeutic particles, therefore avoiding the induction of antibodies caused by repeated treatment for chronic diseases. PMID:19823753

Li, Li; Liu, Jing; Diao, Zhijuan; Shu, Dan

2010-01-01

309

Application of magnetic field hyperthermia and superparamagnetic iron oxide nanoparticles to HIV-1-specific T-cell cytotoxicity  

PubMed Central

The latent HIV-1 reservoir remains the major barrier to HIV-1 eradication. Although successful at limiting HIV replication, highly active antiretroviral therapy is unable to cure HIV infection, thus novel therapeutic strategies are needed to eliminate the virus. Magnetic field hyperthermia (MFH) generates thermoablative cytotoxic temperatures in target-cell populations, and has delivered promising outcomes in animal models, as well as in several cancer clinical trials. MFH has been proposed as a strategy to improve the killing of HIV-infected cells and for targeting the HIV latent reservoirs. We wished to determine whether MFH could be used to enhance cytotoxic T-lymphocyte (CTL) targeting of HIV-infected cells in a proof-of-concept study. Here, for the first time, we apply MFH to an infectious disease (HIV-1) using the superparamagnetic iron oxide nanoparticle FeraSpin R. We attempt to improve the cytotoxic potential of T-cell receptor-transfected HIV-specific CTLs using thermotherapy, and assess superparamagnetic iron oxide nanoparticle toxicity, uptake, and effect on cell function using more sensitive methods than previously described. FeraSpin R exhibited only limited toxicity, demonstrated efficient uptake and cell-surface attachment, and only modestly impacted T-cell function. In contrast to the cancer models, insufficient MFH was generated to enhance CTL killing of HIV-infected cells. MFH remains an exciting new technology in the field of cancer therapeutics, which, as technology improves, may have significant potential to enhance CTL function and act as an adjunctive therapy in the eradication of latently infected HIV-positive cells. PMID:23901272

Williams, James P; Southern, Paul; Lissina, Anya; Christian, Helen C; Sewell, Andrew K; Phillips, Rodney; Pankhurst, Quentin; Frater, John

2013-01-01

310

Effect of cerium oxide nanoparticles on inflammation in vascular endothelial cells  

PubMed Central

Because vascular endothelial cell inflammation is critical in the development of cardiovascular pathology, we hypothesized that direct exposure of human aortic endothelial cells (HAECs) to ultrafine particles induces an inflammatory response. To test the hypothesis, we incubated HAECs for 4 h with different concentrations (0.001–50 ?g/ml) of CeO2 nanoparticles and subsequently measured mRNA levels of the three inflammatory markers intercellular adhesion molecule 1 (ICAM-1), interleukin (IL)-8, and monocyte chemotactic protein (MCP-1) using real-time polymerase chain reaction (PCR). Ceria nanoparticles caused very little inflammatory response in HAECs, even at the highest dose. This material is apparently rather benign in comparison with Y2O3 and ZnO nanoparticles that we have studied previously. These results suggest that inflammation in HAECs following acute exposure to metal oxide nanoparticles depends strongly on particle composition. PMID:19558244

Gojova, Andrea; Lee, Jun-Tae; Jung, Heejung S.; Guo, Bing; Barakat, Abdul I.; Kennedy, Ian M.

2010-01-01

311

Interaction force measurement between E. coli cells and nanoparticles immobilized surfaces by using AFM  

SciTech Connect

To better understand environmental behaviors of nanoparticles (NPs), we used the atomic force microscopy (AFM) to measure interaction forces between E. coli cells and NPs immobilized on surfaces in an aqueous environment. The results showed that adhesion force strength was significantly influenced by particle size for both hematite ( -Fe2 O3 ) and corundum ( -Al2 O3 ) NPs whereas the effect on the repulsive force was not observed. The adhesion force decreased from 6.3 0.7 nN to 0.8 0.4 nN as hematite NPs increased from 26 nm to 98 nm in diameter. Corundum NPs exhibited a similar dependence of adhesion force on particle size. The Johnson Kendall Roberts (JKR) model was employed to estimate the contact area between E. coli cells and NPs, and based on the JKR model a new model that considers local effective contact area was developed. The prediction of the new model matched the size dependence of adhesion force in experimental results. Size effects on adhesion forces may originate from the difference in local effective contact areas as supported by our model. These findings provide fundamental information for interpreting the environmental behaviors and biological interactions of NPs, which barely have been addressed.

Zhang, Wen [Georgia Institute of Technology; Chen, Yongsheng [Georgia Institute of Technology

2011-01-01

312

nanoparticles  

NASA Astrophysics Data System (ADS)

Thermal energy storage (TES) is extremely important in concentrated solar power (CSP) plants since it represents the main difference and advantage of CSP plants with respect to other renewable energy sources such as wind, photovoltaic, etc. CSP represents a low-carbon emission renewable source of energy, and TES allows CSP plants to have energy availability and dispatchability using available industrial technologies. Molten salts are used in CSP plants as a TES material because of their high operational temperature and stability of up to 500°C. Their main drawbacks are their relative poor thermal properties and energy storage density. A simple cost-effective way to improve thermal properties of fluids is to dope them with nanoparticles, thus obtaining the so-called salt-based nanofluids. In this work, solar salt used in CSP plants (60% NaNO3 + 40% KNO3) was doped with silica nanoparticles at different solid mass concentrations (from 0.5% to 2%). Specific heat was measured by means of differential scanning calorimetry (DSC). A maximum increase of 25.03% was found at an optimal concentration of 1 wt.% of nanoparticles. The size distribution of nanoparticle clusters present in the salt at each concentration was evaluated by means of scanning electron microscopy (SEM) and image processing, as well as by means of dynamic light scattering (DLS). The cluster size and the specific surface available depended on the solid content, and a relationship between the specific heat increment and the available particle surface area was obtained. It was proved that the mechanism involved in the specific heat increment is based on a surface phenomenon. Stability of samples was tested for several thermal cycles and thermogravimetric analysis at high temperature was carried out, the samples being stable.

Andreu-Cabedo, Patricia; Mondragon, Rosa; Hernandez, Leonor; Martinez-Cuenca, Raul; Cabedo, Luis; Julia, J. Enrique

2014-10-01

313

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

E-print Network

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 level of activated caspase-3 were both significantly greater in ECCM than in ECUM . These data suggest

Arnold, Jonathan

314

Cytotoxicity of peptide-coated silver nanoparticles on the human intestinal cell line Caco-2.  

PubMed

Silver nanoparticles are used in a wide range of consumer products such as clothing, cosmetics, household goods, articles of daily use and pesticides. Moreover, the use of a nanoscaled silver hydrosol has been requested in the European Union for even nutritional purposes. However, despite the wide applications of silver nanoparticles, there is a lack of information concerning their impact on human health. In order to investigate the effects of silver nanoparticles on human intestinal cells, we used the Caco-2 cell line and peptide-coated silver nanoparticles with defined colloidal, structural and interfacial properties. The particles display core diameter of 20 and 40 nm and were coated with the small peptide L-cysteine L-lysine L-lysine. Cell viability and proliferation were measured using Promegas CellTiter-Blue® Cell Viability assay, DAPI staining and impedance measurements. Apoptosis was determined by Annexin-V/7AAD staining and FACS analysis, membrane damage with Promegas LDH assay and reactive oxygen species by dichlorofluorescein assay. Exposure of proliferating Caco-2 cells to silver nanoparticle induced decreasing adherence capacity and cytotoxicity, whereby the formation of reactive oxygen species could be the mode of action. The effects were dependent on particle size (20, 40 nm), doses (5-100 ?g/mL) and time of incubation (4-48 h). Apoptosis or membrane damage was not detected. PMID:22418598

Böhmert, Linda; Niemann, Birgit; Thünemann, Andreas F; Lampen, Alfonso

2012-07-01

315

Study the cytotoxicity of different kinds of water-soluble nanoparticles in human osteoblast-like MG-63 cells  

SciTech Connect

Highlights: ? Preparation of three kinds of water-soluble QDs: CdTe, CdTe@SiO{sub 2}, Mn:ZnSe. ? Evaluated the cytotoxicity qualitatively and quantitatively. ? Fluorescent staining. ? Detected the total intracellular cadmium in cells. -- Abstract: Quantum nanoparticles have been applied extensively in biological and medical fields, the cytotoxicity of nanoparticles becomes the key point we should concern. In this paper, the cytotoxicity of three kinds of water-soluble nanoparticles: CdTe, CdTe@SiO{sub 2} and Mn:ZnSe was studied. We evaluated the nanoparticles toxicity qualitatively by observing the morphological changes of human osteoblast-like MG-63 cells at different incubation times and colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays were carried out to detect the cell viability quantitatively. The results showed that CdTe nanoparticles with high concentrations caused cells to die largely while CdTe@SiO{sub 2} and Mn:ZnSe nanoparticles had no obvious effect. For further study, we studied the relation between the cell viability and the total cadmium concentration in cells and found that the viability of cells treated with CdTe@SiO{sub 2} nanoparticles was higher than that treated with CdTe nanoparticles. We also discovered that the death rate of cells co-incubated with CdTe nanoparticles was proportional to the total intracellular cadmium concentrations.

Niu, Lu [Department of Analytical Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China)] [Department of Analytical Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China); Li, Yang; Li, Xiaojie [Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Centre, Norman Bethune Medical School, Jilin University, Changchun 130012 (China)] [Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Centre, Norman Bethune Medical School, Jilin University, Changchun 130012 (China); Gao, Xue [Department of Analytical Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China)] [Department of Analytical Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China); Su, Xingguang, E-mail: suxg@jlu.edu.cn [Department of Analytical Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China)] [Department of Analytical Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China)

2012-11-15

316

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. PMID:23963610

Passantino, Lisa; Munoz, Alexandra B.

2014-01-01

317

Gold nanoparticles induce nuclear damage in breast cancer cells, which is further amplified by hyperthermia.  

PubMed

Gold nanoparticles have emerged as promising tools for cancer research and therapy, where they can promote thermal killing. The molecular mechanisms underlying these events are not fully understood. The geometry and size of gold nanoparticles can determine the severity of cellular damage. Therefore, small and big gold nanospheres as well as gold nanoflowers were evaluated side-by-side. To obtain quantitative data at the subcellular and molecular level, we assessed how gold nanoparticles, either alone or in combination with mild hyperthermia, altered the physiology of cultured human breast cancer cells. Our analyses focused on the nucleus, because this organelle is essential for cell survival. We showed that all the examined gold nanoparticles associated with nuclei. However, their biological effects were quantitatively different. Thus, depending on the shape and size, gold nanoparticles changed multiple nuclear parameters. They redistributed stress-sensitive regulators of nuclear biology, altered the nuclear morphology, reorganized nuclear laminae and envelopes, and inhibited nucleolar functions. In particular, gold nanoparticles reduced the de novo biosynthesis of RNA in nucleoli, the subnuclear compartments that produce ribosomes. While small gold nanospheres and nanoflowers, but not big gold nanospheres, damaged the nucleus at normal growth temperature, several of these defects were further exacerbated by mild hyperthermia. Taken together, the toxicity of gold nanoparticles correlated with changes in nuclear organization and function. These results emphasize that the cell nucleus is a prominent target for gold nanoparticles of different morphologies. Moreover, we demonstrated that RNA synthesis in nucleoli provides quantitative information on nuclear damage and cancer cell survival. PMID:24740795

Kodiha, Mohamed; Hutter, Eliza; Boridy, Sebastien; Juhas, Michal; Maysinger, Dusica; Stochaj, Ursula

2014-11-01

318

Axonal alignment and enhanced neuronal differentiation of neural stem cells on graphene-nanoparticle hybrid structures.  

PubMed

Human neural stem cells (hNSCs) cultured on graphene-nanoparticle hybrid structures show a unique behavior wherein the axons from the differentiating hNSCs show enhanced growth and alignment. We show that the axonal alignment is primarily due to the presence of graphene and the underlying nanoparticle monolayer causes enhanced neuronal differentiation of the hNSCs, thus having great implications of these hybrid-nanostructures for neuro-regenerative medicine. PMID:23824715

Solanki, Aniruddh; Chueng, Sy-Tsong Dean; Yin, Perry T; Kappera, Rajesh; Chhowalla, Manish; Lee, Ki-Bum

2013-10-11

319

Charge Transport in Dye-Sensitized Solar Cells Based on Flame-made Nanoparticles  

Microsoft Academic Search

The fundamental understanding on charge-transport properties of flame-synthesized in dye-sensitized solar cells (DSSCs) is established in this work. By employing a one-step flame spray pyrolysis (FSP), predominantly anatase TiO2 nanoparticles with average nanoparticle sizes between 11 and 36 nm were achieved by varying the rate of combustion enthalpy (through varying liquid precursor feed flow rates) and using either an “open-flame”

George Tsekouras; Masanori Miyashita; Yung Kent Kho; Wey Yang Teoh; Attila Janos Mozer; Rose Amal; Shogo Mori; Gordon G. Wallace

2010-01-01

320

In vitro toxicity of nanoparticles in BRL 3A rat liver cells  

Microsoft Academic Search

This study was undertaken to address the current deficient knowledge of cellular response to nanosized particle exposure. The study evaluated the acute toxic effects of metal\\/metal oxide nanoparticles proposed for future use in industrial production methods using the in vitro rat liver derived cell line (BRL 3A). Different sizes of nanoparticles such as silver (Ag; 15, 100nm), molybdenum (MoO3; 30,

S. M. Hussain; K. L. Hess; J. M. Gearhart; K. T. Geiss; J. J. Schlager

2005-01-01

321

Carbon supported Ag nanoparticles as high performance cathode catalyst for H2/O2 anion exchange membrane fuel cell  

PubMed Central

A solution phase-based nanocapsule method was successfully developed to synthesize non-platinum metal catalyst—carbon supported Ag nanoparticles (Ag/C). XRD patterns and TEM image show Ag nanoparticles with a small average size (5.4 nm) and narrow size distribution (2–9 nm) are uniformly dispersed on the carbon black Vulcan XC-72 support. The intrinsic activity and pathway of oxygen reduction reaction (ORR) on the Ag/C and commercial Pt/C were investigated using rotating ring disk electrode (RRDE) tests at room temperature. The results confirmed that the 4-electron pathway of ORR proceeds on small Ag nanoparticles, and showed comparable ORR activities on the self-prepared Ag/C and a commercial Pt/C. A single H2-O2 anion exchange membrane fuel cell (AEMFC) with the Ag/C cathode catalyst exhibited an open circuit potential of 0.98 V and a peak power density of 190 mW/cm2 at 80°C. PMID:24790944

Xin, Le; Zhang, Zhiyong; Wang, Zhichao; Qi, Ji; Li, Wenzhen

2013-01-01

322

Silicon nanoparticles: applications in cell biology and medicine  

PubMed Central

In this review, we describe the synthesis, physical properties, surface functionalization, and biological applications of silicon nanoparticles (also known as quantum dots). We compare them against current technologies, such as fluorescent organic dyes and heavy metal chalcogenide-based quantum dots. In particular, we examine the many different methods that can be used to both create and modify these nanoparticles and the advantages they may have over current technologies that have stimulated research into designing silicon nanoparticles for in vitro and in vivo applications. PMID:17722279

O'Farrell, Norah; Houlton, Andrew; Horrocks, Benjamin R

2006-01-01

323

Detection of breast cancer cells using targeted magnetic nanoparticles and ultra-sensitive magnetic field sensors  

PubMed Central

Introduction Breast cancer detection using mammography has improved clinical outcomes for many women, because mammography can detect very small (5 mm) tumors early in the course of the disease. However, mammography fails to detect 10 - 25% of tumors, and the results do not distinguish benign and malignant tumors. Reducing the false positive rate, even by a modest 10%, while improving the sensitivity, will lead to improved screening, and is a desirable and attainable goal. The emerging application of magnetic relaxometry, in particular using superconducting quantum interference device (SQUID) sensors, is fast and potentially more specific than mammography because it is designed to detect tumor-targeted iron oxide magnetic nanoparticles. Furthermore, magnetic relaxometry is theoretically more specific than MRI detection, because only target-bound nanoparticles are detected. Our group is developing antibody-conjugated magnetic nanoparticles targeted to breast cancer cells that can be detected using magnetic relaxometry. Methods To accomplish this, we identified a series of breast cancer cell lines expressing varying levels of the plasma membrane-expressed human epidermal growth factor-like receptor 2 (Her2) by flow cytometry. Anti-Her2 antibody was then conjugated to superparamagnetic iron oxide nanoparticles using the carbodiimide method. Labeled nanoparticles were incubated with breast cancer cell lines and visualized by confocal microscopy, Prussian blue histochemistry, and magnetic relaxometry. Results We demonstrated a time- and antigen concentration-dependent increase in the number of antibody-conjugated nanoparticles bound to cells. Next, anti Her2-conjugated nanoparticles injected into highly Her2-expressing tumor xenograft explants yielded a significantly higher SQUID relaxometry signal relative to unconjugated nanoparticles. Finally, labeled cells introduced into breast phantoms were measured by magnetic relaxometry, and as few as 1 million labeled cells were detected at a distance of 4.5 cm using our early prototype system. Conclusions These results suggest that the antibody-conjugated magnetic nanoparticles are promising reagents to apply to in vivo breast tumor cell detection, and that SQUID-detected magnetic relaxometry is a viable, rapid, and highly sensitive method for in vitro nanoparticle development and eventual in vivo tumor detection. PMID:22035507

2011-01-01

324

Lenses of SPARC-null Mice Exhibit an Abnormal Cell Surface–Basement Membrane Interface  

Microsoft Academic Search

SPARC (secreted protein acidic and rich in cysteine) is a matricellular protein involved in cell–matrix interactions. We have shown previously that mice deficient in SPARC develop posterior cortical cataract early in life that progresses to a mature opacity and capsule rupture. To evaluate the primary effects of SPARC deficiency in the lens, we examined the lenses of SPARC-null and wild-type

Kazumi Norose; Woo-Kuen Lo; John I Clark; E. Helene Sage; Chin C Howe

2000-01-01

325

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. PMID:24885763

2014-01-01

326

Viola tricolor Induces Apoptosis in Cancer Cells and Exhibits Antiangiogenic Activity on Chicken Chorioallantoic Membrane.  

PubMed

In the present study, the cytotoxic and apoptogenic properties of hydroalcoholic extract and ethyl acetate (EtOAc), n-butanol, and water fractions (0-800??g/mL) of Viola tricolor were investigated in Neuro2a mouse neuroblastoma and MCF-7 human breast cancer cells. In addition, antiangiogenic effect of EtOAc fraction was evaluated on chicken chorioallantoic membrane (CAM). The quality of EtOAc fraction was also characterized using high performance liquid chromatography (HPLC) fingerprint. Cytotoxicity assay revealed that EtOAc fraction was the most potent among all fractions with maximal effect on MCF-7 and minimal toxicity against normal murine fibroblast L929 cells. Apoptosis induction by EtOAc fraction was confirmed by increased sub-G1 peak of propidium iodide (PI) stained cells. This fraction triggered the apoptotic pathway by increased Bax/Bcl-2 ratio and cleaved caspase-3 level. Moreover, treatment with EtOAc fraction significantly decreased the diameter of vessels on CAM, while the number of newly formed blood vessels was not suppressed significantly. Analysis of quality of EtOAc fraction using HPLC fingerprint showed six major peaks with different retention times. The results of the present study suggest that V. tricolor has potential anticancer property by inducing apoptosis and inhibiting angiogenesis. PMID:25243166

Sadeghnia, Hamid Reza; Ghorbani Hesari, Taghi; Mortazavian, Seyed Mohsen; Mousavi, Seyed Hadi; Tayarani-Najaran, Zahra; Ghorbani, Ahmad

2014-01-01

327

Iron oxide/hydroxide nanoparticles with negatively charged shells show increased uptake in Caco-2 cells.  

PubMed

The absorption of commonly used ferrous iron salts from intestinal segments at neutral to slightly alkaline pH is low, mainly because soluble ferrous iron is easily oxidized to poorly soluble ferric iron and because ferrous iron, but not ferric iron, is carried by the divalent metal transporter DMT-1. Moreover, ferrous iron frequently causes gastrointestinal side effects. Iron hydroxide nanoparticles with neutral and hydrophilic carbohydrate shells are alternatively used to ferrous salts. In these formulations gastrointestinal side effects are rare because hundreds of ferric iron atoms are safely packed in nanoscaled cores surrounded by the solubilizing shell; nevertheless, iron bioavailability is even worse compared to ferrous salts. In this study the cell uptake of iron hydroxide and iron oxide nanoparticles (FeONP) with negatively charged shells of different chemical types and sizes was compared to the uptake of those with neutral hydrophilic shells, ferrous sulfate and ferric chloride. The nanoparticle uptake was measured in Caco-2 cells with the iron detecting ferrozine method and visualized by transmission electron microscopy. The toxicity was evaluated using the MTT assay. For nanoparticles with a negatively charged shell the iron uptake was about 40 times higher compared to those with neutral hydrophilic carbohydrate shell or ferric chloride and in the same range as ferrous sulfate. However, in contrast to ferrous sulfate, nanoparticles with negatively charged shells showed no toxicity. Two different uptake mechanisms were proposed: diffusion for hydroxide nanoparticles with neutral hydrophilic shell and adsorptive endocytosis for nanoparticles with negatively charged shells. It needs to be determined whether iron hydroxide nanoparticles with negatively charged shells also show improved bioavailability in iron-deficient patients compared to iron hydroxide nanoparticles with a neutral hydrophilic shell, which exist in the market today. PMID:22587679

Jahn, Markus R; Nawroth, Thomas; Fütterer, Sören; Wolfrum, Uwe; Kolb, Ute; Langguth, Peter

2012-06-01

328

Effect of treatment media on the agglomeration of titanium dioxide nanoparticles: impact on genotoxicity, cellular interaction, and cell cycle.  

PubMed

The widespread use of titanium dioxide (TiO2) nanoparticles in consumer products increases the probability of exposure to humans and the environment. Although TiO2 nanoparticles have been shown to induce DNA damage (comet assay) and chromosome damage (micronucleus assay, MN) in vitro, no study has systematically assessed the influence of medium composition on the physicochemical characteristics and genotoxicity of TiO2 nanoparticles. We assessed TiO2 nanoparticle agglomeration, cellular interaction, induction of genotoxicity, and influence on cell cycle in human lung epithelial cells using three different nanoparticle-treatment media: keratinocyte growth medium (KGM) plus 0.1% bovine serum albumin (KB); a synthetic broncheoalveolar lavage fluid containing PBS, 0.6% bovine serum albumin and 0.001% surfactant (DM); or KGM with 10% fetal bovine serum (KF). The comet assay showed that TiO2 nanoparticles induced similar amounts of DNA damage in all three media, independent of the amount of agglomeration, cellular interaction, or cell-cycle changes measured by flow cytometry. In contrast, TiO2 nanoparticles induced MN only in KF, which is the medium that facilitated the lowest amount of agglomeration, the greatest amount of nanoparticle cellular interaction, and the highest population of cells accumulating in S phase. These results with TiO2 nanoparticles in KF demonstrate an association between medium composition, particle uptake, and nanoparticle interaction with cells, leading to chromosomal damage as measured by the MN assay. PMID:23387956

Prasad, Raju Y; Wallace, Kathleen; Daniel, Kaitlin M; Tennant, Alan H; Zucker, Robert M; Strickland, Jenna; Dreher, Kevin; Kligerman, Andrew D; Blackman, Carl F; Demarini, David M

2013-03-26

329

The Interactions between L-tyrosine based nanoparticles decorated with folic acid and cervical cancer cells under physiological flow.  

PubMed

Many anticancer drugs have been established clinically, but their efficacy can be compromised by nonspecific toxicity and an inability to reach the desired cancerous intracellular spaces. In order to address these issues, researchers have explored the use of folic acid as a targeted moiety to increase specificity of chemotherapeutic drugs. To expand upon such research, we have conjugated folic acid to functionalized poly(ethylene glycol) and subsequently decorated the surface of l-tyrosine polyphosphate (LTP) nanoparticles. These nanoparticles possess the appropriate size (100-500 nm) for internalization as shown by scanning electron microscopy and dynamic light scattering. Under simulated physiological flow, LTP nanoparticles decorated with folic acid (targeted nanoparticles) show a 10-fold greater attachment to HeLa, a cervical cancer cell line, compared to control nanoparticles and to human dermal fibroblasts. The attachment of these targeted nanoparticles progresses at a linear rate, and the strength of this nanoparticle attachment is shown to withstand shear stresses of 3.0 dyn/cm(2). These interactions of the targeted nanoparticles to HeLa are likely a result of a receptor-ligand binding, as a competition study with free folic acid inhibits the nanoparticle attachment. Finally, the targeted nanoparticles encapsulated with a silver based drug show increased efficacy in comparison to nondecorated (plain) nanoparticles and drug alone against HeLa cells. Thus, targeted nanoparticles are a promising delivery platform for developing anticancer therapies that overexpress the folate receptors (FRs). PMID:22957928

Ditto, Andrew J; Shah, Kush N; Robishaw, Nikki K; Panzner, Matthew J; Youngs, Wiley J; Yun, Yang H

2012-11-01

330

Functional investigations on embryonic stem cells labeled with clinically translatable iron oxide nanoparticles  

NASA Astrophysics Data System (ADS)

Stem cell based therapies offer significant potential in the field of regenerative medicine. The development of superparamagnetic iron oxide (SPIO) nanoparticle labeling and magnetic resonance imaging (MRI) have been increasingly used to track the transplanted cells, enabling in vivo determination of cell fate. However, the impact of SPIO-labeling on the cell phenotype and differentiation capacity of embryonic stem cells (ESCs) remains unclear. In this study, we wrapped SPIO nanoparticles with stearic acid grafted PEI600, termed as Stearic-LWPEI-SPIO, to generate efficient and non-toxic ESC labeling tools. Our results showed that efficient labeling of ESCs at an optimized low dosage of Stearic-LWPEI-SPIO nanoparticles did not alter the differentiation and self-renewal properties of ESCs. The localization of the transplanted ESCs observed by MRI correlated well with histological studies. These findings demonstrate that Stearic-LWPEI-SPIO nanoparticles have potential to be clinically translatable MRI probes and may enable non-invasive in vivo tracking of ESCs in experimental and clinical settings during cell-based therapies.Stem cell based therapies offer significant potential in the field of regenerative medicine. The development of superparamagnetic iron oxide (SPIO) nanoparticle labeling and magnetic resonance imaging (MRI) have been increasingly used to track the transplanted cells, enabling in vivo determination of cell fate. However, the impact of SPIO-labeling on the cell phenotype and differentiation capacity of embryonic stem cells (ESCs) remains unclear. In this study, we wrapped SPIO nanoparticles with stearic acid grafted PEI600, termed as Stearic-LWPEI-SPIO, to generate efficient and non-toxic ESC labeling tools. Our results showed that efficient labeling of ESCs at an optimized low dosage of Stearic-LWPEI-SPIO nanoparticles did not alter the differentiation and self-renewal properties of ESCs. The localization of the transplanted ESCs observed by MRI correlated well with histological studies. These findings demonstrate that Stearic-LWPEI-SPIO nanoparticles have potential to be clinically translatable MRI probes and may enable non-invasive in vivo tracking of ESCs in experimental and clinical settings during cell-based therapies. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr01004c

Liu, Jing; Wang, Liqin; Cao, Jianbo; Huang, Yue; Lin, Yu; Wu, Xiaoyun; Wang, Zhiyong; Zhang, Fan; Xu, Xiuqin; Liu, Gang

2014-07-01

331

The Actinobacillus actinomycetemcomitans Autotransporter Adhesin Aae Exhibits Specificity for Buccal Epithelial Cells from Humans and Old World Primates  

PubMed Central

Cells of the gram-negative periodontopathogen Actinobacillus actinomycetemcomitans express a surface-exposed, outer membrane autotransporter protein, designated Aae, which has been implicated in epithelial cell binding. We constructed a mutant strain of A. actinomycetemcomitans that contained a transposon insertion in the Aae structural gene (aae) and tested the mutant to determine its ability to bind to buccal epithelial cells (BECs) isolated from healthy volunteers. Significantly fewer mutant cells than wild-type cells bound to BECs. A broad-host-range plasmid that contained an intact aae gene driven by a heterologous tac promoter restored the ability of the mutant strain to bind to BECs at wild-type levels. This plasmid also conferred upon Escherichia coli the ability to express the Aae protein on its surface and to bind to human BECs. Aae-expressing E. coli also bound to BECs isolated from six Old World primates but not to BECs isolated from four New World primates or nine other nonprimate mammals, as well as to human gingival epithelial cells but not to human pharyngeal, palatal, tongue, bronchial, or cervical epithelial cells. Our findings indicate that Aae mediates binding of A. actinomycetemcomitans to BECs from humans and Old World primates and that this process may contribute to the host range specificity and tissue tropism exhibited by this bacterium. PMID:15784534

Fine, Daniel H.; Velliyagounder, Kabilan; Furgang, David; Kaplan, Jeffrey B.

2005-01-01

332

Different endocytotic uptake mechanisms for nanoparticles in epithelial cells and macrophages  

PubMed Central

Summary Precise knowledge regarding cellular uptake of nanoparticles is of great importance for future biomedical applications. Four different endocytotic uptake mechanisms, that is, phagocytosis, macropinocytosis, clathrin- and caveolin-mediated endocytosis, were investigated using a mouse macrophage (J774A.1) and a human alveolar epithelial type II cell line (A549). In order to deduce the involved pathway in nanoparticle uptake, selected inhibitors specific for one of the endocytotic pathways were optimized regarding concentration and incubation time in combination with fluorescently tagged marker proteins. Qualitative immunolocalization showed that J774A.1 cells highly expressed the lipid raft-related protein flotillin-1 and clathrin heavy chain, however, no caveolin-1. A549 cells expressed clathrin heavy chain and caveolin-1, but no flotillin-1 uptake-related proteins. Our data revealed an impeded uptake of 40 nm polystyrene nanoparticles by J774A.1 macrophages when actin polymerization and clathrin-coated pit formation was blocked. From this result, it is suggested that macropinocytosis and phagocytosis, as well as clathrin-mediated endocytosis, play a crucial role. The uptake of 40 nm nanoparticles in alveolar epithelial A549 cells was inhibited after depletion of cholesterol in the plasma membrane (preventing caveolin-mediated endocytosis) and inhibition of clathrin-coated vesicles (preventing clathrin-mediated endocytosis). Our data showed that a combination of several distinguishable endocytotic uptake mechanisms are involved in the uptake of 40 nm polystyrene nanoparticles in both the macrophage and epithelial cell line. PMID:25383275

Kuhn, Dagmar A; Vanhecke, Dimitri; Michen, Benjamin; Blank, Fabian; Gehr, Peter; Petri-Fink, Alke

2014-01-01

333

Mature Dendritic Cells Infected with Herpes Simplex Virus Type 1 Exhibit Inhibited T-Cell Stimulatory Capacity  

Microsoft Academic Search

Mature dendritic cells (DC) are the most potent antigen-presenting cells within the entire immune system. Interference with the function of these cells therefore constitutes a very powerful mechanism for viruses to escape immune responses. Several members of the Herpesviridae family have provided examples of such escape strategies, including interference with antigen presentation and production of homologous cytokines. In this study

MONIKA KRUSE; OLAF ROSORIUS; FRIEDRICH KRATZER; GERHARD STELZ; CHRISTINE KUHNT; GEROLD SCHULER; JOACHIM HAUBER; ALEXANDER STEINKASSERER

2000-01-01

334

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. PMID:23883738

2013-01-01

335

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

336

Compatibility and toxicity of polymer-coated magnetic nanoparticles on mammalian cell systems  

E-print Network

(cont.) produced normal growth curves in the presence of particles. However, the particles do still exhibit some toxicity towards the cells, as the maximum cell density of cells cultured with particles does not reach that ...

Kral, Kelly M., 1979-

2005-01-01

337

Delivery of proteins to mammalian cells via gold nanoparticle mediated laser transfection  

NASA Astrophysics Data System (ADS)

Nanoparticle laser interactions are in widespread use in cell manipulation. In particular, molecular medicine needs techniques for the directed delivery of molecules into mammalian cells. Proteins are the final mediator of most cellular cascades. However, despite several methodical approaches, the efficient delivery of proteins to cells remains challenging. This paper presents a new protein transfection technique via laser scanning of cells previously incubated with gold nanoparticles. The laser-induced plasmonic effects on the gold nanoparticles cause a transient permeabilization of the cellular membrane, allowing proteins to enter the cell. Applying this technique, it was possible to deliver green fluorescent protein into mammalian cells with an efficiency of 43%, maintaining a high level of cell viability. Furthermore, a functional delivery of Caspase 3, an apoptosis mediating protein, was demonstrated and evaluated in several cellular assays. Compared to conventional protein transfection techniques such as microinjection, the methodical approach presented here enables high-throughput transfection of about 10 000 cells per second. Moreover, a well-defined point in time of delivery is guaranteed by gold nanoparticle mediated laser transfection, allowing the detailed temporal analysis of cellular pathways and protein trafficking.

Heinemann, D.; Kalies, S.; Schomaker, M.; Ertmer, W.; Murua Escobar, H.; Meyer, H.; Ripken, T.

2014-06-01

338

Apoptotic and proinflammatory effect of combustion-generated organic nanoparticles in endothelial cells.  

PubMed

Air pollution exposure in industrialized cities is associated with an increased risk of morbidity and mortality attributed to cardiovascular diseases. Combustion exhausts emitted from motor vehicles and industries represent a major source of nanoparticles in the atmosphere. Flame-generated organic carbon nanoparticles (OC NPs) provide interesting model nanoparticles that simulate fresh combustion emissions near roadways or combustion sources. These model nanoparticles can be produced by controlling flame operating conditions and used to test possible toxicological mechanisms responsible for the observed health effects. OC NPs were used to investigate their possible effect on endothelial cells (EC) growth and production of proinflammatory lipid mediators. Results indicated a dose and time-dependent reduction in cell viability following incubation of EC with OC NPs for 24 and 48h. Fluorescence-activated cell sorting revealed that EC treated with OC NPs showed a cell proliferation index significantly lower than that of control cells and an increased apoptotic cell death. The annexin assay confirmed the increased apoptotic cell death. Moreover, OC NPs also induced a time-dependent increase of proinflammatory lysophospholipid production. These results, establishing that OC NPs induce EC proinflammatory lysophosholipid production and apoptotic cell death, provide the first evidence of the detrimental effect of OC NPs on EC. PMID:23538036

Pedata, Paola; Bergamasco, Nadia; D'Anna, Andrea; Minutolo, Patrizia; Servillo, Luigi; Sannolo, Nicola; Balestrieri, Maria Luisa

2013-06-01

339

Application of antibody-conjugated gold nanoparticles for optical molecular imaging of epithelial carcinoma cells  

NASA Astrophysics Data System (ADS)

Advanced optical technologies for in vivo imaging e.g. OCT and confocal reflectance endomicroscopy while being able to image stromal morphology, are unable to image biomolecular changes associated with carcinogenesis. Furthermore, the contrast between neoplastic and normal tissues from such advanced optical technologies is often too low to be of any clinical value. Due to their favorable optical properties including their ability to resonantly scatter light at surface plasmon resonance to present potentially good contrast for reflectance-mode imaging, we aim to develop gold nanoparticles as optical contrast agents coupled with these optical imaging systems to perform cancer targeting bioimaging for early diagnosis of epithelial carcinoma. In this study, 20 nm gold nanoparticles were synthesized and conjugated with anti-EGFR (Epidermal Growth Factor Receptor). EGFR is a cell surface receptor biomarker that is highly expressed in majority of epithelial cancer compared to normal cells. The resulting anti-EGFR conjugated gold nanoparticles were allowed to interact with the nasopharyngeal carcinoma CNE2 cells in vitro. The exact localization of the gold bioconjugates on the cell surface EGFR receptors was investigated using confocal immunofluorescence microscopy. We have demonstrated that the binding and localization of the gold bioconjugates on the cell surface increased the reflectance and scattering properties of the CNE2 cells and provide good optical contrast for the cancer cells under confocal reflectance microscopy. Thus our study has demonstrated the potential of gold nanoparticles to target and illuminate cancer cells for bioimaging.

Kah, James C. Y.; Sheppard, Colin J. R.; Lee, Caroline G. L.; Olivo, Malini C.

2006-02-01

340

Efficient internalization of silica-coated iron oxide nanoparticles of different sizes by primary human macrophages and dendritic cells  

SciTech Connect

Engineered nanoparticles are being considered for a wide range of biomedical applications, from magnetic resonance imaging to 'smart' drug delivery systems. The development of novel nanomaterials for biomedical applications must be accompanied by careful scrutiny of their biocompatibility. In this regard, particular attention should be paid to the possible interactions between nanoparticles and cells of the immune system, our primary defense system against foreign invasion. On the other hand, labeling of immune cells serves as an ideal tool for visualization, diagnosis or treatment of inflammatory processes, which requires the efficient internalization of the nanoparticles into the cells of interest. Here, we compare novel monodispersed silica-coated iron oxide nanoparticles with commercially available dextran-coated iron oxide nanoparticles. The silica-coated iron oxide nanoparticles displayed excellent magnetic properties. Furthermore, they were non-toxic to primary human monocyte-derived macrophages at all doses tested whereas dose-dependent toxicity of the smaller silica-coated nanoparticles (30 nm and 50 nm) was observed for primary monocyte-derived dendritic cells, but not for the similarly small dextran-coated iron oxide nanoparticles. No macrophage or dendritic cell secretion of pro-inflammatory cytokines was observed upon administration of nanoparticles. The silica-coated iron oxide nanoparticles were taken up to a significantly higher degree when compared to the dextran-coated nanoparticles, irrespective of size. Cellular internalization of the silica-coated nanoparticles was through an active, actin cytoskeleton-dependent process. We conclude that these novel silica-coated iron oxide nanoparticles are promising materials for medical imaging, cell tracking and other biomedical applications.

Kunzmann, Andrea [Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Andersson, Britta [Clinical Allergy Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm (Sweden); Vogt, Carmen [Functional Materials Division, School of Information and Communication Technology, Royal Institute of Technology, Stockholm (Sweden); Feliu, Neus [Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Ye Fei [Functional Materials Division, School of Information and Communication Technology, Royal Institute of Technology, Stockholm (Sweden); Gabrielsson, Susanne [Clinical Allergy Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm (Sweden); Toprak, Muhammet S. [Functional Materials Division, School of Information and Communication Technology, Royal Institute of Technology, Stockholm (Sweden); Buerki-Thurnherr, Tina [Laboratory for Materials, Biology Interactions, Swiss Federal Laboratories of Materials Testing and Research, St. Gallen (Switzerland); Laurent, Sophie [NMR and Molecular Imaging Laboratory, Department of General, Organic and Biomedical Chemistry, University of Mons, Mons (Belgium); Vahter, Marie [Division of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Krug, Harald [Laboratory for Materials, Biology Interactions, Swiss Federal Laboratories of Materials Testing and Research, St. Gallen (Switzerland); Muhammed, Mamoun [Functional Materials Division, School of Information and Communication Technology, Royal Institute of Technology, Stockholm (Sweden); Scheynius, Annika [Clinical Allergy Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm (Sweden); Fadeel, Bengt, E-mail: bengt.fadeel@ki.se [Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden)

2011-06-01

341

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

NASA Astrophysics Data System (ADS)

Glucose-capped gold nanoparticles (Glu-GNPs) have been used to improve cellular targeting and radio-sensitization. In this study, we explored the mechanism of Glu-GNP enhanced radiation sensitivity in radiation-resistant human prostate cancer cells. Cell survival and proliferation were measured using MTT and clonogenic assay. Flow cytometry with staining by propidium iodide (PI) was performed to study the cell cycle changes induced by Glu-GNPs, and western blotting was used to determine the expression of p53 and cyclin proteins that correlated to cell cycle regulation. With 2 Gy of ortho-voltage irradiation, Glu-GNP showed a 1.5-2.0 fold enhancement in growth inhibition when compared to x-rays alone. Comparing the cell cycle change, Glu-GNPs induced acceleration in the G0/G1 phase and accumulation of cells in the G2/M phase at 29.8% versus 18.4% for controls at 24 h. G2/M arrest was accompanied by decreased expression of p53 and cyclin A, and increased expression of cyclin B1 and cyclin E. In conclusion, Glu-GNPs trigger activation of the CDK kinases leading to cell cycle acceleration in the G0/G1 phase and accumulation in the G2/M phase. This activation is accompanied by a striking sensitization to ionizing radiation, which may have clinical implications.

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

2009-09-01

342

Composite fiber structures with antiproliferative agents exhibit advantageous drug delivery and cell growth inhibition in vitro.  

PubMed

Composite core/shell fiber structures loaded with the antiproliferative drugs paclitaxel or farnesylthiosalicylate (FTS) were developed and studied. The latter is a specific nontoxic Ras inhibitor with a mild hydrophobic nature, which can also be used for local cancer treatment and stent applications. The fibers were composed of a dense polyglyconate core and a porous drug-loaded poly(D,L-lactic-glycolic acid) shell, prepared using freeze drying of inverted emulsions. Our study focused on the release profile of the antiproliferative drugs from the fibers, the shell morphology and its degradation and erosion. The postfabrication antiproliferative effect of the drugs was tested in a cell culture. The process parameters were found to affect the drug-release profile via two routes: (1) direct, through water uptake and swelling of the structure leading to FTS release, or through degradation of the host polymer leading to paclitaxel release at a later stage; (2) indirect effect of the microstructure on the release profile. The fabrication process did not reduce the pharmacological activity of either paclitaxel or FTS. FTS-eluting composite fibers proved to effectively induce growth inhibition or cell death by a gradient effect and dose-dependent manner. The combined effect of the targeted mechanism of FTS as a Ras inhibitor together with the localized and controlled release characteristics of the fiber is an advantageous antiproliferative quality. It is therefore suggested that our drug-eluting fibers may be used in biomedical applications that require short release (restenosis) or prolonged release (cancer therapy). PMID:20623695

Kraitzer, Amir; Kloog, Yoel; Haklai, Roni; Zilberman, Meital

2011-01-01

343

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

PubMed

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. 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. In this study, 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 and retinol dehydrogenase 8, manifested light-induced retinal dystrophy. We first examined early-stage age-related macular degeneration 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. PMID:22220722

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

2012-04-01

344

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

PubMed Central

Hyaluronan (HA), a principal constituent of the extracellular matrix (ECM), mediates growth and metastasis of tumor cells. The role of HA in the epithelial-mesenchymal transition (EMT) is well known, and increased ECM remodeling is observed in mesenchymal-like cells. The HA synthesis inhibitor 4-methylumbelliferone (4-MU) is anti-tumorigenic for various malignant tumors. However, the antitumor effect of 4-MU against canine mammary tumor cells that possess a mesenchymal-like phenotype is unclear. We examined the antitumor effect of 4-MU on CF41.Mg mesenchymal-like canine mammary tumor cells. We investigated the influence of 4-MU on the expression of HA synthase (HAS) 1-3 mRNA and observed dose-dependent downregulation of HAS2 mRNA at 24-72 h; in contrast, HAS3 expression was elevated at 24 h. Thus, 4-MU inhibited HA synthesis via HAS2 repression. 4-MU also inhibited cell proliferation and induced apoptosis in the CF41.Mg cells. Our experiments showed that 4-MU-induced apoptosis in CF41.Mg cells involved induction of the pro-apoptotic gene BAX. We also assessed motility and found that 4-MU reduced chemokinesis and chemotaxis in CF41.Mg cells. Our data suggest that 4-MU may serve as a candidate therapeutic agent for the treatment of canine mammary tumors. Since 4-MU exhibits antitumor activity in mesenchymal-like cells, it may also be a useful inhibitor of canine mammary tumor invasion and metastasis. PMID:23426189

SAITO, TERUYOSHI; DAI, TAMURA; ASANO, RYUJI

2013-01-01

345

A stochastic model of cell survival for high-Z nanoparticle radiotherapy  

SciTech Connect

Purpose: The authors present a stochastic framework for the assessment of cell survival in gold nanoparticle radiotherapy. Methods: The authors derive the equations for the effective macroscopic dose enhancement for a population of cells with nonideal distribution of gold nanoparticles (GNP), allowing different number of GNP per cell and different distances with respect to the cellular target. They use the mixed Poisson distribution formalism to model the impact of the aforementioned physical factors on the effective dose enhancement. Results: The authors show relatively large differences in the estimation of cell survival arising from using approximated formulae. They predict degeneration of the cell killing capacity due to different number of GNP per cell and different distances with respect to the cellular target. Conclusions: The presented stochastic framework can be used in interpretation of experimental cell survival or tumor control probability studies.

Zygmanski, Piotr; Tsiamas, Panagiotis; Ngwa, Wil; Berbeco, Ross; Makrigiorgos, Mike [Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115 (United States); Hoegele, Wolfgang [Department of Radiation Oncology, University of Regensburg, Regensburg 93053 (Germany); Cifter, Fulya; Sajo, Erno [University of Massachusetts Lowell, Department of Physics and Applied Physics, Medical Physics Program, Lowell, Massachusetts 01854 (United States)

2013-02-15

346

The promotion of human mesenchymal stem cell proliferation by superparamagnetic iron oxide nanoparticles.  

PubMed

Superparamagnetic iron oxide (SPIO) nanoparticles are very useful in cell imaging; meanwhile, however, biosafety concerns associated with their use, especially on therapeutic stem cells, have arisen. Most studies of biosafety issues focus on whether the nanoparticles have deleterious effects. Here, we report that Ferucarbotran, an ionic SPIO, is not toxic to human mesenchymal stem cells (hMSCs) under the conditions of these experiments but instead increases cell growth. Ferucarbotran-promoted cell growth is due to its ability to diminish intracellular H2O2 through intrinsic peroxidase-like activity. Also, Ferucarbotran can accelerate cell cycle progression, which may be mediated by the free iron (Fe) released from lysosomal degradation and involves the alteration of Fe on the expression of the protein regulators of the cell cycle. PMID:19359036

Huang, Dong-Ming; Hsiao, Jong-Kai; Chen, Ying-Chun; Chien, Li-Ying; Yao, Ming; Chen, Yin-Kai; Ko, Bor-Sheng; Hsu, Szu-Chun; Tai, Lin-Ai; Cheng, Hui-Ying; Wang, Shih-Wei; Yang, Chung-Shi; Chen, Yao-Chang

2009-08-01

347

Radiofrequency field-induced thermal cytotoxicity in cancer cells treated with fluorescent nanoparticles  

PubMed Central

Background Non-ionizing radiation, such as radiofrequency (RF) field and near infrared laser, induces thermal cytotoxicity in cancer cells treated with gold nanoparticles (AuNP). Quantum dots (QD) are fluorescent semiconducting nanoparticles that we hypothesize will induce similar injury following RF field irradiation. Methods AuNP and two types of QD (cadmium-selenide and indium-gallium-phosphide) conjugated to cetuximab (C225), a monoclonal antibody against human epidermal growth factor receptor (EGFR-1), demonstrated concentration-dependent heating in a RF field. We investigated the effect of RF field exposure after targeted nanoparticle treatment in a co-culture of two human cancer cell lines that have differential EGFR-1 expression (a high expressing pancreatic carcinoma, Panc-1, and a low expressing breast carcinoma, Cama-1). Results RF exposed Panc-1 or Cama-1 cells not containing AuNP or QD had a viability greater than 92%. The viability of Panc-1 cells exposed to the RF field after treatment with 50 nM Au-C225 was 39.4% ± 8.3% without injury to bystander Cama-1 cells (viability was 93.7% ± 1.0%, p ~ 0.0006). Panc-1 cells treated with targeted Cd-Se QD were only 47.5% viable after RF field exposure (p < 0.0001 compared to RF only Panc-1 control cells). Targeted InGaP QD decreased Panc-1 viability to 58.2% ± 3.4% after RF field exposure (p ~ 0.0004 compared to Cama-1 and Panc-1 controls). Conclusion We selectively induced RF field cytotoxicity in Panc-1 cells without injury to bystander Cama-1 cells utilizing EGFR-1 targeted nanoparticles, and demonstrated an interesting bifunctionality of fluorescent nanoparticles as agents for both cancer cell imaging and treatment. PMID:20564640

Glazer, Evan S.; Curley, Steven A.

2010-01-01

348

Targeting neural stem cells with titanium dioxide nanoparticles coupled to specific monoclonal antibodies.  

PubMed

Aiming to characterize the use of biomaterials in cancer therapy, we took advantage of the n-type semiconductor properties, which upon irradiation excite their electrons into the conduction band to induce photoelectrochemical reactions generating oxygen reactive species (ROS). Indeed, photoactivated TiO(2) nanoparticles have been shown to kill in vitro either bacteria or tumor cells in culture following UV irradiation, as a consequence of the ROS levels generated; the killing was highly effective although devoid of specificity. In this report, we have directed the TiO(2) nanoparticles to particular targets by coupling them to the monoclonal antibody (mAb) Nilo1, recognizing a surface antigen in neural stem cells within a cell culture, to explore the possibility of making this process specific. TiO(2) nanoparticles generated with particular rutile/anatase ratios were coupled to Nilo1 antibody and the complexes formed were highly stable. The coupled antibody retained the ability to identify neural stem cells and upon UV irradiation, the TiO(2) nanoparticles were activated, inducing the selective photokilling of the antibody-targeted cells. Thus, these data indicate that antibody-TiO(2) complexes could be used to specifically remove target cell subpopulations, as demonstrated with neural stem cells. The possible applications in cancer therapy are discussed. PMID:21586599

Elvira, Gema; Moreno, Berta; Valle, Ignacio Del; Garcia-Sanz, Jose A; Canillas, María; Chinarro, Eva; Jurado, José R; Silva, Augusto

2012-05-01

349

Peripherally Administered Nanoparticles Target Monocytic Myeloid Cells, Secondary Lymphoid Organs and Tumors in Mice  

PubMed Central

Nanoparticles have been extensively developed for therapeutic and diagnostic applications. While the focus of nanoparticle trafficking in vivo has traditionally been on drug delivery and organ-level biodistribution and clearance, recent work in cancer biology and infectious disease suggests that targeting different cells within a given organ can substantially affect the quality of the immunological response. Here, we examine the cell-level biodistribution kinetics after administering ultrasmall Pluronic-stabilized poly(propylene sulfide) nanoparticles in the mouse. These nanoparticles depend on lymphatic drainage to reach the lymph nodes and blood, and then enter the spleen rather than the liver, where they interact with monocytes, macrophages and myeloid dendritic cells. They were more readily taken up into lymphatics after intradermal (i.d.) compared to intramuscular administration, leading to ?50% increased bioavailability in blood. When administered i.d., their distribution favored antigen-presenting cells, with especially strong targeting to myeloid cells. In tumor-bearing mice, the monocytic and the polymorphonuclear myeloid-derived suppressor cell compartments were efficiently and preferentially targeted, rendering this nanoparticulate formulation potentially useful for reversing the highly suppressive activity of these cells in the tumor stroma. PMID:23626707

Kourtis, Iraklis C.; Hirosue, Sachiko; de Titta, Alexandre; Kontos, Stephan; Stegmann, Toon; Hubbell, Jeffrey A.; Swartz, Melody A.

2013-01-01

350

Peripherally administered nanoparticles target monocytic myeloid cells, secondary lymphoid organs and tumors in mice.  

PubMed

Nanoparticles have been extensively developed for therapeutic and diagnostic applications. While the focus of nanoparticle trafficking in vivo has traditionally been on drug delivery and organ-level biodistribution and clearance, recent work in cancer biology and infectious disease suggests that targeting different cells within a given organ can substantially affect the quality of the immunological response. Here, we examine the cell-level biodistribution kinetics after administering ultrasmall Pluronic-stabilized poly(propylene sulfide) nanoparticles in the mouse. These nanoparticles depend on lymphatic drainage to reach the lymph nodes and blood, and then enter the spleen rather than the liver, where they interact with monocytes, macrophages and myeloid dendritic cells. They were more readily taken up into lymphatics after intradermal (i.d.) compared to intramuscular administration, leading to ?50% increased bioavailability in blood. When administered i.d., their distribution favored antigen-presenting cells, with especially strong targeting to myeloid cells. In tumor-bearing mice, the monocytic and the polymorphonuclear myeloid-derived suppressor cell compartments were efficiently and preferentially targeted, rendering this nanoparticulate formulation potentially useful for reversing the highly suppressive activity of these cells in the tumor stroma. PMID:23626707

Kourtis, Iraklis C; Hirosue, Sachiko; de Titta, Alexandre; Kontos, Stephan; Stegmann, Toon; Hubbell, Jeffrey A; Swartz, Melody A

2013-01-01

351

Adhesion, Vitality and Osteogenic Differentiation Capacity of Adipose Derived Stem Cells Seeded on Nitinol Nanoparticle Coatings  

PubMed Central

Autologous cells can be used for a bioactivation of osteoimplants to enhance osseointegration. In this regard, adipose derived stem cells (ASCs) offer interesting perspectives in implantology because they are fast and easy to isolate. However, not all materials licensed for bone implants are equally suited for cell adhesion. Surface modifications are under investigation to promote cytocompatibility and cell growth. The presented study focused on influences of a Nitinol-nanoparticle coating on ASCs. Possible toxic effects as well as influences on the osteogenic differentiation potential of ASCs were evaluated by viability assays, scanning electron microscopy, immunofluorescence and alizarin red staining. It was previously shown that Nitinol-nanoparticles exert no cell toxic effects to ASCs either in soluble form or as surface coating. Here we could demonstrate that a Nitinol-nanoparticle surface coating enhances cell adherence and growth on Nitinol-surfaces. No negative influence on the osteogenic differentiation was observed. Nitinol-nanoparticle coatings offer new possibilities in implantology research regarding bioactivation by autologous ASCs, respectively enhancement of surface attraction to cells. PMID:23308190

Strauss, Sarah; Neumeister, Anne; Barcikowski, Stephan; Kracht, Dietmar; Kuhbier, Jorn W.; Radtke, Christine; Reimers, Kerstin; Vogt, Peter M.

2013-01-01

352

A comprehensive analysis of transfection-assisted delivery of iron oxide nanoparticles to dendritic cells  

PubMed Central

Polylysine (PL) has been used to facilitate dendritic cell (DC) uptake of super paramagnetic iron oxide (SPIO) nanoparticles for use in magnetic resonance imaging (MRI). In this work, we examined the effect of PL on cell toxicity and induction of cell maturation as manifested by the up-regulation of surface molecules. We found that PL became toxic to bone marrow-derived DCs (BMDCs) at the 10 ?g/ ml threshold. Incubation of BMDCs with 20 ?g/ml of PL for 1 h resulted in approximately 90% cell death. However, addition of SPIO nanoparticles rescued DCs from PL-induced death as the combination of SPIO with PL did not cause cytotoxicity until the PL concentration was 1000 ?g/ml. Prolonged exposure to PL induced BMDC maturation as noted by the expression of surface molecules such as MHC class II, CD40, CCR7 and CD86. However, the combination of SPIO and PL did not induce BMDC maturation at 1 h. However prolonged exposure to SPIO nanoparticles induced CD40 expression and protein expression of TNF? and KC. The data suggest that the use of PL to enhance the labeling of DCs with SPIO nanoparticles is a dedicated work. Appropriate calibration of the incubation time and concentrations of PL and SPIO nanoparticles is crucial to the development of MRI technology for noninvasive imaging of DCs in vivo. PMID:23747738

Toki, Shinji; Omary, Reed A.; Wilson, Kevin; Gore, John C.; Peebles, R. Stokes; Pham, Wellington

2014-01-01

353

Antifungal activity of ZnO nanoparticles—the role of ROS mediated cell injury  

NASA Astrophysics Data System (ADS)

Metal oxide nanoparticles have marked antibacterial activity. The toxic effect of these nanoparticles, such as those comprised of ZnO, has been found to occur due to an interaction of the nanoparticle surface with water, and to increase with a decrease in particle size. In the present study, we tested the ability of ZnO nanoparticles to affect the viability of the pathogenic yeast, Candida albicans (C. albicans). A concentration-dependent effect of ZnO on the viability of C. albicans was observed. The minimal fungicidal concentration of ZnO was found to be 0.1 mg ml - 1 ZnO; this concentration caused an inhibition of over 95% in the growth of C. albicans. ZnO nanoparticles also inhibited the growth of C. albicans when it was added at the logarithmic phase of growth. Addition of histidine (a quencher of hydroxyl radicals and singlet oxygen) caused reduction in the effect of ZnO on C. albicans depending on its concentration. An almost complete elimination of the antimycotic effect was achieved following addition of 5 mM of histidine. Exciting the ZnO by visible light increased the yeast cell death. The effects of histidine suggest the involvement of reactive oxygen species, including hydroxyl radicals and singlet oxygen, in cell death. In light of the above results it appears that metal oxide nanoparticles may provide a novel family of fungicidal compounds.

Lipovsky, Anat; Nitzan, Yeshayahu; Gedanken, Aharon; Lubart, Rachel

2011-03-01

354

Relevance of the sterilization-induced effects on the properties of different hydroxyapatite nanoparticles and assessment of the osteoblastic cell response  

PubMed Central

Hydroxyapatite (Hap) is a calcium phosphate with a chemical formula that closely resembles that of the mineral constituents found in hard tissues, thereby explaining its natural biocompatibility and wide biomedical use. Nanostructured Hap materials appear to present a good performance in bone tissue applications because of their ability to mimic the dimensions of bone components. However, bone cell response to individual nanoparticles and/or nanoparticle aggregates lost from these materials is largely unknown and shows great variability. This work addresses the preparation and characterization of two different Hap nanoparticles and their interaction with osteoblastic cells. Hap particles were produced by a wet chemical synthesis (WCS) at 37°C and by hydrothermal synthesis (HS) at 180°C. As the ultimate in vivo applications require a sterilization step, the synthesized particles were characterized ‘as prepared’ and after sterilization (autoclaving, 120°C, 20 min). WCS and HS particles differ in their morphological (size and shape) and physicochemical properties. The sterilization modified markedly the shape, size and aggregation state of WCS nanoparticles. Both particles were readily internalized by osteoblastic cells by endocytosis, and showed a low intracellular dissolution rate. Concentrations of WCS and HS particles less than 500 ?g ml?1 did not affect cell proliferation, F-actin cytoskeleton organization and apoptosis rate and increased the gene expression of alkaline phosphatase and BMP-2. The two particles presented some differences in the elicited cell response. In conclusion, WCS and HS particles might exhibit an interesting profile for bone tissue applications. Results suggest the relevance of a proper particle characterization, and the interest of an individual nanoparticle targeted research. PMID:22809851

Santos, C.; Gomes, P. S.; Duarte, J. A.; Franke, R. P.; Almeida, M. M.; Costa, M. E. V.; Fernandes, M. H.

2012-01-01

355

Delivery of molecules into cells using carbon nanoparticles activated by femtosecond laser pulses  

PubMed Central

A major barrier to drug and gene delivery is crossing the cell's plasma membrane. Physical forces applied to cells via electroporation1, ultrasound2 and laser-irradiation3–6 generate nanoscale holes in the plasma membrane for direct delivery of drugs into the cytoplasm. Inspired by previous work showing that laser excitation of carbon nanoparticles can drive the carbon-steam reaction to generate highly controlled shock waves7–10, here we show carbon black (CB) nanoparticles activated by femtosecond laser pulses can facilitate the delivery of small molecules, proteins and DNA into two types of cells. Our initial results suggest that interaction between the laser energy and CB nanoparticles may generate photoacoustic forces by chemical reaction to create transient holes in the membrane for delivery. PMID:20639882

Chakravarty, Prerona; Qian, Wei; El-Sayed, Mostafa A.; Prausnitz, Mark R.

2010-01-01

356

Multilayer nanoparticle arrays for broad spectrum absorption enhancement in thin film solar cells.  

PubMed

In this paper, we present a theoretical study on the absorption efficiency enhancement of a thin film amorphous Silicon (a-Si) photovoltaic cell over a broad spectrum of wavelengths using multiple nanoparticle arrays. The light absorption efficiency is enhanced in the lower wavelengths by a nanoparticle array on the surface and in the higher wavelengths by another nanoparticle array embedded in the active region. The efficiency at intermediate wavelengths is enhanced by the simultaneous resonance from both nanoparticle layers. We optimize this design by tuning the radius of particles in both arrays, the period of the array and the distance between the two arrays. The optimization results in a total quantum efficiency of 62.35% for a 0.3 ?m thick a-Si substrate. PMID:24922387

Krishnan, Aravind; Das, Snehal; Krishna, Siva Rama; Khan, Mohammed Zafar Ali

2014-05-01

357

Treatment of human astrocytoma U87 cells with silicon dioxide nanoparticles lowers their survival and alters their expression of mitochondrial and cell signaling proteins.  

PubMed

Recent evidence suggests silicon dioxide micro- and nanoparticles induce cytotoxic effects on lung cells. Thus, there is an increasing concern regarding their potential health hazard. Nevertheless, the putative toxicity of nanoparticles in mammalian cells has not yet been systematically investigated. We previously noted that several metallic oxide nanoparticles exert differential cytotoxic effects on human neural and nonneural cells. Therefore, we hypothesized that silicon dioxide nanoparticles induce cytotoxicity in U87 cells by lowering their survival by decreasing cell survival signaling and disturbing mitochondrial function. To investigate this hypothesis, we determined the activities of the key mitochondrial enzymes, citrate synthase and malate dehydrogenase, in astrocytoma U87 cells treated with silicon dioxide nanoparticles. In addition, we studied the expression of the mitochondrial DNA-encoded proteins, cytochrome C oxidase II and nicotinamide adenine dinucleotide (NADPH) dehydrogenase subunit 6, and