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Sample records for nanoparticles exhibits cell

  1. Metallic Nickel Nanoparticles May Exhibit Higher Carcinogenic Potential than Fine Particles in JB6 Cells

    PubMed Central

    Bowman, Linda; Zou, Baobo; Mao, Guochuan; Xu, Jin; Castranova, Vincent; Zhao, Jinshun; Ding, Min

    2014-01-01

    While numerous studies have described the pathogenic and carcinogenic effects of nickel compounds, little has been done on the biological effects of metallic nickel. Moreover, the carcinogenetic potential of metallic nickel nanoparticles is unknown. Activator protein-1 (AP-1) and nuclear factor-?B (NF-?B) have been shown to play pivotal roles in tumor initiation, promotion, and progression. Mutation of the p53 tumor suppressor gene is considered to be one of the steps leading to the neoplastic state. The present study examines effects of metallic nickel fine and nanoparticles on tumor promoter or suppressor gene expressions as well as on cell transformation in JB6 cells. Our results demonstrate that metallic nickel nanoparticles caused higher activation of AP-1 and NF-?B, and a greater decrease of p53 transcription activity than fine particles. Western blot indicates that metallic nickel nanoparticles induced a higher level of protein expressions for R-Ras, c-myc, C-Jun, p65, and p50 in a time-dependent manner. In addition, both metallic nickel nano- and fine particles increased anchorage-independent colony formation in JB6 P+ cells in the soft agar assay. These results imply that metallic nickel fine and nanoparticles are both carcinogenetic in vitro in JB6 cells. Moreover, metallic nickel nanoparticles may exhibit higher carcinogenic potential, which suggests that precautionary measures should be taken in the use of nickel nanoparticles or its compounds in nanomedicine. PMID:24691273

  2. Green Synthesized Silver Nanoparticles Exhibit Reduced Toxicity to Mammalian Cells and Retain Antimicrobial Activity

    EPA Science Inventory

    The interest in silver nanoparticles (AgNPs) and silver nanomaterial stems from their antimicrobial properties. AgNPs are being added to clothing, paint, refrigerators, washing machines and a variety of other commercially available items. Recent in vitro and in vivo studies, howe...

  3. Encapsulated paclitaxel nanoparticles exhibit enhanced anti-tumor efficacy in A549 non-small lung cancer cells.

    PubMed

    Huang, Guojin; Zang, Bao; Wang, Xiaowei; Liu, Gang; Zhao, Jianqiang

    2015-12-01

    In the present study, paclitaxel (PTX) were encapsulated with polyethylene glycol (PEG)-polylactide (PLA)/D-? tocopheryl polyethylene glycol 1000 succinate (TPGS) (PEG-PLA/TPGS) and the enhanced anti-tumor activity of this PTX mixed micelles (PTX-MM) was evaluated in lung cancer cells. The PTX-MM prepared by a solvent evaporation method was demonstrated to have high drug-loading efficiency (23.2%), high encapsulation efficiency (76.4%), and small size (59 nm). In vitro release assay showed the slow release behavior of PTX-MM, suggesting the good stability of the PTX-MM essential for long circulation time. In vitro kinetics assay demonstrated that PTX-MM could promote absorption and increase relative bioavailability. The anti-cancer efficiency of PTX-MM was also examined by both in vitro and in vivo studies. PTX-MM exhibits obvious cytotoxicity against lung cancer cells with much lower IC50 value when compared with commercial formulated PTX or PTX + TPGS. The xenograft tumor model studies on nude mice indicated that PTX-MM inhibits tumor growth more effectively than other formulations. It was also found that most of mixed micelles were integral in tumor site to exhibit anti-cancer activity. Our results suggested that the use of PTX-MM as an anti-cancer drug may be an effective approach to treat lung cancer. PMID:26525950

  4. Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries

    PubMed Central

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

    2014-01-01

    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

  5. Cell tracking using nanoparticles.

    PubMed

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

    2008-09-01

    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

  6. Dense nanoparticles exhibit enhanced vascular wall targeting over neutrally buoyant nanoparticles in human blood flow.

    PubMed

    Thompson, Alex J; Eniola-Adefeso, Omolola

    2015-07-15

    For vascular-targeting carrier (VTC) systems to be effective, carriers must be able to localize and adhere to the vascular wall at the target site. Research suggests that neutrally buoyant nanoparticles are limited by their inability to localize to the endothelium, making them sub-optimal as carriers. This study examines whether particle density can be exploited to improve the targeting (localization and adhesion) efficiency of nanospheres to the vasculature. Silica spheres with 500 nm diameter, which have a density roughly twice that of blood, exhibit improved adhesion to inflamed endothelium in an in vitro model of human vasculature compared to neutrally buoyant polystyrene spheres of the same size. Silica spheres also display better near-wall localization in the presence of red blood cells than they do in pure buffer, likely resulting in the observed improvement in adhesion. Titania spheres (4 times more dense than blood) adhere at levels higher than polystyrene, but only in conditions when gravity or centrifugal force acts in the direction of adhesion. In light of the wide array of materials proposed for use as carrier systems for drug delivery and diagnostics, particle density may be a useful tool for improving the targeting of diseased tissues. PMID:25870170

  7. Core-shell silver nanoparticles for optical labeling of cells.

    PubMed

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

    2014-08-01

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

  8. Nanoparticles functionalized with collagenase exhibit improved tumor accumulation in a murine xenograft model

    PubMed Central

    Murty, Surya; Gilliland, Taylor; Qiao, Peter; Tabtieng, Tate; Higbee, Elizabeth; Al Zaki, Ajlan; Puré, Ellen

    2015-01-01

    Nanoparticles have garnered widespread interest for both the imaging and treatment of cancer due to their unique and tunable pharmacokinetics and their ability to carry a high payload of diverse compounds. However, despite these favorable attributes, the extent of tumor accumulation can be severely restricted due to the dense stroma surrounding the often-permeable blood vessel wall and high intratumoral pressure. In this study, we investigated whether modifying the surface of pegylated gold nanoparticles (AuNPs) with collagenase could improve the accumulation of nanoparticles within a murine tumor xenograft. It was determined that collagenase remains active after surface conjugation and the presence of collagenase has no measureable effect on cell proliferation in vitro. Following intravenous injection, the largest fractions of collagenase-labeled AuNPs were found in the liver and spleen. Histological analysis revealed no signs of toxicity in either of these organs. Blood chemistry revealed normal levels of liver enzymes, but a slightly elevated level of total bilirubin. Within the tumor, AuNPs labeled with collagenase exhibited a 35% increase in accumulation compared with unlabeled AuNPs. Therefore, these studies provide preliminary evidence that the functionalization of nanoparticles with collagenase represent an effective and safe approach to improve tumor accumulation. PMID:26380538

  9. Rotating pigment cells exhibit an intrinsic chirality.

    PubMed

    Yamanaka, Hiroaki; Kondo, Shigeru

    2015-01-01

    In multicellular organisms, cell properties, such as shape, size and function are important in morphogenesis and physiological functions. Recently, 'cellular chirality' has attracted attention as a cellular property because it can cause asymmetry in the bodies of animals. In recent in vitro studies, the left-right bias of cellular migration and of autonomous arrangement of cells under some specific culture conditions were discovered. However, it is difficult to identify the molecular mechanism underlying their intrinsic chirality because the left-right bias observed to date is subtle or is manifested in the stable orientation of cells. Here, we report that zebrafish (Danio rerio) melanophores exhibit clear cellular chirality by unidirectional counterclockwise rotational movement under isolated conditions without any special settings. The chirality is intrinsic to melanophores because the direction of the cellular rotation was not affected by the type of extracellular matrix. We further found that the cellular rotation was generated as a counter action of the clockwise movement of actin cytoskeleton. It suggested that the mechanism that directs actin cytoskeleton in the clockwise direction is pivotal for determining cellular chirality. PMID:25345494

  10. Gold Nanoparticles-Poly(N-isopropylacrylamide) Composites Exhibiting Optically Induced Reversible Properties.

    PubMed

    Byun, Hongsik

    2015-07-01

    A very simple synthetic method is proposed to prepare spiky gold nanoparticles possessing a strong and broad absorption band around the surface of temperature-sensitive poly(N-isopropylacrylamide), poly(NIPAM), particles. The structural properties of the composite particles were thoroughly characterized by UV-visible spectrophotometer, scanning electron microscope, and dynamic light scattering. These composite materials exhibited a reversible swelling and collapsing behavior above and below the lower critical solution temperature. As the surface-adsorbed spiky gold nanoparticles around the poly(NIPAM) possessed a strong and broad absorption band and exhibited the photon-to-heat conversion property, these nanocomposites also showed fast reversible structural diameter changes upon exposure to a broad band light. These types of composite particles may serve as an excellent template for the development of photothermally triggered carrier systems. PMID:26373073

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

    PubMed

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

    2014-05-01

    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

  12. Fabricating solar cells with silicon nanoparticles

    DOEpatents

    Loscutoff, Paul; Molesa, Steve; Kim, Taeseok

    2014-09-02

    A laser contact process is employed to form contact holes to emitters of a solar cell. Doped silicon nanoparticles are formed over a substrate of the solar cell. The surface of individual or clusters of silicon nanoparticles is coated with a nanoparticle passivation film. Contact holes to emitters of the solar cell are formed by impinging a laser beam on the passivated silicon nanoparticles. For example, the laser contact process may be a laser ablation process. In that case, the emitters may be formed by diffusing dopants from the silicon nanoparticles prior to forming the contact holes to the emitters. As another example, the laser contact process may be a laser melting process whereby portions of the silicon nanoparticles are melted to form the emitters and contact holes to the emitters.

  13. Aeromonas species exhibit aggregative adherence to HEp-2 cells.

    PubMed Central

    Neves, M S; Nunes, M P; Milhomem, A M

    1994-01-01

    Clinical and environmental isolates of Aeromonas species (five A. hydrophila isolates, three A. caviae isolates, and two A. sobria isolates) were tested for their adherence to HEp-2 cells. Clinical isolates of A. hydrophila and A. sobria exhibited aggregative adherence similar to that presented by enteroadherent-aggregative Escherichia coli. Bacterial aggregates adhered to cells with a typical "stacked-brick" appearance. In contrast, A. caviae strains showed a diffuse adherence pattern. Images PMID:8027331

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

    SciTech Connect

    Loh, Jing Wen; Saunders, Martin; Lim, Lee-Yong; School of Biomedical, Biomolecular and Chemical Sciences, 35 Stirling Hwy, Crawley 6009

    2012-08-01

    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.

  15. DNA damage in cells exhibiting radiation-induced genomic instability

    SciTech Connect

    Keszenman, Deborah J.; Kolodiuk, Lucia; Baulch, Janet E.

    2015-02-22

    Cells exhibiting radiation induced genomic instability exhibit varied spectra of genetic and chromosomal aberrations. Even so, oxidative stress remains a common theme in the initiation and/or perpetuation of this phenomenon. Isolated oxidatively modified bases, abasic sites, DNA single strand breaks and clustered DNA damage are induced in normal mammalian cultured cells and tissues due to endogenous reactive oxygen species generated during normal cellular metabolism in an aerobic environment. While sparse DNA damage may be easily repaired, clustered DNA damage may lead to persistent cytotoxic or mutagenic events that can lead to genomic instability. In this study, we tested the hypothesis that DNA damage signatures characterised by altered levels of endogenous, potentially mutagenic, types of DNA damage and chromosomal breakage are related to radiation-induced genomic instability and persistent oxidative stress phenotypes observed in the chromosomally unstable progeny of irradiated cells. The measurement of oxypurine, oxypyrimidine and abasic site endogenous DNA damage showed differences in non-double-strand breaks (DSB) clusters among the three of the four unstable clones evaluated as compared to genomically stable clones and the parental cell line. These three unstable clones also had increased levels of DSB clusters. The results of this study demonstrate that each unstable cell line has a unique spectrum of persistent damage and lead us to speculate that alterations in DNA damage signaling and repair may be related to the perpetuation of genomic instability.

  16. DNA damage in cells exhibiting radiation-induced genomic instability

    DOE PAGESBeta

    Keszenman, Deborah J.; Kolodiuk, Lucia; Baulch, Janet E.

    2015-02-22

    Cells exhibiting radiation induced genomic instability exhibit varied spectra of genetic and chromosomal aberrations. Even so, oxidative stress remains a common theme in the initiation and/or perpetuation of this phenomenon. Isolated oxidatively modified bases, abasic sites, DNA single strand breaks and clustered DNA damage are induced in normal mammalian cultured cells and tissues due to endogenous reactive oxygen species generated during normal cellular metabolism in an aerobic environment. While sparse DNA damage may be easily repaired, clustered DNA damage may lead to persistent cytotoxic or mutagenic events that can lead to genomic instability. In this study, we tested the hypothesismore »that DNA damage signatures characterised by altered levels of endogenous, potentially mutagenic, types of DNA damage and chromosomal breakage are related to radiation-induced genomic instability and persistent oxidative stress phenotypes observed in the chromosomally unstable progeny of irradiated cells. The measurement of oxypurine, oxypyrimidine and abasic site endogenous DNA damage showed differences in non-double-strand breaks (DSB) clusters among the three of the four unstable clones evaluated as compared to genomically stable clones and the parental cell line. These three unstable clones also had increased levels of DSB clusters. The results of this study demonstrate that each unstable cell line has a unique spectrum of persistent damage and lead us to speculate that alterations in DNA damage signaling and repair may be related to the perpetuation of genomic instability.« less

  17. Interactions of Model Cell Membranes with Nanoparticles

    NASA Astrophysics Data System (ADS)

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

    2011-12-01

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

  18. Pinellia ternata agglutinin produced in Bombyx mori cells exhibits bioactivity.

    PubMed

    Xu, Tao; Wang, Bo; Wang, Liya; Zhang, Yaozhou; Lv, Zhengbing

    2012-01-01

    Pinellia ternata agglutinin (PTA) is highly homologous to many other monocot mannose-binding lectins which reportedly possess antitumor activities. Its production in silkworm cells has great application potential because the baculovirus expression system can produce post-translationally modified proteins at low cost. In the current study, the pta gene was cloned and expressed in silkworm cells, and the expressed protein was analyzed using a hemagglutination assay. A preliminary in vitro study on its anti-proliferative activity was performed. The results show that the recombinant PTA with an apparent molecular mass of 29 kDa can hemagglutinate rabbit erythrocytes and this activity can be inhibited by D-mannan at a low concentration. In addition, the recombinant hemagglutinin exhibited a dose-dependent anti-proliferative activity on hepatoma cells. The results of the current study suggest that PTA and other important bioactive proteins could be produced by silkworm bioreactor for biomedicine research and application. PMID:22611529

  19. Modeling of interactions between nanoparticles and cell membranes

    NASA Astrophysics Data System (ADS)

    Ban, Young-Min

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

  20. Kupffer Cell Isolation for Nanoparticle Toxicity Testing.

    PubMed

    Bourgognon, Maxime; Klippstein, Rebecca; Al-Jamal, Khuloud T

    2015-01-01

    The large majority of in vitro nanotoxicological studies have used immortalized cell lines for their practicality. However, results from nanoparticle toxicity testing in immortalized cell lines or primary cells have shown discrepancies, highlighting the need to extend the use of primary cells for in vitro assays. This protocol describes the isolation of mouse liver macrophages, named Kupffer cells, and their use to study nanoparticle toxicity. Kupffer cells are the most abundant macrophage population in the body and constitute part of the reticulo-endothelial system (RES), responsible for the capture of circulating nanoparticles. The Kupffer cell isolation method reported here is based on a 2-step perfusion method followed by purification on density gradient. The method, based on collagenase digestion and density centrifugation, is adapted from the original protocol developed by Smedsrød et al. designed for rat liver cell isolation and provides high yield (up to 14 x 10(6) cells per mouse) and high purity (>95%) of Kupffer cells. This isolation method does not require sophisticated or expensive equipment and therefore represents an ideal compromise between complexity and cell yield. The use of heavier mice (35-45 g) improves the yield of the isolation method but also facilitates remarkably the procedure of portal vein cannulation. The toxicity of functionalized carbon nanotubes f-CNTs was measured in this model by the modified LDH assay. This method assesses cell viability by measuring the lack of structural integrity of Kupffer cell membrane after incubation with f-CNTs. Toxicity induced by f-CNTs can be measured consistently using this assay, highlighting that isolated Kupffer cells are useful for nanoparticle toxicity testing. The overall understanding of nanotoxicology could benefit from such models, making the nanoparticle selection for clinical translation more efficient. PMID:26327223

  1. Organically Modified Silica Nanoparticles Interaction with Macrophage Cells: Assessment of Cell Viability on the Basis of Physicochemical Properties.

    PubMed

    Kumar, Dhiraj; Mutreja, Isha; Keshvan, Prashant C; Bhat, Madhusudan; Dinda, Amit K; Mitra, Susmita

    2015-11-01

    Silica nanoparticles have drawn a lot of attention for nanomedicine application, and this is attributed to their biocompatibility and ease of surface functionalization. However, successful utilization of these inorganic systems for biomedical application depends on their physicochemical properties. This study, therefore, discusses in vitro toxicity of organically modified silica nanoparticles on the basis of size, shape, and surface properties of silica nanoparticles. Spherical- and oval-shaped nanoparticles having hydroxyl and amine groups were synthesized in Tween 80 micelles using different organosilanes. Nanoparticles of similar size and morphology were considered for comparative assessment. "As-prepared" nanoparticles were characterized in terms of size, shape, and surface properties using ZetaSizer, transmission electron microscopy, and Fourier transform infrared to establish the above parameters. In vitro analysis in terms of nanoparticle-based toxicity was performed on J-774 (macrophage) cell line using propidium iodide-4',6-diamidino-2-phenylindol and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Fluorescent dye-entrapped nanoparticles were used to visualize the uptake of the nanoparticles by macrophage cells. Results from cell studies suggested low levels of toxicity for different nanoparticle formulations studied, therefore are suitable for nanocarrier application for poorly soluble molecules. On the contrary, the nanoparticles of similar size and shape, having amine groups and low net negative charge, do not exhibit any in vitro cytotoxicity. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3943-3951, 2015. PMID:26295279

  2. Variation in the uptake of nanoparticles by monolayer cultured cells using high resolution MeV ion beam imaging

    NASA Astrophysics Data System (ADS)

    Tao, Ye; Mi, Zhaohong; Vanga, Sudheer Kumar; Chen, Ce-Belle; Bettiol, Andrew A.; Watt, Frank

    2015-04-01

    Gold nanoparticle uptake by cells is being increasingly studied because of its potential in biomedical applications. In this work, we show how scanning transmission ion microscopy can be employed to visualize and quantify 50 nm gold nanoparticles taken up by individual cells. Preliminary studies have indicated that the cellular content of gold nanoparticles exhibits a wide variation (up to a factor of 10) among individual cells. This cell-to-cell variation can affect the efficiency of utilizing gold nanoparticles for therapeutic or diagnostic purposes.

  3. Identification of mouse mutant cells exhibiting the plastic mutant phenotype.

    PubMed

    Yamauchi, Masatake; Fukutsu, Kumiko; Sakagami, Mari; Yamada, Yuji

    2010-08-01

    The initial processes involved in radiation carcinogenesis have not been clearly elucidated. We isolated mouse mutant cells exhibiting plasticity in their mutation phenotypes. These mutant cells were originally isolated from an irradiated cell population as 6-thioguanine resistant (6TGR) mutants that were deficient in hypoxanthine phosphoribosyl transferase (Hprt, E.C.2.4.2.8) activity at the frequency of approximately 6.2 x 10(-5). Approximately 10% of 6TGR cells showed plasticity in their mutant phenotypes and reverted to HAT-resistant (HATR), which is Hprt-proficient, wild type phenotype. Eventually we identified the plastic mutants in the un-irradiated wild type cell population as well and found that ionizing irradiation enhanced the frequency of the plastic mutation approximately 24 times. Treatment with 5-aza-cytidine did not affect the plasticity of mutant phenotypes identified in this study, suggesting that DNA methylation was not involved in the plastic changes of the mutant phenotypes. The plastic mutant phenotype identified in our study is a new type of genomic instability induced by ionizing irradiation, and it is likely to be involved in one of the primary changes that occur in the process of radiation carcinogenesis, and may explain one element of carcinogenesis, which is composed of multi-stages. PMID:20811140

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

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

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

  5. Planktonic and biofilm-grown nitrogen-cycling bacteria exhibit different susceptibilities to copper nanoparticles.

    PubMed

    Reyes, Vincent C; Opot, Stephen O; Mahendra, Shaily

    2015-04-01

    Proper characterization of nanoparticle (NP) interactions with environmentally relevant bacteria under representative conditions is necessary to enable their sustainable manufacture, use, and disposal. Previous nanotoxicology research based on planktonic growth has not adequately explored biofilms, which serve as the predominant mode of bacterial growth in natural and engineered environments. Copper nanoparticle (Cu-NP) impacts on biofilms were compared with respective planktonic cultures of the ammonium-oxidizing Nitrosomonas europaea, nitrogen-fixing Azotobacter vinelandii, and denitrifying Paracoccus denitrificans using a suite of independent toxicity diagnostics. Median inhibitory concentration (IC50) values derived from adenosine triphosphate (ATP) for Cu-NPs were lower in N. europaea biofilms (19.6?±?15.3?mg/L) than in planktonic cells (49.0?±?8.0?mg/L). However, in absorbance-based growth assays, compared with unexposed controls, N. europaea growth rates in biofilms were twice as resilient to inhibition than those in planktonic cultures. Similarly, relative to unexposed controls, growth rates and yields of P. denitrificans in biofilms exposed to Cu-NPs were 40-fold to 50-fold less inhibited than those in planktonic cells. Physiological evaluation of ammonium oxidation and nitrate reduction suggested that biofilms were also less inhibited by Cu-NPs than planktonic cells. Furthermore, functional gene expression for ammonium oxidation (amoA) and nitrite reduction (nirK) showed lower inhibition by NPs in biofilms relative to planktonic-grown cells. These results suggest that biofilms mitigate NP impacts, and that nitrogen-cycling bacteria in wastewater, wetlands, and soils might be more resilient to NPs than planktonic-based assessments suggest. PMID:25556815

  6. Imaging nanoparticles in cells by nanomechanical holography

    SciTech Connect

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

    2008-06-01

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

  7. Interaction of dermatologically relevant nanoparticles with skin cells and skin

    PubMed Central

    Rancan, Fiorenza; Ahlberg, Sebastian; Nazemi, Berouz; Choe, Chun Sik; Darvin, Maxim E; Hadam, Sabrina; Blume-Peytavi, Ulrike; Loza, Kateryna; Diendorf, Jörg; Epple, Matthias; Graf, Christina; Rühl, Eckart; Meinke, Martina C; Lademann, Jürgen

    2014-01-01

    Summary The investigation of nanoparticle interactions with tissues is complex. High levels of standardization, ideally testing of different material types in the same biological model, and combinations of sensitive imaging and detection methods are required. Here, we present our studies on nanoparticle interactions with skin, skin cells, and biological media. Silica, titanium dioxide and silver particles were chosen as representative examples for different types of skin exposure to nanomaterials, e.g., unintended environmental exposure (silica) versus intended exposure through application of sunscreen (titanium dioxide) or antiseptics (silver). Because each particle type exhibits specific physicochemical properties, we were able to apply different combinations of methods to examine skin penetration and cellular uptake, including optical microscopy, electron microscopy, X-ray microscopy on cells and tissue sections, flow cytometry of isolated skin cells as well as Raman microscopy on whole tissue blocks. In order to assess the biological relevance of such findings, cell viability and free radical production were monitored on cells and in whole tissue samples. The combination of technologies and the joint discussion of results enabled us to look at nanoparticle–skin interactions and the biological relevance of our findings from different angles. PMID:25551064

  8. In vitro effects of nanoparticles on renal cells

    PubMed Central

    L'Azou, Béatrice; Jorly, Joana; On, Dinhill; Sellier, Elisabeth; Moisan, Frédéric; Fleury-Feith, Jocelyne; Cambar, Jean; Brochard, Patrick; Ohayon-Courtès, Céline

    2008-01-01

    Background The ability of nanoparticles to cross the lung-blood barrier suggests that they may translocate to blood and to targets distant from their portal of entry. Nevertheless, nanotoxicity in organs has received little attention. The purpose of this study was to evaluate nanotoxicity in renal cells using in vitro models. Various carbon black (CB) (FW2–13 nm, Printex60-21 nm and LB101-95 nm) and titanium dioxide (TiO2-15 and TiO2-50 nm) nanoparticles were characterized on size by electron microscopy. We evaluated theirs effects on glomerular mesangial (IP15) and epithelial proximal tubular (LLC-PK1) renal cells, using light microscopy, WST-1 assay, immunofluorescence labeling and DCFH-DA for reactive oxygen species (ROS) assay. Results Nanoparticles induced a variety of cell responses. On both IP15 and LLC-PK1 cells, the smallest FW2 NP was found to be the most cytotoxic with classic dose-behavior. For the other NPs tested, different cytotoxic profiles were found, with LLC-PK1 cells being more sensitive than IP15 cells. Exposure to FW2 NPs, evidenced in our experiments as the most cytotoxic particle type, significantly enhanced production of ROS in both IP15 and LLC-PK1 cells. Immunofluorescence microscopy using latex beads indicated that depending on their size, the cells internalized particles, which accumulated in the cell cytoplasm. Additionally using transmission electronic microscope micrographs show nanoparticles inside the cells and trapped in vesicles. Conclusion The present data constitute the first step towards determining in vitro dose effect of manufactured CB and TiO2 NPs in renal cells. Cytotoxicological assays using epithelial tubular and glomerular mesangial cell lines rapidly provide information and demonstrated that NP materials exhibit varying degrees of cytotoxicity. It seems clear that in vitro cellular systems will need to be further developed, standardized and validated (relative to in vivo effects) in order to provide useful screening data about the relative toxicity of nanoparticles. PMID:19099552

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

    PubMed

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

    2014-09-29

    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

  10. Functionalized magnetic-fluorescent hybrid nanoparticles for cell labelling

    NASA Astrophysics Data System (ADS)

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

    2011-05-01

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

  11. Functionalized magnetic-fluorescent hybrid nanoparticles for cell labelling.

    PubMed

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

    2011-05-01

    A facile method of synthesizing 60 nm magnetic-fluorescent core-shell bifunctional nanocomposites with the ability to label cells is presented. Hydrophobic trioctylphosphine oxide (TOPO)-capped CdSe@ZnS quantum dots (QDs) were assembled on polyethyleneimine (PEI)-coated Fe(3)O(4) nanoparticles (MNP). Polyethyleneimine was utilized for the realization of multifunction, including attaching 4 nm TOPO capped CdSe@ZnS quantum dots onto magnetite particles, altering the surface properties of quantum dots from hydrophobic to hydrophilic as well as preventing the formation of large aggregates. Results show that these water-soluble hybrid nanocomposites exhibit good colloidal stability and retain good magnetic and fluorescent properties. Because TOPO-capped QDs are assembled instead of their water-soluble equivalents, the nanocomposites are still highly luminescent with no shift in the PL peak position and present long-term fluorescence stability. Moreover, TAT peptide (GRKKRRQRRRPQ) functionalized hybrid nanoparticles were also studied due to their combined magnetic enrichment and optical detection for cell separation and rapid cell labelling. A cell viability assay revealed good biocompatibility of these hybrid nanoparticles. The potential application of the new magnetic-fluorescent nanocomposites in biological and medicine is demonstrated. PMID:21503355

  12. Air stable organic-inorganic nanoparticles hybrid solar cells

    DOEpatents

    Qian, Lei; Yang, Jihua; Xue, Jiangeng; Holloway, Paul H.

    2015-09-29

    A solar cell includes a low work function cathode, an active layer of an organic-inorganic nanoparticle composite, a ZnO nanoparticle layer situated between and physically contacting the cathode and active layers; and a transparent high work function anode that is a bilayer electrode. The inclusion of the ZnO nanoparticle layer results in a solar cell displaying a conversion efficiency increase and reduces the device degradation rate. Embodiments of the invention are directed to novel ZnO nanoparticles that are advantageous for use as the ZnO nanoparticle layers of the novel solar cells and a method to prepare the ZnO nanoparticles.

  13. ZnFe2O4 nanoparticles as radiosensitizers in radiotherapy of human prostate cancer cells.

    PubMed

    Meidanchi, Alireza; Akhavan, Omid; Khoei, Samideh; Shokri, Ali A; Hajikarimi, Zahra; Khansari, Nakisa

    2015-01-01

    Nanoparticles of high-Z elements exhibit stronger photoelectric effects than soft tissues under gamma irradiation. Hence, they can be used as effective radiosensitizers for increasing the efficiency of current radiotherapy. In this work, superparamagnetic zinc ferrite spinel (ZnFe2O4) nanoparticles were synthesized by a hydrothermal reaction method and used as radiosensitizers in cancer therapy. The magnetic nanoparticles showed fast separation from solutions (e.g., ~1 min for 2 mg mL(-1) of the nanoparticles in ethanol) by applying an external magnetic field (~1T). The ZnFe2O4 nanoparticles were applied in an in vitro radiotherapy of lymph node carcinoma of prostate cells (as high radioresistant cells) under gamma irradiation of (60)Co source. The nanoparticles exhibited no significant effects on the cancer cells up to the high concentration of 100 ?g mL(-1), in the absence of gamma irradiation. The gamma irradiation alone (2Gy dose) also showed no significant effects on the cells. However, gamma irradiation in the presence of 100 ?g mL(-1) ZnFe2O4 nanoparticles resulted in ~53% inactivation of the cells (~17 times higher than the inactivation that occurred under gamma irradiation alone) after 24h. The higher cell inactivation was assigned to interaction of gamma radiation with nanoparticles (photoelectric effect), resulting in a high level electron release in the media of the radioresistant cells. Our results indicated that ZnFe2O4 nanoparticles not only can be applied in increasing the efficiency of radiotherapy, but also can be easily separated from the cell environment by using an external magnetic field after the radiotherapy. PMID:25492003

  14. Nanoparticle Solar Cell Final Technical Report

    SciTech Connect

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

    2008-06-17

    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.

  15. Analysis of the Cytotoxicity of Carbon-Based Nanoparticles, Diamond and Graphite, in Human Glioblastoma and Hepatoma Cell Lines

    PubMed Central

    Wierzbicki, Mateusz; Jaworski, S?awomir; Kutwin, Marta; Sawosz, Ewa; Chwalibog, André; Pijanowska, Dorota Genowefa; Pluta, Krzysztof Dariusz

    2015-01-01

    Nanoparticles have attracted a great deal of attention as carriers for drug delivery to cancer cells. However, reports on their potential cytotoxicity raise questions of their safety and this matter needs attentive consideration. In this paper, for the first time, the cytotoxic effects of two carbon based nanoparticles, diamond and graphite, on glioblastoma and hepatoma cells were compared. First, we confirmed previous results that diamond nanoparticles are practically nontoxic. Second, graphite nanoparticles exhibited a negative impact on glioblastoma, but not on hepatoma cells. The studied carbon nanoparticles could be a potentially useful tool for therapeutics delivery to the brain tissue with minimal side effects on the hepatocytes. Furthermore, we showed the influence of the nanoparticles on the stable, fluorescently labeled tumor cell lines and concluded that the labeled cells are suitable for drug cytotoxicity tests. PMID:25816103

  16. Colloidal Nanoparticles for Intermediate Band Solar Cells.

    PubMed

    Vörös, Márton; Galli, Giulia; Zimanyi, Gergely T

    2015-07-28

    The Intermediate Band (IB) solar cell concept is a promising idea to transcend the Shockley-Queisser limit. Using the results of first-principles calculations, we propose that colloidal nanoparticles (CNPs) are a viable and efficient platform for the implementation of the IB solar cell concept. We focused on CdSe CNPs and we showed that intragap states present in the isolated CNPs with reconstructed surfaces combine to form an IB in arrays of CNPs, which is well separated from the valence and conduction band edges. We demonstrated that optical transitions to and from the IB are active. We also showed that the IB can be electron doped in a solution, e.g., by decamethylcobaltocene, thus activating an IB-induced absorption process. Our results, together with the recent report of a nearly 10% efficient CNP solar cell, indicate that colloidal nanoparticle intermediate band solar cells are a promising platform to overcome the Shockley-Queisser limit. PMID:26042468

  17. Biocompatibility of cerium dioxide and silicon dioxide nanoparticles with endothelial cells

    PubMed Central

    Strobel, Claudia; Förster, Martin

    2014-01-01

    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

  18. Cell-Mediated Delivery of Nanoparticles: Taking Advantage of Circulatory Cells to Target Nanoparticles

    PubMed Central

    Anselmo, Aaron C.; Mitragotri, Samir

    2014-01-01

    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

  19. Synthesis of folate- pegylated polyester nanoparticles encapsulating ixabepilone for targeting folate receptor overexpressing breast cancer cells.

    PubMed

    Siafaka, P; Betsiou, M; Tsolou, A; Angelou, E; Agianian, B; Koffa, M; Chaitidou, S; Karavas, E; Avgoustakis, K; Bikiaris, D

    2015-12-01

    The aim of this study was the preparation of novel polyester nanoparticles based on folic acid (FA)-functionalized poly(ethylene glycol)-poly(propylene succinate) (PEG-PPSu) copolymer and loaded with the new anticancer drug ixabepilone (IXA). These nanoparticles may serve as a more selective (targeted) treatment of breast cancer tumors overexpressing the folate receptor. The synthesized materials were characterized by (1)H-NMR, FTIR, XRD and DSC. The nanoparticles were prepared by a double emulsification and solvent evaporation method and characterized with regard to their morphology by scanning electron microscopy, drug loading with HPLC-UV and size by dynamic light scattering. An average size of 195 nm and satisfactory drug loading efficiency (3.5 %) were observed. XRD data indicated that IXA was incorporated into nanoparticles in amorphous form. The nanoparticles exhibited sustained drug release properties in vitro. Based on in vitro cytotoxicity studies, the blank FA-PEG-PPSu nanoparticles were found to be non-toxic to the cells. Fluorescent nanoparticles were prepared by conjugating Rhodanine B to PEG-PPSu, and live cell, fluorescence, confocal microscopy was applied in order to demonstrate the ability of FA-PEG-PPSu nanoparticles to enter into human breast cancer cells expressing the folate receptor. PMID:26543021

  20. Gold Nanoparticles Enhanced Electroporation for Mammalian Cell Transfection

    PubMed Central

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

    2015-01-01

    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

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

    PubMed

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

    2014-08-01

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

  2. Detection of squamous carcinoma cells using gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Dai, Wei-Yun; Lee, Sze-tsen; Hsu, Yih-Chih

    2015-03-01

    The goal of this study is to use gold nanoparticle as a diagnostic agent to detect human squamous carcinoma cells. Gold nanoparticles were synthesized and the gold nanoparticle size was 34.3 ± 6.2 nm. Based on the over-expression of epidermal growth factor receptor (EGFR) biomarkers in squamous carcinoma cells, we hypothesized that EGFR could be a feasible biomarker with a target moiety for detection. We further modified polyclonal antibodies of EGFR on the surface of gold nanoparticles. We found selected squamous carcinoma cells can be selectively detected using EGFR antibody-modified gold nanoparticles via receptor-mediated endocytosis. Cell death was also examined to determine the survival status of squamous carcinoma cells with respect to gold nanoparticle treatment and EGFR polyclonal antibody modification.

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

    NASA Astrophysics Data System (ADS)

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

    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.

  4. Canine Osteosarcoma Cells Exhibit Resistance to Aurora Kinase Inhibitors

    PubMed Central

    Cannon, Claire M.; Pozniak, John; Scott, Milcah C.; Ito, Daisuke; Gorden, Brandi H.; Graef, Ashley J.; Modiano, Jaime F.

    2015-01-01

    We evaluated the effect of Aurora kinase inhibitors AZD1152 and VX680 on canine osteosarcoma cell lines. Cytotoxicity was seen in all four cell lines; however, half-maximal inhibitory concentrations were significantly higher than in human and canine leukemia cells. AZD1152 reduced Aurora kinase B phosphorylation, indicating resistance was not due to failure of target recognition. Efflux mediated by ABCB1 and ABCG2 transporters is one known mechanism of resistance against these drugs and verapamil enhanced AZD1152-induced apoptosis; however, these transporters were only expressed by a small percentage of cells in each line and the effects of verapamil were modest, suggesting other mechanisms contribute to resistance. Our results indicate canine osteosarcoma cells are resistant to Aurora kinase inhibitors and suggest that these compounds are unlikely to be useful as single agents for this disease. Further investigation of these resistance mechanisms and the potential utility of Aurora kinase inhibitors in multi-agent protocols is warranted. PMID:23410058

  5. Histone H1 null vertebrate cells exhibit altered nucleosome architecture

    PubMed Central

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

    2010-01-01

    In eukaryotic nuclei, DNA is wrapped around an octamer of core histones to form nucleosomes, and chromatin fibers are thought to be stabilized by linker histones of the H1 type. Higher eukaryotes express multiple variants of histone H1; chickens possess six H1 variants. Here, we generated and analyzed the phenotype of a complete deletion of histone H1 genes in chicken cells. The H1-null cells showed decreased global nucleosome spacing, expanded nuclear volumes, and increased chromosome aberration rates, although proper mitotic chromatin structure appeared to be maintained. Expression array analysis revealed that the transcription of multiple genes was affected and was mostly downregulated in histone H1-deficient cells. This report describes the first histone H1 complete knockout cells in vertebrates and suggests that linker histone H1, while not required for mitotic chromatin condensation, plays important roles in nucleosome spacing and interphase chromatin compaction and acts as a global transcription regulator. PMID:20156997

  6. Modified Bleomycin Disaccharides Exhibiting Improved Tumor Cell Targeting

    PubMed Central

    2015-01-01

    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

  7. Cerium fluoride nanoparticles protect cells against oxidative stress.

    PubMed

    Shcherbakov, Alexander B; Zholobak, Nadezhda M; Baranchikov, Alexander E; Ryabova, Anastasia V; Ivanov, Vladimir K

    2015-05-01

    A novel facile method of non-doped and fluorescent terbium-doped cerium fluoride stable aqueous sols synthesis is proposed. Intense green luminescence of CeF3:Tb nanoparticles can be used to visualize these nanoparticles' accumulation in cells using confocal laser scanning microscopy. Cerium fluoride nanoparticles are shown for the first time to protect both organic molecules and living cells from the oxidative action of hydrogen peroxide. Both non-doped and terbium-doped CeF3 nanoparticles are shown to provide noteworthy protection to cells against the vesicular stomatitis virus. PMID:25746257

  8. Protein Corona Influences Cellular Uptake of Gold Nanoparticles by Phagocytic and Nonphagocytic Cells in a Size-Dependent Manner.

    PubMed

    Cheng, Xiaju; Tian, Xin; Wu, Anqing; Li, Jianxiang; Tian, Jian; Chong, Yu; Chai, Zhifang; Zhao, Yuliang; Chen, Chunying; Ge, Cuicui

    2015-09-23

    The interaction at nanobio is a critical issue in designing safe nanomaterials for biomedical applications. Recent studies have reported that it is nanoparticle-protein corona rather than bare nanoparticle that determines the nanoparticle-cell interactions, including endocytic pathway and biological responses. Here, we demonstrate the effects of protein corona on cellular uptake of different sized gold nanoparticles in different cell lines. The experimental results show that protein corona significantly decreases the internalization of Au NPs in a particle size- and cell type-dependent manner. Protein corona exhibits much more significant inhibition on the uptake of large-sized Au NPs by phagocytic cell than that of small-sized Au NPs by nonphagocytic cell. The endocytosis experiment indicates that different endocytic pathways might be responsible for the differential roles of protein corona in the interaction of different sized Au NPs with different cell lines. Our findings can provide useful information for rational design of nanomaterials in biomedical application. PMID:26364560

  9. Inhibiting EGFR clustering and cell proliferation with gold nanoparticles.

    PubMed

    Paviolo, Chiara; Chon, James W M; Clayton, Andrew H A

    2015-04-01

    Gold nanoparticles are functionalized with epidermal growth factor (EGF) molecules and incubated with HeLa cells. These new complexes mechanically interfere with the activation of EGF receptors in a length-dependent manner. Protein-functionalized gold nanoparticles hold great potential for unveiling the fundamental characteristics of cell receptors and for future pharmacological studies on receptor targeting. PMID:25504553

  10. Trypsinization-dependent cell labeling with fluorescent nanoparticles

    PubMed Central

    2014-01-01

    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

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

    PubMed

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

    2014-07-01

    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

  12. Paclitaxel-loaded poly(D,L-lactide-co-glycolide) nanoparticles for radiotherapy in hypoxic human tumor cells in vitro.

    PubMed

    Jin, Cheng; Bai, Ling; Wu, Hong; Liu, Junye; Guo, Guozhen; Chen, Jingyuan

    2008-06-01

    Radioresistant hypoxic cells may contribute to the failure of radiation therapy in controlling certain tumors. Some studies have suggested the radiosensitizing effect of paclitaxel. The poly (D,L-lactide-co-glycolide)(PLGA) nanoparticles containing paclitaxel were prepared by o/w emulsification-solvent evaporation method. The physicochemical characteristics of the nanoparticles (i.e., encapsulation efficiency, particle size distribution, morphology, in vitro release) were studied. The morphology of the two human tumor cell lines: a carcinoma cervicis (HeLa) and a hepatoma (HepG(2)), treated with paclitaxel-loaded nanoparticles was photomicrographed. Flow cytometry was used to quantify the number of the tumor cells held in the G(2)/M phase of the cell cycle. The cellular uptake of nanoparticles was evaluated by transmission electronic microscopy. Cell viability was determined by the ability of single cell to form colonies in vitro. The prepared nanoparticles were spherical in shape with size between 200 nm and 800 nm. The encapsulation efficiency was 85.5%. The release behaviour of paclitaxel from the nanoparticles exhibited a biphasic pattern characterised by a fast initial release during the first 24 h, followed by a slower and continuous release. Co-culture of the two tumor cell lines with paclitaxel-loaded nanoparticles demonstrated that the cell morphology was changed and the released paclitaxel retained its bioactivity to block cells in the G(2)/M phase. The cellular uptake of nanoparticles was observed. The free paclitaxel and paclitaxel-loaded nanoparticles effectively sensitized hypoxic HeLa and HepG(2) cells to radiation. Under this experimental condition, the radiosensitization of paclitaxel-loaded nanoparticles was more significant than that of free paclitaxel. PMID:18367873

  13. Manipulating directional cell motility using intracellular superparamagnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Bradshaw, Michael; Clemons, Tristan D.; Ho, Diwei; Gutiérrez, Lucía; Lázaro, Francisco J.; House, Michael J.; St. Pierre, Timothy G.; Fear, Mark W.; Wood, Fiona M.; Iyer, K. Swaminathan

    2015-03-01

    This study investigated the ability for magnetic nanoparticles to influence cellular migration in the presence of an external magnetic field. We found that the direction of migrating keratinocytes can be controlled and the migration speed of fibroblasts can be increased with the internalisation of these nanoparticles in the presence of a magnetic field. The possibility of shepherding cells towards a region of interest through the use of internalized nanoparticles is an attractive prospect for cell tracking, cell therapies, and tissue engineering applications.This study investigated the ability for magnetic nanoparticles to influence cellular migration in the presence of an external magnetic field. We found that the direction of migrating keratinocytes can be controlled and the migration speed of fibroblasts can be increased with the internalisation of these nanoparticles in the presence of a magnetic field. The possibility of shepherding cells towards a region of interest through the use of internalized nanoparticles is an attractive prospect for cell tracking, cell therapies, and tissue engineering applications. Electronic supplementary information (ESI) available: Nanoparticle characterisation, supporting experimental data, video time course study of cellular uptake of the nanoparticles and complete experimental details are all provided in the ESI. See DOI: 10.1039/c4nr06594h

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

    NASA Astrophysics Data System (ADS)

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

    2014-08-01

    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.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. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr02008a

  15. Hsp70 as an indicator of stress in the cells after contact with nanoparticles

    NASA Astrophysics Data System (ADS)

    Hardilová, Šárka; Havrdová, Markéta; Paná?ek, Aleš; Kvítek, Libor; Zbo?il, Radek

    2015-05-01

    In recent years, production of nanoparticles is increased and thus grows our contact with them too. Question of safety is closely related to the issue of use nanoparticles. There are a number of tests that monitor the viability, ROS production, the effect on the DNA and cell cycle, however, rarely encountered studies on stress in the cells after contact with nanoparticles. Heat shock proteins (HSP) are among the substances that can be used for monitoring stress in cells. HSP are structures with a chaperone activity. They are evolutionarily very old, conservative and they are found with a high degree of homology in prokaryotes and eukaryotes including humans. They exist at low concentrations under physiological conditions, while in the denaturing conditions e.g. high or low temperature, radiation, exposure to chemicals, heavy metals, or nanoparticles their expression is changed. HSPs are involved in maintaining homeostasis in the cell that the denatured protein conformations allow recovery to the original stage. One of the most common proteins from HSP family is Hsp70 - protein with a molecular weight of 70 kDa. The level of Hsp70 in a cell after exposure to the stress changes depending on the stress level to which the cell is exposed to and a time period during which lasted stressful conditions. Our research monitors stress levels of cells manifesting by Hsp70 production after contact with silver nanoparticles. Nanoparticles show different toxicity towards different types of target cells, which is reflected in the values of IC50 - concentration that kills 50% tested cells. Concentration of test substance toxic to one cell type may be innocuous to cells of another type. IC50 obtained from the MTT assay provides a suitable default data and if multiples of IC50 values are used, we can compare and generalize. Studies can be used to compare stress levels in cells that show different sensitivity to the tested nanoparticles compared with cells under optimal growth conditions. The study was done on two types of mouse fibroblasts NIH-3T3 and L929. While NIH-3T3 cells exhibit stress response proportional to the concentration of silver nanoparticles, for L929 cells this was not observed.

  16. Femto-, pico- and nano-second refractive nonlinearities exhibited by Au nanoparticles

    NASA Astrophysics Data System (ADS)

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

    2011-09-01

    Gold nanoparticles (AuNPs) have proven to be powerful tools in various ultrafast photonic, plasmonic and nanomedical applications. Numerous advances in the use of AuNPs include research on their interesting and remarkably fast changes influenced by Surface Plasmon Resonance excitations. Within this work we report theoretical and experimental results for the physical mechanisms that originate a nonlinearity of refractive index during different temporal regimes for a high-purity silica matrix containing Au nanoparticles. The nanocomposites were prepared by ion implantation into a silica matrix, followed by a thermal annealing. We used an optical Kerr gate with 80 fs pulses at 830 nm and a vectorial self-diffraction technique with 26 ps and with 7 ns at 532 nm in order to investigate the magnitude and response time of the resulting third order nonlinearity. In all cases we were able to measure and identify an electronic polarization responsible for the nonlinear refraction. For the pico- and nano-second near resonance irradiations, a contribution of a thermal effect could be stimulated and then the optical Kerr response enhanced. The presence of saturable absorption for the pico- and nano-second experiments was measured. We observe that our samples behave like waveguides in the near infrared spectrum and we estimate that they posses potential applications for all-optical switching devices.

  17. Controlled self-assembly of multiferroic core-shell nanoparticles exhibiting strong magneto-electric effects

    SciTech Connect

    Sreenivasulu, Gollapudi; Hamilton, Sean L.; Lehto, Piper R.; Srinivasan, Gopalan; Popov, Maksym; Chavez, Ferman A.

    2014-02-03

    Ferromagnetic-ferroelectric composites show strain mediated coupling between the magnetic and electric sub-systems due to magnetostriction and piezoelectric effects associated with the ferroic phases. We have synthesized core-shell multiferroic nano-composites by functionalizing 10–100?nm barium titanate and nickel ferrite nanoparticles with complementary coupling groups and allowing them to self-assemble in the presence of a catalyst. The core-shell structure was confirmed by electron microscopy and magnetic force microscopy. Evidence for strong strain mediated magneto-electric coupling was obtained by static magnetic field induced variations in the permittivity over 16–18?GHz and polarization and by electric field induced by low-frequency ac magnetic fields.

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

    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.

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

    PubMed

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

    2014-01-01

    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

  20. Detecting and Tracking Nonfluorescent Nanoparticles Probes in Live Cells

    SciTech Connect

    Wang, Gufeng; Fang, Ning

    2012-01-17

    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.

  1. Uptake and cytotoxicity of chitosan nanoparticles in human liver cells

    SciTech Connect

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

    2010-12-01

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

  2. EphB4 Expressing Stromal Cells Exhibit an Enhanced Capacity for Hematopoietic Stem Cell Maintenance.

    PubMed

    Nguyen, Thao M; Arthur, Agnieszka; Panagopoulos, Romana; Paton, Sharon; Hayball, John D; Zannettino, Andrew C W; Purton, Louise E; Matsuo, Koichi; Gronthos, Stan

    2015-09-01

    The tyrosine kinase receptor, EphB4, mediates cross-talk between stromal and hematopoietic populations during bone remodeling, fracture repair and arthritis, through its interactions with the ligand, ephrin-B2. This study demonstrated that transgenic EphB4 mice (EphB4 Tg), over-expressing EphB4 under the control of collagen type-1 promoter, exhibited higher frequencies of osteogenic cells and hematopoietic stem/progenitor cells (HSC), correlating with a higher frequency of long-term culture-initiating cells (LTC-IC), compared with wild type (WT) mice. EphB4 Tg stromal feeder layers displayed a greater capacity to support LTC-IC in vitro, where blocking EphB4/ephrin-B2 interactions decreased LTC-IC output. Similarly, short hairpin RNA-mediated EphB4 knockdown in human bone marrow stromal cells reduced their ability to support high ephrin-B2 expressing CD34(+) HSC in LTC-IC cultures. Notably, irradiated EphB4 Tg mouse recipients displayed enhanced bone marrow reconstitution capacity and enhanced homing efficiency of transplanted donor hematopoietic stem/progenitor cells relative to WT controls. Studies examining the expression of hematopoietic supportive factors produced by stromal cells indicated that CXCL12, Angiopoietin-1, IL-6, FLT-3 ligand, and osteopontin expression were more highly expressed in EphB4 Tg stromal cells compared with WT controls. These findings indicate that EphB4 facilitates stromal-mediated support of hematopoiesis, and constitute a novel component of the HSC niche. PMID:26033476

  3. Nanoparticle-Based ARV Drug Combinations for Synergistic Inhibition of Cell-Free and Cell-Cell HIV Transmission.

    PubMed

    Jiang, Yonghou; Cao, Shijie; Bright, Danielle K; Bever, Alaina M; Blakney, Anna K; Suydam, Ian T; Woodrow, Kim A

    2015-12-01

    Nanocarrier-based drug delivery systems are playing an emerging role in human immunodeficiency virus (HIV) chemoprophylaxis and treatment due to their ability to alter the pharmacokinetics and improve the therapeutic index of various antiretroviral (ARV) drug compounds used alone and in combination. Although several nanocarriers have been described for combination delivery of ARV drugs, measurement of drug-drug activities facilitated by the use of these nanotechnology platforms has not been fully investigated for topical prevention. Here, we show that physicochemically diverse ARV drugs can be encapsulated within polymeric nanoparticles to deliver multidrug combinations that provide potent HIV chemoprophylaxis in relevant models of cell-free, cell-cell, and mucosal tissue infection. In contrast to existing approaches that coformulate ARV drug combinations together in a single nanocarrier, we prepared single-drug-loaded nanoparticles that were subsequently combined upon administration. ARV drug-nanoparticles were prepared using emulsion-solvent evaporation techniques to incorporate maraviroc (MVC), etravirine (ETR), and raltegravir (RAL) into poly(lactic-co-glycolic acid) (PLGA) nanoparticles. We compared the antiviral potency of the free and formulated drug combinations for all pairwise and triple drug combinations against both cell-free and cell-associated HIV-1 infection in vitro. The efficacy of ARV-drug nanoparticle combinations was also assessed in a macaque cervicovaginal explant model using a chimeric simian-human immunodeficiency virus (SHIV) containing the reverse transcriptase (RT) of HIV-1. We observed that our ARV-NPs maintained potent HIV inhibition and were more effective when used in combinations. In particular, ARV-NP combinations involving ETR-NP exhibited significantly higher antiviral potency and dose-reduction against both cell-free and cell-associated HIV-1 BaL infection in vitro. Furthermore, ARV-NP combinations that showed large dose-reduction were identified to be synergistic, whereas the equivalent free-drug combinations were observed to be strictly additive. Higher intracellular drug concentration was measured for cells dosed with the triple ARV-NP combination compared to the equivalent unformulated drugs. Finally, as a first step toward evaluating challenge studies in animal models, we also show that our ARV-NP combinations inhibit RT-SHIV virus propagation in macaque cervicovaginal tissue and block virus transmission by migratory cells emigrating from the tissue. Our results demonstrate that ARV-NP combinations control HIV-1 transmission more efficiently than free-drug combinations. These studies provide a rationale to better understand the role of nanocarrier systems in facilitating multidrug effects in relevant cells and tissues associated with HIV infection. PMID:26529558

  4. Silver polyvinyl pyrrolidone nanoparticles exhibit a capsular polysaccharide influenced bactericidal effect against Streptococcus pneumoniae

    PubMed Central

    Bibbs, Ronda K.; Harris, Rhonda D.; Peoples, Veolanda A.; Barnett, Cleon; Singh, Shree R.; Dennis, Vida A.; Coats, Mamie T.

    2014-01-01

    Streptococcus pneumoniae remains a leading cause of morbidity and mortality worldwide. The highly adaptive nature of S. pneumoniae exemplifies the need for next generation antimicrobials designed to avoid high level resistance. Metal based nanomaterials fit this criterion. Our study examined the antimicrobial activity of gold nanospheres, silver coated polyvinyl pyrrolidone (AgPVP), and titanium dioxide (TiO2) against various serotypes of S. pneumoniae. Twenty nanometer spherical AgPVP demonstrated the highest level of killing among the tested materials. AgPVP (0.6 mg/mL) was able to kill pneumococcal serotypes 2, 3, 4, and 19F within 4 h of exposure. Detailed analysis of cultures during exposure to AgPVP showed that both the metal ions and the solid nanoparticles participate in the killing of the pneumococcus. The bactericidal effect of AgPVP was lessened in the absence of the pneumococcal capsular polysaccharide. Capsule negative strains, JD908 and RX1, were only susceptible to AgPVP at concentrations at least 33% higher than their respective capsule expressing counterparts. These findings suggest that mechanisms of killing used by nanomaterials are not serotype dependent and that the capsular polysaccharide participates in the inhibition. In the near future these mechanisms will be examined as targets for novel antimicrobials. PMID:25520713

  5. Size-dependent cytotoxicity of europium doped NaYF ? nanoparticles in endothelial cells.

    PubMed

    Chen, Shizhu; Zhang, Cuimiao; Jia, Guang; Duan, Jianlei; Wang, Shuxiang; Zhang, Jinchao

    2014-10-01

    Lanthanide-doped sodium yttrium fluoride (NaYF4) nanoparticles exhibit novel optical properties which make them be widely used in various fields. The extensive applications increase the chance of human exposure to these nanoparticles and thus raise deep concerns regarding their riskiness. In the present study, we have synthesized europium doped NaYF4 (NaYF4:Eu(3+)) nanoparticles with three diameters and used endothelial cells (ECs) as a cell model to explore the potential toxic effect. The cell viability, cytomembrane integrity, cellular uptake, intracellular localization, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), apoptosis detection, caspase-3 activity and expression of inflammatory gene were studied. The results indicated that these nanoparticles could be uptaken into ECs and decrease the cell viability, induce the intracellular lactate dehydrogenase (LDH) release, increase the ROS level, and decrease the cell MMP in a size-dependent manner. Besides that, the cells were suffered to apoptosis with the caspase-3 activation, and the inflammation specific gene expressions (ICAM1 and VCAM1) were also increased. Our results suggest that the damage pathway may be related to the ROS generation and mitochondrial damage. The results provide novel evidence to elucidate their toxicity mechanisms and may be helpful for more rational applications of these compounds in the future. PMID:25175221

  6. Genotoxicity of Superparamagnetic Iron Oxide Nanoparticles in Granulosa Cells

    PubMed Central

    Pöttler, Marina; Staicu, Andreas; Zaloga, Jan; Unterweger, Harald; Weigel, Bianca; Schreiber, Eveline; Hofmann, Simone; Wiest, Irmi; Jeschke, Udo; Alexiou, Christoph; Janko, Christina

    2015-01-01

    Nanoparticles that are aimed at targeting cancer cells, but sparing healthy tissue provide an attractive platform of implementation for hyperthermia or as carriers of chemotherapeutics. According to the literature, diverse effects of nanoparticles relating to mammalian reproductive tissue are described. To address the impact of nanoparticles on cyto- and genotoxicity concerning the reproductive system, we examined the effect of superparamagnetic iron oxide nanoparticles (SPIONs) on granulosa cells, which are very important for ovarian function and female fertility. Human granulosa cells (HLG-5) were treated with SPIONs, either coated with lauric acid (SEONLA) only, or additionally with a protein corona of bovine serum albumin (BSA; SEONLA-BSA), or with dextran (SEONDEX). Both micronuclei testing and the detection of ?H2A.X revealed no genotoxic effects of SEONLA-BSA, SEONDEX or SEONLA. Thus, it was demonstrated that different coatings of SPIONs improve biocompatibility, especially in terms of genotoxicity towards cells of the reproductive system. PMID:26540051

  7. Nanoparticle-labeled stem cells: a novel therapeutic vehicle

    PubMed Central

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

    2010-01-01

    Nanotechnology has been described as a general purpose technology. It has already generated a range of inventions and innovations. Development of nanotechnology will provide clinical medicine with a range of new diagnostic and therapeutic opportunities such as medical imaging, medical diagnosis, drug delivery, and cancer detection and management. Nanoparticles such as manganese, polystyrene, silica, titanium oxide, gold, silver, carbon, quantum dots, and iron oxide have received enormous attention in the creation of new types of analytical tools for biotechnology and life sciences. Labeling of stem cells with nanoparticles overcame the problems in homing and fixing stem cells to their desired site and guiding extension of stem cells to specific directions. Although the biologic effects of some nanoparticles have already been assessed, information on toxicity and possible mechanisms of various particle types remains inadequate. The aim of this review is to give an overview of the mechanisms of internalization and distribution of nanoparticles inside stem cells, as well as the influence of different types of nanoparticles on stem cell viability, proliferation, differentiation, and cytotoxicity, and to assess the role of nanoparticles in tracking the fate of stem cells used in tissue regeneration. PMID:22291483

  8. Size Effect of YSZ Nanoparticles on Sintering of Ni Nanoparticles in Ni/YSZ Anode of Solid Oxide Fuel Cell via Multi-Nanoparticle Molecular Dynamics Simulation

    NASA Astrophysics Data System (ADS)

    Xu, Jingxiang; Higuchi, Yuji; Ozawa, Nobuki; Kubo, Momoji

    2015-03-01

    Sintering of Ni nanoparticles leads to the degradation of a Ni/YSZ porous electrode of solid oxide fuel cell. We reported that the YSZ nanoparticle framework plays an important role in inhibition of sintering by using our multi-nanoparticle molecular dynamics simulation method. Size of YSZ nanoparticles affects the framework of YSZ nanoparticles and changes the sintering in Ni/YSZ porous structure. However, the mechanism of different sintering behavior by changing the size of YSZ nanoparticle has not been revealed. In this study, we used our multi-nanoparticle molecular dynamics simulation method to investigate the size effect of YSZ nanoparticles on the sintering of Ni nanoparticles in the Ni/YSZ porous structure. Then, Ni nanoparticles make contact with each other and the sintering proceeds by growth of contact area between Ni nanoparticles when YSZ nanoparticles are large. In contrast, the sintering of Ni nanoparticles is suppressed when YSZ nanoparticles are small. It is found that interfacial area between Ni and YSZ in the small YSZ nanoparticles model is larger than that in the large YSZ nanoparticles model. Thus, the movement of Ni nanoparticles is disturbed, and the sintering is inhibited.

  9. Plasmonic silver nanoparticles loaded titania nanotube arrays exhibiting enhanced photoelectrochemical and photocatalytic activities

    NASA Astrophysics Data System (ADS)

    Nishanthi, S. T.; Iyyapushpam, S.; Sundarakannan, B.; Subramanian, E.; Pathinettam Padiyan, D.

    2015-01-01

    A combination of electrochemical anodization and photochemical reduction is employed to fabricate highly ordered silver loaded titania nanotubes (Ag/TNT) arrays. The Ag/TNT samples show an extended optical absorbance from UV to visible region owing to the surface plasmon resonance effect of Ag. The photoluminescence intensity of Ag/TNT is significantly lower than that of pure titania revealing a decrease in charge carrier recombination. The photoelectrochemical properties of the prepared samples are studied using linear sweep and transient photocurrent measurements. Compared with pure TNT, the Ag loaded samples show a higher photoelectrochemical activity. The results demonstrate an efficient separation of photogenerated electron-hole pairs and the consequent increase in lifetime of charge carriers by Ag/TNT. The photocatalytic results of methyl orange dye degradation show that the Ag/TNT-3-05 sample exhibits the maximum degradation efficiency of 98.85% with kinetic rate constant of 0.0236(5) min-1 for 180 min light illumination.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  11. Enhanced magnetic resonance imaging and staining of cancer cells using ferrimagnetic H-ferritin nanoparticles with increasing core size

    PubMed Central

    Cai, Yao; Cao, Changqian; He, Xiaoqing; Yang, Caiyun; Tian, Lanxiang; Zhu, Rixiang; Pan, Yongxin

    2015-01-01

    Purpose This study is to demonstrate the nanoscale size effect of ferrimagnetic H-ferritin (M-HFn) nanoparticles on magnetic properties, relaxivity, enzyme mimetic activities, and application in magnetic resonance imaging (MRI) and immunohistochemical staining of cancer cells. Materials and methods M-HFn nanoparticles with different sizes of magnetite cores in the range of 2.7–5.3 nm were synthesized through loading different amounts of iron into recombinant human H chain ferritin (HFn) shells. Core size, crystallinity, and magnetic properties of those M-HFn nanoparticles were analyzed by transmission electron microscope and low-temperature magnetic measurements. The MDA-MB-231 cancer cells were incubated with synthesized M-HFn nanoparticles for 24 hours in Dulbecco’s Modified Eagle’s Medium. In vitro MRI of cell pellets after M-HFn labeling was performed at 7 T. Iron uptake of cells was analyzed by Prussian blue staining and inductively coupled plasma mass spectrometry. Immunohistochemical staining by using the peroxidase-like activity of M-HFn nanoparticles was carried out on MDA-MB-231 tumor tissue paraffin sections. Results The saturation magnetization (Ms), relaxivity, and peroxidase-like activity of synthesized M-HFn nanoparticles were monotonously increased with the size of ferrimagnetic cores. The M-HFn nanoparticles with the largest core size of 5.3 nm exhibit the strongest saturation magnetization, the highest peroxidase activity in immunohistochemical staining, and the highest r2 of 321 mM?1 s?1, allowing to detect MDA-MB-231 breast cancer cells as low as 104 cells mL?1. Conclusion The magnetic properties, relaxivity, and peroxidase-like activity of M-HFn nanoparticles are size dependent, which indicates that M-HFn nanoparticles with larger magnetite core can significantly enhance performance in MRI and staining of cancer cells. PMID:25878496

  12. Delivering Nanoparticles to Lungs While Avoiding Liver and Spleen through Adsorption on Red Blood Cells

    PubMed Central

    Anselmo, Aaron C.; Gupta, Vivek; Zern, Blaine J.; Pan, Daniel; Zakrewsky, Michael; Muzykantov, Vladimir; Mitragotri, Samir

    2014-01-01

    Nanoparticulate drug delivery systems are one of the most widely investigated approaches for developing novel therapies for a variety of diseases. However, rapid clearance and poor targeting limit their clinical utility. Here, we describe an approach to harness the flexibility, circulation, and vascular mobility of red blood cells (RBCs) to simultaneously overcome these limitations (Cellular Hitchhiking). A non-covalent attachment of nanoparticles to RBCs simultaneously increases their level in blood over a 24 hour period and allows transient accumulation in the lungs, while, reducing their uptake by liver and spleen. RBC-adsorbed nanoparticles exhibited ~3-fold increase in blood persistence and ~7-fold higher accumulation in lungs. RBC-adsorbed nanoparticles improved lung/liver and lung/spleen nanoparticles accumulation by over 15-fold and 10-fold, respectively. Accumulation in lungs is attributed to mechanical transfer of particles from RBC surface to lung endothelium. Independent tracing both nanoparticles and RBCs in vivo confirmed that RBCs themselves do not accumulate in lungs. Attachment of anti-ICAM-1 antibody to the exposed surface of NPs that were attached to RBCs led to further increase in lung targeting and retention over 24 hours. Cellular hitchhiking onto RBCs provides a new platform for improving the blood pharmacokinetics and vascular delivery of nanoparticles while simultaneously avoiding uptake by liver and spleen, thus opening the door for new applications. PMID:24182189

  13. Electrical transport and optical studies of ferromagnetic Cobalt doped ZnO nanoparticles exhibiting a metal-insulator transition

    E-print Network

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

    2007-12-08

    The observed correlation of oxygen vacancies and room temperature ferromagnetic ordering in Co doped ZnO1-o nanoparticles reported earlier (Naeem et al Nanotechnology 17, 2675-2680) has been further explored by transport and optical measurements. In these particles room temperature ferromagnetic ordering had been observed to occur only after annealing in forming gas. In the current work the optical properties have been studied by diffuse reflection spectroscopy in the UV-Vis region and the band gap of the Co doped compositions has been found to decrease with Co addition. Reflections minima are observed at the energies characteristic of Co+2 d-d (tethrahedral symmetry) crystal field transitions, further establishing the presence of Co in substitutional sites. Electrical transport measurements on palletized samples of the nanoparticles show that the effect of a forming gas is to strongly decrease the resistivity with increasing Co concentration. For the air annealed and non-ferromagnetic samples the variation in the resistivity as a function of Co content are opposite to those observed in the particles prepared in forming gas. The ferromagnetic samples exhibit an apparent change from insulator to metal with increasing temperatures for T>380K and this change becomes more pronounced with increasing Co content. The magnetic and resistive behaviors are correlated by considering the model by Calderon et al [M. J. Calderon and S. D. Sarma, Annals of Physics 2007 (Accepted doi: 10.1016/j.aop.2007.01.010] where the ferromagnetism changes from being mediated by polarons in the low temperature insulating region to being mediated by the carriers released from the weakly bound states in the higher temperature metallic region.

  14. Nanoparticle accumulation and transcytosis in brain endothelial cell layers

    NASA Astrophysics Data System (ADS)

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

    2013-10-01

    The blood-brain barrier (BBB) is a selective barrier, which controls and limits access to the central nervous system (CNS). The selectivity of the BBB relies on specialized characteristics of the endothelial cells that line the microvasculature, including the expression of intercellular tight junctions, which limit paracellular permeability. Several reports suggest that nanoparticles have a unique capacity to cross the BBB. However, direct evidence of nanoparticle transcytosis is difficult to obtain, and we found that typical transport studies present several limitations when applied to nanoparticles. In order to investigate the capacity of nanoparticles to access and transport across the BBB, several different nanomaterials, including silica, titania and albumin- or transferrin-conjugated gold nanoparticles of different sizes, were exposed to a human in vitro BBB model of endothelial hCMEC/D3 cells. Extensive transmission electron microscopy imaging was applied in order to describe nanoparticle endocytosis and typical intracellular localisation, as well as to look for evidence of eventual transcytosis. Our results show that all of the nanoparticles were internalised, to different extents, by the BBB model and accumulated along the endo-lysosomal pathway. Rare events suggestive of nanoparticle transcytosis were also observed for several of the tested materials.The blood-brain barrier (BBB) is a selective barrier, which controls and limits access to the central nervous system (CNS). The selectivity of the BBB relies on specialized characteristics of the endothelial cells that line the microvasculature, including the expression of intercellular tight junctions, which limit paracellular permeability. Several reports suggest that nanoparticles have a unique capacity to cross the BBB. However, direct evidence of nanoparticle transcytosis is difficult to obtain, and we found that typical transport studies present several limitations when applied to nanoparticles. In order to investigate the capacity of nanoparticles to access and transport across the BBB, several different nanomaterials, including silica, titania and albumin- or transferrin-conjugated gold nanoparticles of different sizes, were exposed to a human in vitro BBB model of endothelial hCMEC/D3 cells. Extensive transmission electron microscopy imaging was applied in order to describe nanoparticle endocytosis and typical intracellular localisation, as well as to look for evidence of eventual transcytosis. Our results show that all of the nanoparticles were internalised, to different extents, by the BBB model and accumulated along the endo-lysosomal pathway. Rare events suggestive of nanoparticle transcytosis were also observed for several of the tested materials. Electronic supplementary information (ESI) available: Nanoparticle characterization in relevant media by Dynamic Light Scattering and SDS-PAGE. Transport study for silica nanoparticles across the BBB layer. Additional Electron Microscopy images of cells treated with the different nanoparticles investigated and details of the filters of the transwell systems. See DOI: 10.1039/c3nr02905k

  15. Glucose-conjugated chitosan nanoparticles for targeted drug delivery and their specific interaction with tumor cells

    NASA Astrophysics Data System (ADS)

    Li, Jing; Ma, Fang-Kui; Dang, Qi-Feng; Liang, Xing-Guo; Chen, Xi-Guang

    2014-12-01

    A novel targeted drug delivery system, glucose-conjugated chitosan nanoparticles (GCNPs), was developed for specific recognition and interaction with glucose transporters (Gluts) over-expressed by tumor cells. GC was synthesized by using succinic acid as a linker between glucosamine and chitosan (CS), and successful synthesis was confirmed by NMR and elemental analysis. GCNPs were prepared by ionic crosslinking method, and characterized in terms of morphology, size, and zeta potential. The optimally prepared nanoparticles showed spherical shapes with an average particle size of (187.9 ± 3.8) nm and a zeta potential of (- 15.43 ± 0.31) mV. The GCNPs showed negligible cytotoxicity to mouse embryo fibroblast and 4T1 cells. Doxorubicin (DOX) could be efficiently entrapped into GCNPs, with a loading capacity and encapsulation efficiency of 20.11% and 64.81%, respectively. DOX-loaded nanoparticles exhibited sustained-release behavior in phosphate buffered saline (pH 7.4). In vitro cellular uptake studies showed that the GCNPs had better endocytosis ability than CSNPs, and the antitumor activity of DOX/GCNPs was 4-5 times effectiveness in 4T1 cell killing than that of DOX/CSNPs. All the results demonstrate that nanoparticles decorated with glucose have specific interactions with cancer cells via the recognition between glucose and Gluts. Therefore, Gluts-targeted GCNPs may be promising delivery agents in cancer therapies.

  16. Cancer cells recovering from damage exhibit mitochondrial restructuring and increased aerobic glycolysis

    SciTech Connect

    Akakura, Shin; Ostrakhovitch, Elena; Sanokawa-Akakura, Reiko; Tabibzadeh, Siamak

    2014-06-13

    Highlights: • Some cancer cells recover from severe damage that causes cell death in majority of cells. • Damage-Recovered (DR) cancer cells show reduced mitochondria, mDNA and mitochondrial enzymes. • DR cells show increased aerobic glycolysis, ATP, cell proliferation, and resistance to damage. • DR cells recovered from in vivo damage also show increased glycolysis and proliferation rate. - Abstract: Instead of relying on mitochondrial oxidative phosphorylation, most cancer cells rely heavily on aerobic glycolysis, a phenomenon termed as “the Warburg effect”. We considered that this effect is a direct consequence of damage which persists in cancer cells that recover from damage. To this end, we studied glycolysis and rate of cell proliferation in cancer cells that recovered from severe damage. We show that in vitro Damage-Recovered (DR) cells exhibit mitochondrial structural remodeling, display Warburg effect, and show increased in vitro and in vivo proliferation and tolerance to damage. To test whether cancer cells derived from tumor microenvironment can show similar properties, we isolated Damage-Recovered (T{sup DR}) cells from tumors. We demonstrate that T{sup DR} cells also show increased aerobic glycolysis and a high proliferation rate. These findings show that Warburg effect and its consequences are induced in cancer cells that survive severe damage.

  17. In Vitro Cytotoxicity of Nanoparticles in Mammalian Germline Stem Cells

    PubMed Central

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

    2010-01-01

    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

  18. Three dimensional spheroid cell culture for nanoparticle safety testing.

    PubMed

    Sambale, Franziska; Lavrentieva, Antonina; Stahl, Frank; Blume, Cornelia; Stiesch, Meike; Kasper, Cornelia; Bahnemann, Detlef; Scheper, Thomas

    2015-07-10

    Nanoparticles are widely employed for many applications and the number of consumer products, incorporating nanotechnology, is constantly increasing. A novel area of nanotechnology is the application in medical implants. The widespread use of nanoparticles leads to their higher prevalence in our environment. This, in turn, raises concerns regarding potential risks to humans. Previous studies have shown possible hazardous effects of some nanoparticles on mammalian cells grown in two-dimensional (2D) cultures. However, 2D in vitro cell cultures display several disadvantages such as changes in cell shape, cell function, cell responses and lack of cell-cell contacts. For this reason, the development of better models for mimicking in vivo conditions is essential. In the present work, we cultivated A549 cells and NIH-3T3 cells in three-dimensional (3D) spheroids and investigated the effects of zinc oxide (ZnO-NP) and titanium dioxide nanoparticles (TiO2-NP). The results were compared to cultivation in 2D monolayer culture. A549 cells in 3D cell culture formed loose aggregates which were more sensitive to the toxicity of ZnO-NP in comparison to cells grown in 2D monolayers. In contrast, NIH-3T3 cells showed a compact 3D spheroid structure and no differences in the sensitivity of the NIH-3T3 cells to ZnO-NP were observed between 2D and 3D cultures. TiO2-NP were non-toxic in 2D cultures but affected cell-cell interaction during 3D spheroid formation of A549 and NIH-3T3 cells. When TiO2-NP were directly added during spheroid formation in the cultures of the two cell lines tested, several smaller spheroids were formed instead of a single spheroid. This effect was not observed if the nanoparticles were added after spheroid formation. In this case, a slight decrease in cell viability was determined only for A549 3D spheroids. The obtained results demonstrate the importance of 3D cell culture studies for nanoparticle safety testing, since some effects cannot be revealed in 2D cell culture. PMID:25595712

  19. Nanogel-quantum dot hybrid nanoparticles for live cell imaging

    SciTech Connect

    Hasegawa, Urara; Nomura, Shin-ichiro M.; Kaul, Sunil C.; Hirano, Takashi; Akiyoshi, Kazunari; E-mail: akiyoshi.org@tmd.ac.jp

    2005-06-17

    We report here a novel carrier of quantum dots (QDs) for intracellular labeling. Monodisperse hybrid nanoparticles (38 nm in diameter) of QDs were prepared by simple mixing with nanogels of cholesterol-bearing pullulan (CHP) modified with amino groups (CHPNH{sub 2}). The CHPNH{sub 2}-QD nanoparticles were effectively internalized into the various human cells examined. The efficiency of cellular uptake was much higher than that of a conventional carrier, cationic liposome. These hybrid nanoparticles could be a promising fluorescent probe for bioimaging.

  20. Nanoparticle-GFP “chemical nose” sensor for cancer cells identification

    PubMed Central

    Moyano, Daniel F.; Rotello, Vincent M.

    2014-01-01

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

  1. Encapsulation of honokiol into self-assembled pectin nanoparticles for drug delivery to HepG2 cells.

    PubMed

    Zhang, Yuxia; Chen, Tong; Yuan, Pei; Tian, Rui; Hu, Wenjing; Tang, Yalan; Jia, Yuntao; Zhang, Liangke

    2015-11-20

    Self-assembled pectin nanoparticles was prepared and evaluated for delivering the hydrophobic drug, honokiol (HK), to HepG2 cells. These hydrophobic drug-loaded nanoparticles were developed without using any surfactant and organic solvent. Hydroxypropyl-?-cyclodextrin (HCD) was used to fabricate an inclusion complex with HK (HKHCD) to increase the solubility of the drug and thus facilitate its encapsulation and dispersion in the pectin nanoparticles. Investigation of the in vitro release indicated that the drug-loaded nanoparticles exhibited a higher drug release rate than free honokiol and an effective sustained-release. Cytotoxicity, cell apoptosis and cellular uptake studies further confirmed that the pectin nanoparticles with galactose residues generated higher cytotoxicity than free honokiol on HepG2 cells which highly expressed asialoglycoprotein receptors (ASGR). Nevertheless, these findings were not observed in ASGR-negative A549 cells under similar condition. Therefore, pectin nanoparticles demonstrated a specific active targeting ability to ASGR-positive HepG2 cells and could be used as a potential drug carrier for treatment of liver-related tumors. PMID:26344251

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

    Tissue engineering and advanced manufacturing of human stem cells requires a suite of tools to control gene expression spatiotemporally in culture. Inducible gene expression systems offer cell-extrinsic control, typically through addition of small molecules, but small molecule inducers typically contain few functional groups for further chemical modification. Doxycycline (DXC), a potent small molecule inducer of tetracycline (Tet) transgene systems, was conjugated to a hyperbranched dendritic polymer (Boltorn H40) and subsequently reacted with polyethylene glycol (PEG). The resulting PEG-H40-DXC nanoparticle exhibited pH-sensitive drug release behavior and successfully controlled gene expression in stem-cell-derived fibroblasts with a Tet-On system. While free DXC inhibited fibroblast proliferation and matrix metalloproteinase (MMP) activity, PEG-H40-DXC nanoparticles maintained higher fibroblast proliferation levels and MMP activity. The results demonstrate that the PEG-H40-DXC nanoparticle system provides an effective tool to controlling gene expression in human stem cell derivatives.Tissue engineering and advanced manufacturing of human stem cells requires a suite of tools to control gene expression spatiotemporally in culture. Inducible gene expression systems offer cell-extrinsic control, typically through addition of small molecules, but small molecule inducers typically contain few functional groups for further chemical modification. Doxycycline (DXC), a potent small molecule inducer of tetracycline (Tet) transgene systems, was conjugated to a hyperbranched dendritic polymer (Boltorn H40) and subsequently reacted with polyethylene glycol (PEG). The resulting PEG-H40-DXC nanoparticle exhibited pH-sensitive drug release behavior and successfully controlled gene expression in stem-cell-derived fibroblasts with a Tet-On system. While free DXC inhibited fibroblast proliferation and matrix metalloproteinase (MMP) activity, PEG-H40-DXC nanoparticles maintained higher fibroblast proliferation levels and MMP activity. The results demonstrate that the PEG-H40-DXC nanoparticle system provides an effective tool to controlling gene expression in human stem cell derivatives. Electronic supplementary information (ESI) available: ESI containing 1H NMR spectra and additional fibroblast characterization data. See DOI: 10.1039/c3nr04794f

  3. Nanoparticle-Delivered Antisense MicroRNA-21 Enhances the Effects of Temozolomide on Glioblastoma Cells.

    PubMed

    Ananta, Jeyarama S; Paulmurugan, Ramasamy; Massoud, Tarik F

    2015-12-01

    Glioblastoma (GBM) generally exhibits high IC50 values for its standard drug treatment, temozolomide (TMZ). MicroRNA-21 (miR-21) is an oncomiR overexpressed in GBM, thus controlling important aspects of glioma biology. We hypothesized that PLGA nanoparticles carrying antisense miR-21 to glioblastoma cells might beneficially knock down endogenous miR-21 prior to TMZ treatment. PLGA nanoparticles encapsulating antisense miR-21 were effective in intracellular delivery and sustained silencing (p < 0.01) of miR-21 function in U87 MG, LN229, and T98G cells. Prior antisense miR-21 delivery significantly reduced the number of viable cells (p < 0.001), and increased (1.6-fold) cell cycle arrest at G2/M phase upon TMZ treatment in U87 MG cells. There was overexpression of the miR-21 target genes PTEN (by 67%) and caspase-3 (by 15%) upon cotreatment. This promising PLGA nanoparticle-based platform for antisense miR-21 delivery to GBM is an effective cotherapeutic strategy in cell culture, warranting the need for further studies prior to future clinical translation. PMID:26559642

  4. Investigation of Biophysical Mechanisms in Gold Nanoparticle Mediated Laser Manipulation of Cells Using a Multimodal Holographic and Fluorescence Imaging Setup

    PubMed Central

    Rakoski, Mirko S.; Heinemann, Dag; Schomaker, Markus; Ripken, Tammo; Meyer, Heiko

    2015-01-01

    Laser based cell manipulation has proven to be a versatile tool in biomedical applications. In this context, combining weakly focused laser pulses and nanostructures, e.g. gold nanoparticles, promises to be useful for high throughput cell manipulation, such as transfection and photothermal therapy. Interactions between laser pulses and gold nanoparticles are well understood. However, it is still necessary to study cell behavior in gold nanoparticle mediated laser manipulation. While parameters like cell viability or perforation efficiency are commonly addressed, the influence of the manipulation process on other essential cell parameters is not sufficiently investigated yet. Thus, we set out to study four relevant cell properties: cell volume and area, ion exchange and cytoskeleton structure after gold nanoparticle based laser manipulation. For this, we designed a multimodal imaging and manipulation setup. 200 nm gold nanoparticles were attached unspecifically to canine cells and irradiated by weakly focused 850 ps laser pulses. Volume and area change in the first minute post laser manipulation was monitored using digital holography. Calcium imaging and cells expressing a marker for filamentous actin (F-actin) served to analyze the ion exchange and the cytoskeleton, respectively. High radiant exposures led to cells exhibiting a tendency to shrink in volume and area, possibly due to outflow of cytoplasm. An intracellular raise in calcium was observed and accompanied by an intercellular calcium wave. This multimodal approach enabled for the first time a comprehensive analysis of the cell behavior in gold nanoparticle mediated cell manipulation. Additionally, this work can pave the way for a better understanding and the evaluation of new applications in the context of cell transfection or photothermal therapy. PMID:25909631

  5. Performance enhancement of polymer solar cells using copper oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Wanninayake, Aruna P.; Gunashekar, Subhashini; Li, Shengyi; Church, Benjamin C.; Abu-Zahra, Nidal

    2015-06-01

    Copper oxide (CuO) is a p-type semiconductor with a band gap energy of 1.5 eV, this is close to the ideal energy gap of 1.4 eV required for solar cells to allow good solar spectral absorption. The inherent electrical characteristics of CuO nanoparticles make them attractive candidates for improving the performance of polymer solar cells when incorporated into the active polymer layer. The UV-visible absorption spectra and external quantum efficiency of P3HT/PC70BM solar cells containing different weight percentages of CuO nanoparticles showed a clear enhancement in the photo absorption of the active layer, this increased the power conversion efficiency of the solar cells by 24% in comparison to the reference cell. The short circuit current of the reference cell was found to be 5.234 mA cm-2 and it seemed to increase to 6.484 mA cm-2 in cells containing 0.6 mg of CuO NPs; in addition, the fill factor increased from 61.15% to 68.0%, showing an enhancement of 11.2%. These observations suggest that the optimum concentration of CuO nanoparticles was 0.6 mg in the active layer. These significant findings can be applied to design high-efficiency polymer solar cells containing inorganic nanoparticles.

  6. Toxicity of Cerium Oxide Nanoparticles in Human Lung Cancer Cells

    SciTech Connect

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

    2006-12-31

    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.

  7. Differential nanoreprotoxicity of silver nanoparticles in male somatic cells and spermatogonial stem cells

    PubMed Central

    Zhang, Xi-Feng; Choi, Yun-Jung; Han, Jae Woong; Kim, Eunsu; Park, Jung Hyun; Gurunathan, Sangiliyandi; Kim, Jin-Hoi

    2015-01-01

    Background Silver nanoparticles (AgNPs) possess unique physical, chemical, and biological properties. AgNPs have been increasingly used as anticancer, antiangiogenic, and antibacterial agents for the treatment of bacterial infections in open wounds as well as in ointments, bandages, and wound dressings. The present study aimed to investigate the effects of two different sizes of AgNPs (10 nm and 20 nm) in male somatic Leydig (TM3) and Sertoli (TM4) cells and spermatogonial stem cells (SSCs). Methods Here, we demonstrate a green and simple method for the synthesis of AgNPs using Bacillus cereus culture supernatants. The synthesized AgNPs were characterized using ultraviolet and visible absorption spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and transmission electron microscopy (TEM). The toxicity of the synthesized AgNPs was evaluated by the effects on cell viability, metabolic activity, oxidative stress, apoptosis, and expression of genes encoding steroidogenic and tight junction proteins. Results AgNPs inhibited the viability and proliferation of TM3 and TM4 cells in a dose- and size-dependent manner by damaging cell membranes and inducing the generation of reactive oxygen species, which in turn affected SSC growth on TM3 and TM4 as feeder cells. Small AgNPs (10 nm) were more cytotoxic than medium-sized nanoparticles (20 nm). TEM revealed the presence of AgNPs in the cell cytoplasm and nucleus, and detected mitochondrial damage and enhanced formation of autosomes and autolysosomes in the AgNP-treated cells. Flow cytometry analysis using Annexin V/propidium iodide staining showed massive cell death by apoptosis or necrosis. Real-time polymerase chain reaction and western blot analyses indicated that in TM3 and TM4 cells, AgNPs activated the p53, p38, and pErk1/2 signaling pathways and significantly downregulated the expression of genes related to testosterone synthesis (TM3) and tight junctions (TM4). Furthermore, the exposure of TM3 and TM4 cells to AgNPs inhibited proliferation and self-renewal of SSCs. Conclusion Our results suggest that AgNPs exhibit size-dependent nanoreprotoxicity in male somatic cells and SSCs, strongly suggesting that applications of AgNPs in commercial products must be carefully evaluated. Further studies of AgNPs-induced nanoreprotoxicity in animal models are required. PMID:25733828

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

    PubMed

    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

    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

  9. Human Mesenchymal Stem Cell Spheroids in Fibrin Hydrogels Exhibit Improved Cell Survival and Potential for Bone Healing

    PubMed Central

    Murphy, Kaitlin C.; Fang, Sophia Y.; Leach, J. Kent

    2014-01-01

    Mesenchymal stem cells (MSC) have great therapeutic potential for the repair of nonhealing bone defects due to their proliferative capacity, multilineage potential, trophic factor secretion, and lack of immunogenicity. However, a major barrier to the translation of cell-based therapies into clinical practice is ensuring their survival and function upon implantation into the defect site. We hypothesized that forming MSC into more physiologic 3-dimensional spheroids, rather than employing dissociated cells from 2-dimensional monolayer culture, would enhance their survival when exposed to a harsh microenvironment while maintaining their osteogenic potential. MSC spheroids were formed using the hanging drop method with increasing cell numbers. Compared to larger spheroids, the smallest spheroids which contained 15,000 cells exhibited increased metabolic activity, reduced apoptosis, and the most uniform distribution of proliferating cells. Spheroids were then entrapped in fibrin gels and cultured in serum-free media and 1% oxygen. Compared to identical numbers of dissociated MSC in fibrin gels, spheroids exhibited significantly reduced apoptosis and secreted up to 100-fold more VEGF. We also observed that fibrin gels containing spheroids and those containing an equivalent number of dissociated cells exhibited similar expression levels of early and late markers of osteogenic differentiation. These data demonstrate that MSC spheroids exhibit greater resistance to apoptosis and enhanced proangiogenic potential, while maintaining similar osteogenic potential to dissociated MSC entrapped in a clinically relevant biomaterial, supporting the use of MSC spheroids in cell-based approaches to bone repair. PMID:24781147

  10. Dimers of Melampomagnolide B Exhibit Potent Anticancer Activity against Hematological and Solid Tumor Cells.

    PubMed

    Janganati, Venumadhav; Ponder, Jessica; Jordan, Craig T; Borrelli, Michael J; Penthala, Narsimha Reddy; Crooks, Peter A

    2015-11-25

    Novel carbamate (7a-7h) and carbonate (7i, 7j, and 8) dimers of melampomagnolide B have been synthesized by reaction of the melampomagnolide-B-triazole carbamate synthon 6 with various terminal diamino- and dihydroxyalkanes. Dimeric carbamate products 7b, 7c, and 7f exhibited potent growth inhibition (GI50 = 0.16-0.99 ?M) against the majority of cell lines in the NCI panel of 60 human hematological and solid tumor cell lines. Compound 7f and 8 exhibited anticancer activity that was 300-fold and 1 × 10(6)-fold more cytotoxic than DMAPT, respectively, at a concentration of 10 ?M against rat 9L-SF gliosarcoma cells. Compounds 7a-7j and 8 were also screened against M9-ENL1 and acute myelogenous leukemia (AML) primary cell lines and exhibited 2- to 10-fold more potent antileukemic activity against M9-ENL1 cells (EC50 = 0.57-2.90 ?M) when compared to parthenolide (EC50 = 6.0) and showed potent antileukemic activity against five primary AML cell lines (EC50 = 0.76-7.3 ?M). PMID:26540463

  11. Toxicity of Calcium Hydroxide Nanoparticles on Murine Fibroblast Cell Line

    PubMed Central

    Dianat, Omid; Azadnia, Sina; Mozayeni, Mohammad Ali

    2015-01-01

    Introduction: One of the major contributing factors, which may cause failure of endodontic treatment, is the presence of residual microorganisms in the root canal system. For years, most dentists have been using calcium hydroxide (CH) as the intracanal medicament between treatment sessions to eliminate remnant microorganisms. Reducing the size of CH particles into nanoparticles enhances the penetration of this medicament into dentinal tubules and increases their antimicrobial efficacy. This in vitro study aimed to compare the cytotoxicity of CH nanoparticles and conventional CH on fibroblast cell line using the Mosmann’s Tetrazolium Toxicity (MTT) assay. Methods and Materials: This study was conducted on L929 murine fibroblast cell line by cell culture and evaluation of the direct effect of materials on the cultured cells. Materials were evaluated in two groups of 10 samples each at 24, 48 and 72 h. At each time point, 10 samples along with 5 positive and 5 negative controls were evaluated. The samples were transferred into tubes and exposed to fibroblast cells. The viability of cells was then evaluated. The Two-way ANOVA was used for statistical analysis and the level of significance was set at 0.05. Results: Cytotoxicity of both materials decreased over time and for conventional CH was lower than that of nanoparticles. However, this difference was not statistically significant (P>0.05). Conclusion: The cytotoxicity of CH nanoparticles was similar to that of conventional CH. PMID:25598810

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

    PubMed

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

    2005-06-01

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

  13. Single metallic nanoparticle imaging for protein detection in cells

    E-print Network

    Cognet, Laurent; Boyer, David; Choquet, Daniel; Tamarat, Philippe; Lounis, Brahim

    2003-01-01

    We performed a visualization of membrane proteins labeled with 10-nm gold nanoparticles in cells, using an all-optical method based on photothermal interference contrast. The high sensitivity of the method and the stability of the signals allows 3D imaging of individual nanoparticles without the drawbacks of photobleaching and blinking inherent to fluorescent markers. A simple analytical model is derived to account for the measurements of the signal amplitude and the spatial resolution. The photothermal interference contrast method provides an efficient, reproducible, and promising way to visualize low amounts of proteins in cells by optical means.

  14. Red Blood Cell Membrane-Cloaked Nanoparticles For Drug Delivery

    NASA Astrophysics Data System (ADS)

    Carpenter, Cody Westcott

    Herein we describe the development of the Red Blood Cell coated nanoparticle, RBC-NP. Purified natural erythrocyte membrane is used to coat drug-loaded poly(lacticco-glycolic acid) (PLGA). Synthetic PLGA co-polymer is biocompatible and biodegradable and has already received US FDA approval for drug-delivery and diagnostics. This work looks specifically at the retention of immunosuppressive proteins on RBC-NPs, right-sidedness of natural RBC membranes interfacing with synthetic polymer nanoparticles, sustained and retarded drug release of RBC-NPs as well as further surface modification of RBC-NPs for increased targeting of model cancer cell lines.

  15. Particle-Cell Contact Enhances Antibacterial Activity of Silver Nanoparticles

    PubMed Central

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

    2013-01-01

    Background It is generally accepted that antibacterial properties of Ag nanoparticles (AgNPs) are dictated by their dissolved fraction. However, dissolution-based concept alone does not fully explain the toxic potency of nanoparticulate silver compared to silver ions. Methodology/Principal Findings Herein, we demonstrated that the direct contact between bacterial cell and AgNPs' surface enhanced the toxicity of nanosilver. More specifically, cell-NP contact increased the cellular uptake of particle-associated Ag ions – the single and ultimate cause of toxicity. To prove that, we evaluated the toxicity of three different AgNPs (uncoated, PVP-coated and protein-coated) to six bacterial strains: Gram-negative Escherichia coli, Pseudomonas fluorescens, P. putida and P. aeruginosa and Gram-positive Bacillus subtilis and Staphylococcus aureus. While the toxicity of AgNO3 to these bacteria varied only slightly (the 4-h EC50 ranged from 0.3 to 1.2 mg Ag/l), the 4-h EC50 values of protein-coated AgNPs for various bacterial strains differed remarkably, from 0.35 to 46 mg Ag/l. By systematically comparing the intracellular and extracellular free Ag+ liberated from AgNPs, we demonstrated that not only extracellular dissolution in the bacterial test environment but also additional dissolution taking place at the particle-cell interface played an essential role in antibacterial action of AgNPs. The role of the NP-cell contact in dictating the antibacterial activity of Ag-NPs was additionally proven by the following observations: (i) separation of bacterial cells from AgNPs by particle-impermeable membrane (cut-off 20 kDa, ?4 nm) significantly reduced the toxicity of AgNPs and (ii) P. aeruginosa cells which tended to attach onto AgNPs, exhibited the highest sensitivity to all forms of nanoparticulate Ag. Conclusions/Significance Our findings provide new insights into the mode of antibacterial action of nanosilver and explain some discrepancies in this field, showing that “Ag-ion” and “particle-specific” mechanisms are not controversial but, rather, are two faces of the same coin. PMID:23737965

  16. Physical Property Control on the Cellular Uptake Pathway and Spatial Distribution of Nanoparticles in Cells.

    PubMed

    Ahn, Sungsook; Seo, Eunseok; Kim, Ki Hean; Lee, Sang Joon

    2015-06-01

    Nanoparticles have been developed in broad biomedical research in terms of effective cellular interactions to treat and visualize diseased cells. Considering the charge and polar functional groups of proteins that are embedded in cellular membranes, charged nanoparticles have been strategically developed to enhance electrostatic cellular interactions. In this study, we show that cellular uptake efficiency, pathway, and spatial distribution of gold nanoparticles in a cell are significantly modulated based on the surface condition of gold nanoparticles and human cancer cells that were tuned by controlling the pH of the medium and by introducing an electron beam. Cellular uptake efficiency is increased when electrostatic attraction is induced between the cells and the gold nanoparticles. Cell surface modification changes the cellular uptake pathways of the gold nanoparticles and concentrates the gold nanoparticles at the membrane region. Surface modification of the gold nanoparticles also contributes to deep penetration and homogeneous spatial distributions in a cell. PMID:26353594

  17. Mesenchymal Stem Cells Exhibit Regulated Exocytosis in Response to Chemerin and IGF

    PubMed Central

    Kumar, J. Dinesh; Holmberg, Chris; Balabanova, Silvia; Borysova, Lyudmyla; Burdyga, Ted; Beynon, Robert; Dockray, Graham J.; Varro, Andrea

    2015-01-01

    Mesenchymal stem cells (MSCs) play important roles in tissue repair and cancer progression. Our recent work suggests that some mesenchymal cells, notably myofibroblasts exhibit regulated exocytosis resembling that seen in neuroendocrine cells. We now report that MSCs also exhibit regulated exocytosis. Both a G-protein coupled receptor agonist, chemerin, and a receptor tyrosine kinase stimulant, IGF-II, evoked rapid increases in secretion of a marker protein, TGF?ig-h3. The calcium ionophore, ionomycin, also rapidly increased secretion of TGF?ig-h3 while inhibitors of translation (cycloheximide) or secretory protein transport (brefeldin A) had no effect, indicating secretion from preformed secretory vesicles. Inhibitors of the chemerin and IGF receptors specifically reduced the secretory response. Confocal microscopy of MSCs loaded with Fluo-4 revealed chemerin and IGF-II triggered intracellular Ca2+ oscillations requiring extracellular calcium. Immunocytochemistry showed co-localisation of TGF?ig-h3 and MMP-2 to secretory vesicles, and transmission electron-microscopy showed dense-core secretory vesicles in proximity to the Golgi apparatus. Proteomic studies on the MSC secretome identified 64 proteins including TGF?ig-h3 and MMP-2 that exhibited increased secretion in response to IGF-II treatment for 30min and western blot of selected proteins confirmed these data. Gene ontology analysis of proteins exhibiting regulated secretion indicated functions primarily associated with cell adhesion and in bioassays chemerin increased adhesion of MSCs and adhesion, proliferation and migration of myofibroblasts. Thus, MSCs exhibit regulated exocytosis that is compatible with an early role in tissue remodelling. PMID:26513261

  18. Fibroblasts Cultured on Nanowires Exhibit Low Motility, Impaired Cell Division, and DNA Damage

    PubMed Central

    Persson, Henrik; Købler, Carsten; Mølhave, Kristian; Samuelson, Lars; Tegenfeldt, Jonas O; Oredsson, Stina; Prinz, Christelle N

    2013-01-01

    Nanowires are commonly used as tools for interfacing living cells, acting as biomolecule-delivery vectors or electrodes. It is generally assumed that the small size of the nanowires ensures a minimal cellular perturbation, yet the effects of nanowires on cell migration and proliferation remain largely unknown. Fibroblast behaviour on vertical nanowire arrays is investigated, and it is shown that cell motility and proliferation rate are reduced on nanowires. Fibroblasts cultured on long nanowires exhibit failed cell division, DNA damage, increased ROS content and respiration. Using focused ion beam milling and scanning electron microscopy, highly curved but intact nuclear membranes are observed, showing no direct contact between the nanowires and the DNA. The nanowires possibly induce cellular stress and high respiration rates, which trigger the formation of ROS, which in turn results in DNA damage. These results are important guidelines to the design and interpretation of experiments involving nanowire-based transfection and electrical characterization of living cells. PMID:23813871

  19. Buffalo (Bubalus bubalis) term amniotic-membrane-derived cells exhibited mesenchymal stem cells characteristics in vitro.

    PubMed

    Ghosh, Kaushalya; Kumar, Rajesh; Singh, Jarnail; Gahlawat, S K; Kumar, Dharmendra; Selokar, Naresh Lalaji; Yadav, S P; Gulati, B R; Yadav, P S

    2015-10-01

    Recent studies suggested that placentae amniotic membrane is a valuable source of stem cells in human as well as in livestock species. Advantages of amnion over other sources of stem cells included abundant availability, ethically non-objectionable and non-invasive source. The aim of the present study was the isolation, culture and characterization of amniotic-membrane-derived mesenchymal stem cells from term placentae collected postpartum in buffalo. We have observed that both presumptive epithelial-like and fibroblast-like cells were cultured and maintained from term amnion. These cells were shown the positive expression of pluripotency markers (OCT-4, SOX-2, NANOG, TERT), mesenchymal stem cell markers (CD29, CD44, CD105) and negative for haematopoietic marker (CD34) genes at different passages. In addition, these cells were also positive for alkaline phosphatase staining. Stem-ness potential of any stem cells is determined by their potential to differentiate into specific lineages of cell type. In the present study, we have successfully differentiated the amniotic-membrane-derived cells into adipogenic, chondrogenic and osteogenic lineages of cells in vitro. In conclusion, the results of this study demonstrate that amniotic-membrane-derived cells expressed pluripotent and mesenchymal stem cells markers and have propensity to differentiate into cells of mesenchymal lineage cell type upon directed differentiation in vitro. PMID:26019121

  20. Nanoparticle PEBBLE sensors in live cells and in vivo

    PubMed Central

    Smith, Ron

    2009-01-01

    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

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

    PubMed

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

    2013-01-01

    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

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

    NASA Astrophysics Data System (ADS)

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

    2010-10-01

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

  3. Mutagenic Effects of Iron Oxide Nanoparticles on Biological Cells.

    PubMed

    Dissanayake, Niluka M; Current, Kelley M; Obare, Sherine O

    2015-01-01

    In recent years, there has been an increased interest in the design and use of iron oxide materials with nanoscale dimensions for magnetic, catalytic, biomedical, and electronic applications. The increased manufacture and use of iron oxide nanoparticles (IONPs) in consumer products as well as industrial processes is expected to lead to the unintentional release of IONPs into the environment. The impact of IONPs on the environment and on biological species is not well understood but remains a concern due to the increased chemical reactivity of nanoparticles relative to their bulk counterparts. This review article describes the impact of IONPs on cellular genetic components. The mutagenic impact of IONPs may damage an organism's ability to develop or reproduce. To date, there has been experimental evidence of IONPs having mutagenic interactions on human cell lines including lymphoblastoids, fibroblasts, microvascular endothelial cells, bone marrow cells, lung epithelial cells, alveolar type II like epithelial cells, bronchial fibroblasts, skin epithelial cells, hepatocytes, cerebral endothelial cells, fibrosarcoma cells, breast carcinoma cells, lung carcinoma cells, and cervix carcinoma cells. Other cell lines including the Chinese hamster ovary cells, mouse fibroblast cells, murine fibroblast cells, Mytilus galloprovincialis sperm cells, mice lung cells, murine alveolar macrophages, mice hepatic and renal tissue cells, and vero cells have also shown mutagenic effects upon exposure to IONPs. We further show the influence of IONPs on microorganisms in the presence and absence of dissolved organic carbon. The results shed light on the OPEN ACCESS Int. J. Mol. Sci. 2015, 16 23483 transformations IONPs undergo in the environment and the nature of the potential mutagenic impact on biological cells. PMID:26437397

  4. Mutagenic Effects of Iron Oxide Nanoparticles on Biological Cells

    PubMed Central

    Dissanayake, Niluka M.; Current, Kelley M.; Obare, Sherine O.

    2015-01-01

    In recent years, there has been an increased interest in the design and use of iron oxide materials with nanoscale dimensions for magnetic, catalytic, biomedical, and electronic applications. The increased manufacture and use of iron oxide nanoparticles (IONPs) in consumer products as well as industrial processes is expected to lead to the unintentional release of IONPs into the environment. The impact of IONPs on the environment and on biological species is not well understood but remains a concern due to the increased chemical reactivity of nanoparticles relative to their bulk counterparts. This review article describes the impact of IONPs on cellular genetic components. The mutagenic impact of IONPs may damage an organism’s ability to develop or reproduce. To date, there has been experimental evidence of IONPs having mutagenic interactions on human cell lines including lymphoblastoids, fibroblasts, microvascular endothelial cells, bone marrow cells, lung epithelial cells, alveolar type II like epithelial cells, bronchial fibroblasts, skin epithelial cells, hepatocytes, cerebral endothelial cells, fibrosarcoma cells, breast carcinoma cells, lung carcinoma cells, and cervix carcinoma cells. Other cell lines including the Chinese hamster ovary cells, mouse fibroblast cells, murine fibroblast cells, Mytilus galloprovincialis sperm cells, mice lung cells, murine alveolar macrophages, mice hepatic and renal tissue cells, and vero cells have also shown mutagenic effects upon exposure to IONPs. We further show the influence of IONPs on microorganisms in the presence and absence of dissolved organic carbon. The results shed light on the transformations IONPs undergo in the environment and the nature of the potential mutagenic impact on biological cells. PMID:26437397

  5. Comparative evaluation of the impact on endothelial cells induced by different nanoparticle structures and functionalization

    PubMed Central

    Müller, Ines; Ernst, Peter; Schäfer, Miriam; Rosman, Christina; Schick, Isabel; Köhler, Oskar; Oehring, Hartmut; Breus, Vladimir V; Basché, Thomas; Sönnichsen, Carsten; Tremel, Wolfgang

    2015-01-01

    Summary In the research field of nanoparticles, many studies demonstrated a high impact of the shape, size and surface charge, which is determined by the functionalization, of nanoparticles on cell viability and internalization into cells. This work focused on the comparison of three different nanoparticle types to give a better insight into general rules determining the biocompatibility of gold, Janus and semiconductor (quantum dot) nanoparticles. Endothelial cells were subject of this study, since blood is the first barrier after intravenous nanoparticle application. In particular, stronger effects on the viability of endothelial cells were found for nanoparticles with an elongated shape in comparison to spherical ones. Furthermore, a positively charged nanoparticle surface (NH2, CyA) leads to the strongest reduction in cell viability, whereas neutral and negatively charged nanoparticles are highly biocompatible to endothelial cells. These findings are attributed to a rapid internalization of the NH2-functionalized nanoparticles in combination with the damage of intracellular membranes. Interestingly, the endocytotic pathway seems to be a size-dependent process whereas nanoparticles with a size of 20 nm are internalized by caveolae-mediated endocytosis and nanoparticles with a size of 40 nm are taken up by clathrin-mediated internalization and macropinocytosis. Our results can be summarized to formulate five general rules, which are further specified in the text and which determine the biocompatibility of nanoparticles on endothelial cells. Our findings will help to design new nanoparticles with optimized properties concerning biocompatibility and uptake behavior with respect to the respective intended application. PMID:25821668

  6. Effects of As2O3 nanoparticles on cell growth and apoptosis of NB4 cells

    PubMed Central

    DONG, XIAOYAN; MA, NING; LIU, MENGMENG; LIU, ZILING

    2015-01-01

    The aim of the present study was to explore the preparation of arsenic trioxide (As2O3) nanoparticles and examine the antitumor effects of these nanoparticles on NB4 cells. As2O3 nanoparticles were prepared using the sol-gel method and characterized using transmission electron microscopy and energy dispersive spectroscopy. The results indicated that the As2O3 nanoparticles prepared in the present study were round or elliptical, well dispersed and had an ~40-nm or <10-nm diameter. The antitumor effects of As2O3 nanoparticles at various concentrations were analyzed by flow cytometry and the MTT assay, and were compared with those of traditional As2O3 solution. At the same concentration and incubation time (48 h), the survival rate of cells treated with As2O3 nanoparticles was significantly lower than that of cells treated with the As2O3 solution. The growth inhibition rate under both treatments was time- and dose-dependent. In addition, at the same concentration and incubation time, the apoptosis rate of the cells treated with As2O3 nanoparticles was significantly higher than that of the cells treated with the As2O3 solution. Furthermore, As2O3 nanoparticles resulted in a greater reduction in the expression of the anti-apoptotic protein B-cell lymphoma 2 compared with the As2O3 solution. In conclusion, As2O3 nanoparticles, prepared using the sol-gel method, were found to produce a stronger cytotoxic effect on tumor cells than that produced by the As2O3 solution, possibly by inhibiting Bcl-2 expression.

  7. Enhanced reactive oxygen species overexpression by CuO nanoparticles in poorly differentiated hepatocellular carcinoma cells

    NASA Astrophysics Data System (ADS)

    Kung, Mei-Lang; Hsieh, Shu-Ling; Wu, Chih-Chung; Chu, Tian-Huei; Lin, Yu-Chun; Yeh, Bi-Wen; Hsieh, Shuchen

    2015-01-01

    Copper oxide nanoparticles (CuO NPs) are known to exhibit toxic effects on a variety of cell types and organs. To determine the oxidative impact of CuO NPs on hepatocellular carcinoma (HCC) cells, well-differentiated (HepG2) and poorly differentiated (SK-Hep-1) cells were exposed to CuO NPs. Cell viability assay showed that the median inhibition concentration (IC50) for SK-Hep-1 and HepG2 cells was 25 ?g ml-1 and 85 ?g ml-1, respectively. Cellular fluorescence intensity using DCFH-DA staining analysis revealed significant intracellular reactive oxygen species (ROS) generation of up to 242% in SK-Hep-1 cells, compared with 86% in HepG2 cells. HPLC analysis demonstrated that a CuO NP treatment caused cellular GSH depletion of 58% and a GSH/GSSG ratio decrease to ~0.1 in SK-Hep-1 cells. The oxidative stress caused by enhanced superoxide anion production was observed in both HepG2 (146%) and SK-Hep-1 (192%) cells. The Griess assay verified that CuO NPs induced NO production (170%) in SK-Hep-1 cells. Comet assay and western blot further demonstrated that CuO NPs induced severe DNA strand breakage (70%) in SK-Hep-1 cells and caused DNA damage via increased ?-H2AX levels. These results suggest that well-differentiated HepG2 cells possess a robust antioxidant defense system against CuO NP-induced ROS stress and exhibit more tolerance to oxidative stress. Conversely, poorly differentiated SK-Hep-1 cells exhibited a deregulated antioxidant defense system that allowed accumulation of CuO NP-induced ROS and resulted in severe cytotoxicity.Copper oxide nanoparticles (CuO NPs) are known to exhibit toxic effects on a variety of cell types and organs. To determine the oxidative impact of CuO NPs on hepatocellular carcinoma (HCC) cells, well-differentiated (HepG2) and poorly differentiated (SK-Hep-1) cells were exposed to CuO NPs. Cell viability assay showed that the median inhibition concentration (IC50) for SK-Hep-1 and HepG2 cells was 25 ?g ml-1 and 85 ?g ml-1, respectively. Cellular fluorescence intensity using DCFH-DA staining analysis revealed significant intracellular reactive oxygen species (ROS) generation of up to 242% in SK-Hep-1 cells, compared with 86% in HepG2 cells. HPLC analysis demonstrated that a CuO NP treatment caused cellular GSH depletion of 58% and a GSH/GSSG ratio decrease to ~0.1 in SK-Hep-1 cells. The oxidative stress caused by enhanced superoxide anion production was observed in both HepG2 (146%) and SK-Hep-1 (192%) cells. The Griess assay verified that CuO NPs induced NO production (170%) in SK-Hep-1 cells. Comet assay and western blot further demonstrated that CuO NPs induced severe DNA strand breakage (70%) in SK-Hep-1 cells and caused DNA damage via increased ?-H2AX levels. These results suggest that well-differentiated HepG2 cells possess a robust antioxidant defense system against CuO NP-induced ROS stress and exhibit more tolerance to oxidative stress. Conversely, poorly differentiated SK-Hep-1 cells exhibited a deregulated antioxidant defense system that allowed accumulation of CuO NP-induced ROS and resulted in severe cytotoxicity. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr05843g

  8. Genotoxicity of Superparamagnetic Iron Oxide Nanoparticles in Granulosa Cells.

    PubMed

    Pöttler, Marina; Staicu, Andreas; Zaloga, Jan; Unterweger, Harald; Weigel, Bianca; Schreiber, Eveline; Hofmann, Simone; Wiest, Irmi; Jeschke, Udo; Alexiou, Christoph; Janko, Christina

    2015-01-01

    Nanoparticles that are aimed at targeting cancer cells, but sparing healthy tissue provide an attractive platform of implementation for hyperthermia or as carriers of chemotherapeutics. According to the literature, diverse effects of nanoparticles relating to mammalian reproductive tissue are described. To address the impact of nanoparticles on cyto- and genotoxicity concerning the reproductive system, we examined the effect of superparamagnetic iron oxide nanoparticles (SPIONs) on granulosa cells, which are very important for ovarian function and female fertility. Human granulosa cells (HLG-5) were treated with SPIONs, either coated with lauric acid (SEONLA) only, or additionally with a protein corona of bovine serum albumin (BSA; SEON(LA-BSA)), or with dextran (SEON(DEX)). Both micronuclei testing and the detection of ?H2A.X revealed no genotoxic effects of SEON(LA-BSA), SEON(DEX) or SEON(LA). Thus, it was demonstrated that different coatings of SPIONs improve biocompatibility, especially in terms of genotoxicity towards cells of the reproductive system. PMID:26540051

  9. Platinum nanoparticle deposition on polymeric membranes for fuel cell applications

    NASA Astrophysics Data System (ADS)

    Moreira, A. J.; Lopera, S.; Ordonez, N.; Mansano, R. D.

    2012-06-01

    This work aimed to show an alternative to produce platinum nanoparticles directly on a polymeric membrane using plasma technique, in order to make these nanoparticles adhere to the membrane, in size, shape and homogeneity controlled by the process without damaging the polymeric material. In this manner the cell's production time is reduced since the catalyst is directly deposited on the polymeric membrane; the time of the process is approximately five minutes for each side of the membrane, and the total time for each membrane is 10 minutes. With this exposure time, and the advantage of controlling the other parameters such as pressure, RF power, gas flow rate and temperature of the electrode, it was possible to obtain platinum nanoparticles with dimensions of about 50 nm scattered homogenously on the membrane, without damaging the structure of the polymeric material and, consequently, affecting its performance. Together with platinum nanoparticles were also deposited carbon nanoparticles, so that these acted as catalyst support, avoiding self poisoning. Electrochemical activity tests were performed to test the efficiency of the cell where it was exposed to different pressures and flow rates of O2 and H2, reaching open-circuit voltage of 750 mVolts.

  10. Mediastinal Germ Cell Tumor Exhibiting a Discrepancy between Tumor Markers and Imaging: A Case Study

    PubMed Central

    Takenaka, Kei; Mukohara, Toru; Hirai, Chihoko; Funakoshi, Yohei; Nakamura, Yukiko; Chayahara, Naoko; Toyoda, Masanori; Kiyota, Naomi; Itoh, Tomoo; Yokozaki, Hiroshi; Minami, Hironobu

    2015-01-01

    We report a mediastinal germ cell tumor (GCT) that exhibited a discrepancy between the time course of serum human chorionic gonadotropin (hCG) levels and clinical consequences. An otherwise healthy man, aged 34 years, was diagnosed with a nonseminomatous GCT, most likely embryonal carcinoma (EC), based on a mediastinal tumor biopsy. Standard chemotherapy resulted in an optimal decrease in serum hCG levels. However, multiple lesions in the liver continued to enlarge, which led to his death. Autopsy revealed few viable tumor cells in the liver, with the great majority of the tumor cells appearing to have undergone necrosis, suggesting that they responded to the chemotherapy. The residual tumor cells in the mediastinum and the liver were similar to syncytiotrophoblast cells, suggesting a cho-riocarcinoma (CC). On immunohistochemical analysis, the mediastinal tumor cells in the diagnostic biopsy specimen expressed both CD30 and hCG, whereas residual mediastinal and hepatic tumor cells in the autopsy specimen after chemotherapy also expressed hCG, but not CD30. These findings suggested that the patient suffered from a primary mixed GCT consisting of an EC and a CC. Both pre- and postchemotherapy tumors strongly expressed matrix metalloproteinase-2, supporting the aggressive and invasive features of the tumor phenotype. We speculate that the extremely invasive tumor destroyed normal liver structure, whereas chemotherapy and central necrosis reduced the number of viable cells themselves, causing a discordant decrease in serum hCG levels. PMID:26351441

  11. Biogenic-production of SnO2 nanoparticles and its cytotoxic effect against hepatocellular carcinoma cell line (HepG2).

    PubMed

    Roopan, Selvaraj Mohana; Kumar, Subramanian Hari Subbish; Madhumitha, Gunabalan; Suthindhiran, Krishnamurthy

    2015-02-01

    In this paper, we have established for the first time, the terrific efficiency of aqueous extract of agricultural waste dried peel of sugar apple (Annona squamosa) in the rapid synthesis of stable SnO2 nanoparticles. In topical years, the deployment of secondary metabolites from plant extract has emerged as a novel technology for the synthesis of various nanoparticles. In this paper, we have studied the potential of SnO2 nanoparticles assembly using agricultural waste source for the first time. The synthesized nanoparticles were characterized and confirmed as SnO2 nanoparticles by using UV-visible spectroscopy, XRD, and TEM analysis. The motivation of this study was to examine cytotoxicity study of SnO2 nanoparticles against hepatocellular carcinoma cell line (HepG2). SnO2 nanoparticles inhibited the cell proliferation in a dose- and time-dependent manner with an IC50 value of 148 ?g/mL. The treated cells showed an altered morphology with increasing concentrations of SnO2 nanoparticles. Our result shows that the SnO2 nanoparticles exhibit moderate cytotoxicity towards the hepatocellular carcinoma (HepG2) at tested concentrations. PMID:25410804

  12. Carbohydrate-Based Nanocarriers Exhibiting Specific Cell Targeting with Minimum Influence from the Protein Corona.

    PubMed

    Kang, Biao; Okwieka, Patricia; Schöttler, Susanne; Winzen, Svenja; Langhanki, Jens; Mohr, Kristin; Opatz, Till; Mailänder, Volker; Landfester, Katharina; Wurm, Frederik R

    2015-06-15

    Whenever nanoparticles encounter biological fluids like blood, proteins adsorb on their surface and form a so-called protein corona. Although its importance is widely accepted, information on the influence of surface functionalization of nanocarriers on the protein corona is still sparse, especially concerning how the functionalization of PEGylated nanocarriers with targeting agents will affect protein corona formation and how the protein corona may in turn influence the targeting effect. Herein, hydroxyethyl starch nanocarriers (HES-NCs) were prepared, PEGylated, and modified on the outer PEG layer with mannose to target dendritic cells (DCs). Their interaction with human plasma was then studied. Low overall protein adsorption with a distinct protein pattern and high specific affinity for DC binding were observed, thus indicating an efficient combination of "stealth" and targeting behavior. PMID:25940402

  13. Effect of Fe3O4 Nanoparticles on Skin Tumor Cells and Dermal Fibroblasts

    PubMed Central

    Alili, Lirija; Chapiro, Swetlana; Marten, Gernot U.; Schmidt, Annette M.; Zanger, Klaus; Brenneisen, Peter

    2015-01-01

    Iron oxide (Fe3O4) nanoparticles have been used in many biomedical approaches. The toxicity of Fe3O4 nanoparticles on mammalian cells was published recently. Though, little is known about the viability of human cells after treatment with Fe3O4 nanoparticles. Herein, we examined the toxicity, production of reactive oxygen species, and invasive capacity after treatment of human dermal fibroblasts (HDF) and cells of the squamous tumor cell line (SCL-1) with Fe3O4 nanoparticles. These nanoparticles had an average size of 65?nm. Fe3O4 nanoparticles induced oxidative stress via generation of reactive oxygen species (ROS) and subsequent initiation of lipid peroxidation. Furthermore, the question was addressed of whether Fe3O4 nanoparticles affect myofibroblast formation, known to be involved in tumor invasion. Herein, Fe3O4 nanoparticles prevent the expression alpha-smooth muscle actin and therefore decrease the number of myofibroblastic cells. Moreover, our data show in vitro that concentrations of Fe3O4 nanoparticles, which are nontoxic for normal cells, partially reveal a ROS-triggered cytotoxic but also a pro-invasive effect on the fraction of squamous cancer cells surviving the treatment with Fe3O4 nanoparticles. The data herein show that the Fe3O4 nanoparticles appear not to be adequate for use in therapeutic approaches against cancer cells, in contrast to recently published data with cerium oxide nanoparticles. PMID:26090418

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

  16. Nanobarcoding: a novel method of single nanoparticle detection in cells and tissues for nanomedical biodistribution studies

    NASA Astrophysics Data System (ADS)

    Eustaquio, Trisha; Leary, James F.

    2011-10-01

    Determination of whether nanoparticles accumulate in target or non-target tissues is critical in assessing a nanoparticle formulation for nanomedical purposes. There is an overwhelming need for a sensitive and efficient imaging-based method that can (1) detect small numbers of (even single) nanoparticles, (2) associate nanoparticle uptake with cell type, and (3) allow for rapid detection in large tissue samples. We propose a novel method for nanoparticle detection that utilizes an oligonucleotide "nanobarcode" conjugated to the nanoparticle surface, which amplifies the optical signal from a single nanoparticle via in situ PCR. Herein, we describe the design process of the nanobarcoding method.

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

    NASA Astrophysics Data System (ADS)

    Kieu, Tri Minh

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

  18. Helicobacter pylori Protein JHP0290 Exhibits Proliferative and Anti-Apoptotic Effects in Gastric Epithelial Cells

    PubMed Central

    Tavares, Raquel; Pathak, Sushil Kumar

    2015-01-01

    The influence of Helicobacter pylori infection on gastric epithelial cell proliferation, apoptosis and signaling pathways contributes to the development of infection-associated diseases. Here we report that JHP0290, which is a poorly functionally characterized protein from H. pylori, regulates multiple responses in human gastric epithelial cells. The differential expression and release of JHP0290 homologues was observed among H. pylori strains. JHP0290 existed in monomeric and dimeric forms in H. pylori cell extracts and culture broth. Recombinant purified JHP0290 (rJHP0290) also showed monomeric and dimeric forms, whereas the rJHP0290 C162A mutant exhibited only a monomeric form. The dimeric form of the protein was found to bind more efficiently to gastric epithelial cells than the monomeric form. The exposure of gastric epithelial cells to rJHP0290 induced proliferation in a dose-dependent manner. Faster progression into the cell cycle was observed in rJHP0290-challenged gastric epithelial cells. Furthermore, we detected an anti-apoptotic effect of rJHP0290 in gastric epithelial cells when the cells were treated with rJHP0290 in combination with Camptothecin (CPT), which is an inducer of apoptosis. CPT-induced caspase 3 activation was significantly reduced in the presence of rJHP0290. In addition, the activation of ERK MAPK and the transcription factor NF?B was observed in rJHP0290-challenged gastric epithelial cells lines. Our results suggest that JHP0290 may affect H. pylori-induced gastric diseases via the regulation of gastric epithelial cell proliferation and anti-apoptotic pathways. PMID:25879227

  19. Carbon composites with metal nanoparticles for Alcohol fuel cells

    NASA Astrophysics Data System (ADS)

    Ventrapragada, Lakshman; Siddhardha, R. S.; Podilla, Ramakrishna; Muthukumar, V. S.; Creager, Stephen; Rao, A. M.; Ramamurthy, Sai Sathish

    2015-03-01

    Graphene due to its high surface area and superior conductivity has attracted wide attention from both industrial and scientific communities. We chose graphene as a substrate for metal nanoparticle deposition for fuel cell applications. There are many chemical routes for fabrication of metal-graphene composites, but they have an inherent disadvantage of low performance due to the usage of surfactants, that adsorb on their surface. Here we present a design for one pot synthesis of gold nanoparticles and simultaneous deposition on graphene with laser ablation of gold strip and functionalized graphene. In this process there are two natural advantages, the nanoparticles are synthesized without any surfactants, therefore they are pristine and subsequent impregnation on graphene is linker free. These materials are well characterized with electron microscopy to find their morphology and spectroscopic techniques like Raman, UV-Vis. for functionality. This gold nanoparticle decorated graphene composite has been tested for its electrocatalytic oxidation of alcohols for alkaline fuel cell applications. An electrode made of this composite showed good stability for more than 200 cycles of operation and reported a low onset potential of 100 mV more negative, an important factor for direct ethanol fuel cells.

  20. Sensitization of ovarian cancer cells to cisplatin by gold nanoparticles

    PubMed Central

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

    2014-01-01

    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

  1. Interaction of Biofunctionalized Nanoparticles with Receptors on Cell Surfaces: MC Simulations

    NASA Astrophysics Data System (ADS)

    Dormidontova, Elena; Wang, Shihu

    2015-03-01

    One of the areas of active development of modern nanomedicine is drug/gene delivery and imaging application of nanoparticles functionalized by ligands, aptamers or antibodies capable of specific interactions with cell surface receptors. Being a complex multifunctional system different structural aspects of nanoparticles affect their interactions with cell surfaces and the surface properties of cells can be different (e.g. density, distribution and mobility of receptors). Computer simulations allow a systematic investigation of the influence of multiple factors and provide a unified platform for the comparison. Using Monte Carlo simulations we investigate the influence of the nanoparticle properties (nanoparticle size, polymer tether length, polydispersity, density, ligand energy, valence and density) on nanoparticle-cell surface interactions and make predictions regarding favorable nanoparticle design for achieving multiple ligand-receptor binding. We will also discuss the implications of nanoparticle design on the selectivity of attachment to cells with high receptor density while ``ignoring'' cells with a low density of receptors.

  2. Synthesis of nanoparticles of P3HT and PCBM for optimizing morphology in polymeric solar cells

    NASA Astrophysics Data System (ADS)

    Satapathi, Soumitra; Gill, Hardeep Singh; Li, Lian; Samuelson, Lynne; Kumar, Jayant; Mosurkal, Ravi

    2014-12-01

    Nanoparticles (NPs) with opposite charges of a donor polymer, poly(3-hexyl thiophene) (P3HT) and an acceptor molecule, phenyl-C61-butyric acid methyl ester (PCBM) were synthesized using simple mini-emulsion technique. The NPs were examined by dynamic light scattering, atomic force microscopy and scanning electron microscopy to confirm the formation of the NPs. The NPs were assembled into thin films by spin-coating of a blend of the NPs dispersion. The built-up of a five layered film was monitored by UV-vis absorption spectroscopy. Our preliminary study demonstrated that a solar cell made from an annealed NP film can exhibit photovoltaic response.

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

    PubMed Central

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

    2011-01-01

    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

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

    PubMed Central

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

    2010-01-01

    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 explore the hypothesis that human endometrial side population (SP) cells correspond to somatic stem cells. We isolated, identified and characterized the SP corresponding to the stromal and epithelial compartments using endometrial SP genes signature, immunophenotyping and characteristic telomerase pattern. We analyzed the clonogenic activity of SP cells under hypoxic conditions and the differentiation capacity in vitro to adipogenic and osteogenic lineages. Finally, we demonstrated the functional capability of endometrial SP to develop human endometrium after subcutaneous injection in NOD-SCID mice. Briefly, SP cells of human endometrium from epithelial and stromal compartments display genotypic, phenotypic and functional features of SSC. PMID:20585575

  5. Single-cell imaging detection of nanobarcoded nanoparticle biodistributions in tissues for nanomedicine

    NASA Astrophysics Data System (ADS)

    Eustaquio, Trisha; Cooper, Christy L.; Leary, James F.

    2011-03-01

    In nanomedicine, biodistribution studies are critical to evaluate the safety and efficacy of nanoparticles. Currently, extensive biodistribution studies are hampered by the limitations of bulk tissue and single-cell imaging techniques. To ameliorate these limitations, we have developed a novel method for single nanoparticle detection that incorporates a conjugated oligonucleotide as a "nanobarcode" for detection via in situ PCR. This strategy magnifies the detection signal from single nanoparticles, facilitating rapid evaluation of nanoparticle uptake by cell type over larger areas. The nanobarcoding method can enable precise analysis of nanoparticle biodistributions and expedite translation of these nanoparticles to the clinic.

  6. Glass frits coated with silver nanoparticles for silicon solar cells

    NASA Astrophysics Data System (ADS)

    Li, Yingfen; Gan, Weiping; Zhou, Jian; Li, Biyuan

    2015-06-01

    Glass frits coated with silver nanoparticles were prepared by electroless plating. Gum Arabic (GA) was used as the activating agent of glass frits without the assistance of stannous chloride or palladium chloride. The silver-coated glass frits prepared with different GA dosages were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and thermogravimetric analysis (TGA). The characterization results indicated that silver-coated glass frits had the structures of both glass and silver. Spherical silver nanoparticles were distributed on the glass frits evenly. The density and particle size of silver nanoparticles on the glass frits can be controlled by adjusting the GA dosage. The silver-coated glass frits were applied to silver pastes to act as both the densification promoter and silver crystallite formation aid in the silver electrodes. The prepared silver-coated glass frits can improve the photovoltaic performances of solar cells.

  7. Infectious dengue vesicles derived from CD61+ cells in acute patient plasma exhibited a diaphanous appearance.

    PubMed

    Hsu, Alan Yi-Hui; Wu, Shang-Rung; Tsai, Jih-Jin; Chen, Po-Lin; Chen, Ya-Ping; Chen, Tsai-Yun; Lo, Yu-Chih; Ho, Tzu-Chuan; Lee, Meed; Chen, Min-Ting; Chiu, Yen-Chi; Perng, Guey Chuen

    2015-01-01

    The levels of neutralizing antibody to a pathogen are an effective indicator to predict efficacy of a vaccine in trial. And yet not all the trial vaccines are in line with the theory. Using dengue virus (DENV) to investigate the viral morphology affecting the predictive value, we evaluated the viral morphology in acute dengue plasma compared to that of Vero cells derived DENV. The virions in plasma were infectious and heterogeneous in shape with a "sunny-side up egg" appearance, viral RNA was enclosed with CD61+ cell-derived membrane interspersed by the viral envelope protein, defined as dengue vesicles. The unique viral features were also observed from ex vivo infected human bone marrow. Dengue vesicles were less efficiently neutralized by convalescent patient serum, compared to virions produced from Vero cells. Our results exhibit a reason why potencies of protective immunity fail in vivo and significantly impact dengue vaccine and drug development. PMID:26657027

  8. Infectious dengue vesicles derived from CD61+ cells in acute patient plasma exhibited a diaphanous appearance

    PubMed Central

    Hsu, Alan Yi-Hui; Wu, Shang-Rung; Tsai, Jih-Jin; Chen, Po-Lin; Chen, Ya-Ping; Chen, Tsai-Yun; Lo, Yu-Chih; Ho, Tzu-Chuan; Lee, Meed; Chen, Min-Ting; Chiu, Yen-Chi; Perng, Guey Chuen

    2015-01-01

    The levels of neutralizing antibody to a pathogen are an effective indicator to predict efficacy of a vaccine in trial. And yet not all the trial vaccines are in line with the theory. Using dengue virus (DENV) to investigate the viral morphology affecting the predictive value, we evaluated the viral morphology in acute dengue plasma compared to that of Vero cells derived DENV. The virions in plasma were infectious and heterogeneous in shape with a “sunny-side up egg” appearance, viral RNA was enclosed with CD61+ cell-derived membrane interspersed by the viral envelope protein, defined as dengue vesicles. The unique viral features were also observed from ex vivo infected human bone marrow. Dengue vesicles were less efficiently neutralized by convalescent patient serum, compared to virions produced from Vero cells. Our results exhibit a reason why potencies of protective immunity fail in vivo and significantly impact dengue vaccine and drug development. PMID:26657027

  9. Tunable metamaterial binary nano-particle dispersed liquid crystal cells

    NASA Astrophysics Data System (ADS)

    Aylo, Rola; Banerjee, Partha P.; Nehmetallah, Georges

    2010-08-01

    Metamaterials with tunable properties are of great importance due to potential applications in super-resolution lensing and sensors. In this paper we study the feasibility of the fabrication of a metamaterial using binary nanoparticle-dispersed liquid crystal cell (NDLCC). Depending on the angle between the director axis of the LCC and the incident beam, types, radii, and volume filling fractions of the nanoparticles, a negative index of refraction cell is obtained in a certain range of frequencies. The effective index of refraction is calculated using the effective medium theory. The scattering, extinction, and absorption of such a NDLCC cell is also found. Finally, the influence of the various parameters to obtain such a negative index metamaterial has been investigated.

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

    NASA Astrophysics Data System (ADS)

    Wang, Feng

    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.

  11. Polystyrene nanoparticles internalization in human gastric adenocarcinoma cells.

    PubMed

    Forte, Maurizio; Iachetta, Giuseppina; Tussellino, Margherita; Carotenuto, Rosa; Prisco, Marina; De Falco, Maria; Laforgia, Vincenza; Valiante, Salvatore

    2016-03-01

    The increase in the use of nanoparticles, as a promising tool for drug delivery or as a food additive, raises questions about their interaction with biological systems, especially in terms of evoked responses. In this work, we evaluated the kinetics of uptake of 44nm (NP44) and 100nm (NP100) unmodified polystyrene nanoparticles (PS-NPs) in gastric adenocarcinoma (AGS) cells, as well as the endocytic mechanism involved, and the effect on cell viability and gene expression of genes involved in cell cycle regulation and inflammation processes. We showed that NP44 accumulate rapidly and more efficiently in the cytoplasm of AGS compared to NP100; both PS-NPs showed an energy dependent mechanism of internalization and a clathrin-mediated endocytosis pathway. Dose response treatments revealed a non-linear curve. PS-NPs also affected cell viability, inflammatory gene expression and cell morphology. NP44 strongly induced an up-regulation of IL-6 and IL-8 genes, two of the most important cytokines involved in gastric pathologies. Our study suggests that parameters such as time, size and concentration of NPs must be taken carefully into consideration during the development of drug delivery systems based on NPs and for the management of nanoparticles associated risk factors. PMID:26585375

  12. Evaluating mononuclear cells as nanoparticle delivery vehicles for the treatment of breast tumors

    NASA Astrophysics Data System (ADS)

    Murton, Jaclyn K.; Hu, Chelin; Ahmed, Mona M.; Hathaway, Helen J.; Nysus, Monique; Anderson Daniels, Tamara; Norenberg, Jeffrey P.; Adolphi, Natalie L.

    2015-08-01

    In breast cancer, certain types of circulating immune cells respond to long-range chemical signals from tumors by leaving the blood stream to actively infiltrate tumor tissue. The aim of this study was to evaluate whether immune cells could be used to deliver therapeutic nanoparticles into breast tumors in mice. Mononuclear splenocytes (MS) were harvested from donor mice, labeled with Indium-111, injected intravenously into immune-competent recipient mice (3 tumor-bearing and 3 control), and imaged longitudinally by SPECT/CT. For comparison, the biodistribution of bonemarrow derived macrophages (BMDM) in one pair of mice was also imaged. Quantitative analysis of the SPECT images demonstrates that, after 24 hours, the concentration of MS detected in mammary tumors is more than 3-fold higher than the concentration detected in normal mammary glands. The ratio of MS concentration in mammary tissue to MS concentration in non-target tissues (muscle, lung, heart, liver, spleen, and kidney) was enhanced in tumor-bearing mice (compared to controls), with statistical significance achieved for mammary/muscle (p<0.01), mammary/lung (p<0.05), and mammary/kidney (p<0.05). By contrast, BMDM did not show a different affinity for tumors relative to normal mammary tissue. MS were incubated with 100 nm red fluorescent nanoparticles, and flow cytometry demonstrated that ~35% of the MS population exhibited strong phagocytic uptake of the nanoparticles. After intravenous injection into tumor-bearing mice, fluorescence microscopy images of tumor sections show qualitatively that nanoparticle-loaded MS retain the ability to infiltrate mammary tumors. Taken together, these results suggest that MS carriers are capable of actively targeting therapeutic nanoparticles to breast tumors.

  13. Quantification of single-cell nanoparticle concentrations and the distribution of these concentrations in cell population.

    PubMed

    Rashkow, Jason T; Patel, Sunny C; Tappero, Ryan; Sitharaman, Balaji

    2014-05-01

    Quantification of nanoparticle uptake into cells is necessary for numerous applications in cellular imaging and therapy. Herein, synchrotron X-ray fluorescence (SXRF) microscopy, a promising tool to quantify elements in plant and animal cells, was employed to quantify and characterize the distribution of titanium dioxide (TiO2) nanosphere uptake in a population of single cells. These results were compared with average nanoparticle concentrations per cell obtained by widely used inductively coupled plasma mass spectrometry (ICP-MS). The results show that nanoparticle concentrations per cell quantified by SXRF were of one to two orders of magnitude greater compared with ICP-MS. The SXRF results also indicate a Gaussian distribution of the nanoparticle concentration per cell. The results suggest that issues relevant to the field of single-cell analysis, the limitation of methods to determine physical parameters from large population averages leading to potentially misleading information and the lack of any information about the cellular heterogeneity are equally relevant for quantification of nanoparticles in cell populations. PMID:24554576

  14. Dendritic Cells Differentiated from Human Umbilical Cord Blood-Derived Monocytes Exhibit Tolerogenic Characteristics.

    PubMed

    Kim, Sun Kyung; Yun, Cheol-Heui; Han, Seung Hyun

    2015-12-01

    Human umbilical cord blood (UCB) is rich in diverse hematopoietic stem cells that are competent to differentiate into various cell types with immunological compatibility at transplantation. Thus, UCB is a potential source for the preparation of dendritic cells (DCs) to be used for cell therapy against inflammatory disorders or cancers. However, the immunological properties of UCB-derived DCs are not fully characterized. In this study, we investigated the phenotypes and functions of UCB monocyte-derived DCs (UCB-DCs) in comparison with those of adult peripheral blood (APB) monocyte-derived DCs (APB-DCs). UCB-DCs contained less CD1a(+) DCs, which is known as immunostimulatory DCs, than APB-DCs. UCB-DCs exhibited lower expression of CD80, MHC proteins, and DC-SIGN, but higher endocytic activity, than APB-DCs. Lipopolysaccharide stimulation of UCB-DCs minimally augmented the expression of maturation markers and production of interleukin (IL)-12 and tumor necrosis factor (TNF)-?, but potently expressed IL-10. When UCB-DCs were cocultured with CD14(+) cell-depleted allogeneic peripheral blood mononuclear cells, they weakly induced the proliferation, surface expression of activation markers, and interferon (IFN)-? production of T lymphocytes compared with APB-DCs. UCB possessed higher levels of prostaglandin E2 (PGE2) than APB, which might be responsible for tolerogenic phenotypes and functions of UCB-DCs. Indeed, APB-DCs prepared in the presence of PGE2 exhibited CD1a(-)CD14(+) phenotypes with tolerogenic properties, including weak maturation, impaired IL-12 production, and negligible T lymphocyte activation as UCB-DCs did. Taken together, we suggest that UCB-DCs have tolerogenic properties, which might be due to PGE2 highly sustained in UCB. PMID:26203805

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

    NASA Astrophysics Data System (ADS)

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

    2009-12-01

    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.

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

    PubMed

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

    2014-01-01

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

  17. Self-assembled targeting of cancer cells by iron(III)-doped, silica nanoparticles

    E-print Network

    Kummel, Andrew C.

    Self-assembled targeting of cancer cells by iron(III)- doped, silica nanoparticles K. K. Pohaku microscopy in an epithelial breast cancer cell line. This process was also confirmed using fluorescence nanoparticles that bind the cell-surface transferrin receptor (TfR) overexpressed in cancer cells.30

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

    PubMed

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

    2014-11-01

    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

  19. Core-shell polymer nanoparticles for prevention of GSH drug detoxification and cisplatin delivery to breast cancer cells

    NASA Astrophysics Data System (ADS)

    Surnar, Bapurao; Sharma, Kavita; Jayakannan, Manickam

    2015-10-01

    Platinum drug delivery against the detoxification of cytoplasmic thiols is urgently required for achieving efficacy in breast cancer treatment that is over expressed by glutathione (GSH, thiol-oligopeptide). GSH-resistant polymer-cisplatin core-shell nanoparticles were custom designed based on biodegradable carboxylic functional polycaprolactone (PCL)-block-poly(ethylene glycol) diblock copolymers. The core of the nanoparticle was fixed as 100 carboxylic units and the shell part was varied using various molecular weight poly(ethylene glycol) monomethyl ethers (MW of PEGs = 100-5000 g mol-1) as initiator in the ring-opening polymerization. The complexation of cisplatin aquo species with the diblocks produced core-shell nanoparticles of 75 nm core with precise size control the particles up to 190 nm. The core-shell nanoparticles were found to be stable in saline solution and PBS and they exhibited enhanced stability with increase in the PEG shell thickness at the periphery. The hydrophobic PCL layer on the periphery of the cisplatin core behaved as a protecting layer against the cytoplasmic thiol residues (GSH and cysteine) and exhibited <5% of drug detoxification. In vitro drug-release studies revealed that the core-shell nanoparticles were ruptured upon exposure to lysosomal enzymes like esterase at the intracellular compartments. Cytotoxicity studies were performed both in normal wild-type mouse embryonic fibroblast cells (Wt-MEFs), and breast cancer (MCF-7) and cervical cancer (HeLa) cell lines. Free cisplatin and polymer drug core-shell nanoparticles showed similar cytotoxicity effects in the HeLa cells. In MCF-7 cells, the free cisplatin drug exhibited 50% cell death whereas complete cell death (100%) was accomplished by the polymer-cisplatin core-shell nanoparticles. Confocal microscopic images confirmed that the core-shell nanoparticles were taken up by the MCF-7 and HeLa cells and they were accumulated both at the cytoplasm as well at peri-nuclear environments. The present investigation lays a new foundation for the polymer-based core-shell nanoparticles approach for overcoming detoxification in platinum drugs for the treatment of GSH over-expressed breast cancer cells.Platinum drug delivery against the detoxification of cytoplasmic thiols is urgently required for achieving efficacy in breast cancer treatment that is over expressed by glutathione (GSH, thiol-oligopeptide). GSH-resistant polymer-cisplatin core-shell nanoparticles were custom designed based on biodegradable carboxylic functional polycaprolactone (PCL)-block-poly(ethylene glycol) diblock copolymers. The core of the nanoparticle was fixed as 100 carboxylic units and the shell part was varied using various molecular weight poly(ethylene glycol) monomethyl ethers (MW of PEGs = 100-5000 g mol-1) as initiator in the ring-opening polymerization. The complexation of cisplatin aquo species with the diblocks produced core-shell nanoparticles of 75 nm core with precise size control the particles up to 190 nm. The core-shell nanoparticles were found to be stable in saline solution and PBS and they exhibited enhanced stability with increase in the PEG shell thickness at the periphery. The hydrophobic PCL layer on the periphery of the cisplatin core behaved as a protecting layer against the cytoplasmic thiol residues (GSH and cysteine) and exhibited <5% of drug detoxification. In vitro drug-release studies revealed that the core-shell nanoparticles were ruptured upon exposure to lysosomal enzymes like esterase at the intracellular compartments. Cytotoxicity studies were performed both in normal wild-type mouse embryonic fibroblast cells (Wt-MEFs), and breast cancer (MCF-7) and cervical cancer (HeLa) cell lines. Free cisplatin and polymer drug core-shell nanoparticles showed similar cytotoxicity effects in the HeLa cells. In MCF-7 cells, the free cisplatin drug exhibited 50% cell death whereas complete cell death (100%) was accomplished by the polymer-cisplatin core-shell nanoparticles. Confocal microscopic images confirmed that the core-shell nanoparticle

  20. Nanoparticle scaffolds for syngas-fed solid oxide fuel cells

    SciTech Connect

    Boldrin, Paul; Ruiz-Trejo, Enrique; Yu, Jingwen; Gruar, Robert I.; Tighe, Christopher J.; Chang, Kee-Chul; Ilavsky, Jan; Darr, Jawwad A.; Brandon, Nigel

    2014-12-17

    Incorporation of nanoparticles into devices such as solid oxide fuel cells (SOFCs) may provide benefits such as higher surface areas or finer control over microstructure. However, their use with traditional fabrication techniques such as screen-printing is problematic. Here, we show that mixing larger commercial particles with nanoparticles allows traditional ink formulation and screen-printing to be used while still providing benefits of nanoparticles such as increased porosity and lower sintering temperatures. SOFC anodes were produced by impregnating ceria–gadolinia (CGO) scaffolds with nickel nitrate solution. The scaffolds were produced from inks containing a mixture of hydrothermally-synthesised nanoparticle CGO, commercial CGO and polymeric pore formers. The scaffolds were heat-treated at either 1000 or 1300 °C, and were mechanically stable. In situ ultra-small X-ray scattering (USAXS) shows that the nanoparticles begin sintering around 900–1000 °C. Analysis by USAXS and scanning electron microscopy (SEM) revealed that the low temperature heat-treated scaffolds possessed higher porosity. Impregnated scaffolds were used to produce symmetrical cells, with the lower temperature heat-treated scaffolds showing improved gas diffusion, but poorer charge transfer. Using these scaffolds, lower temperature heat-treated cells of Ni–CGO/200 ?m YSZ/CGO-LSCF performed better at 700 °C (and below) in hydrogen, and performed better at all temperatures using syngas, with power densities of up to 0.15 W cm-2 at 800 °C. This approach has the potential to allow the use of a wider range of materials and finer control over microstructure.

  1. Nanoparticle scaffolds for syngas-fed solid oxide fuel cells

    DOE PAGESBeta

    Boldrin, Paul; Ruiz-Trejo, Enrique; Yu, Jingwen; Gruar, Robert I.; Tighe, Christopher J.; Chang, Kee-Chul; Ilavsky, Jan; Darr, Jawwad A.; Brandon, Nigel

    2014-12-17

    Incorporation of nanoparticles into devices such as solid oxide fuel cells (SOFCs) may provide benefits such as higher surface areas or finer control over microstructure. However, their use with traditional fabrication techniques such as screen-printing is problematic. Here, we show that mixing larger commercial particles with nanoparticles allows traditional ink formulation and screen-printing to be used while still providing benefits of nanoparticles such as increased porosity and lower sintering temperatures. SOFC anodes were produced by impregnating ceria–gadolinia (CGO) scaffolds with nickel nitrate solution. The scaffolds were produced from inks containing a mixture of hydrothermally-synthesised nanoparticle CGO, commercial CGO and polymericmore »pore formers. The scaffolds were heat-treated at either 1000 or 1300 °C, and were mechanically stable. In situ ultra-small X-ray scattering (USAXS) shows that the nanoparticles begin sintering around 900–1000 °C. Analysis by USAXS and scanning electron microscopy (SEM) revealed that the low temperature heat-treated scaffolds possessed higher porosity. Impregnated scaffolds were used to produce symmetrical cells, with the lower temperature heat-treated scaffolds showing improved gas diffusion, but poorer charge transfer. Using these scaffolds, lower temperature heat-treated cells of Ni–CGO/200 ?m YSZ/CGO-LSCF performed better at 700 °C (and below) in hydrogen, and performed better at all temperatures using syngas, with power densities of up to 0.15 W cm-2 at 800 °C. This approach has the potential to allow the use of a wider range of materials and finer control over microstructure.« less

  2. Polylactide-based Paclitaxel-loaded Nanoparticles Fabricated by Dispersion Polymerization: Characterization, Evaluation in Cancer Cell Lines, and Preliminary Biodistribution Studies

    PubMed Central

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

    2015-01-01

    The macromonomer method was used to prepare crosslinked, paclitaxel-loaded polylactide-polyethylene glycol (stealth) nanoparticles using free-radical dispersion polymerization. The method can facilitate the attachment of other molecules to the nanoparticle surface to make it multifunctional. Proton NMR and FT-IR spectra confirm the synthesis of polylactide macromonomer and crosslinking agent. Formation of stealth nanoparticles was confirmed by scanning and transmission electron microscopy. The drug release isotherm of paclitaxel-loaded nanoparticles shows that the encapsulated drug is released over 7 days. In vitro cytotoxicity assay in selected breast and ovarian cancer cell lines reveal that the blank nanoparticle is biocompatible compared to medium-only treated controls. In addition, the paclitaxel-loaded nanoparticles exhibit similar cytotoxicity compared to paclitaxel in solution. Confocal microscopy reveals that the nanoparticles are internalized by MCF-7 breast cancer cells within one hour. Preliminary biodistribution studies also show nanoparticle accumulation in tumour xenograft model. The nanoparticles are suitable for the controlled delivery of bioactive agents. PMID:24961596

  3. UCP2- and non-UCP2-mediated electric current in eukaryotic cells exhibits different properties.

    PubMed

    Wang, Ruihua; MoYung, K C; Zhang, M H; Poon, Karen

    2015-12-01

    Using live eukaryotic cells, including cancer cells, MCF-7 and HCT-116, normal hepatocytes and red blood cells in anode and potassium ferricyanide in cathode of MFC could generate bio-based electric current. Electrons and protons generated from the metabolic reaction in both cytosol and mitochondria contributing to the leaking would mediate the generation of electric current. Both resveratrol (RVT) and 2,4-dinitrophenol (DNP) used to induce proton leak in mitochondria were found to promote electric current production in all cells except red blood cells without mitochondria. Proton leak might be important for electric current production by bringing the charge balance in cells to enhance the further electron leak. The induced electric current by RVT can be blocked by Genipin, an inhibitor of UCP2-mediated proton leak, while that induced by DNP cannot. RVT could reduce reactive oxygen species (ROS) level in cells better than that of DNP. In addition, RVT increased mitochondrial membrane potential (MMP), while DNP decreased it. Results highly suggested the existence of at least two types of electric current that showed different properties. They included UCP2-mediated and non-UCP2-mediated electric current. UCP2-mediated electric current exhibited higher reactive oxygen species (ROS) reduction effect per unit electric current production than that of non-UCP2-mediated electric current. Higher UCP2-mediated electric current observed in cancer cells might contribute to the mechanism of drug resistence. Correlation could not be established between electric current production with either ROS and MMP without distinguishing the types of electric current. PMID:26276275

  4. Detecting polymeric nanoparticles with coherent anti-stokes Raman scattering microscopy in tissues exhibiting fixative-induced autofluorescence

    NASA Astrophysics Data System (ADS)

    Garrett, N. L.; Godfrey, L.; Lalatsa, A.; Serrano, D. R.; Uchegbu, I. F.; Schatzlein, A.; Moger, J.

    2015-03-01

    Recent advances in pharmaceutical nanotechnology have enabled the development of nano-particulate medicines with enhanced drug performance. Although the fate of these nano-particles can be macroscopically tracked in the body (e.g. using radio-labeling techniques), there is little information about the sub-cellular scale mechanistic processes underlying the particle-tissue interactions, or how these interactions may correlate with pharmaceutical efficacy. To rationally engineer these nano-particles and thus optimize their performance, these mechanistic interactions must be fully understood. Coherent Anti-Stokes Raman scattering (CARS) microscopy provides a label-free means for visualizing biological samples, but can suffer from a strong non-resonant background in samples that are prepared using aldehyde-based fixatives. We demonstrate how formalin fixative affects the detection of polymeric nanoparticles within kidneys following oral administration using CARS microscopy, compared with samples that were snap-frozen. These findings have implications for clinical applications of CARS for probing nanoparticle distribution in tissue biopsies.

  5. Cyclometalated Ruthenium(II) Anthraquinone Complexes Exhibit Strong Anticancer Activity in Hypoxic Tumor Cells.

    PubMed

    Zeng, Leli; Chen, Yu; Huang, Huaiyi; Wang, Jinquan; Zhao, Donglei; Ji, Liangnian; Chao, Hui

    2015-10-19

    Hypoxia is the critical feature of the tumor microenvironment that is known to lead to resistance to many chemotherapeutic drugs. Six novel ruthenium(II) anthraquinone complexes were designed and synthesized; they exhibit similar or superior cytotoxicity compared to cisplatin in hypoxic HeLa, A549, and multidrug-resistant (A549R) tumor cell lines. Their anticancer activities are related to their lipophilicity and cellular uptake; therefore, these physicochemical properties of the complexes can be changed by modifying the ligands to obtain better anticancer candidates. Complex 1, the most potent member of the series, is highly active against hypoxic HeLa cancer cells (IC50 =0.53??M). This complex likely has 46-fold better activity than cisplatin (IC50 =24.62??M) in HeLa cells. This complex tends to accumulate in the mitochondria and the nucleus of hypoxic HeLa cells. Further mechanistic studies show that complex 1 induced cell apoptosis during hypoxia through multiple pathways, including those of DNA damage, mitochondrial dysfunction, and the inhibition of DNA replication and HIF-1? expression, making it an outstanding candidate for further in vivo studies. PMID:26338207

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

    SciTech Connect

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

    2008-09-05

    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.

  7. RECQL5 and BLM exhibit divergent functions in cells defective for the Fanconi anemia pathway

    PubMed Central

    Kim, Tae Moon; Son, Mi Young; Dodds, Sherry; Hu, Lingchuan; Luo, Guangbin; Hasty, Paul

    2015-01-01

    Fanconi anemia (FA) patients exhibit bone marrow failure, developmental defects and cancer. The FA pathway maintains chromosomal stability in concert with replication fork maintenance and DNA double strand break (DSB) repair pathways including RAD51-mediated homologous recombination (HR). RAD51 is a recombinase that maintains replication forks and repairs DSBs, but also rearranges chromosomes. Two RecQ helicases, RECQL5 and Bloom syndrome mutated (BLM) suppress HR through nonredundant mechanisms. Here we test the impact deletion of RECQL5 and BLM has on mouse embryonic stem (ES) cells deleted for FANCB, a member of the FA core complex. We show that RECQL5, but not BLM, conferred resistance to mitomycin C (MMC, an interstrand crosslinker) and camptothecin (CPT, a type 1 topoisomerase inhibitor) in FANCB-defective cells. RECQL5 suppressed, while BLM caused, breaks and radials in FANCB-deleted cells exposed to CPT or MMC, respectively. RECQL5 protected the nascent replication strand from MRE11-mediated degradation and restarted stressed replication forks in a manner additive to FANCB. By contrast BLM restarted, but did not protect, replication forks in a manner epistatic to FANCB. RECQL5 also lowered RAD51 levels in FANCB-deleted cells at stressed replication sites implicating a rearrangement avoidance mechanism. Thus, RECQL5 and BLM impact FANCB-defective cells differently in response to replication stress with relevance to chemotherapeutic regimes. PMID:25520194

  8. Studies regarding the protective effects exhibited by antidepressants on cell models.

    PubMed

    Purdel, Nicoleta Carmen; D?nciulescu Miulescu, Rucsandra; Neam?u, Marius Cristian; Avramescu, Elena Taina; Ilie, Mihaela; Manda, Gina; Margin?, Denisa Marilena

    2015-01-01

    The study aimed to assess in vitro the short-term effects exerted by fluoxetine, sertraline and venlafaxine on certain physiological properties in two different study models: U937 monocytes and erythrocytes isolated from patients treated with the above-mentioned molecules. Results on U937 cell suspensions revealed the depolarization of the cell membrane induced by the three antidepressants. The maximal depolarization effect was registered after 15 minutes of cell exposure and was concentration-dependent, in a non-monotonic manner. The effect was also dependent on the tested compound, fluoxetine presenting the strongest depolarizing effect compared to sertraline and venlafaxine. The erythrocyte susceptibility to lipid peroxidation and glucose-6-phosphate dehydrogenase activity were assessed on red blood cells isolated from patients with depressive disorder. Our results revealed that antidepressant treatment induced the antioxidant defense, by decreasing erythrocyte susceptibility to lipid peroxidation and increasing glucose-6-phosphate dehydrogenase activity. The effect is more intense in the case of severe pathology and less evident in the case of moderate or minor disorder, as expressed by MADRS (Montgomery-Åsberg Depression Rating Scale) score. Our results could indicate that selected antidepressants at therapeutic concentrations, besides their known pharmacological effects, exhibit a protective effect against oxidative stress and also influence cells with immune properties. PMID:26429173

  9. Effect of ?-cyclodextrin on the internalization of nanoparticles into intestine epithelial cells.

    PubMed

    García-González, Lorena; Yépez-Mulía, Lilián; Ganem, Adriana

    2016-01-01

    The influence of ?-cyclodextrin on the interaction and internalization of PLGA nanoparticles into intestine epithelial cells was assessed. For this purpose ?-cyclodextrin was adsorbed on PLGA nanoparticles. Interaction of nanoparticles with Caco-2 cells, determined by fluorescence, was expressed as the number of particles per cell. Confocal microscopy confirmed the localization of the particles in the cell monolayer. The results showed that adsorption of ?-cyclodextrin on the surface of PLGA nanoparticles reduces interaction with mucin, enhancing in this way the internalization into the Caco-2 cells. PMID:26478186

  10. Polymeric nanoparticle-based delivery of microRNA-199a-3p inhibits proliferation and growth of osteosarcoma cells

    PubMed Central

    Zhang, Linlin; lyer, Arun K; Yang, Xiaoqian; Kobayashi, Eisuke; Guo, Yuqi; Mankin, Henry; Hornicek, Francis J; Amiji, Mansoor M; Duan, Zhenfeng

    2015-01-01

    Our prior screening of microRNAs (miRs) identified that miR-199a-3p expression is reduced in osteosarcoma cells, one of the most common types of bone tumor. miR-199a-3p exhibited functions of tumor cell growth inhibition, suggesting the potential application of miR-199a-3p as an anticancer agent. In the study reported here, we designed and developed a lipid-modified dextran-based polymeric nanoparticle platform for encapsulation of miRs, and determined the efficiency and efficacy of delivering miR-199a-3p into osteosarcoma cells. In addition, another potent miR, let-7a, which also displayed tumor suppressive ability, was selected as a candidate miR for evaluation. Fluorescence microscopy studies and real-time polymerase chain reaction results showed that dextran nanoparticles could deliver both miR-199a-3p and let-7a into osteosarcoma cell lines (KHOS and U-2OS) successfully. Western blotting analysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays demonstrated that dextran nanoparticles loaded with miRs could efficiently downregulate the expression of target proteins and effectively inhibit the growth and proliferation of osteosarcoma cells. These results demonstrate that a lipid-modified dextran-based polymeric nanoparticle platform may be an effective nonviral carrier for potential miR-based anticancer therapeutics. PMID:25931818

  11. Nanoparticle analysis of cancer cells by light transmission spectroscopy.

    PubMed

    Sun, N; Johnson, J; Stack, M S; Szajko, J; Sander, C; Rebuyon, R; Deatsch, A; Easton, J; Tanner, C E; Ruggiero, S T

    2015-09-01

    We have measured the optical properties of cancer and normal whole cells and lysates using light transmission spectroscopy (LTS). LTS provides both the optical extinction coefficient in the wavelength range from 220 to 1100nm and (by spectral inversion using a Mie model) the particle distribution density in the size range from 1 to 3000nm. Our current work involves whole cells and lysates of cultured human oral cells in liquid suspension. We found systematic differences in the optical extinction between cancer and normal whole cells and lysates, which translate to different particle size distributions (PSDs) for these materials. Specifically, we found that cancer cells have distinctly lower concentrations of nanoparticles with diameters less than 100nm and have higher concentrations of particles with diameters from 100 to 1000nm-results that hold for both whole cells and lysates. We also found a power-law dependence of particle density with diameter over several orders of magnitude. PMID:25981981

  12. Cellular uptake and toxicity effects of silver nanoparticles in mammalian kidney cells.

    PubMed

    Mili?, Mirta; Leitinger, Gerd; Pavi?i?, Ivan; Zebi? Avdi?evi?, Maja; Dobrovi?, Slaven; Goessler, Walter; Vinkovi? Vr?ek, Ivana

    2015-06-01

    The rapid progress and early commercial acceptance of silver-based nanomaterials is owed to their biocidal activity. Besides embracing the antimicrobial potential of silver nanoparticles (AgNPs), it is imperative to give special attention to the potential adverse health effects of nanoparticles owing to prolonged exposure. Here, we report a detailed study on the in vitro interactions of citrate-coated AgNPs with porcine kidney (Pk15) cells. As uncertainty remains whether biological/cellular responses to AgNPs are solely as a result of the release of silver ions or whether the AgNPs themselves have toxic effects, we investigated the effects of Ag(+) on Pk15 cells for comparison. Next, we investigated the cellular uptake of both AgNPs and Ag(+) in Pk15 cells at various concentrations applied. The detected Ag contents in cells exposed to 50?mg?l(-1) AgNPs and 50?mg?l(-1) Ag(+) were 209 and 25?µg of Ag per 10(6) cells, respectively. Transmission electron microscopy (TEM) images indicated that the Pk15 cells internalized AgNPs by endocytosis. Both forms of silver, nano and ionic, decreased the number of viable Pk15 cells after 24?h in a dose-dependent manner. In spite of a significant uptake into the cells, AgNPs had only insignificant toxicity at concentrations lower than 25?mg?l(-1) , whereas Ag(+) exhibited a significant decrease in cell viability at one-fifth of this concentration. The Comet assay suggested that a rather high concentration of AgNP (above 25?mg?l(-1) ) is able to induce genotoxicity in Pk15 cells. Further studies must seek deeper understanding of AgNP behavior in biological media and their interactions with cellular membranes. PMID:25352480

  13. Targeting cancer stem cells by using the nanoparticles

    PubMed Central

    Hong, In-Sun; Jang, Gyu-Beom; Lee, Hwa-Yong; Nam, Jeong-Seok

    2015-01-01

    Cancer stem cells (CSCs) have been shown to be markedly resistant to conventional cancer treatments such as chemotherapy and radiation therapy. Therefore, therapeutic strategies that selectively target CSCs will ultimately lead to better cancer treatments. Currently, accessible conventional therapeutic agents mainly eliminate the bulk tumor but do not eliminate CSCs. Therefore, the discovery and improvement of CSC-targeting therapeutic agents are necessary. Nanoparticles effectively inhibit multiple types of CSCs by targeting specific signaling pathways (Wnt/?-catenin, Notch, transforming growth factor-?, and hedgehog signaling) and/or specific markers (aldehyde dehydrogenases, CD44, CD90, and CD133) critically involved in CSC function and maintenance. In this review article, we summarized a number of findings to provide current information about their therapeutic potential of nanoparticles in various cancer cell types and CSCs. PMID:26425092

  14. Nanoparticles for Fidgety Cell Movement and Enhanced Wound Healing.

    PubMed

    Jozic, Ivan; Daunert, Sylvia; Tomic-Canic, Marjana; Pastar, Irena

    2015-09-01

    Complex spatiotemporal interaction of Rho GTPases with microtubules (MTs) and MT-associated proteins drives directed cellular migration. In this issue, Charafeddine et al. describe a role for a novel MT-severing enzyme, fidgetin-like 2 (FL2), in directional migration of keratinocytes and fibroblasts. FL2 normally localizes to the leading edge of the cell cortex where it shears MTs, thus dictating the size and distribution of focal adhesions by regulating cytoskeletal remodeling. Small interfering RNA (siRNA)-directed knockdown of FL2 increases cell migration and focal adhesion area in vitro through possible interaction with Rho GTPases. Efficient FL2 knockdown in murine wounds was achieved using nanoparticles as a siRNA delivery vehicle, and this resulted in enhanced wound closure in vivo. Effective siRNA nanoparticle targeting of MT-severing enzymes offers promise of controlled and targeted delivery that may maximize therapeutic success for patients with burn wounds and chronic wound disorders. PMID:26269405

  15. Mitochondria of highly metastatic breast cancer cell line MDA-MB-231 exhibits increased autophagic properties.

    PubMed

    Tu, Yi-Fang; Kaipparettu, Benny A; Ma, Yewei; Wong, Lee-Jun C

    2011-09-01

    Autophagy is a cellular housekeeping process that removes damaged or unwanted cellular components and recycles them to build new constituents. It is essential for tumor growth under adverse environment. Mitochondria play an important role in the formation of autophagosome and its subsequent docking and fusion with lysosome. To understand the contribution of mitochondria to the regulation of homeostatic autophagy in cancer cells, we used the transmitochondrial cytoplasmic hybrid (cybrid) model. Cybrid system allowed us to compare mitochondria from different cell types including highly metastatic breast cancer cell line MDA-MB-231 (c231), less metastatic breast cancer cell lines: MDA-MB-436 (c436) and MDA-MB-468 (c468), as well as non-cancerous mammary epithelial cell MCF-10A (c10A) in a defined nuclear background. The c231 exhibited lower LC3-II levels but higher ratio of LC3-II/LC3-I than c436, c468 and c10A. In addition, c231 displayed more punctate LC3-positive cells and had lower levels of sequestosome 1 (p62/SQSTM1) than other cybrids. These suggested that mitochondria could contribute to the increased autophagy and autophagic flux in metastatic cancer. This increased autophagy was found to be non-selective autophagy instead of selective mitophagy since LC3 puncta in c231 did not co-localize with mitochondria labeled by Mitotracker red or Tomm 20. The promotion of mitochondrial permeability transition (MPT) in c231 also contributed to increased autophagy. Block of MPT by the inhibition of low-conductance stage of MPT pores resulted in a decrease of LC3 puncta in c231. These results suggested that mitochondria from highly metastatic breast cancer cell line MDA-MB-231 can promote homeostatic autophagy of cancer through opening low-conductance MPT pores. PMID:21570379

  16. Induction of apoptosis in human cancer cells by targeting mitochondria with gold nanoparticles.

    PubMed

    Mkandawire, M M; Lakatos, M; Springer, A; Clemens, A; Appelhans, D; Krause-Buchholz, U; Pompe, W; Rödel, G; Mkandawire, M

    2015-06-28

    A major challenge in designing cancer therapies is the induction of cancer cell apoptosis, although activation of intrinsic apoptotic pathways by targeting gold nanoparticles to mitochondria is promising. We report an in vitro procedure targeting mitochondria with conjugated gold nanoparticles and investigating effects on apoptosis induction in the human breast cancer cell line Jimt-1. Gold nanoparticles were conjugated to a variant of turbo green fluorescent protein (mitoTGFP) harbouring an amino-terminal mitochondrial localization signal. Au nanoparticle conjugates were further complexed with cationic maltotriose-modified poly(propylene imine) third generation dendrimers. Fluorescence and transmission electron microscopy revealed that Au nanoparticle conjugates were directed to mitochondria upon transfection, causing partial rupture of the outer mitochondrial membrane, triggering cell death. The ability to target Au nanoparticles into mitochondria of breast cancer cells and induce apoptosis reveals an alternative application of Au nanoparticles in photothermal therapy of cancer. PMID:26022234

  17. Silver Nanoparticle Enhanced Freestanding Thin-Film Silicon Solar Cells

    NASA Astrophysics Data System (ADS)

    Winans, Joshua David

    As the supply of fossil fuels diminishes in quantity the demand for alternative energy sources will consistently increase. Solar cells are an environmentally friendly and proven technology that suffer in sales due to a large upfront cost. In order to help facilitate the transition from fossil fuels to photovoltaics, module costs must be reduced to prices well below $1/Watt. Thin-film solar cells are more affordable because of the reduced materials costs, but lower in efficiency because less light is absorbed before passing through the cell. Silver nanoparticles placed at the front surface of the solar cell absorb and reradiate the energy of the light in ways such that more of the light ends being captured by the silicon. Silver nanoparticles can do this because they have free electron clouds that can take on the energy of an incident photon through collective action. This bulk action of the electrons is called a plasmon. This work begins by discussing the economics driving the need for reduced material use, and the pros and cons of taking this step. Next, the fundamental theory of light-matter interaction is briefly described followed by an introduction to the study of plasmonics. Following that we discuss a traditional method of silver nanoparticle formation and the initial experimental studies of their effects on the ability of thin-film silicon to absorb light. Then, Finite-Difference Time-Domain simulation software is used to simulate the effects of nanoparticle morphology and size on the scattering of light at the surface of the thin-film.

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

    PubMed Central

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

    2011-01-01

    Background The epidermal growth factor receptor (EGFR) is overexpressed in 80% of non-small cell lung cancer (NSCLC) and is associated with poor survival. In recent years, EGFR-targeted inhibitors have been tested in the clinic for NSCLC. Despite the emergence of novel therapeutics and their application in cancer therapy, the overall survival rate of lung cancer patients remains 15%. To develop more effective therapies for lung cancer we have combined the anti-EGFR antibody (Clone 225) as a molecular therapeutic with hybrid plasmonic magnetic nanoparticles (NP) and tested on non-small cell lung cancer (NSCLC) cells. Methodology/Principal Findings Cell viability was determined by trypan-blue assay. Cellular protein expression was determined by Western blotting. C225-NPs were detected by electron microscopy and confocal microscopy, and EGFR expression using immunocytochemistry. C225-NP exhibited a strong and selective antitumor effect on EGFR-expressing NSCLC cells by inhibiting EGFR-mediated signal transduction and induced autophagy and apoptosis in tumor cells. Optical images showed specificity of interactions between C225-NP and EGFR-expressing NSCLC cells. No binding of C225-NP was observed for EGFR-null NSCLC cells. C225-NP exhibited higher efficiency in induction of cell killing in comparison with the same amount of free C225 antibody in tumor cells with different levels of EGFR expression. Furthermore, in contrast to C225-NP, free C225 antibody did not induce autophagy in cells. However, the therapeutic efficacy of C225-NP gradually approached the level of free antibodies as the amount of C225 antibody conjugated per nanoparticle was decreased. Finally, attaching C225 to NP was important for producing the enhanced tumor cell killing as addition of mixture of free C225 and NP did not demonstrate the same degree of cell killing activity. Conclusions/Significance We demonstrated for the first time the molecular mechanism of C225-NP induced cytotoxic effects in lung cancer cells that are not characteristic for free molecular therapeutics thus increasing efficacy of therapy against NSCLC. PMID:22087216

  19. A Tetrameric Peptide Derived from Bovine Lactoferricin Exhibits Specific Cytotoxic Effects against Oral Squamous-Cell Carcinoma Cell Lines

    PubMed Central

    Solarte, Víctor A.; Rosas, Jaiver E.; Rivera, Zuly J.; Arango-Rodríguez, Martha L.; García, Javier E.; Vernot, Jean-Paul

    2015-01-01

    Several short linear peptides derived from cyclic bovine lactoferricin were synthesized and tested for their cytotoxic effect against the oral cavity squamous-cell carcinoma (OSCC) cell lines CAL27 and SCC15. As a control, an immortalized and nontumorigenic cell line, Het-1A, was used. Linear peptides based on the RRWQWR core sequence showed a moderate cytotoxic effect and specificity towards tumorigenic cells. A tetrameric peptide, LfcinB(20–25)4, containing the RRWQWR motif, exhibited greater cytotoxic activity (>90%) in both OSCC cell lines compared to the linear lactoferricin peptide or the lactoferrin protein. Additionally, this tetrameric peptide showed the highest specificity towards tumorigenic cells among the tested peptides. Interestingly, this effect was very fast, with cell shrinkage, severe damage to cell membrane permeability, and lysis within one hour of treatment. Our results are consistent with a necrotic effect rather than an apoptotic one and suggest that this tetrameric peptide could be considered as a new candidate for the therapeutic treatment of OSCC. PMID:26609531

  20. Microfluidic Synthesis of Hybrid Nanoparticles with Controlled Lipid Layers: Understanding Flexibility-Regulated Cell-Nanoparticle Interaction.

    PubMed

    Zhang, Lu; Feng, Qiang; Wang, Jiuling; Zhang, Shuai; Ding, Baoquan; Wei, Yujie; Dong, Mingdong; Ryu, Ji-Young; Yoon, Tae-Young; Shi, Xinghua; Sun, Jiashu; Jiang, Xingyu

    2015-10-27

    The functionalized lipid shell of hybrid nanoparticles plays an important role for improving their biocompatibility and in vivo stability. Yet few efforts have been made to critically examine the shell structure of nanoparticles and its effect on cell-particle interaction. Here we develop a microfluidic chip allowing for the synthesis of structurally well-defined lipid-polymer nanoparticles of the same sizes, but covered with either lipid-monolayer-shell (MPs, monolayer nanoparticles) or lipid-bilayer-shell (BPs, bilayer nanoparticles). Atomic force microscope and atomistic simulations reveal that MPs have a lower flexibility than BPs, resulting in a more efficient cellular uptake and thus anticancer effect than BPs do. This flexibility-regulated cell-particle interaction may have important implications for designing drug nanocarriers. PMID:26448362

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

    PubMed Central

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

    2014-01-01

    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. PMID:25452724

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

    NASA Astrophysics Data System (ADS)

    Dobson, Jon

    2013-03-01

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

  3. Amorphous silica nanoparticles enhance cross-presentation in murine dendritic cells

    SciTech Connect

    Hirai, Toshiro; Yoshioka, Yasuo; Takahashi, Hideki; Ichihashi, Ko-ichi; Yoshida, Tokuyuki; Tochigi, Saeko; Nagano, Kazuya; Abe, Yasuhiro; The Center for Advanced Medical Engineering and Informatics, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 ; Nabeshi, Hiromi; Yoshikawa, Tomoaki; Tsutsumi, Yasuo; Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saitoasagi, Ibaraki, Osaka 567-0085; The Center for Advanced Medical Engineering and Informatics, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871

    2012-10-26

    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.

  4. Biocompatible fluorescent nanoparticles for in vivo stem cell tracking.

    PubMed

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

    2013-06-21

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

  5. Biocompatible fluorescent nanoparticles for in vivo stem cell tracking

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

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

  6. Influence of surface charge on the potential toxicity of PLGA nanoparticles towards Calu-3 cells

    PubMed Central

    Mura, Simona; Hillaireau, Herve; Nicolas, Julien; Le Droumaguet, Benjamin; Gueutin, Claire; Zanna, Sandrine; Tsapis, Nicolas; Fattal, Elias

    2011-01-01

    Background Because of the described hazards related to inhalation of manufactured nanoparticles, we investigated the lung toxicity of biodegradable poly (lactide-co-glycolide) (PLGA) nanoparticles displaying various surface properties on human bronchial Calu-3 cells. Methods Positively and negatively charged as well as neutral nanoparticles were tailored by coating their surface with chitosan, Poloxamer, or poly (vinyl alcohol), respectively. Nanoparticles were characterized in terms of size, zeta potential, and surface chemical composition, confirming modifications provided by hydrophilic polymers. Results Although nanoparticle internalization by lung cells was clearly demonstrated, the cytotoxicity of the nanoparticles was very limited, with an absence of inflammatory response, regardless of the surface properties of the PLGA nanoparticles. Conclusion These in vitro results highlight the safety of biodegradable PLGA nanoparticles in the bronchial epithelium and provide initial data on their potential effects and the risks associated with their use as nanomedicines. PMID:22114491

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

    NASA Astrophysics Data System (ADS)

    Gazeau, Florence; Lévy, Michael; Wilhelm, Claire

    2011-03-01

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

  8. Polyelectrolyte coating of ferumoxytol nanoparticles for labeling of dendritic cells

    NASA Astrophysics Data System (ADS)

    Celikkin, Nehar; Jakubcová, Lucie; Zenke, Martin; Hoss, Mareike; Wong, John Erik; Hieronymus, Thomas

    2015-04-01

    Engineered magnetic nanoparticles (MNPs) are emerging to be used as cell tracers, drug delivery vehicles, and contrast agents for magnetic resonance imaging (MRI) for enhanced theragnostic applications in biomedicine. In vitro labeling of target cell populations with MNPs and their implantation into animal models and patients shows promising outcomes in monitoring successful cell engraftment, differentiation and migration by using MRI. Dendritic cells (DCs) are professional antigen-presenting cells that initiate adaptive immune responses. Thus, DCs have been the focus of cellular immunotherapy and are increasingly applied in clinical trials. Here, we addressed the coating of different polyelectrolytes (PE) around ferumoxytol particles using the layer-by-layer technique. The impact of PE-coated ferumoxytol particles for labeling of DCs and Flt3+ DC progenitors was then investigated. The results from our studies revealed that PE-coated ferumoxytol particles can be readily employed for labeling of DC and DC progenitors and thus are potentially suitable as contrast agents for MRI tracking.

  9. Do cancer cells in human and meristematic cells in plant exhibit similar responses toward plant extracts with cytotoxic activities?

    PubMed

    Khalifa, Noha S; Barakat, Hoda S; Elhallouty, Salwa; Salem, Dina

    2015-01-01

    We examined the effect of water extracts of Persea americana fruit, and of the leaves of Tabernamontana divericata, Nerium oleander and Annona cherimolia (positive control) on Vicia faba root cells. We had confirmed in our previously published data the cytotoxicity of these plant extracts on four human cancer cell lines: liver (HepG-2), lung (A549), colon (HT-29) and breast (MCF-7). Vicia faba roots were soaked in plant extracts at dilutions of 100, 1,250, 2,500, 5,000, 10,000, 20,000 ppm for 4 and 24 h. All treatments resulted in a significant reduction in the mitotic index in a dose dependant manner. Root cells treated with T. divericata, N. oleander and A. cherimolia exhibited a decrease in prophase cell percentage, increase in micronuclei and chromosomal abnormalities as concentration increased. The P. americana treatment showed the highest cytotoxic effect on cancer cells, prophase cell percentage increased linearly with the applied concentration and no micronuclei were detected. This study shows that root tip assay of beans can be used in initial screening for new plant extracts to validate their use as candidates for containing active cytotoxic agents against malignant cells. This will greatly help in exploring new plant extracts as drugs for cancer treatment. PMID:24705601

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

    PubMed

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

    2013-11-01

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

  11. SERS measurement of the bladder cancer cells with the nanoparticles.

    PubMed

    Jin, Di; Chen, Haige; Cao, Ming; Yang, Guoliang; Xue, Wei; Huang, Yiran

    2015-09-01

    The surfaced enhanced Raman spectroscopy (SERS) of bladder cancer cells and tissues were measured in this paper. Both depth SERS and map SERS of SCABER bladder cancer cells were measured with confocal Raman microscope using gold nanoparticles as the enhance substrate. We also measured SERS of normal bladder tissue and bladder cancer tissue, and analyzed the difference of two different tissues. The SERS spectra of more samples need to be measured and analyzed for bladder cancer tissue and the normal bladder tissue in the future and the spectra will be helpful for bladder cancer diagnosis. PMID:26525026

  12. Nanoparticle assisted photothermal deformation of individual neuronal organelles and cells

    PubMed Central

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

    2014-01-01

    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. PMID:25426326

  13. Facile synthesis and characterization of highly dispersed platinum nanoparticles for fuel cells

    E-print Network

    Liu, Fuqiang

    Facile synthesis and characterization of highly dispersed platinum nanoparticles for fuel cells synthesis and characterization of highly-dispersed platinum nano- particles supported on Ketjen carbon black

  14. EGFP-Based Protein Nanoparticles with Cell-Penetrating Peptide for Efficient siRNA Delivery.

    PubMed

    Guan, Xingang; Hu, Xiuli; Cui, Fengchao; Li, Yunqi; Jing, Xiabing; Xie, Zhigang

    2015-11-01

    Development of an innovative nucleic acid nanocarriers still represents a challenge. In this study, we develop a protein nanoparticle (H6-TatEGFP) and examine its siRNA condensing activity. Gel retardation assay show that protein nanoparticle can condense siRNA into stable nanoparticle/siRNA complexes. UsingCy3-labelled siRNA, we also evaluate siRNA transport characteristic of protein nanoparticles in tumor cells, the results indicate that H6-TatEGFP nanoparticle may be a potential nanocarrier for siRNA in tumor cells. PMID:26109167

  15. Silver nanoparticles-induced cytotoxicity requires ERK activation in human bladder carcinoma cells.

    PubMed

    Castiglioni, Sara; Cazzaniga, Alessandra; Perrotta, Cristiana; Maier, Jeanette A M

    2015-09-17

    Silver nanoparticles are toxic both in vitro and in vivo. We have investigated the possibility to exploit the cytotoxic potential of silver nanoparticles in T24 bladder carcinoma cells using both bare and PolyVinylPyrrolidone-coated silver nanoparticles. We show that the two types of silver nanoparticles promote morphological changes and cytoskeletal disorganization, are cytotoxic and induce cell death. These effects are due to the increased production of reactive oxygen species which are responsible, at least in part, for the sustained activation of ERK1/2. Indeed, both cytotoxicity and ERK1/2 activation are prevented by exposing the cells to the anti-oxidant N-acetylcysteine. Also blocking the ERK1/2 pathway with the MEK inhibitor PD98059 protects the cells from nanoparticles' cytotoxicity. Our findings suggest that ERK activation plays a role in silver nanoparticle-mediated cytotoxicity in T24 cells. PMID:26149761

  16. The "sweet" side of the protein corona: effects of glycosylation on nanoparticle-cell interactions.

    PubMed

    Wan, Sha; Kelly, Philip M; Mahon, Eugene; Stöckmann, Henning; Rudd, Pauline M; Caruso, Frank; Dawson, Kenneth A; Yan, Yan; Monopoli, Marco P

    2015-02-24

    The significance of a protein corona on nanoparticles in modulating particle properties and their biological interactions has been widely acknowledged. The protein corona is derived from proteins in biological fluids, many of which are glycosylated. To date, the glycans on the proteins have been largely overlooked in studies of nanoparticle-cell interactions. In this study, we demonstrate that glycosylation of the protein corona plays an important role in maintaining the colloidal stability of nanoparticles and influences nanoparticle-cell interactions. The removal of glycans from the protein corona enhances cell membrane adhesion and cell uptake of nanoparticles in comparison with the fully glycosylated form, resulting in the generation of a pro-inflammatory milieu by macrophages. This study highlights that the post-translational modification of proteins can significantly impact nanoparticle-cell interactions by modulating the protein corona properties. PMID:25599105

  17. Gold Nanoparticles Electroporation Enhanced Polyplex Delivery to Mammalian Cells

    PubMed Central

    Huang, Shuyan; Deshmukh, Harshavardhan; Rajagopalan, Kartik Kumar; Wang, Shengnian

    2015-01-01

    Non-viral methods have been explored as the replacement of viral systems for their low toxicity and immunogenicity. However, they have yet to reach levels competitive to their viral counterparts. In this paper, we combined physical and chemical methods to improve the performance of polyplex delivery of DNA and siRNA. Specifically, gold nanoparticles (AuNPs) were used to carry polyplex (a chemical approach) while electroporation (a physical approach) was applied for fast and direct cytosolic delivery. In this hybrid approach, cationic polymer molecules condense and/or protect genetic probes as usual while AuNPs help fix polycations to reduce their cytotoxicity and promote the transfection efficiency of electroporation. AuNPs of various sizes were first coated with polyethylenimine (PEI), which were further conjugated with DNA plasmids or siRNA molecules to form AuNPs-polyplex. The hybrid nanoparticles were then mixed with cells and introduced into cell cytosol by electroporation. The delivery efficiency was evaluated with both model anchor cells (i.e., NIH 3T3) and suspension cells (i.e., K562), together with their impact on cell viability. We found that AuNP-polyplex showed 1.5~2 folds improvement on the transfection efficiency with no significant increase of toxicity when compared to free plasmid delivery by electroporation alone. Such a combination of physical and chemical delivery concept may stimulate further exploration in the delivery of various therapeutic materials for both in vitro and in vivo applications. PMID:24777715

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

    PubMed Central

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

    2011-01-01

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

  19. Synthesis and fluorescence properties of N-substituted 1-cyanobenz[f]isoindole chitosan polymers and nanoparticles for live cell imaging.

    PubMed

    Gonil, Pattarapond; Sajomsang, Warayuth; Ruktanonchai, Uracha Rungsardthong; Na Ubol, Preeyawis; Treetong, Alongkot; Opanasopit, Praneet; Puttipipatkhachorn, Satit

    2014-08-11

    Highly fluorescent N-substituted 1-cyanobenz[f]isoindole chitosans (CBI-CSs) with various degrees of N-substitution (DS) were synthesized by reacting chitosan (CS) with naphthalene-2,3-dicarboxaldehyde (NDA) in the presence of cyanide under mild acidic conditions. Introduction of 1-cyanobenz[f]isoindole moieties into the CS backbone resulted in lowering of polymer thermal stability and crystallinity. The fluorescence quantum yield (?f) of CBI-CS was found to be DS- and molecular-weight-dependent, with ?f decreasing as DS and molecular weight were increased. At similar DS values, CBI-CS exhibited 26 times higher ?f in comparison with fluorescein isothiocyanate-substituted chitosan (FITC-CS). CBI-CS/TPP nanoparticles were fabricated using an ionotropic gelation method in which pentasodium triphosphate (TPP) acted as a cross-linking agent. CS and CBI-CS exhibited low cytotoxicity to normal skin fibroblast cells over a concentration range of 0.1-1000 ?g/mL, while an increased cytotoxicity level was evident in CBI-CS/TPP nanoparticles at concentrations greater than 100 ?g/mL. In contrast with CBI-CS polymers, the CBI-CS/TPP nanoparticles exhibited lower fluorescence; however, confocal microscopy results showed that living normal skin fibroblast cells became fluorescent on nanoparticle uptake. These results suggest that CBI-CS and fabricated nanoparticles thereof may be promising fluorescence probes for live cell imaging. PMID:24956200

  20. Engineered nanoparticles interacting with cells: size matters

    PubMed Central

    2014-01-01

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

  1. Lymphoid Organ-Resident Dendritic Cells Exhibit Unique Transcriptional Fingerprints Based on Subset and Site

    PubMed Central

    Elpek, Kutlu G.; Bellemare-Pelletier, Angelique; Malhotra, Deepali; Reynoso, Erika D.; Lukacs-Kornek, Veronika; DeKruyff, Rosemarie H.; Turley, Shannon J.

    2011-01-01

    Lymphoid organ-resident DC subsets are thought to play unique roles in determining the fate of T cell responses. Recent studies focusing on a single lymphoid organ identified molecular pathways that are differentially operative in each DC subset and led to the assumption that a given DC subset would more or less exhibit the same genomic and functional profiles throughout the body. Whether the local milieu in different anatomical sites can also influence the transcriptome of DC subsets has remained largely unexplored. Here, we interrogated the transcriptional relationships between lymphoid organ-resident DC subsets from spleen, gut- and skin-draining lymph nodes, and thymus of C57BL/6 mice. For this purpose, major resident DC subsets including CD4 and CD8 DCs were sorted at high purity and gene expression profiles were compared using microarray analysis. This investigation revealed that lymphoid organ-resident DC subsets exhibit divergent genomic programs across lymphoid organs. Interestingly, we also found that transcriptional and biochemical properties of a given DC subset can differ between lymphoid organs for lymphoid organ-resident DC subsets, but not plasmacytoid DCs, suggesting that determinants of the tissue milieu program resident DCs for essential site-specific functions. PMID:21886840

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

    PubMed

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

    2014-05-21

    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

  3. Patients with posttraumatic stress disorder exhibit an altered phenotype of regulatory T cells

    PubMed Central

    2014-01-01

    Background Regulatory T cells (Tregs) play a key role in immune homeostasis in vivo. Tregs have a critical role in preventing the development of autoimmune diseases and defects in Treg function are implicated in various autoimmune disorders. Individuals with posttraumatic stress disorder (PTSD) have higher prevalence of autoimmune disorders than the general population. We hypothesized that war veterans with PTSD would exhibit a decreased number and/or altered phenotype of Tregs. Methods We analyzed peripheral blood mononuclear cells (PBMCs) of patients with PTSD (N?=?21) (mean age?=?45.9) and age-matched healthy controls (N?=?23) (mean age?=?45.7) to determine the proportion of Tregs and their phenotype according to the expression of CD127 and HLA-DR markers which describe the differentiation stages of Tregs. In addition, we analyzed the expression of membrane ectoenzyme CD39 on Tregs of the study groups, an important component of the suppressive machinery of Tregs. Results We found no differences in the proportion of Tregs between PTSD patients and controls, but PTSD patients had a higher percentage of CD127-HLA-DR- Tregs and a lower percentage of CD127loHLA-DR+ Tregs compared to controls. There was no difference in expression of CD39 on Tregs of the study groups. Conclusions Although the proportions of Tregs in PTSD patients were unchanged, we found that they exhibit a different phenotype of Tregs that might be less suppressive. Impaired differentiation and function of Tregs is likely involved in disruption of immune homeostasis in PTSD. PMID:25670936

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

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

    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.

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

    SciTech Connect

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

    2011-11-15

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

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

    PubMed Central

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

    2011-01-01

    The production of man-made nanoparticles for various modern applications has increased exponentially in recent years, but the potential health effects of most nanoparticles are not well characterized. Unfortunately, in vitro nanoparticle toxicity studies are extremely limited by yet unresolved problems relating to dosimetry. In the present study, we systematically characterized manganese (Mn) nanoparticle sizes and examined the nanoparticle-induced oxidative signaling in dopaminergic neuronal cells. Differential interference contrast (DIC) microscopy and transmission electron microscopy (TEM) studies revealed that Mn nanoparticles range in size from single nanoparticles (~25 nM) to larger agglomerates when in treatment media. Manganese nanoparticles were effectively internalized in N27 dopaminergic neuronal cells, and they induced a time-dependent upregulation of the transporter protein transferrin. Exposure to 25–400 µg/mL Mn nanoparticles induced cell death in a time- and dose-dependent manner. Mn nanoparticles also significantly increased ROS, accompanied by a caspase-mediated proteolytic cleavage of proapoptotic protein kinase C? (PKC?), as well as activation loop phosphorylation. Blocking Mn nanoparticle-induced ROS failed to protect against the neurotoxic effects, suggesting the involvement of other pathways. Further mechanistic studies revealed changes in Beclin1 and LC3, indicating that Mn nanoparticles induce autophagy. Primary mesencephalic neuron exposure to Mn nanoparticles induced loss of TH positive dopaminergic neurons and neuronal processes. Collectively, our results suggest that Mn nanoparticles effectively enter dopaminergic neuronal cells and exert neurotoxic effects by activating an apoptotic signaling pathway and autophagy, emphasizing the need for assessing possible health risks associated with an increased use of Mn nanoparticles in modern applications. PMID:21856324

  8. Effect of ZnO nanoparticles on nasopharyngeal cancer cells viability and respiration

    NASA Astrophysics Data System (ADS)

    Prasanth, R.; Gopinath, D.

    2013-03-01

    Development of a therapeutic drugs based on nanoparticles requires a better understanding of the mechanism of selective cyto-toxic effects of nanopaticles over cancer cells. Scanning electrochemical microscopy provides opportunity to measure the real time chemical process at cell proximity in the presence of nanoparticle. Herein, the respiration process in nasopharyngeal cancer cells is investigated with the help of scanning electrochemical microscopy. The cell viability has been tested with MTT assay. The results show that ZnO nanoparticles have time and dose dependent effect in nasopharyngeal cancer cells and the cell respiration rate decreases with time.

  9. In vitro imaging of embryonic stem cells using multiphoton luminescence of gold nanoparticles.

    PubMed

    Nagesha, D; Laevsky, G S; Lampton, P; Banyal, R; Warner, C; DiMarzio, C; Sridhar, S

    2007-01-01

    Recent advances in nonlinear optical techniques and materials such as quantum wells, nanowires and noble-metal nanoparticles have led to advances in cellular imaging wherein various nanoparticles have been shown to improve both in vitro and in vivo visualization. In this paper, we demonstrate in vitro imaging using multi-photon photoluminescence of gold nanoparticles from two different cell types Dictyostelium discoideum and mouse embryonic stem cells. By observing nanoparticles we show that embryonic stem cells maintained their ability to proliferate for several passages while grown in the presence of gold nanoparticles. The advantages of multi-photon luminescence using gold nanoparticles have important implications for use in stem cell proliferation experiments and in vitro experiments to monitor differentiation. PMID:18203448

  10. In vitro imaging of embryonic stem cells using multiphoton luminescence of gold nanoparticles

    PubMed Central

    Nagesha, D; Laevsky, GS; Lampton, P; Banyal, R; Warner, C; DiMarzio, C; Sridhar, S

    2007-01-01

    Recent advances in nonlinear optical techniques and materials such as quantum wells, nanowires and noble-metal nanoparticles have led to advances in cellular imaging wherein various nanoparticles have been shown to improve both in vitro and in vivo visualization. In this paper, we demonstrate in vitro imaging using multi-photon photoluminescence of gold nanoparticles from two different cell types – Dictyostelium discoideum and mouse embryonic stem cells. By observing nanoparticles we show that embryonic stem cells maintained their ability to proliferate for several passages while grown in the presence of gold nanoparticles. The advantages of multi-photon luminescence using gold nanoparticles have important implications for use in stem cell proliferation experiments and in vitro experiments to monitor differentiation. PMID:18203448

  11. Scaffold-independent Patterning of Cells using Magnetic Nanoparticles

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

    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.

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

    PubMed Central

    McCurley, Nathanael; Mellman, Ira

    2010-01-01

    Background Fine control of lysosomal degradation for limited processing of internalized antigens is a hallmark of professional antigen presenting cells. Previous work in mice has shown that dendritic cells (DCs) contain lysosomes with remarkably low protease content. Combined with the ability to modulate lysosomal pH during phagocytosis and maturation, murine DCs enhance their production of class II MHC-peptide complexes for presentation to T cells. Methodology/Principal Findings In this study we extend these findings to human DCs and distinguish between different subsets of DCs based on their ability to preserve internalized antigen. Whereas DCs derived in vitro from CD34+ hematopoietic progenitor cells or isolated from peripheral blood of healthy donors are protease poor, DCs derived in vitro from monocytes (MDDCs) are more similar to macrophages (M?s) in protease content. Unlike other DCs, MDDCs also fail to reduce their intralysosomal pH in response to maturation stimuli. Indeed, functional characterization of lysosomal proteolysis indicates that MDDCs are comparable to M?s in the rapid degradation of antigen while other human DC subtypes are attenuated in this capacity. Conclusions/Significance Human DCs are comparable to murine DCs in exhibiting a markedly reduced level of lysosomal proteolysis. However, as an important exception to this, human MDDCs stand apart from all other DCs by a heightened capacity for proteolysis that resembles that of M?s. Thus, caution should be exercised when using human MDDCs as a model for DC function and cell biology. PMID:20689855

  13. Human induced pluripotent stem cells labeled with fluorescent magnetic nanoparticles for targeted imaging and hyperthermia therapy for gastric cancer

    PubMed Central

    Li, Chao; Ruan, Jing; Yang, Meng; Pan, Fei; Gao, Guo; Qu, Su; Shen, You-Lan; Dang, Yong-Jun; Wang, Kan; Jin, Wei-Lin; Cui, Da-Xiang

    2015-01-01

    Objective Human induced pluripotent stem (iPS) cells exhibit great potential for generating functional human cells for medical therapies. In this paper, we report for use of human iPS cells labeled with fluorescent magnetic nanoparticles (FMNPs) for targeted imaging and synergistic therapy of gastric cancer cells in vivo. Methods Human iPS cells were prepared and cultured for 72 h. The culture medium was collected, and then was co-incubated with MGC803 cells. Cell viability was analyzed by the MTT method. FMNP-labeled human iPS cells were prepared and injected into gastric cancer-bearing nude mice. The mouse model was observed using a small-animal imaging system. The nude mice were irradiated under an external alternating magnetic field and evaluated using an infrared thermal mapping instrument. Tumor sizes were measured weekly. Results iPS cells and the collected culture medium inhibited the growth of MGC803 cells. FMNP-labeled human iPS cells targeted and imaged gastric cancer cells in vivo, as well as inhibited cancer growth in vivo through the external magnetic field. Conclusion FMNP-labeled human iPS cells exhibit considerable potential in applications such as targeted dual-mode imaging and synergistic therapy for early gastric cancer. PMID:26487961

  14. Tuning surface plasmon resonance by the plastic deformation of Au nanoparticles within a diamond anvil cell

    NASA Astrophysics Data System (ADS)

    Bao, Yongjun; Zhao, Bin; Tang, Xinyu; Hou, Dongjie; Cai, Jian; Tang, Shan; Liu, Junsong; Wang, Fei; Cui, Tian

    2015-11-01

    In this work, surface plasmon resonance (SPR) is tuned by controlling the deformation of Au nanoparticles within a diamond anvil cell (DAC). Colloidal Au nanoparticles were loaded into a DAC and pressurized into a mixture of ice and Au nanoparticles. The Au nanoparticles were reshaped by their anisotropic compression of surrounding ice, which leads to the spectral variations of absorption peaks, broadening or red-shifting. These spectral features are well tuned by controlling the deformation process of Au nanoparticle with choosing the initial intended thickness of DAC gasket. The mechanical properties of Au nanoparticles are also revealed by the shape-dependent SPR in nanometer scale. This result provides us a way to fabricate Au nanoparticles into new shapes and tune SPR of metallic nanoparticles with pressure.

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

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

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

  16. Coating Solid Lipid Nanoparticles with Hyaluronic Acid Enhances Antitumor Activity against Melanoma Stem-like Cells

    PubMed Central

    Shen, Hongxin; Shi, Sanjun; Zhang, Zhirong; Gong, Tao; Sun, Xun

    2015-01-01

    Successful anticancer chemotherapy requires targeting tumors efficiently and further potential to eliminate cancer stem cell (CSC) subpopulations. Since CD44 is present on many types of CSCs, and it binds specially to hyaluronic acid (HA), we tested whether coating solid lipid nanoparticles with hyaluronan (HA-SLNs)would allow targeted delivery of paclitaxel (PTX) to CD44-overexpressing B16F10 melanoma cells. First, we developed a model system based on melanoma stem-like cells for experiments in vitro and in mouse xenografts, and we showed that cells expressing high levels of CD44 (CD44+) displayed a strong CSC phenotype while cells expressing low levels of CD44 (CD44-) did not. This phenotype included sphere and colony formation, higher proportion of side population cells, expression of CSC-related markers (ALDH, CD133, Oct-4) and tumorigenicity in vivo. Next we showed that administering PTX-loaded HA-SLNs led to efficient intracellular delivery of PTX and induced substantial apoptosis in CD44+ cells in vitro. In the B16F10-CD44+ lung metastasis model, PTX-loaded HA-SLNs targeted the tumor-bearing lung tissues well and subsequently exhibited significant antitumor effects with a relative low dose of PTX, which provided significant survival benefit without evidence of adverse events. These findings suggest that the HA-SLNs targeting system shows promise for enhancing cancer therapy. PMID:25897340

  17. Magnetite nanoparticles induced adaptive mechanisms counteract cell death in human pulmonary fibroblasts.

    PubMed

    Radu, Mihaela; Dinu, Diana; Sima, Cornelia; Burlacu, Radu; Hermenean, Anca; Ardelean, Aurel; Dinischiotu, Anca

    2015-10-01

    Magnetite nanoparticles (MNP) have attracted great interest for biomedical applications due to their unique chemical and physical properties, but the MNP impact on human health is not fully known. Consequently, our study proposes to highlight the biochemical mechanisms that underline the toxic effects of MNP on a human lung fibroblast cell line (MRC-5). The cytotoxicity generated by MNP in MRC-5 cells was dose and time-dependent. MNP-treated MRC-5 cells accumulated large amount of iron and reactive oxygen species (ROS) and exhibited elevated antioxidant scavenger enzymes. Reduced glutathione (GSH) depletion and enhanced lipid peroxidation (LPO) processes were also observed. The cellular capacity to counteract the oxidative damage was sustained by high levels of heat shock protein 60 (Hsp60), a protein that confers resistance against ROS attack and inhibition of cell death. While significant augmentations in nitric oxide (NO) and prostaglandine E2 (PGE2) levels were detected after 72 h of MNP-exposure only, caspase-1 was activated earlier starting with 24h post-treatment. Taken together, our results suggest that MRC-5 cells have the capacity to develop cell protection mechanisms against MNP. Detailed knowledge of the mechanisms induced by MNP in cell culture could be essential for their prospective use in various in vivo biochemical applications. PMID:26065626

  18. Photovoltaic study of dye sensitized solar cells based on TiO2, ZnO:Al3+ nanoparticles

    NASA Astrophysics Data System (ADS)

    Sánchez Godoy, H. E.; Rodríguez-Rojas, R. A.; Castañeda-Contreras, J.; Marañón-Ruiz, V. F.; Pérez-Ladrón de Guevara, H.; López-Luke, T.; De la Rosa-Cruz

    2015-10-01

    A technique to fabricate dye (rhodamine B) sensitized solar cells based on Titanium Oxide (TiO2) and Zinc Oxide (ZnO) nanoparticles are reported. The TiO2 was synthesized using the sol-gel method and the ZnO was synthesized by hydrolysis method to obtain nanoparticles of ~ 5 nm and 150 nm respectively. ZnO was doped with Al3+ in order to enhance the photovoltaic efficiency to promote the electrons mobility. The photovoltaic conversion characterization of films of TiO2, ZnO and ZnO:Al3+ nanoparticles is also reported. The generated photocurrent was measured by two methods; one of those uses a three electrode electrochemical cell and the other use an electronic array where the cells were exposed to UV lamp and the sun light. The role of the TiO2, ZnO and Al3+ doped ZnO nanoparticles is discussed to obtain a better efficiency in the generation of photocurrent (PC). The results exhibited by the electrochemical cell method, efficiencies of 0.55 (PC=187 ?A/cm2) and 0.22 (PC=149 ?A/cm2) for TiO2 and undoped ZnO respectively. However, when ZnO is doped with Al3+ at the higher concentration the efficiency was 0.44. While using the electronic array the results exhibited efficiencies of 0.31 (PC=45 ?A/cm2) and 0.09 (PC=16 ?A/cm2) for TiO2 and undoped ZnO respectively. However, when ZnO is doped with Al3+ at the higher concentration the efficiency was 0.44 and 0.48 for electrochemical cell and electronic array respectively. This shows that Al3+ enhances the photogenerated charge carriers increasing the mobility of electrons.

  19. Titanium dioxide nanoparticles cause genotoxicity in human lung epithelial cells

    EPA Science Inventory

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

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

    NASA Astrophysics Data System (ADS)

    Subia, B.; Kundu, S. C.

    2013-01-01

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

  1. Morphological effect of oscillating magnetic nanoparticles in killing tumor cells

    PubMed Central

    2014-01-01

    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

  2. Morphological effect of oscillating magnetic nanoparticles in killing tumor cells

    NASA Astrophysics Data System (ADS)

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

    2014-04-01

    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.

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

    PubMed

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

    2014-08-01

    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

  4. Characterization and anticancer potential of ferulic acid-loaded chitosan nanoparticles against ME-180 human cervical cancer cell lines

    NASA Astrophysics Data System (ADS)

    Panwar, Richa; Sharma, Asvene K.; Kaloti, Mandeep; Dutt, Dharm; Pruthi, Vikas

    2015-10-01

    Ferulic acid (FA) is a widely distributed hydroxycinnamic acid found in various cereals and fruits exhibiting potent antioxidant and anticancer activities. However, due to low solubility and permeability, its availability to biological systems is limited. Non-toxic chitosan-tripolyphosphate pentasodium (CS-TPP) nanoparticles (NPs) are used to load sparingly soluble molecules and drugs, increasing their bioavailability. In the present work, we have encapsulated FA into the CS-TPP NPs to increase its potential as a therapeutic agent. Different concentrations of FA were tested to obtain optimum sized FA-loaded CS-TPP nanoparticles (FA/CS-TPP NPs) by ionic gelation method. Nanoparticles were characterized by scanning electron microscopy, Fourier transformation infrared spectroscopy (FTIR), thermogravimetric analyses and evaluated for their anticancer activity against ME-180 human cervical cancer cell lines. The FTIR spectra confirmed the encapsulation of FA and thermal analysis depicted its degradation profile. A concentration-dependent relationship between FA encapsulation efficiency and FA/CS-TPP NPs diameter was observed. Smooth and spherical FA-loaded cytocompatible nanoparticles with an average diameter of 125 nm were obtained at 40 µM FA conc. The cytotoxicity of 40 µM FA/CS-TPP NPs against ME-180 cervical cancer cell lines was found to be higher as compared to 40 µM native FA. Apoptotic morphological changes as cytoplasmic remnants and damaged wrinkled cells in ME-180 cells were visualized using scanning electron microscopic and fluorescent microscopic techniques. Data concluded that chitosan enveloped FA nanoparticles could be exploited as an excellent therapeutic drug against cancer cells proliferation.

  5. Toxicity of silver nanoparticles in mouse embryonic stem cells and chemical based reprogramming of somatic cells to sphere cells

    NASA Astrophysics Data System (ADS)

    Rajanahalli Krishnamurthy, Pavan

    Abstract 1: Silver nanoparticles (Ag Np's) have an interesting surface chemistry and unique plasmonic properties. They are used in a wide variety of applications ranging from consumer products like socks, medical dressing, computer chips and it is also shown to have antimicrobial, anti bacterial activity and wound healing. Ag Np toxicity studies have been limited to date which needs to be critically addressed due to its wide applications. Mouse embryonic stem (MES) cells represent a unique cell population with the ability to undergo both self renewal and differentiation. They exhibit very stringent and tightly regulated mechanisms to circumvent DNA damage and stress response. We used 10 nm coated (polysaccharide) and uncoated Ag Np's to test its toxic effects on MES cells. MES cells and embryoid bodies (EB's) were treated with two concentrations of Ag Np's: 5 microg/ml and 50 ug/ml and exposed for 24, 48 and 72 hours. Increased cell death, ROS production and loss of mitochondrial membrane potential and alkaline phosphatase (AP) occur in a time and a concentration dependant manner. Due to increased cell death, there is a progressive increase in Annexin V (apoptosis) and Propidium Iodide (PI) staining (necrosis). Oct4 and Nanog undergo ubiquitination and dephosphorylation post-translational modifications in MES cells thereby altering gene expression of pluripotency factors and differentiation of EB's into all the three embryonic germ layers with specific growth factors were also inhibited after Ag Np exposure. Flow cytometry analysis revealed Ag Np's treated cells had altered cell cycle phases correlating with altered self renewal capacity. Our results suggest that Ag Np's effect MES cell self renewal, pluripotency and differentiation and serves as a perfect model system for studying toxicity induced by engineered Ag Np's. Abstract 2: The reprogramming of fibroblasts to pluripotent stem cells and the direct conversion of fibroblasts to functional neurons has been successfully manipulated by ectopic expression of defined factors. We demonstrate that mouse fibroblasts can be converted into sphere cells by detaching fibroblast cells by proteases and then using AlbuMAX I-containing culture medium without genetic alteration. AlbuMAX I is a lipid-rich albumin. Albumin-associated lipids arachidonic acid (AA) and pluronic F-68 were responsible for this effect. The converted colonies were positive for both alkaline phosphatase and stage specific embryonic antigen-1 (SSEA-1) staining. Global gene expression analysis indicated that the sphere cells were in an intermediate state compared with MES cells and MEF cells. The sphere cells were able to differentiate into tissues representing all three embryonic germ layers following retinoic acid treatment, and also differentiated into smooth muscle cells following treatment with vascular endothelial growth factor (VEGF). The study presented a potential novel approach to transdifferentiate mouse fibroblast cells into other cell lineages mediated by AlbuMAX I-containing culture medium.

  6. Polyethylenimine-coated SPION exhibits potential intrinsic anti-metastatic properties inhibiting migration and invasion of pancreatic tumor cells.

    PubMed

    Mulens-Arias, Vladimir; Rojas, José Manuel; Pérez-Yagüe, Sonia; Morales, María del Puerto; Barber, Domingo F

    2015-10-28

    Due to its aggressive behavior, pancreatic cancer is one of the principal causes of cancer-related deaths. The highly metastatic potential of pancreatic tumor cells demands the development of more effective anti-metastatic approaches for this disease. Although polyethylenimine-coated superparamagnetic iron oxide nanoparticles (PEI-coated SPIONs) have been studied for their utility as transfection agents, little is known of their effect on tumor cell biology. Here we demonstrated that PEI-coated SPIONs have potent inhibitory effects on pancreatic tumor cell migration/invasion, through inhibition of Src kinase and decreased expression of MT1-MMP and MMP2 metalloproteinases. When treated with PEI-coated SPIONs, the pancreatic tumor cell line Pan02 showed reduced invadosome density and thus, a decrease in their ability to invade through basement membrane. These nanoparticles temporarily downmodulated microRNA-21, thereby upregulating the cell migration inhibitors PTEN, PDCD4 and Sprouty-1. PEI-coated SPIONs thus show intrinsic, possibly anti-metastatic properties for modulating pancreatic tumor cell migration machinery, which indicates their potential as anti-metastatic agents for treatment of pancreatic cancer. PMID:26264831

  7. Effect of Plasmonic Silver Nanoparticles ?n the Photovoltaic Properties of Graetzel Solar Cells

    NASA Astrophysics Data System (ADS)

    Kislov, D. A.

    It is shown that the addition of silver nanoparticles in the construction of solar cells leads to a significant increase in their efficiency. Apart from that found a significant effect of silver nanoparticles on the capacitive and transport properties Graetzel solar cells.

  8. Copper nanoparticle incorporated plasmonic organic bulk-heterojunction solar cells

    NASA Astrophysics Data System (ADS)

    Liu, Zhihai; Lee, Seung Yong; Lee, Eun-Cheol

    2014-12-01

    By embedding copper nanoparticles into poly(3,4-thylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) layers, the power conversion efficiency of organic bulk-heterojunction solar cell using poly(3-hexylthiophene) (P3HT) was increased from 3.58% to 3.96%, and that of the device based on poly[[4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5-b']dithiophene-2,6-diyl][3-fluoro-2-[(2-ethylhexyl)carbonyl]thieno[3,4-b]thiophenediyl

  9. Interfacial phenomena in droplet evaporation and nanoparticle-cell systems

    NASA Astrophysics Data System (ADS)

    Fang, Xiaohua

    2005-11-01

    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.

  10. Enhancing the methanol tolerance of platinum nanoparticles for the cathode reaction of direct methanol fuel cells through a geometric design

    NASA Astrophysics Data System (ADS)

    Feng, Yan; Ye, Feng; Liu, Hui; Yang, Jun

    2015-11-01

    Mastery over the structure of nanoparticles might be an effective way to enhance their performance for a given application. Herein we demonstrate the design of cage-bell nanostructures to enhance the methanol tolerance of platinum (Pt) nanoparticles while remaining their catalytic activity for oxygen reduction reaction. This strategy starts with the synthesis of core-shell-shell nanoparticles with Pt and silver (Ag) residing respectively in the core and inner shell regions, which are then agitated with saturated sodium chloride (NaCl) solution to eliminate the Ag component from the inner shell region, leading to the formation of bimetallic nanoparticles with a cage-bell structure, defined as a movable Pt core enclosed by a metal shell with nano-channels, which exhibit superior methanol-tolerant property in catalyzing oxygen reduction reaction due to the different diffusion behaviour of methanol and oxygen in the porous metal shell of cage-bell structured nanoparticles. In particular, the use of remarkably inexpensive chemical agent (NaCl) to promote the formation of cage-bell structured particles containing a wide spectrum of metal shells highlights its engineering merit to produce highly selective electrocatalysts on a large scale for the cathode reaction of direct methanol fuel cells.

  11. Enhancing the methanol tolerance of platinum nanoparticles for the cathode reaction of direct methanol fuel cells through a geometric design

    PubMed Central

    Feng, Yan; Ye, Feng; Liu, Hui; Yang, Jun

    2015-01-01

    Mastery over the structure of nanoparticles might be an effective way to enhance their performance for a given application. Herein we demonstrate the design of cage-bell nanostructures to enhance the methanol tolerance of platinum (Pt) nanoparticles while remaining their catalytic activity for oxygen reduction reaction. This strategy starts with the synthesis of core-shell-shell nanoparticles with Pt and silver (Ag) residing respectively in the core and inner shell regions, which are then agitated with saturated sodium chloride (NaCl) solution to eliminate the Ag component from the inner shell region, leading to the formation of bimetallic nanoparticles with a cage-bell structure, defined as a movable Pt core enclosed by a metal shell with nano-channels, which exhibit superior methanol-tolerant property in catalyzing oxygen reduction reaction due to the different diffusion behaviour of methanol and oxygen in the porous metal shell of cage-bell structured nanoparticles. In particular, the use of remarkably inexpensive chemical agent (NaCl) to promote the formation of cage-bell structured particles containing a wide spectrum of metal shells highlights its engineering merit to produce highly selective electrocatalysts on a large scale for the cathode reaction of direct methanol fuel cells. PMID:26578100

  12. Enhancing the methanol tolerance of platinum nanoparticles for the cathode reaction of direct methanol fuel cells through a geometric design.

    PubMed

    Feng, Yan; Ye, Feng; Liu, Hui; Yang, Jun

    2015-01-01

    Mastery over the structure of nanoparticles might be an effective way to enhance their performance for a given application. Herein we demonstrate the design of cage-bell nanostructures to enhance the methanol tolerance of platinum (Pt) nanoparticles while remaining their catalytic activity for oxygen reduction reaction. This strategy starts with the synthesis of core-shell-shell nanoparticles with Pt and silver (Ag) residing respectively in the core and inner shell regions, which are then agitated with saturated sodium chloride (NaCl) solution to eliminate the Ag component from the inner shell region, leading to the formation of bimetallic nanoparticles with a cage-bell structure, defined as a movable Pt core enclosed by a metal shell with nano-channels, which exhibit superior methanol-tolerant property in catalyzing oxygen reduction reaction due to the different diffusion behaviour of methanol and oxygen in the porous metal shell of cage-bell structured nanoparticles. In particular, the use of remarkably inexpensive chemical agent (NaCl) to promote the formation of cage-bell structured particles containing a wide spectrum of metal shells highlights its engineering merit to produce highly selective electrocatalysts on a large scale for the cathode reaction of direct methanol fuel cells. PMID:26578100

  13. Casein-coated Iron Oxide Nanoparticles for High MRI Contrast Enhancement and Efficient Cell Targeting

    PubMed Central

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

    2013-01-01

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

  14. Cytotoxicity of various types of gold-mesoporous silica nanoparticles in human breast cancer cells

    PubMed Central

    Liu, Guomu; Li, Qiongshu; Ni, Weihua; Zhang, Nannan; Zheng, Xiao; Wang, Yingshuai; Shao, Dan; Tai, Guixiang

    2015-01-01

    Recently, gold nanoparticles (AuNPs) have shown promising biological applications due to their unique electronic and optical properties. However, the potential toxicity of AuNPs remains a major hurdle that impedes their use in clinical settings. Mesoporous silica is very suitable for the use as a coating material for AuNPs and might not only reduce the cytotoxicity of cetyltrimethylammonium bromide-coated AuNPs but might also facilitate the loading and delivery of drugs. Herein, three types of rod-like gold-mesoporous silica nanoparticles (termed bare AuNPs, core–shell Au@mSiO2NPs, and Janus Au@mSiO2NPs) were specially designed, and the effects of these AuNPs on cellular uptake, toxic behavior, and mechanism were then systematically studied. Our results indicate that bare AuNPs exerted higher toxicity than the Au@mSiO2NPs and that Janus Au@mSiO2NPs exhibited the lowest toxicity in human breast cancer MCF-7 cells, consistent with the endocytosis capacity of the nanoparticles, which followed the order, bare AuNPs > core–shell Au@mSiO2NPs > Janus Au@mSiO2NPs. More importantly, the AuNPs-induced apoptosis of MCF-7 cells exhibited features that were characteristic of intracellular reactive oxygen species (ROS) generation, activation of c-Jun-N-terminal kinase (JNK) phosphorylation, an enhanced Bax-to-Bcl-2 ratio, and loss of the mitochondrial membrane potential. Simultaneously, cytochrome c was released from mitochondria, and the caspase-3/9 cascade was activated. Moreover, both ROS scavenger (N-acetylcysteine) and JNK inhibitor (SP600125) partly blocked the induction of apoptosis in all AuNPs-treated cells. Taken together, these findings suggest that all AuNPs induce apoptosis through the ROS-/JNK-mediated mitochondrial pathway. Thus, Janus Au@mSiO2NPs exhibit the potential for applications in biomedicine, thus aiding the clinical translation of AuNPs. PMID:26491285

  15. Relating Intercellular Variability in Nanoparticle Uptake with Biological Consequence: A Quantitative X-ray Fluorescence Study for Radiosensitization of Cells.

    PubMed

    Turnbull, Tyron; Douglass, Michael; Paterson, David; Bezak, Eva; Thierry, Benjamin; Kempson, Ivan

    2015-11-01

    Internalized gold nanoparticles were quantified in large numbers of individual prostate cancer cells using large area synchrotron X-ray fluorescence microscopy. Cells were also irradiated with a 6 MV linear accelerator to assess the biological consequence of radiosensitization with gold nanoparticles. A large degree of heterogeneity in nanoparticle uptake between cells resulted in influenced biological effect. PMID:26461268

  16. A Cell-Based Model Exhibiting Branching and Anastomosis during Tumor-Induced Angiogenesis

    E-print Network

    Jiang, Yi

    ). Endothelial cells are activated via two recep- tor tyrosine kinases, FMS-like tyrosine kinase-1 and fetal, including cell-cell and cell-matrix interactions, cell surface receptor binding, and intracellular signaling cells, which form the interior lining of blood vessels, have cell surface receptors specific to VEGF (7

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

    PubMed Central

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

    2013-01-01

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

  18. The Cell Division Protein FtsZ from Streptococcus pneumoniae Exhibits a GTPase Activity Delay.

    PubMed

    Salvarelli, Estefanía; Krupka, Marcin; Rivas, Germán; Mingorance, Jesus; Gómez-Puertas, Paulino; Alfonso, Carlos; Rico, Ana Isabel

    2015-10-01

    The cell division protein FtsZ assembles in vitro by a mechanism of cooperative association dependent on GTP, monovalent cations, and Mg(2+). We have analyzed the GTPase activity and assembly dynamics of Streptococcus pneumoniae FtsZ (SpnFtsZ). SpnFtsZ assembled in an apparently cooperative process, with a higher critical concentration than values reported for other FtsZ proteins. It sedimented in the presence of GTP as a high molecular mass polymer with a well defined size and tended to form double-stranded filaments in electron microscope preparations. GTPase activity depended on K(+) and Mg(2+) and was inhibited by Na(+). GTP hydrolysis exhibited a delay that included a lag phase followed by a GTP hydrolysis activation step, until reaction reached the GTPase rate. The lag phase was not found in polymer assembly, suggesting a transition from an initial non-GTP-hydrolyzing polymer that switches to a GTP-hydrolyzing polymer, supporting models that explain FtsZ polymer cooperativity. PMID:26330552

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

    NASA Astrophysics Data System (ADS)

    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

    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

  20. Photocurrent enhancements of organic solar cells by altering dewetting of plasmonic Ag nanoparticles

    PubMed Central

    Fleetham, Tyler; Choi, Jea-Young; Choi, Hyung Woo; Alford, Terry; Jeong, Doo Seok; Lee, Taek Sung; Lee, Wook Seong; Lee, Kyeong-Seok; Li, Jian; Kim, Inho

    2015-01-01

    Incorporation of metal nanoparticles into active layers of organic solar cells is one of the promising light trapping approaches. The size of metal nanoparticles is one of key factors to strong light trapping, and the size of thermally evaporated metal nanoparticles can be tuned by either post heat treatment or surface modification of substrates. We deposited Ag nanoparticles on ITO by varying nominal thicknesses, and post annealing was carried out to increase their size in radius. PEDOT:PSS was employed onto the ITO substrates as a buffer layer to alter the dewetting behavior of Ag nanoparticles. The size of Ag nanoparticles on PEDOT:PSS were dramatically increased by more than three times compared to those on the ITO substrates. Organic solar cells were fabricated on the ITO and PEDOT:PSS coated ITO substrates with incorporation of those Ag nanoparticles, and their performances were compared. The photocurrents of the cells with the active layers on PEDOT:PSS with an optimal choice of the Ag nanoparticles were greatly enhanced whereas the Ag nanoparticles on the ITO substrates did not lead to the photocurrent enhancements. The origin of the photocurrent enhancements with introducing the Ag nanoparticles on PEDOT:PSS are discussed. PMID:26388104

  1. Photocurrent enhancements of organic solar cells by altering dewetting of plasmonic Ag nanoparticles

    NASA Astrophysics Data System (ADS)

    Fleetham, Tyler; Choi, Jea-Young; Choi, Hyung Woo; Alford, Terry; Jeong, Doo Seok; Lee, Taek Sung; Lee, Wook Seong; Lee, Kyeong-Seok; Li, Jian; Kim, Inho

    2015-09-01

    Incorporation of metal nanoparticles into active layers of organic solar cells is one of the promising light trapping approaches. The size of metal nanoparticles is one of key factors to strong light trapping, and the size of thermally evaporated metal nanoparticles can be tuned by either post heat treatment or surface modification of substrates. We deposited Ag nanoparticles on ITO by varying nominal thicknesses, and post annealing was carried out to increase their size in radius. PEDOT:PSS was employed onto the ITO substrates as a buffer layer to alter the dewetting behavior of Ag nanoparticles. The size of Ag nanoparticles on PEDOT:PSS were dramatically increased by more than three times compared to those on the ITO substrates. Organic solar cells were fabricated on the ITO and PEDOT:PSS coated ITO substrates with incorporation of those Ag nanoparticles, and their performances were compared. The photocurrents of the cells with the active layers on PEDOT:PSS with an optimal choice of the Ag nanoparticles were greatly enhanced whereas the Ag nanoparticles on the ITO substrates did not lead to the photocurrent enhancements. The origin of the photocurrent enhancements with introducing the Ag nanoparticles on PEDOT:PSS are discussed.

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

    PubMed Central

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

    2013-01-01

    In this study, in vitro cytotoxicity of nickel zinc (NiZn) ferrite nanoparticles against human colon cancer HT29, breast cancer MCF7, and liver cancer HepG2 cells was examined. The morphology, homogeneity, and elemental composition of NiZn ferrite nanoparticles were investigated by scanning electron microscopy, transmission electron microscopy, and energy dispersive X-ray spectroscopy, respectively. The exposure of cancer cells to NiZn ferrite nanoparticles (15.6–1,000 ?g/mL; 72 hours) has resulted in a dose-dependent inhibition of cell growth determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The quantification of caspase-3 and -9 activities and DNA fragmentation to assess the cell death pathway of the treated cells showed that both were stimulated when exposed to NiZn ferrite nanoparticles. Light microscopy examination of the cells exposed to NiZn ferrite nanoparticles demonstrated significant changes in cellular morphology. The HepG2 cells were most prone to apoptosis among the three cells lines examined, as the result of treatment with NiZn nanoparticles. In conclusion, NiZn ferrite nanoparticles are suggested to have potential cytotoxicity against cancer cells. PMID:23885175

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

    NASA Astrophysics Data System (ADS)

    Khiterer, Mariya

    2007-05-01

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

  4. ZnO Nanoparticles Affect Bacillus subtilis Cell Growth and Biofilm Formation

    PubMed Central

    Hsueh, Yi-Huang; Ke, Wan-Ju; Hsieh, Chien-Te; Lin, Kuen-Song; Tzou, Dong-Ying; Chiang, Chao-Lung

    2015-01-01

    Zinc oxide nanoparticles (ZnO NPs) are an important antimicrobial additive in many industrial applications. However, mass-produced ZnO NPs are ultimately disposed of in the environment, which can threaten soil-dwelling microorganisms that play important roles in biodegradation, nutrient recycling, plant protection, and ecological balance. This study sought to understand how ZnO NPs affect Bacillus subtilis, a plant-beneficial bacterium ubiquitously found in soil. The impact of ZnO NPs on B. subtilis growth, FtsZ ring formation, cytosolic protein activity, and biofilm formation were assessed, and our results show that B. subtilis growth is inhibited by high concentrations of ZnO NPs (? 50 ppm), with cells exhibiting a prolonged lag phase and delayed medial FtsZ ring formation. RedoxSensor and Phag-GFP fluorescence data further show that at ZnO-NP concentrations above 50 ppm, B. subtilis reductase activity, membrane stability, and protein expression all decrease. SDS-PAGE Stains-All staining results and FT-IR data further demonstrate that ZnO NPs negatively affect exopolysaccharide production. Moreover, it was found that B. subtilis biofilm surface structures became smooth under ZnO-NP concentrations of only 5–10 ppm, with concentrations ? 25 ppm significantly reducing biofilm formation activity. XANES and EXAFS spectra analysis further confirmed the presence of ZnO in co-cultured B. subtilis cells, which suggests penetration of cell membranes by either ZnO NPs or toxic Zn+ ions from ionized ZnO NPs, the latter of which may be deionized to ZnO within bacterial cells. Together, these results demonstrate that ZnO NPs can affect B. subtilis viability through the inhibition of cell growth, cytosolic protein expression, and biofilm formation, and suggest that future ZnO-NP waste management strategies would do well to mitigate the potential environmental impact engendered by the disposal of these nanoparticles. PMID:26039692

  5. Interaction of multi-functional silver nanoparticles with living cells

    NASA Astrophysics Data System (ADS)

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

    2010-04-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-08-01

    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.

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

    PubMed

    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

    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

  8. A New Interleukin-13 Amino-Coated Gadolinium Metallofullerene Nanoparticle for Targeted MRI Detection of Glioblastoma Tumor Cells.

    PubMed

    Li, Tinghui; Murphy, Susan; Kiselev, Boris; Bakshi, Kanwarpal S; Zhang, Jianyuan; Eltahir, Amnah; Zhang, Yafen; Chen, Ying; Zhu, Jie; Davis, Richey M; Madsen, Louis A; Morris, John R; Karolyi, Daniel R; LaConte, Stephen M; Sheng, Zhi; Dorn, Harry C

    2015-06-24

    The development of new nanoparticles as next-generation diagnostic and therapeutic ("theranostic") drug platforms is an active area of both chemistry and cancer research. Although numerous gadolinium (Gd) containing metallofullerenes as diagnostic magnetic resonance imaging (MRI) contrast agents have been reported, the metallofullerene cage surface, in most cases, consists of negatively charged carboxyl or hydroxyl groups that limit attractive forces with the cellular surface. It has been reported that nanoparticles with a positive charge will bind more efficiently to negatively charged phospholipid bilayer cellular surfaces, and will more readily undergo endocytosis. In this paper, we report the preparation of a new functionalized trimetallic nitride template endohedral metallofullerene (TNT EMF), Gd3N@C80(OH)x(NH2)y, with a cage surface bearing positively charged amino groups (-NH3(+)) and directly compare it with a similar carboxyl and hydroxyl functionalized derivative. This new nanoparticle was characterized by X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), and infrared spectroscopy. It exhibits excellent (1)H MR relaxivity. Previous studies have clearly demonstrated that the cytokine interleukin-13 (IL-13) effectively targets glioblastoma multiforme (GBM) cells, which are known to overexpress IL-13R?2. We also report that this amino-coated Gd-nanoplatform, when subsequently conjugated with interleukin-13 peptide IL-13-Gd3N@C80(OH)x(NH2)y, exhibits enhanced targeting of U-251 GBM cell lines and can be effectively delivered intravenously in an orthotopic GBM mouse model. PMID:26022213

  9. Uptake of Gold Nanoparticles in Breathless (Hypoxic) Cancer Cells.

    PubMed

    Neshatian, Mehrnoosh; Chung, Stephen; Yohan, Darren; Yang, Celina; Chithrani, Devika B

    2015-07-01

    Gold nanoparticles (GNPs) are emerging as promising novel agents for cancer therapy. However, the oxygen concentration in human tumors is highly heterogeneous, and there are many regions with very low levels of oxygen (hypoxia). A majority of solid tumors contain regions with oxygen pressure values of less than 0.7% in the gas phase. The purpose of this study was to investigate NP stability, toxicity, and cellular uptake under hypoxic conditions. GNPs 50 nm in diameter were used, and the experiment was performed under 0.2% (hypoxic) and 21% (normoxic) oxygen levels using MCF-7 and HeLa cells. Hypoxic cells with prolonged exposure (eighteen hours) to hypoxia had a higher NP uptake at both 6- and 24-hour NP incubation time points. No significant toxicity was introduced by NPs under hypoxic and normoxic conditions. These findings will play a vital role in the optimization of GNP-based therapeutics in cancer treatment. PMID:26307839

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

    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.

  11. Toxicological mode of action of ZnO nanoparticles: Impact on immune cells.

    PubMed

    Roy, Ruchi; Das, Mukul; Dwivedi, Premendra D

    2015-02-01

    The use of nanoscale materials is growing exponentially as concerns rise about the human hazards to it. It is assumed that living beings are coevolved with nanoparticles ever since the origin of life on earth and therefore, they must have developed the defense and toxicity mitigating mechanisms for nanoparticles. Although having peculiar properties these new materials also present new health risks upon interacting with biological systems. Zinc oxide is the most widely used nanoparticles among various nanomaterials. Recently, these nanoparticles have been shown to specifically kill cancerous cells; therefore, it is believed that these nanoparticles may be used as an alternative anti-tumor agent. However, it is also known that these nanoparticles pose several deleterious effects to living beings. It is therefore critical to understand the nature and origin of the toxicity imposed by these nanomaterials. Keeping these points in mind the present review provides updated information on various aspects of toxicities induced by these engineered nanoparticles. PMID:25193324

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

    PubMed Central

    2014-01-01

    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

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

    PubMed

    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

    2013-05-01

    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. PMID:23536050

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

    NASA Astrophysics Data System (ADS)

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

    2013-09-01

    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

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

    NASA Astrophysics Data System (ADS)

    Yuan, Zhaolin

    2015-01-01

    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.

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

    PubMed

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

    2014-12-21

    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

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

    PubMed

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

    2010-11-01

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

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

    SciTech Connect

    Ahamed, Maqusood; Karns, Michael; Goodson, Michael; Rowe, John; Hussain, Saber M.; Schlager, John J.

    2008-12-15

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

    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.

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

    PubMed Central

    2014-01-01

    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. PMID:25242904

  2. Magnetic Carbon nanoparticles enabled efficient photothermal alteration of mammalian cells

    NASA Astrophysics Data System (ADS)

    Cardenas, Nelson; Thomas, Patrick; Yu, Lingfeng; Mohanty, Samarendra

    2011-03-01

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

  3. Array-based sensing with nanoparticles: “Chemical noses” for sensing biomolecules and cell surfaces

    PubMed Central

    Miranda, Oscar R.; Creran, Brian; Rotello, Vincent M.

    2010-01-01

    Nanoparticle-based arrays have been used to distinguish a wide range of biomolecular targets through pattern recognition. In this report, we highlight new “chemical nose” methodologies that use nanoparticle systems to provide high sensitivity sensing of biomolecular targets, including fluorescent polymer/gold nanoparticle complexes that can discriminate between different bioanalytes including proteins, bacteria, and mammalian cells as well as dye-based micellar systems for the detection of clinically important metallo- and non-metallo proteins. PMID:20801707

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

    E-print Network

    Bauer, Michael

    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 ...

  5. PLGA Nanoparticle-Peptide Conjugate Effectively Targets Intercellular Cell-Adhesion Molecule-1

    PubMed Central

    Zhang, Na; Chittapuso, Chuda; Ampassavate, Chadarat; Siahaan, Teruna J.; Berkland, Cory

    2008-01-01

    Targeted delivery of therapeutics possesses the potential to localize therapeutic agents to a specific tissue as a mechanism to enhance treatment efficacy and abrogate side effects. Antibodies have been used clinically as therapeutic agents and are currently being explored for targeting drug-loaded nanoparticles. Peptides such as RGD peptides are also being developed as an inexpensive and stable alternative to antibodies. In this study, cyclo(1,12)PenITDGEATDSGC (cLABL) peptide was used to target nanoparticles to human umbilical cord vascular endothelial cells (HUVEC) monolayers that have upregulated intercellular cell-adhesion molecule-1 (ICAM-1) expression. The cLABL peptide has been previously demonstrated to possess high avidity for ICAM-1 receptors on the cell surface. Poly(DL-lactic-co-glycolic acid) nanoparticles conjugated with polyethylene glycol and cLABL demonstrated rapid binding to HUVEC with upregulated ICAM-1, which was induced by treating cells with the proinflammatory cytokine, interferon-?. Binding of the nanoparticles could be efficiently blocked by pre-incubating cells with free peptide suggesting that the binding of the nanoparticles is specifically mediated by surface peptide binding to ICAM-1 on HUVEC. The targeted nanoparticles were rapidly endocytosed and trafficked to lysosomes to a greater extent than the untargeted PLGA-PEG nanoparticles. Verification of peptide-mediated nanoparticle targeting to ICAM-1 may ultimately lead to targeting therapeutic agents to inflammatory sites expressing upregulated ICAM-1. PMID:17997512

  6. In vitro toxicity of silica nanoparticles in human lung cancer cells

    SciTech Connect

    Lin Weisheng; Huang Yuewern; Zhou Xiaodong; Ma Yinfa . E-mail: yinfa@umr.edu

    2006-12-15

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

  7. Hyperthermia HeLa cell treatment with silica coated manganese oxide nanoparticles

    E-print Network

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

    2009-01-01

    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.

  8. DNA-gadolinium-gold nanoparticles for in vivo T1 MR imaging of transplanted human neural stem cells.

    PubMed

    Nicholls, Francesca J; Rotz, Matthew W; Ghuman, Harmanvir; MacRenaris, Keith W; Meade, Thomas J; Modo, Michel

    2016-01-01

    The unambiguous imaging of transplanted cells remains a major challenge to understand their biological function and therapeutic efficacy. In vivo imaging of implanted cells is reliant on tagging these to differentiate them from host tissue, such as the brain. We here characterize a gold nanoparticle conjugate that is functionalized with modified deoxythymidine oligonucleotides bearing Gd(III) chelates and a red fluorescent Cy3 moiety to visualize in vivo transplanted human neural stem cells. This DNA-Gd@Au nanoparticle (DNA-Gd@AuNP) exhibits an improved T1 relaxivity and excellent cell uptake. No significant effects of cell uptake have been found on essential cell functions. Although T1 relaxivity is attenuated within cells, it is sufficiently preserved to afford the in vivo detection of transplanted cells using an optimized voxel size. In vivo MR images were corroborated by a post-mortem histological verification of DNA-Gd@AuNPs in transplanted cells. With 70% of cells being correctly identified using the DNA-Gd-AuNPs indicates an overall reliable detection. Less than 1% of cells were false positive for DNA-Gd@AuNPs, but a significant number of 30% false negatives reveals a dramatic underestimation of transplanted cells using this approach. DNA-Gd@AuNPs therefore offer new opportunities to visualize transplanted cells unequivocally using T1 contrast and use cellular MRI as a tool to derive biologically relevant information that allows us to understand how the survival and location of implanted cells determines therapeutic efficacy. PMID:26615367

  9. Induction of apoptosis in human cancer cells by targeting mitochondria with gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Mkandawire, M. M.; Lakatos, M.; Springer, A.; Clemens, A.; Appelhans, D.; Krause-Buchholz, U.; Pompe, W.; Rödel, G.; Mkandawire, M.

    2015-06-01

    A major challenge in designing cancer therapies is the induction of cancer cell apoptosis, although activation of intrinsic apoptotic pathways by targeting gold nanoparticles to mitochondria is promising. We report an in vitro procedure targeting mitochondria with conjugated gold nanoparticles and investigating effects on apoptosis induction in the human breast cancer cell line Jimt-1. Gold nanoparticles were conjugated to a variant of turbo green fluorescent protein (mitoTGFP) harbouring an amino-terminal mitochondrial localization signal. Au nanoparticle conjugates were further complexed with cationic maltotriose-modified poly(propylene imine) third generation dendrimers. Fluorescence and transmission electron microscopy revealed that Au nanoparticle conjugates were directed to mitochondria upon transfection, causing partial rupture of the outer mitochondrial membrane, triggering cell death. The ability to target Au nanoparticles into mitochondria of breast cancer cells and induce apoptosis reveals an alternative application of Au nanoparticles in photothermal therapy of cancer.A major challenge in designing cancer therapies is the induction of cancer cell apoptosis, although activation of intrinsic apoptotic pathways by targeting gold nanoparticles to mitochondria is promising. We report an in vitro procedure targeting mitochondria with conjugated gold nanoparticles and investigating effects on apoptosis induction in the human breast cancer cell line Jimt-1. Gold nanoparticles were conjugated to a variant of turbo green fluorescent protein (mitoTGFP) harbouring an amino-terminal mitochondrial localization signal. Au nanoparticle conjugates were further complexed with cationic maltotriose-modified poly(propylene imine) third generation dendrimers. Fluorescence and transmission electron microscopy revealed that Au nanoparticle conjugates were directed to mitochondria upon transfection, causing partial rupture of the outer mitochondrial membrane, triggering cell death. The ability to target Au nanoparticles into mitochondria of breast cancer cells and induce apoptosis reveals an alternative application of Au nanoparticles in photothermal therapy of cancer. Electronic supplementary information (ESI) available: PPI-Mal-III G3 dendrimers; SEM of AuNPs and TEM of AuNP interaction with cancerous cells; and comparison of brightfield and caspase 3 fluorescence staining verifying apoptosis. See DOI: 10.1039/c5nr01483b

  10. Effects of hydroxyapatite nanoparticles on proliferation and apoptosis of human hepatoma BEL-7402 cells

    PubMed Central

    Liu, Zhi-Su; Tang, Sheng-Li; Ai, Zhong-Li

    2003-01-01

    AIM: To study the effect of hydroxyapatite (HAP) nanoparticles on human hepatoma cell line BEL-7402 in vitro. METHODS: The human hepatoma cell line BEL-7402 was cultured and treated with HAP nanoparticles at various concentrations. Growth suppression was detected with MTT colorimetric assay, cell apoptotic alterations were evaluated by cytochemical staining (Hoechst 33258), transmission electron microscopy (TEM), and flow cytometry (FCM). RESULTS: HAP nanoparticles inhibited the growth of hepatoma cells in a dose-dependent manner, with IC50 values of 29.30 mg/L. Treated with 50-200 mg/L HAP nanoparticles for 48 h, BEL-7402 cells apoptosis with nuclear chromatin condensation and fragmentation as well as cell shrinkage and the formation of apoptotic bodies were observed under cytochemical staining and transmission electron microscopy. FCM analysis showed hypodiploid peaks on histogram, the apoptotic rates at the concentrations of 50, 75, 100, 150 and 200 mg/L of HAP nanoparticles were 20.35 ± 2.23%, 25.35 ± 1.92%, 29.34 ± 4.61%, 44.92 ± 3.78% and 53.64 ± 3.49%, respectively, which were all significantly higher than that of control group 2.23 ± 0.14%. There was a significant correlation between HAP nanoparticle concentration and apoptotic rate (r = 0.994, P < 0.01). CONCLUSION: HAP nanoparticles not only inhibit proliferation but also induce apoptosis of human hepatoma cell line BEL-7402 in vitro. PMID:12970886

  11. Stable Self-Assembly of Bovine ?-Lactalbumin Exhibits Target-Specific Antiproliferative Activity in Multiple Cancer Cells.

    PubMed

    Mahanta, Sailendra; Paul, Subhankar

    2015-12-30

    Self-assembly of a protein is a natural phenomenon; however, the process can be performed under a suitable condition in vitro. Since proteins are nontoxic, biodegradable, and biocompatible in nature, they are used in various industrial applications such as biocatalyst, therapeutic agent, and drug carriers. Moreover, their flexible structural state and specific activity are being used as sensors and immensely attract many new applications. However, the inherent potential of protein self-assembly for various applications is yet to be explored in detail. In this study, spherical self-assembly of bovine ?-lactalbumin (nsBLA) was synthesized using an optimized ethanol-mediated desolvation process with an average diameter of approximately 300 nm. The self-assembly was found to be highly stable against thermal, pH, and proteases stress. When nsBLA was administered in various cancer cells, it demonstrated high cytotoxicity in three different cancer cells via reactive oxygen species (ROS) generation, whereas it exhibited negligible toxicity in normal human and murine cells. When nsBLA was conjugated with folic acid, it improved the cytotoxicity and perhaps mediated through enhanced cellular uptake in cancer cells through binding with folate receptors. Further, experimental results confirmed that the cancer cell death induced by nsBLA was not caused by apoptosis but a necrotic-like death mechanism. When compared with a well-known protein-based anticancer agent BAMLET (bovine ?-lactalbumin made lethal against tumor cell), the self-assembled BLA clearly exhibited higher cytotoxicity to cancer cells than BAMLET. While BAMLET exhibits poor biocompatibility, our nsBLA demonstrated excellent biocompatibility to normal cells. Therefore, in this study, we prepared self-assembled ?-lactalbumin that exhibits strong inherent antiproliferative potential in multiple cancer cells which can be used for efficient therapeutic approach in cancer. PMID:26440360

  12. Development and characterization of multifunctional nanoparticles for drug delivery to cancer cells

    NASA Astrophysics Data System (ADS)

    Nahire, Rahul Rajaram

    Lipid and polymeric nanoparticles, although proven to be effective drug delivery systems compared to free drugs, have shown considerable limitations pertaining to their uptake and release at tumor sites. Spatial and temporal control over the delivery of anticancer drugs has always been challenge to drug delivery scientists. Here, we have developed and characterized multifunctional nanoparticles (liposomes and polymersomes) which are targeted specifically to cancer cells, and release their contents with tumor specific internal triggers. To enable these nanoparticles to be tracked in blood circulation, we have imparted them with echogenic characteristic. Echogenicity of nanoparticles is evaluated using ultrasound scattering and imaging experiments. Nanoparticles demonstrated effective release with internal triggers such as elevated levels of MMP-9 enzyme found in the extracellular matrix of tumor cells, decreased pH of lysosome, and differential concentration of reducing agents in cytosol of cancer cells. We have also successfully demonstrated the sensitivity of these particles towards ultrasound to further enhance the release with internal triggers. To ensure the selective uptake by folate receptor- overexpressing cancer cells, we decorated these nanoparticles with folic acid on their surface. Fluorescence microscopic images showed significantly higher uptake of folate-targeted nanoparticles by MCF-7 (breast cancer) and PANC-1 (pancreatic cancer) cells compared to particles without any targeting ligand on their surface. To demonstrate the effectiveness of these nanoparticles to carry the drugs inside and kill cancer cells, we encapsulated doxorubicin and/or gemcitabine employing the pH gradient method. Drug loaded nanoparticles showed significantly higher killing of the cancer cells compared to their non-targeted counterparts and free drugs. With further development, these nanoparticles certainly have potential to be used as a multifunctional nanocarriers for image guided, targeted delivery of anticancer drugs.

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

    PubMed

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

    2014-06-01

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

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

    SciTech Connect

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

    2011-05-09

    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.

  15. Development of polymeric–cationic peptide composite nanoparticles, a nanoparticle-in-nanoparticle system for controlled gene delivery

    PubMed Central

    Jain, Arvind K; Massey, Ashley; Yusuf, Helmy; McDonald, Denise M; McCarthy, Helen O; Kett, Vicky L

    2015-01-01

    We report the formulation of novel composite nanoparticles that combine the high transfection efficiency of cationic peptide-DNA nanoparticles with the biocompatibility and prolonged delivery of polylactic acid–polyethylene glycol (PLA-PEG). The cationic cell-penetrating peptide RALA was used to condense DNA into nanoparticles that were encapsulated within a range of PLA-PEG copolymers. The composite nanoparticles produced exhibited excellent physicochemical properties including size <200 nm and encapsulation efficiency >80%. Images of the composite nanoparticles obtained with a new transmission electron microscopy staining method revealed the peptide-DNA nanoparticles within the PLA-PEG matrix. Varying the copolymers modulated the DNA release rate >6 weeks in vitro. The best formulation was selected and was able to transfect cells while maintaining viability. The effect of transferrin-appended composite nanoparticles was also studied. Thus, we have demonstrated the manufacture of composite nanoparticles for the controlled delivery of DNA. PMID:26648722

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

    SciTech Connect

    Nguyen, Minh Vu Chuong; Zhang, Leilei; Lhomme, Stanislas; Mouz, Nicolas

    2012-03-16

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

  17. Cyclic RGD-targeting of reversibly-stabilized DNA nanoparticles enhances cell uptake and transfection in vitro

    PubMed Central

    ZHOU, QING-HUI; YOU, YE-ZI; WU, CHAO; HUANG, YI; OUPICKÝ, DAVID

    2015-01-01

    Reversibly-stabilized DNA nanoparticles (rSDN) were prepared by coating reducible polycation/DNA complexes with multivalent N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers. RGD targeted rSDN were formulated by linking cyclic c(RGDyK) to the surface layer of rSDN. Cellular uptake in B16F10 mouse melanoma cells, human endothelial (HUVEC) cells, and THLE immortalized hepatic cells was quantified by real-time PCR. RGD-targeted rSDN exhibited ~2 fold higher cell uptake in integrin-positive cells: B16F10 and HUVEC compared to THLE cells with low integrin content. RGD targeting mediated increased transfection activity in B16F10 cells but not in THLE cells. Overall, the studies show that rSDN can be effectively targeted with RGD while exhibiting reduced non-specific cell interactions and favorable stability. As such, these gene delivery vectors have the potential to permit targeting therapeutic genes to tumors by systemic delivery. In addition, the study shows that real-time PCR could be used effectively for quantification of cellular uptake of gene delivery vectors. PMID:19263264

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

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

    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.

  19. Superparamagnetic iron oxide nanoparticles exert different cytotoxic effects on cells grown in monolayer cell culture versus as multicellular spheroids

    NASA Astrophysics Data System (ADS)

    Theumer, Anja; Gräfe, Christine; Bähring, Franziska; Bergemann, Christian; Hochhaus, Andreas; Clement, Joachim H.

    2015-04-01

    The aim of this study was to investigate the interaction of superparamagnetic iron oxide nanoparticles (SPION) with human blood-brain barrier-forming endothelial cells (HBMEC) in two-dimensional cell monolayers as well as in three-dimensional multicellular spheroids. The precise nanoparticle localisation and the influence of the NP on the cellular viability and the intracellular Akt signalling were studied in detail. Long-term effects of different polymer-coated nanoparticles (neutral fluidMAG-D, anionic fluidMAG-CMX and cationic fluidMAG-PEI) and the corresponding free polymers on cellular viability of HBMEC were investigated by real time cell analysis studies. Nanoparticles exert distinct effects on HBMEC depending on the nanoparticles' surface charge and concentration, duration of incubation and cellular context. The most severe effects were caused by PEI-coated nanoparticles. Concentrations above 25 ?g/ml led to increased amounts of dead cells in monolayer culture as well as in multicellular spheroids. On the level of intracellular signalling, context-dependent differences were observed. Monolayer cultures responded on nanoparticle incubation with an increase in Akt phosphorylation whereas spheroids on the whole show a decreased Akt activity. This might be due to the differential penetration and distribution of PEI-coated nanoparticles.

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

    PubMed

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

    2013-01-01

    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

  1. Facile Synthesis of Biocompatible Fluorescent Nanoparticles for Cellular Imaging and Targeted Detection of Cancer Cells.

    PubMed

    Tang, Fu; Wang, Chun; Wang, Xiaoyu; Li, Lidong

    2015-11-18

    In this work, we report the facile synthesis of functional core-shell structured nanoparticles with fluorescence enhancement, which show specific targeting of cancer cells. Biopolymer poly-l-lysine was used to coat the silver core with various shell thicknesses. Then, the nanoparticles were functionalized with folic acid as a targeting agent for folic acid receptor. The metal-enhanced fluorescence effect was observed when the fluorophore (5-(and-6)-carboxyfluorescein-succinimidyl ester) was conjugated to the modified nanoparticle surface. Cellular imaging assay of the nanoparticles in folic acid receptor-positive cancer cells showed their excellent biocompatibility and selectivity. The as-prepared functional nanoparticles demonstrate the efficiency of the metal-enhanced fluorescence effect and provide an alternative approach for the cellular imaging and targeting of cancer cells. PMID:26544019

  2. An evidence on G2/M arrest, DNA damage and caspase mediated apoptotic effect of biosynthesized gold nanoparticles on human cervical carcinoma cells (HeLa)

    SciTech Connect

    Jeyaraj, M.; Arun, R.; Sathishkumar, G.; MubarakAli, D.; Rajesh, M.; Sivanandhan, G.; Kapildev, G.; Manickavasagam, M.; Thajuddin, N.; Ganapathi, A.

    2014-04-01

    Highlights: • Gold nanoparticles (AuNPs) have been synthesized using Podophyllum hexandrum L. • AuNPs induces the oxidative stress to cell death in human cervical carcinoma cells. • It activates the caspase-cascade to cellular death. • It is actively blocks G2/M phase of cell cycle. - Abstract: Current prospect of nanobiotechnology involves in the greener synthesis of nanostructured materials particularly noble metal nanoparticles for various biomedical applications. In this study, biologically (Podophyllum hexandrum L.) synthesized crystalline gold nanoparticles (AuNPs) with the size range between 5 and 35 nm were screened for its anticancereous potential against human cervical carcinoma cells (HeLa). Stoichiometric proportion of the reaction mixture and conditions were optimized to attain stable nanoparticles with narrow size range. Different high throughput techniques like transmission electron microscope (TEM), X-ray diffraction (XRD) and UV–vis spectroscopy were adopted for the physio-chemical characterization of AuNPs. Additionally, Fourier transform infrared spectroscopy (FTIR) study revealed that the water soluble fractions present in the plant extract solely influences the reduction of AuNPs. Sublimely, synthesized AuNPs exhibits an effective in vitro anticancer activity against HeLa cells via induction of cell cycle arrest and DNA damage. Furthermore, it was evidenced that AuNPs treated cells are undergone apoptosis through the activation of caspase cascade which subsequently leads to mitochondrial dysfunction. Thereby, this study proves that biogenic colloidal AuNPs can be developed as a promising drug candidature for human cervical cancer therapy.

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

    NASA Astrophysics Data System (ADS)

    Shah, Neha B.

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

  4. Photothermal therapy of cancer cells mediated by blue hydrogel nanoparticles

    PubMed Central

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

    2013-01-01

    Aim The aim of this study was to investigate in vitro the utility of biologically compatible, nontoxic and cell-specific targetable hydrogel nanoparticles (NPs), which have Coomassie® Brilliant Blue G dye (Sigma-Aldrich, MO, USA) covalently linked into their polyacrylamide matrix, as candidates for photothermal therapy (PTT) of cancer cells. Materials & methods Hydrogel NPs with Coomassie Brilliant Blue G dye covalently linked into their polyacrylamide matrix were fabricated using a reverse micelle microemulsion polymerization method and were found to be 80–95 nm in diameter, with an absorbance value of 0.52. PTT-induced hyperthermia/thermolysis was achieved at 37°C using an inexpensive, portable, light-emitting diode array light source (590 nm, 25 mW/cm2). Results & conclusion Hydrogel NPs with Coomassie Brilliant Blue G dye linked into their polyacrylamide matrix are effective in causing PTT-induced thermolysis in immortalized human cervical cancer cell line (HeLa) cells for varying NP concentrations and treatment times. These multifunctional particles have previously been used in cancer studies to enable delineation, for glioma surgery and in photoacoustic imaging studies. The addition of the PTT function would enable a three-pronged theranostic approach to cancer medicine, such as guided tumor surgery with intra-operative photoacoustic imaging and intra-operative PTT. PMID:23432340

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

    PubMed

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

    2010-05-31

    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

  6. Antibody-mediated targeting of iron oxide nanoparticles to the folate receptor alpha increases tumor cell association in vitro and in vivo

    PubMed Central

    Ndong, Christian; Toraya-Brown, Seiko; Kekalo, Katsiaryna; Baker, Ian; Gerngross, Tillman U; Fiering, Steven N; Griswold, Karl E

    2015-01-01

    Active molecular targeting has become an important aspect of nanoparticle development for oncology indications. Here, we describe molecular targeting of iron oxide nanoparticles (IONPs) to the folate receptor alpha (FOLR?) using an engineered antibody fragment (Ffab). Compared to control nanoparticles targeting the non-relevant botulinum toxin, the Ffab-IONP constructs selectively accumulated on FOLR?-overexpressing cancer cells in vitro, where they exhibited the capacity to internalize into intracellular vesicles. Similarly, Ffab-IONPs homed to FOLR?-positive tumors upon intraperitoneal administration in an orthotopic murine xenograft model of ovarian cancer, whereas negative control particles showed no detectable tumor accumulation. Interestingly, Ffab-IONPs built with custom 120 nm nanoparticles exhibited lower in vitro targeting efficiency when compared to those built with commercially sourced 180 nm nanoparticles. In vivo, however, the two Ffab-IONP platforms achieved equivalent tumor homing, although the smaller 120 nm IONPs were more prone to liver sequestration. Overall, the results show that Ffab-mediated targeting of IONPs yields specific, high-level accumulation within cancer cells, and this fact suggests that Ffab-IONPs could have future utility in ovarian cancer diagnostics and therapy. PMID:25878495

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

    PubMed

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

    2013-06-10

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-07-01

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

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

    PubMed Central

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

    2012-01-01

    Surface recognition of biosystems is a critical component in the development of novel biosensors, delivery vehicles and for the therapeutic regulation of biological processes. Monolayer-protected nanoparticles present a highly versatile scaffold for selective interaction with biomacromolecules and cells. Through engineering of the monolayer surface, nanoparticles can be tailored for surface recognition of biomolecules and cells. This review highlights recent progress in nanoparticle-biomacromolecule/cellular interactions, emphasizing the effect of the surface monolayer structure on the interactions with proteins, DNA and cell surfaces. The extension of these tailored interactions to hybrid nanomaterials, biosensing platforms and delivery vehicles is also discussed. PMID:21671432

  10. Memory CD8+ T cells exhibit increased antigen threshold requirements for recall proliferation

    PubMed Central

    Mehlhop-Williams, Erin R.

    2014-01-01

    A hallmark of immunological memory is the ability of previously primed T cells to undergo rapid recall responses upon antigen reencounter. Classic work has suggested that memory T cells proliferate in response to lower doses of antigen than naive T cells and with reduced requirements for co-stimulation. In contrast to this premise, we observed that naive but not memory T cells proliferate in vivo in response to limited antigen presentation. To reconcile these observations, we tested the antigen threshold requirement for cell cycle entry in naive and central memory CD8+ T cells. Although both naive and memory T cells detect low dose antigen, only naive T cells activate cell cycle effectors. Direct comparison of TCR signaling on a single cell basis indicated that central memory T cells do not activate Zap70, induce cMyc expression, or degrade p27 in response to antigen levels that activate these functions in naive T cells. The reduced sensitivity of memory T cells may result from both decreased surface TCR expression and increased expression of protein tyrosine phosphatases as compared with naive T cells. Our data describe a novel aspect of memory T cell antigen threshold sensitivity that may critically regulate recall expansion. PMID:24493801

  11. MRI of Breast Tumor Initiating Cells Using the Extra Domain-B of Fibronectin Targeting Nanoparticles

    PubMed Central

    Sun, Yujin; Kim, Hoe Suk; Park, Jinho; Li, Mulan; Tian, Lianji; Choi, YoonSeok; Choi, Byung Ihn; Jon, Sangyong; Moon, Woo Kyung

    2014-01-01

    The identification of breast tumor initiating cells (BTICs) is important for the diagnosis and therapy of breast cancers. This study was undertaken to evaluate whether the extra domain-B of fibronectin (EDB-FN) could be used as a new biomarker for BTICs and whether EDB-FN targeting superparamagnetic iron oxide nanoparticles (SPIONs) could be used as a magnetic resonance imaging (MRI) contrast agent for BTIC imaging in vitro and in vivo. BTICs (NDY-1) exhibited high EDB-FN expression, whereas non-BTICs (MCF-7, BT-474, SUM-225, MDA-MB-231) did not exhibit EDB-FN expression. Furthermore, Cy3.3-labeled EDB-FN specific peptides (APTEDB) showed preferential binding to the targeted NDY-1 cells. To construct an EDB-FN targeted imaging probe, APTEDB was covalently attached to a thermally cross-linked SPION (TCL-SPION) to yield APTEDB-TCL-SPION. In the in vitro MRI of cell phantoms, selective binding of APTEDB-TCL-SPION to NDY-1 cells was evident, but little binding was observed in MCF-7 cells. After the intravenous injection of APTEDB-TCL-SPION into the NDY-1 mouse tumor xenograft model, a significant decrease in the signal within the tumor was observed in the T2*-weighted images; however, there was only a marginal change in the signal of non-targeting SPIONs such as APTscramble-TCL-SPION or TCL-SPION. Taken together, we report for the first time that EDB-FN was abundantly expressed in BTICs and may therefore be useful as a new biomarker for identifying BTICs. Our study also suggests that APTEDB-TCL-SPION could be used as an MRI contrast agent for BTIC imaging. PMID:24955145

  12. Microfluidic synthesis of chitosan-based nanoparticles for fuel cell applications.

    PubMed

    Majedi, Fatemeh Sadat; Hasani-Sadrabadi, Mohammad Mahdi; Emami, Shahriar Hojjati; Taghipoor, Mojtaba; Dashtimoghadam, Erfan; Bertsch, Arnaud; Moaddel, Homayoun; Renaud, Philippe

    2012-08-11

    A microfluidic platform is developed for the synthesis of monodisperse, 100 nm, chitosan based nanoparticles using nanogelation with ATP. The resulting nanoparticles tuned and enhanced transport and electrochemical properties of Nafion based nanocomposite membranes, which is highly favorable for fuel cell applications. PMID:22760418

  13. Laser-ablated titania nanoparticles for aqueous processed hybrid solar cells.

    PubMed

    Körstgens, V; Pröller, S; Buchmann, T; Moseguí González, D; Song, L; Yao, Y; Wang, W; Werhahn, J; Santoro, G; Roth, S V; Iglev, H; Kienberger, R; Müller-Buschbaum, P

    2015-02-21

    Titania nanoparticles are produced by laser ablation in liquid in order to initiate functionalization of titania with the polymer for the active layer. By combining these titania nanoparticles and water-soluble poly[3-(potassium-6-hexanoate)thiophene-2,5-diyl] (P3P6T) hybrid solar cells are realized. PMID:25623567

  14. Nanoparticle-induced light scattering for improved performance of quantum-well solar cells

    E-print Network

    Yu, Edward T.

    Ti/20 nm Pd/200 nm Au metallization deposited by electron-beam evaporation and a standard lift-off or metal nanoparticles. The integration of metal or dielectric nanoparticles above the quantum-well solar-junction limit of 31%.4 In quantum-well solar cells, for which maximum predicted the- oretical power conversion

  15. The Fate of ZnO Nanoparticles Administered to Human Bronchial Epithelial Cells

    PubMed Central

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

    2014-01-01

    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

  16. The Role of Dextran Coatings on the Cytotoxicity Properties of Ceria Nanoparticles Toward Bone Cancer Cells

    NASA Astrophysics Data System (ADS)

    Yazici, Hilal; Alpaslan, Ece; Webster, Thomas J.

    2015-04-01

    Cerium oxide nanoparticles have demonstrated great potential as antioxidant and radioprotective agents for nanomedicine applications especially for cancer therapy. The surface chemistry of nanoparticles is an important property that has a significant effect on their performance in biological applications including cancer diagnosis, cancer treatment, and bacterial infection. Recently, various nanosized cerium oxide particles with different types of polymer coatings have been developed to improve aqueous solubility and allow for surface functionalization for distinct applications. In this study, the role of ceria nanoparticles coated with dextran on the cytotoxicity properties of bone cancer cells was shown. Specifically, 0.1 M and 0.01 M dextran-coated, <5-nm ceria nanoparticles, were synthesized. The cytotoxicity of 0.1 M and 0.01 M dextran-coated ceria nanoparticles was evaluated against osteosarcoma cells. A change in cell viability was observed when treating osteosarcoma cells with 0.1 M dextran-coated ceria nanoparticles in the 250 -1000 ?g/mL concentration range. In contrast, minimal toxicity to bone cancer cells was observed for the 0.01 M dextran coating after 3 days compared with the 0.1 M dextran coating. These results indicated that surface dextran functionalization had a positive impact on the cytotoxicity of cerium oxide nanoparticles against osteosarcoma cells.

  17. Labeling of HeLa cells using ZrO2:Yb(3+)-Er(3+) nanoparticles with upconversion emission.

    PubMed

    Ceja-Fdez, Andrea; López-Luke, Tzarara; Oliva, Jorge; Vivero-Escoto, Juan; Gonzalez-Yebra, Ana Lilia; Rojas, Ruben A Rodriguez; Martínez-Pérez, Andrea; de la Rosa, Elder

    2015-04-01

    This work reports the synthesis, structural characterization, and optical properties of ZrO2:Yb(3+)-Er(3+) (2–1 mol%) nanocrystals. The nanoparticles were coated with 3-aminopropyl triethoxysilane (APTES) and further modified with biomolecules, such as Biotin-Anti-rabbit (mouse IgG) and rabbit antibody-AntiKi-67, through a conjugation method. The conjugation was successfully confirmed by Fourier transform infrared, zeta potential, and dynamic light scattering. The internalization of the conjugated nanoparticles in human cervical cancer (HeLa) cells was followed by two-photon confocal microscopy. The ZrO2:Yb(3+)-Er(3+) nanocrystals exhibited strong red emission under 970-nm excitation. Moreover, the luminescence change due to the addition of APTES molecules and biomolecules on the nanocrystals was also studied. These results demonstrate that ZrO2:Yb(3+)-Er(3+) nanocrystals can be successfully functionalized with biomolecules to develop platforms for biolabeling and bioimaging. PMID:25879389

  18. Labeling of HeLa cells using ZrO2:Yb3+-Er3+ nanoparticles with upconversion emission

    NASA Astrophysics Data System (ADS)

    Ceja-Fdez, Andrea; López-Luke, Tzarara; Oliva, Jorge; Vivero-Escoto, Juan; Gonzalez-Yebra, Ana Lilia; Rojas, Ruben A. Rodriguez; Martínez-Pérez, Andrea; de la Rosa, Elder

    2015-04-01

    This work reports the synthesis, structural characterization, and optical properties of ZrO2:Yb3+-Er3+ (2-1 mol%) nanocrystals. The nanoparticles were coated with 3-aminopropyl triethoxysilane (APTES) and further modified with biomolecules, such as Biotin-Anti-rabbit (mouse IgG) and rabbit antibody-AntiKi-67, through a conjugation method. The conjugation was successfully confirmed by Fourier transform infrared, zeta potential, and dynamic light scattering. The internalization of the conjugated nanoparticles in human cervical cancer (HeLa) cells was followed by two-photon confocal microscopy. The ZrO2:Yb3+-Er3+ nanocrystals exhibited strong red emission under 970-nm excitation. Moreover, the luminescence change due to the addition of APTES molecules and biomolecules on the nanocrystals was also studied. These results demonstrate that ZrO2:Yb3+-Er3+ nanocrystals can be successfully functionalized with biomolecules to develop platforms for biolabeling and bioimaging.

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

    NASA Astrophysics Data System (ADS)

    Burford, Christopher

    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.

  20. Effect of different magnetic nanoparticle coatings on the efficiency of stem cell labeling

    NASA Astrophysics Data System (ADS)

    Horák, Daniel; Babi?, Michal; Jendelová, Pavla; Herynek, Vít; Trchová, Miroslava; Likav?anová, Katarina; Kapcalová, Miroslava; Hájek, Milan; Syková, Eva

    2009-05-01

    Maghemite nanoparticles with various coatings were prepared by the coprecipitation method and characterized by transmission electron microscopy, dynamic light scattering and IR in terms of morphology, size, polydispersity and surface coating. The labeling efficiency and the viability of both rat and human mesenchymal stem cells labeled with Endorem ®, poly( L-lysine) (PLL)-modified Endorem ®, uncoated ?-Fe 2O 3, D-mannose-, PLL- or poly( N,N-dimethylacrylamide) (PDMAAm)-coated ?-Fe 2O 3 nanoparticles were compared. Coated ?-Fe 2O 3 nanoparticles labeled cells better than did Endorem ®. High relaxation rates and in vitro magnetic resonance imaging of cells labeled with coated nanoparticles showed clearly visible contrast compared with unlabeled cells or cells labeled with Endorem ®.

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

    E-print Network

    Lee, Jungmin

    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 ...

  2. Magnetic nanoparticle effects on the red blood cells

    NASA Astrophysics Data System (ADS)

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

    2009-05-01

    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.

  3. Differentiation of cancer cell type and phenotype using quantum dot-gold nanoparticle sensor arrays

    PubMed Central

    Liu, Qian; Yeh, Yi-Cheun; Rana, Subinoy; Jiang, Ying; Guo, Lin; Rotello, Vincent M.

    2012-01-01

    We demonstrate rapid and efficient sensing of mammalian cell types and states using nanoparticle-based sensor arrays. These arrays are comprised of cationic quantum dots (QDs) and gold nanoparticles (AuNPs) that interact with cell surfaces to generate distinguishable fluorescence responses based on cell surface signatures. The use of QDs as the recognition elements as well as the signal transducers presents the potential for direct visualization of selective cell surface interactions. Notably, this sensor is unbiased, precluding the requirement of pre-knowledge of cell state biomarkers and thus providing a general approach for phenotypic profiling of cell states, with additional potential for imaging applications. PMID:23022266

  4. Effect of silver nanoparticles on human mesenchymal stem cell differentiation

    PubMed Central

    Diendorf, Jörg; Epple, Matthias; Schildhauer, Thomas A; Köller, Manfred

    2014-01-01

    Summary Background: Silver nanoparticles (Ag-NP) are one of the fastest growing products in nano-medicine due to their enhanced antibacterial activity at the nanoscale level. In biomedicine, hundreds of products have been coated with Ag-NP. For example, various medical devices include silver, such as surgical instruments, bone implants and wound dressings. After the degradation of these materials, or depending on the coating technique, silver in nanoparticle or ion form can be released and may come into close contact with tissues and cells. Despite incorporation of Ag-NP as an antibacterial agent in different products, the toxicological and biological effects of silver in the human body after long-term and low-concentration exposure are not well understood. In the current study, we investigated the effects of both ionic and nanoparticulate silver on the differentiation of human mesenchymal stem cells (hMSCs) into adipogenic, osteogenic and chondrogenic lineages and on the secretion of the respective differentiation markers adiponectin, osteocalcin and aggrecan. Results: As shown through laser scanning microscopy, Ag-NP with a size of 80 nm (hydrodynamic diameter) were taken up into hMSCs as nanoparticulate material. After 24 h of incubation, these Ag-NP were mainly found in the endo-lysosomal cell compartment as agglomerated material. Cytotoxicity was observed for differentiated or undifferentiated hMSCs treated with high silver concentrations (?20 µg·mL?1 Ag-NP; ?1.5 µg·mL?1 Ag+ ions) but not with low-concentration treatments (?10 µg·mL?1 Ag-NP; ?1.0 µg·mL?1 Ag+ ions). Subtoxic concentrations of Ag-NP and Ag+ ions impaired the adipogenic and osteogenic differentiation of hMSCs in a concentration-dependent manner, whereas chondrogenic differentiation was unaffected after 21 d of incubation. In contrast to aggrecan, the inhibitory effect of adipogenic and osteogenic differentiation was confirmed by a decrease in the secretion of specific biomarkers, including adiponectin (adipocytes) and osteocalcin (osteoblasts). Conclusion: Aside from the well-studied antibacterial effect of silver, little is known about the influence of nano-silver on cell differentiation processes. Our results demonstrate that ionic or nanoparticulate silver attenuates the adipogenic and osteogenic differentiation of hMSCs even at non-toxic concentrations. Therefore, more studies are needed to investigate the effects of silver species on cells at low concentrations during long-term treatment. PMID:25551033

  5. Release of Magnetic Nanoparticles from Cell-Encapsulating Biodegradable Nanobiomaterials

    PubMed Central

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

    2013-01-01

    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

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

    NASA Astrophysics Data System (ADS)

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

    2011-07-01

    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

  7. The Plasma Membrane Calcium Pump in Pancreatic Cancer Cells Exhibiting the Warburg Effect Relies on Glycolytic ATP*

    PubMed Central

    James, Andrew D.; Patel, Waseema; Butt, Zohra; Adiamah, Magretta; Dakhel, Raga; Latif, Ayse; Uggenti, Carolina; Swanton, Eileithyia; Imamura, Hiromi; Siriwardena, Ajith K.; Bruce, Jason I. E.

    2015-01-01

    Evidence suggests that the plasma membrane Ca2+-ATPase (PMCA), which is critical for maintaining a low intracellular Ca2+ concentration ([Ca2+]i), utilizes glycolytically derived ATP in pancreatic ductal adenocarcinoma (PDAC) and that inhibition of glycolysis in PDAC cell lines results in ATP depletion, PMCA inhibition, and an irreversible [Ca2+]i overload. We explored whether this is a specific weakness of highly glycolytic PDAC by shifting PDAC cell (MIA PaCa-2 and PANC-1) metabolism from a highly glycolytic phenotype toward mitochondrial metabolism and assessing the effects of mitochondrial versus glycolytic inhibitors on ATP depletion, PMCA inhibition, and [Ca2+]i overload. The highly glycolytic phenotype of these cells was first reversed by depriving MIA PaCa-2 and PANC-1 cells of glucose and supplementing with ?-ketoisocaproate or galactose. These culture conditions resulted in a significant decrease in both glycolytic flux and proliferation rate, and conferred resistance to ATP depletion by glycolytic inhibition while sensitizing cells to mitochondrial inhibition. Moreover, in direct contrast to cells exhibiting a high glycolytic rate, glycolytic inhibition had no effect on PMCA activity and resting [Ca2+]i in ?-ketoisocaproate- and galactose-cultured cells, suggesting that the glycolytic dependence of the PMCA is a specific vulnerability of PDAC cells exhibiting the Warburg phenotype. PMID:26294767

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

    E-print Network

    Adalsteinsson, Viktor A.

    Cancer is an inflammatory disease of tissue that is largely influenced by the interactions between multiple cell types, secreted factors, and signal transduction pathways. While single-cell sequencing continues to refine ...

  9. Hydrous RuO2 nanoparticles as an efficient NIR-light induced photothermal agent for ablation of cancer cells in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    Xiao, Zhiyin; Jiang, Xiaohong; Li, Bo; Liu, Xijian; Huang, Xiaojuan; Zhang, Yuxin; Ren, Qilong; Luo, Jie; Qin, Zongyi; Hu, Junqing

    2015-07-01

    Metal oxides are receiving an incremental attention in recent years for their potential applications in ablation of cancer cells due to their efficient photothermal conversion and good biocompatibility, but the large sizes and poor photo-stability will seriously limit their practical application. Herein, hydrous RuO2 nanoparticles were synthesized by a facile hydrothermal treatment and surface-modified with polyvinylpyrrolidone (PVP) coating. PVP-coated RuO2 nanoparticles exhibit a well dispertion in saline solution, strong characteristic plasmonic absorption in NIR region, enhanced photothermal conversion efficiency of 54.8% and remarkable photo-stability under the irridation of an 808 nm laser. The nanoparticles were further employed as a new photothermal ablation agent for cancer cells which led rapidly to cellular deaths both in vitro and in vivo.Metal oxides are receiving an incremental attention in recent years for their potential applications in ablation of cancer cells due to their efficient photothermal conversion and good biocompatibility, but the large sizes and poor photo-stability will seriously limit their practical application. Herein, hydrous RuO2 nanoparticles were synthesized by a facile hydrothermal treatment and surface-modified with polyvinylpyrrolidone (PVP) coating. PVP-coated RuO2 nanoparticles exhibit a well dispertion in saline solution, strong characteristic plasmonic absorption in NIR region, enhanced photothermal conversion efficiency of 54.8% and remarkable photo-stability under the irridation of an 808 nm laser. The nanoparticles were further employed as a new photothermal ablation agent for cancer cells which led rapidly to cellular deaths both in vitro and in vivo. Electronic supplementary information (ESI) available: Characterizations including TEM, TG, EDS, etc. See DOI: 10.1039/c5nr00965k

  10. Silica nanoparticles for cell imaging and intracellular sensing

    NASA Astrophysics Data System (ADS)

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

    2013-11-01

    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.

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

    PubMed

    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

    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

  12. Mesenchymal Stem Cells Obtained from Synovial Fluid Mesenchymal Stem Cell-Derived Induced Pluripotent Stem Cells on a Matrigel Coating Exhibited Enhanced Proliferation and Differentiation Potential

    PubMed Central

    Zhang, Hong; Liu, Wen-Jing; Jiang, Rui; Li, Wen-Yu; Zheng, You-Hua; Zhang, Zhi-Guang

    2015-01-01

    Induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) serve as a promising source for cell-based therapies in regenerative medicine. However, optimal methods for transforming iPSCs into MSCs and the characteristics of iPSC-MSCs obtained from different methods remain poorly understood. In this study, we developed a one-step method for obtaining iPSC-MSCs (CD146+STRO-1+ MSCs) from human synovial fluid MSC-derived induced iPSCs (SFMSC-iPSCs). CD146-STRO-1-SFMSCs were reprogrammed into iPSCs by transduction with lentivirus-mediated Sox2, Oct-3/4, klf4, and c-Myc. SFMSC-iPSCs were maintained with mTeSR1 medium in Matrigel-coated culture plates. Single dissociated cells were obtained by digesting the SFMSC-iPSCs with trypsin. The dissociated cells were then plated into Matrigel-coated culture plate with alpha minimum essential medium supplemented with 10% fetal bovine serum, 1× Glutamax, and the ROCK inhibitor Y-27632. Cells were then passaged in standard cell culture plates with alpha minimum essential medium supplemented with 10% fetal bovine serum and 1× Glutamax. After passaging in vitro, the cells showed a homogenous spindle-shape similar to their ancestor cells (SFMSCs), but with more robust proliferative activity. Flow cytometric analysis revealed typical MSC surface markers, including expression of CD73, CD90, CD105, and CD44 and lack of CD45, CD34, CD11b, CD19, and HLA-DR. However, these cells were positive for CD146 and stro-1, which the ancestor cells were not. Moreover, the cells could also be induced to differentiate in osteogenic, chondrogenic, and adipogenic lineages in vitro. The differentiation potential was improved compared with the ancestor cells in vitro. The cells were not found to exhibit oncogenicity in vivo. Therefore, the method presented herein facilitated the generation of STRO-1+CD146+ MSCs from SFMSC-iPSCs exhibiting enhanced proliferation and differentiation potential. PMID:26649753

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

    PubMed Central

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

    2014-01-01

    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

  14. Hematopoietic and mesenchymal stem cells: polymeric nanoparticle uptake and lineage differentiation

    PubMed Central

    Brüstle, Ivonne; Simmet, Thomas; Nienhaus, Gerd Ulrich; Landfester, Katharina

    2015-01-01

    Summary The combination of stem cell therapy and nanoparticles promises to enhance the effect of cellular therapies by using nanocarriers as drug delivery devices to guide the further differentiation or homing of stem cells. The impact of nanoparticles on primary cell types remains much more elusive as most groups study the nanoparticle–cell interaction in malignant cell lines. Here, we report on the influence of polymeric nanoparticles on human hematopoietic stem cells (hHSCs) and mesenchymal stem cells (hMSCs). In this study we systematically investigated the influence of polymeric nanoparticles on the cell functionality and differentiation capacity of hHSCs and hMSCs to obtain a deeper knowledge of the interaction of stem cells and nanoparticles. As model systems of nanoparticles, two sets of either bioinert (polystyrene without carboxylic groups on the surface) or biodegradable (PLLA without magnetite) particles were analyzed. Flow cytometry and microscopy analysis showed high uptake rates and no toxicity for all four tested particles in hMSCs and hHSCs. During the differentiation process, the payload of particles per cell decreased. The PLLA–Fe particle showed a significant increase in the IL-8 release in hMSCs but not in hHSCs. We assume that this is due to an increase of free intracellular iron ions but obviously also depends on the cell type. For hHSCs and hMSCs, lineage differentiation into erythrocytes, granulocytes, and megakaryocytes or adipocytes, osteocytes and chondrocytes, was not influenced by the particles when analyzed with lineage specific cluster of differentiation markers. On the other hand qPCR analysis showed significant changes in the expression of some (but not all) investigated lineage markers for both primary cell types. PMID:25821678

  15. NANOPARTICLES AND THEIR APPLICATIONS IN CELL AND MOLECULAR BIOLOGY

    PubMed Central

    Wang, Edina C.; Wang, Andrew Z.

    2013-01-01

    Nanoparticles can be engineered with distinctive compositions, sizes, shapes, and surface chemistries to enable novel techniques in a wide range of biological applications. The unique properties of nanoparticles and their behavior in biological milieu also enable exciting and integrative approaches to studying fundamental biological questions. This review will provide an overview of various types of nanoparticles and concepts of targeting nanoparticles. We will also discuss the advantages and recent applications of using nanoparticles as tools for drug delivery, imaging, sensing, and for the understanding of basic biological processes. PMID:24104563

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

    NASA Astrophysics Data System (ADS)

    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

    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

  17. Nucleosome-binding protein HMGN2 exhibits antitumor activity in oral squamous cell carcinoma

    PubMed Central

    HU, ANKANG; DONG, XIAOQIAN; LIU, XIQIAN; ZHANG, PING; ZHANG, YONGHONG; SU, NING; CHEN, QIANMING; FENG, YUN

    2014-01-01

    Natural killer (NK) cells and cytolytic T lymphocytes (CTLs) serve as effectors in the antitumor response. High mobility group nucleosomal binding domain 2 (HMGN2) is a candidate effector molecule involved in CTL and NK cell function. In the current study, recombinant human HMGN2 was isolated and purified from transformed Escherichia coli. Tca8113 cells, an oral squamous cell carcinoma line, were treated with a variety of HMGN2 protein concentrations and cell growth was analyzed. HMGN2 significantly inhibited the growth of Tca8113 cells and was predicted to arrest cells in the S phase. Moreover, HMGN2 treatment increased the apoptosis rate of Tca8113 cells. Western blotting indicated the upregulation of p53 and Bax proteins, whereas Bcl-2 was significantly downregulated. In addition, caspase-3 was found to be activated. Furthermore, the HMGN2 protein may suppress the growth of Tca8113 cells in vivo. The results of the current study indicated that the HMGN2 protein may inhibit the growth of oral squamous cell carcinoma and HMGN2 may represent an antitumor effector molecule of CTL or NK cells. PMID:24348831

  18. Effects of PVA coated nanoparticles on human immune cells

    PubMed Central

    Strehl, Cindy; Gaber, Timo; Maurizi, Lionel; Hahne, Martin; Rauch, Roman; Hoff, Paula; Häupl, Thomas; Hofmann-Amtenbrink, Margarethe; Poole, A Robin; Hofmann, Heinrich; Buttgereit, Frank

    2015-01-01

    Nanotechnology provides new opportunities in human medicine, mainly for diagnostic and therapeutic purposes. The autoimmune disease rheumatoid arthritis (RA) is often diagnosed after irreversible joint structural damage has occurred. There is an urgent need for a very early diagnosis of RA, which can be achieved by more sensitive imaging methods. Superparamagnetic iron oxide nanoparticles (SPION) are already used in medicine and therefore represent a promising tool for early diagnosis of RA. The focus of our work was to investigate any potentially negative effects resulting from the interactions of newly developed amino-functionalized amino-polyvinyl alcohol coated (a-PVA) SPION (a-PVA-SPION), that are used for imaging, with human immune cells. We analyzed the influence of a-PVA-SPION with regard to cell survival and cell activation in human whole blood in general, and in human monocytes and macrophages representative of professional phagocytes, using flow cytometry, multiplex suspension array, and transmission electron microscopy. We found no effect of a-PVA-SPION on the viability of human immune cells, but cytokine secretion was affected. We further demonstrated that the percentage of viable macrophages increased on exposure to a-PVA-SPION. This effect was even stronger when a-PVA-SPION were added very early in the differentiation process. Additionally, transmission electron microscopy analysis revealed that both monocytes and macrophages are able to endocytose a-PVA-SPION. Our findings demonstrate an interaction between human immune cells and a-PVA-SPION which needs to be taken into account when considering the use of a-PVA-SPION in human medicine. PMID:26056442

  19. Ectoenzyme switches the surface of magnetic nanoparticles for selective binding of cancer cells.

    PubMed

    Du, Xuewen; Zhou, Jie; Xu, Bing

    2015-06-01

    Enzymatic switch, such as phosphorylation and dephosphorylation of proteins, is the most important mechanism for cellular signal transductions. Inspired by Nature and encouraged by our recent unexpected observation of the dephosphorylation of d-tyrosine phosphate-contain small peptides, we modify the surface of magnetic nanoparticles (MNP) with d-tyrosine phosphate that is a substrate of alkaline phosphatase (ALP). Our studies find that ALP is able to remove the phosphate groups from the magnetic nanoparticles. Most importantly, placental alkaline phosphatase (ALPP), an ectoenzyme that locates on cell surface with catalytic domains outside the plasma membrane and is overexpressed on many cancer cells, dephosphorylate the d-tyrosine phosphates on the surface of the magnetic nanoparticle and enable the magnetic nanoparticles to adhere selectively to the cancer cells, such as HeLa cells. Unlikely commonly used antibodies, the selectivity of the magnetic nanoparticles to cancer cells originates from the enzymatic reaction catalyzed by ALPP. The use of enzymatic reaction to modulate the surface of various nanostructures may lead to a general method to broadly target cancer cells without relying on specific ligand-receptor interactions (e.g., antibodies). This work, thus, illustrates a fundamentally new concept to allow cells to actively engineer the surface of colloids materials, such as magnetic nanoparticles, for various applications. PMID:25586118

  20. Magneto-reactance based detection of MnO nanoparticle-embedded Lewis lung carcinoma cells

    NASA Astrophysics Data System (ADS)

    Devkota, J.; Howell, M.; Mukherjee, P.; Srikanth, H.; Mohapatra, S.; Phan, M. H.

    2015-05-01

    We demonstrate the capacity of detecting magnetically weak manganese oxide (MnO) nanoparticles and the Lewis lung carcinoma (LLC) cancer cells that have taken up these nanoparticles using a novel biosensor based on the magneto-reactance (MX) effect of a soft ferromagnetic amorphous ribbon with a microhole-patterned surface. While the magnetic moment of the MnO nanoparticles is relatively small, and a magneto-impedance based sensor fails to detect them in solution (0.05 mg/ml manganese oxide lipid micellar nanoparticles) and inside cells at low concentrations (8.25 × 104 cells/ml), the detection of these nanoparticles and the LLC cells containing them is achieved with the MX-based sensor, which, respectively, reaches the detection sensitivity of ˜3.6% and 2.8% as compared to the blank cells. Since the MnO nanoparticles are a promising contrast agent for magnetic resonance imaging (MRI) of lung cells, the MX-based biosensing technique can be developed as a pre-detection method for MRI of lung cancer cells.

  1. SiC nanoparticles cyto- and genotoxicity to Hep-G2 cells

    NASA Astrophysics Data System (ADS)

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

    2009-05-01

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

  2. Cytotoxicity and GMI bio-sensor detection of maghemite nanoparticles internalized into cells

    NASA Astrophysics Data System (ADS)

    Blanc-Béguin, F.; Nabily, S.; Gieraltowski, J.; Turzo, A.; Querellou, S.; Salaun, P. Y.

    2009-02-01

    In this work we determine conditions to produce cell samples for imaging with detection of the modification of the magnetic field by maghemite (Fe 2O 3) nanoparticles acting as a high sensitivity magnetic bio-sensor based on the giant magneto-impedance (GMI) effect. Mat Ly Lu cells are grown for 24 h with various maghemite nanoparticles concentrations (from 0 to 6 mg/ml). The percentage of viable cells is determined by counting labeled cells with trypan blue under an optical microscope. The quantity of nanoparticles internalized into the cells is evaluated by X-ray fluorescence analysis and expressed in iron moles per cell. The GMI bio-sensor was tested with the various samples. We observed that the best sensitivity of the GMI bio-sensor was obtained at a frequency of 1 MHz. To confirm these results in the presence of cell samples, four measurement frequencies were pre-selected (from 1 to 100 MHz) and tested. Cell growth conditions compatible with an acceptable percentage of cell viability for various concentrations of nanoparticles were also determined. These experiments allow us to conclude that cell growth with 0.1 mg/ml of nanoparticles for 24 h shows modifications of the magnetic field detectable optimally at 1 MHz frequency.

  3. Tracking Transplanted Stem Cells Using Magnetic Resonance Imaging and the Nanoparticle Labeling Method in Urology

    PubMed Central

    Kim, Jae Heon; Lee, Hong J.; Song, Yun Seob

    2015-01-01

    A reliable in vivo imaging method to localize transplanted cells and monitor their viability would enable a systematic investigation of cell therapy. Most stem cell transplantation studies have used immunohistological staining, which does not provide information about the migration of transplanted cells in vivo in the same host. Molecular imaging visualizes targeted cells in a living host, which enables determining the biological processes occurring in transplanted stem cells. Molecular imaging with labeled nanoparticles provides the opportunity to monitor transplanted cells noninvasively without sacrifice and to repeatedly evaluate them. Among several molecular imaging techniques, magnetic resonance imaging (MRI) provides high resolution and sensitivity of transplanted cells. MRI is a powerful noninvasive imaging modality with excellent image resolution for studying cellular dynamics. Several types of nanoparticles including superparamagnetic iron oxide nanoparticles and magnetic nanoparticles have been used to magnetically label stem cells and monitor viability by MRI in the urologic field. This review focuses on the current role and limitations of MRI with labeled nanoparticles for tracking transplanted stem cells in urology. PMID:26413510

  4. In vitro developmental toxicity test detects inhibition of stem cell differentiation by silica nanoparticles

    SciTech Connect

    Park, Margriet V.D.Z. Annema, Wijtske; Salvati, Anna; Lesniak, Anna; Elsaesser, Andreas; Barnes, Clifford; McKerr, George; Howard, C. Vyvyan; Lynch, Iseult; Dawson, Kenneth A.; Piersma, Aldert H.; Jong, Wim H. de

    2009-10-01

    While research into the potential toxic properties of nanomaterials is now increasing, the area of developmental toxicity has remained relatively uninvestigated. The embryonic stem cell test is an in vitro screening assay used to investigate the embryotoxic potential of chemicals by determining their ability to inhibit differentiation of embryonic stem cells into spontaneously contracting cardiomyocytes. Four well characterized silica nanoparticles of various sizes were used to investigate whether nanomaterials are capable of inhibition of differentiation in the embryonic stem cell test. Nanoparticle size distributions and dispersion characteristics were determined before and during incubation in the stem cell culture medium by means of transmission electron microscopy (TEM) and dynamic light scattering. Mouse embryonic stem cells were exposed to silica nanoparticles at concentrations ranging from 1 to 100 {mu}g/ml. The embryonic stem cell test detected a concentration dependent inhibition of differentiation of stem cells into contracting cardiomyocytes by two silica nanoparticles of primary size 10 (TEM 11) and 30 (TEM 34) nm while two other particles of primary size 80 (TEM 34) and 400 (TEM 248) nm had no effect up to the highest concentration tested. Inhibition of differentiation of stem cells occurred below cytotoxic concentrations, indicating a specific effect of the particles on the differentiation of the embryonic stem cells. The impaired differentiation of stem cells by such widely used particles warrants further investigation into the potential of these nanoparticles to migrate into the uterus, placenta and embryo and their possible effects on embryogenesis.

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

    E-print Network

    Xiao, Zeyu

    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 ...

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

    E-print Network

    Hsu, W. Chuck

    2012-01-01

    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 ...

  7. Live cell plasma membranes do not exhibit a miscibility phase transition over a wide range of temperatures.

    PubMed

    Lee, Il-Hyung; Saha, Suvrajit; Polley, Anirban; Huang, Hector; Mayor, Satyajit; Rao, Madan; Groves, Jay T

    2015-03-26

    Lipid/cholesterol mixtures derived from cell membranes as well as their synthetic reconstitutions exhibit well-defined miscibility phase transitions and critical phenomena near physiological temperatures. This suggests that lipid/cholesterol-mediated phase separation plays a role in the organization of live cell membranes. However, macroscopic lipid-phase separation is not generally observed in cell membranes, and the degree to which properties of isolated lipid mixtures are preserved in the cell membrane remain unknown. A fundamental property of phase transitions is that the variation of tagged particle diffusion with temperature exhibits an abrupt change as the system passes through the transition, even when the two phases are distributed in a nanometer-scale emulsion. We support this using a variety of Monte Carlo and atomistic simulations on model lipid membrane systems. However, temperature-dependent fluorescence correlation spectroscopy of labeled lipids and membrane-anchored proteins in live cell membranes shows a consistently smooth increase in the diffusion coefficient as a function of temperature. We find no evidence of a discrete miscibility phase transition throughout a wide range of temperatures: 14-37 °C. This contrasts the behavior of giant plasma membrane vesicles (GPMVs) blebbed from the same cells, which do exhibit phase transitions and macroscopic phase separation. Fluorescence lifetime analysis of a DiI probe in both cases reveals a significant environmental difference between the live cell and the GPMV. Taken together, these data suggest the live cell membrane may avoid the miscibility phase transition inherent to its lipid constituents by actively regulating physical parameters, such as tension, in the membrane. PMID:25747462

  8. Human Primary Immune Cells Exhibit Distinct Mechanical Properties that Are Modified by Inflammation.

    PubMed

    Bufi, Nathalie; Saitakis, Michael; Dogniaux, Stéphanie; Buschinger, Oscar; Bohineust, Armelle; Richert, Alain; Maurin, Mathieu; Hivroz, Claire; Asnacios, Atef

    2015-05-01

    T lymphocytes are key modulators of the immune response. Their activation requires cell-cell interaction with different myeloid cell populations of the immune system called antigen-presenting cells (APCs). Although T lymphocytes have recently been shown to respond to mechanical cues, in particular to the stiffness of their environment, little is known about the rigidity of APCs. In this study, single-cell microplate assays were performed to measure the viscoelastic moduli of different human myeloid primary APCs, i.e., monocytes (Ms, storage modulus of 520 +90/-80 Pa), dendritic cells (DCs, 440 +110/-90 Pa), and macrophages (MPHs, 900 +110/-100 Pa). Inflammatory conditions modulated these properties, with storage moduli ranging from 190 Pa to 1450 Pa. The effect of inflammation on the mechanical properties was independent of the induction of expression of commonly used APC maturation markers, making myeloid APC rigidity an additional feature of inflammation. In addition, the rigidity of human T lymphocytes was lower than that of all myeloid cells tested and among the lowest reported (Young's modulus of 85 ± 5 Pa). Finally, the viscoelastic properties of myeloid cells were dependent on both their filamentous actin content and myosin IIA activity, although the relative contribution of these parameters varied within cell types. These results indicate that T lymphocytes face different cell rigidities when interacting with myeloid APCs in vivo and that this mechanical landscape changes under inflammation. PMID:25954876

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

    PubMed Central

    1995-01-01

    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

  10. Copper Oxide Nanoparticles Induce Autophagic Cell Death in A549 Cells

    PubMed Central

    Zhao, Yan; Guo, Feng; Jiang, Chengyu

    2012-01-01

    Metal oxide nanoparticles (NPs) are among the most highly produced nanomaterials, and have many diverse functions in catalysis, environmental remediation, as sensors, and in the production of personal care products. In this study, the toxicity of several widely used metal oxide NPs such as copper oxide, silica, titanium oxide and ferric oxide NPs, were evaluated In vitro. We exposed A549, H1650 and CNE-2Z cell lines to metal oxide NPs, and found CuO NPs to be the most toxic, SiO2 mild toxic, while the other metal oxide NPs had little effect on cell viability. Furthermore, the autophagic biomarker LC3-II significantly increased in A549 cells treated with CuO NPs, and the use of the autophagy inhibitors wortmannin and 3-methyladenin significantly improved cell survival. These results indicate that the cytoxicity of CuO NPs may involve the autophagic pathway in A549 cells. PMID:22916263

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

    PubMed

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

    2014-05-01

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

  12. Mixing Effect of Gold and Silver Nanoparticles on Enhancement in Performance of Organic Thin-Film Solar Cells

    NASA Astrophysics Data System (ADS)

    Akiyama, Tsuyoshi; Yamamoto, Tomoki; Oku, Takeo; Yahiro, Masayuki; Kurihara, Takashi; Adachi, Chihaya; Yamada, Sunao

    2013-12-01

    Bulk-heterojunction organic thin-film solar cells incorporating gold and silver nanoparticles were fabricated and evaluated. These nanoparticles were embedded in the hole-transport layer of the solar cells. Plasmonic absorption peaks of isolated gold and silver nanoparticles were confirmed from extinction spectra even in the hole-transport material. The incorporation of gold and silver nanoparticles increased the photoelectric conversion efficiency of organic thin-film solar cells, whose enhancement ratio was further increased by mixing gold and silver nanoparticles.

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

    PubMed Central

    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

    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

  14. Number of Nanoparticles per Cell through a Spectrophotometric Method - A key parameter to Assess Nanoparticle-based Cellular Assays

    PubMed Central

    Unciti-Broceta, Juan D.; Cano-Cortés, Victoria; Altea-Manzano, Patricia; Pernagallo, Salvatore; Díaz-Mochón, Juan J.; Sánchez-Martín, Rosario M.

    2015-01-01

    Engineered nanoparticles (eNPs) for biological and biomedical applications are produced from functionalised nanoparticles (NPs) after undergoing multiple handling steps, giving rise to an inevitable loss of NPs. Herein we present a practical method to quantify nanoparticles (NPs) number per volume in an aqueous suspension using standard spectrophotometers and minute amounts of the suspensions (up to 1??L). This method allows, for the first time, to analyse cellular uptake by reporting NPs number added per cell, as opposed to current methods which are related to solid content (w/V) of NPs. In analogy to the parameter used in viral infective assays (multiplicity of infection), we propose to name this novel parameter as multiplicity of nanofection. PMID:25976173

  15. A Magnetic Nanoparticle-Based Multiple-Gene Delivery System for Transfection of Porcine Kidney Cells

    PubMed Central

    Wang, Yan; Cui, Haixin; Li, Kui; Sun, Changjiao; Du, Wei; Cui, Jinhui; Zhao, Xiang; Chen, Wenjie

    2014-01-01

    Superparamagnetic nanoparticles are promising candidates for gene delivery into mammalian somatic cells and may be useful for reproductive cloning using the somatic cell nuclear transfer technique. However, limited investigations of their potential applications in animal genetics and breeding, particularly multiple-gene delivery by magnetofection, have been performed. Here, we developed a stable, targetable and convenient system for delivering multiple genes into the nuclei of porcine somatic cells using magnetic Fe3O4 nanoparticles as gene carriers. After surface modification by polyethylenimine, the spherical magnetic Fe3O4 nanoparticles showed strong binding affinity for DNA plasmids expressing the genes encoding a green (DNAGFP) or red (DNADsRed) fluorescent protein. At weight ratios of DNAGFP or DNADsRed to magnetic nanoparticles lower than or equal to 10?1 or 5?1, respectively, the DNA molecules were completely bound by the magnetic nanoparticles. Atomic force microscopy analyses confirmed binding of the spherical magnetic nanoparticles to stretched DNA strands up to several hundred nanometers in length. As a result, stable and efficient co-expression of GFP and DsRed in porcine kidney PK-15 cells was achieved by magnetofection. The results presented here demonstrate the potential application of magnetic nanoparticles as an attractive delivery system for animal genetics and breeding studies. PMID:25048709

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

    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

  17. Nitric oxide releasing iron oxide magnetic nanoparticles for biomedical applications: cell viability, apoptosis and cell death evaluations

    NASA Astrophysics Data System (ADS)

    de Lima, R.; de Oliveira, J. L.; Ludescher, A.; Molina, M. M.; Itri, R.; Seabra, A. B.; Haddad, P. S.

    2013-04-01

    Nitric oxide (NO) is involved in several physiological and pathophysiological processes, such as control of vascular tone and immune responses against microbes. Thus, there is great interest in the development of NO-releasing materials to carry and deliver NO for biomedical applications. Magnetic iron oxide nanoparticles have been used in important pharmacological applications, including drug-delivery. In this work, magnetic iron oxide nanoparticles were coated with thiol-containing hydrophilic ligands: mercaptosuccinic acid (MSA) and dimercaptosuccinic acid (DMSA). Free thiol groups on the surface of MSA- or DMSA- coated nanoparticles were nitrosated, leading to the formation of NO-releasing iron oxide nanoparticles. The cytotoxicity of MSA- or DMSA-coated magnetic nanoparticles (MNP) (thiolated nanoparticles) and nitrosated MSA- or nitrosated DMSA- coated MNPs (NO-releasing nanoparticles) were evaluated towards human lymphocytes. The results showed that MNP-MSA and MNP-DMSA have low cytotoxicity effects. On the other hand, NO-releasing MNPs were found to increase apoptosis and cell death compared to free NO-nanoparticles. Therefore, the cytotoxicity effects observed for NO-releasing MNPs may result in important biomedical applications, such as the treatment of tumors cells.

  18. In-vitro Optimization of Nanoparticle-Cell Labeling Protocols for In-vivo Cell Tracking Applications.

    PubMed

    Betzer, Oshra; Meir, Rinat; Dreifuss, Tamar; Shamalov, Katerina; Motiei, Menachem; Shwartz, Amit; Baranes, Koby; Cohen, Cyrille J; Shraga-Heled, Niva; Ofir, Racheli; Yadid, Gal; Popovtzer, Rachela

    2015-01-01

    Recent advances in theranostic nanomedicine can promote stem cell and immune cell-based therapy. Gold nanoparticles (GNPs) have been shown to be promising agents for in-vivo cell-tracking in cell-based therapy applications. Yet a crucial challenge is to develop a reliable protocol for cell upload with, on the one hand, sufficient nanoparticles to achieve maximum visibility of cells, while on the other hand, assuring minimal effect of particles on cell function and viability. Previous studies have demonstrated that the physicochemical parameters of GNPs have a critical impact on their efficient uptake by cells. In the current study we have examined possible variations in GNP uptake, resulting from different incubation period and concentrations in different cell-lines. We have found that GNPs effectively labeled three different cell-lines - stem, immune and cancer cells, with minimal impairment to cell viability and functionality. We further found that uptake efficiency of GNPs into cells stabilized after a short period of time, while GNP concentration had a significant impact on cellular uptake, revealing cell-dependent differences. Our results suggest that while heeding the slight variations within cell lines, modifying the loading time and concentration of GNPs, can promote cell visibility in various nanoparticle-dependent in-vivo cell tracking and imaging applications. PMID:26507853

  19. In-vitro Optimization of Nanoparticle-Cell Labeling Protocols for In-vivo Cell Tracking Applications

    PubMed Central

    Betzer, Oshra; Meir, Rinat; Dreifuss, Tamar; Shamalov, Katerina; Motiei, Menachem; Shwartz, Amit; Baranes, Koby; Cohen, Cyrille J.; Shraga-Heled, Niva; Ofir, Racheli; Yadid, Gal; Popovtzer, Rachela

    2015-01-01

    Recent advances in theranostic nanomedicine can promote stem cell and immune cell-based therapy. Gold nanoparticles (GNPs) have been shown to be promising agents for in-vivo cell-tracking in cell-based therapy applications. Yet a crucial challenge is to develop a reliable protocol for cell upload with, on the one hand, sufficient nanoparticles to achieve maximum visibility of cells, while on the other hand, assuring minimal effect of particles on cell function and viability. Previous studies have demonstrated that the physicochemical parameters of GNPs have a critical impact on their efficient uptake by cells. In the current study we have examined possible variations in GNP uptake, resulting from different incubation period and concentrations in different cell-lines. We have found that GNPs effectively labeled three different cell-lines - stem, immune and cancer cells, with minimal impairment to cell viability and functionality. We further found that uptake efficiency of GNPs into cells stabilized after a short period of time, while GNP concentration had a significant impact on cellular uptake, revealing cell-dependent differences. Our results suggest that while heeding the slight variations within cell lines, modifying the loading time and concentration of GNPs, can promote cell visibility in various nanoparticle-dependent in-vivo cell tracking and imaging applications. PMID:26507853

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

    NASA Astrophysics Data System (ADS)

    Zharov, V. P.; Letfullin, R. R.; Galitovskaya, E. N.

    2005-08-01

    Laser-induced bubble formation around nanoparticles may play a crucial role in selective laser nanophotothermolysis of cancer cells targeted with nanoparticles. In this paper, we propose theoretically, and confirm experimentally, a new dynamic mode for selective cancer treatment that involves the overlapping of bubbles inside the cell volume. This bubbles-overlapping mode (BOM) can dramatically increase the efficiency of cancer treatment by laser-heated nanoparticles as a result of the large damage range. On the basis of nanoparticle optics below the diffraction limit and the kinetic model of bubble dynamics, we found the criteria and conditions (interparticle distance and particle size and concentration) for BOM initiation in cancer cells by laser radiation. Using MDA-MB-231 breast cancer cells, we showed that the optimal size range of the gold nanoparticles for effective laser initiation of BOM is 30-40 nm and the lower concentration limit is n ap 2.44 × 1011 cm-3 (i.e. the absolute number of particles homogeneously distributed inside a tumour cell is n ap 430). It was demonstrated that the formation of nanoclusters on the cell surface with sizes larger than the sizes of individual nanoparticles, may further increase the efficiency of the laser treatment of cancer.

  1. Gold nanoparticles as physiological markers of urine internalization into urothelial cells in vivo

    PubMed Central

    Hudoklin, Samo; Zupan?i?, Daša; Makovec, Darko; Kreft, Mateja Erdani; Romih, Rok

    2013-01-01

    Background Urothelial bladder is the reservoir of urine and the urothelium minimizes the exchange of urine constituents with this tissue. Our aim was to test 1.9 nm biocompatible gold nanoparticles as a novel marker of internalization into the urothelial cells under physiological conditions in vivo. Methods We compared normal and neoplastic mice urothelium. Neoplastic lesions were induced by 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in drinking water for 10 weeks. Nanoparticles, intravenously injected into normal and BBN-treated mice, were filtered through the kidneys and became constituents of the urine within 90 minutes after injection. Results Gold nanoparticles were densely accumulated in the urine, while their internalization into urothelial cells depended on the cell differentiation stage. In the terminally differentiated superficial urothelial cells of normal animals, nanoparticles were occasionally found in the endosomes, but not in the fusiform vesicles. Regions of exfoliated cells were occasionally found in the normal urothelium. Superficial urothelial cells located next to exfoliated regions contained gold nanoparticles in the endosomes and in the cytosol beneath the apical plasma membrane. The urothelium of BBN-treated animals developed fat hyperplasia with moderate dysplasia. The superficial cells of BBN-treated animals were partially differentiated as demonstrated by the lack of fusiform vesicles. These cells contained the gold nanoparticles distributed in the endosomes and throughout their cytosol. Conclusion Gold nanoparticles are a valuable marker to study urine internalization into urothelial cells in vivo. Moreover, they can be used as a sensitive marker of differentiation and functionality of urothelial cells. PMID:24143099

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

    PubMed

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

    2013-03-15

    The cancer-testis antigen NY-ESO-1 has been used as a target for different immunotherapies like vaccinations and adoptive transfer of antigen-specific cytotoxic T cells, as it is expressed in various tumor types and has limited expression in normal cells. The in vitro generation of T cells with defined antigen specificity by T cell receptor (TCR) gene transfer is an established method to create cells for immunotherapy. However, an extensive characterization of TCR which are candidates for treatment of patients is crucial for successful therapies. The TCR has to be efficiently expressed, their affinity to the desired antigen should be high enough to recognize low amounts of endogenously processed peptides on tumor cells, and the TCR should not be cross-reactive to other antigens. We characterized three NY-ESO-1 antigen-reactive cytotoxic T lymphocyte clones which were generated by different approaches of T cell priming (autologous, allogeneic), and transferred their TCR into donor T cells for more extensive evaluations. Although one TCR most efficiently bound MHC-multimers loaded with NY-ESO-1 peptide, T cells expressing this transgenic TCR were not able to recognize endogenously processed antigen. A second TCR recognized HLA-A2 independent of the bound peptide beside its much stronger recognition of NY-ESO-1 bound to HLA-A2. A third TCR displayed an intermediate but peptide-specific performance in all functional assays and, therefore, is the most promising candidate TCR for further clinical development. Our data indicate that multiple parameters of TCR gene-modified T cells have to be evaluated to identify an optimal TCR candidate for adoptive therapy. PMID:22907642

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

    PubMed

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

    2014-12-01

    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

  4. Novel cytotoxic exhibition mode of antimicrobial peptide anoplin in MEL cells, the cell line of murine Friend leukemia virus-induced leukemic cells.

    PubMed

    Zhu, Li-Na; Fu, Cai-Yun; Zhang, Shi-Fu; Chen, Wei; Jin, Yuan-Ting; Zhao, Fu-Kun

    2013-09-01

    Anoplin is a recently discovered antimicrobial peptide (AMP) isolated from the venom sac of the spider wasp Anoplius samariensis, and it is one of the shortest ?-helical AMP found naturally to date consisting of only ten amino acids. Previous results showed that anoplin exhibits potent antimicrobial activity but little hemolytic activity. In this study, we synthesized anoplin, studied its cytotoxicity in Friend virus-induced leukemia cells [murine erythroleukemia (MEL) cells], and proposed its possible mechanism. Our results showed that anoplin could inhibit the proliferation of MEL cells in a dose-dependent and time-dependent manner via disrupting the integrity of cell membrane, which indicated that anoplin exerts its cytotoxicity efficacy. In addition, the cell cycle distribution of MEL cells was arrested in the G?/G? phase significantly. However, anoplin could not induce obvious apoptosis in MEL cells, as well as anoplin could not induce visible changes on morphology and quantity in the bone marrow cells isolated from normal mice. All of these results indicate that anoplin, as generally believed, is a selective AMP, a value characteristic in the design of safe therapeutic agents. The cytotoxicity of anoplin on MEL cells was mainly attributable to the plasma membrane perturbation and also to the intracellular events such as the arrest of cell cycle. Although this is an initial study that explored the activity of anoplin in vitro rather than in vivo, with the increasing resistance of conventional chemotherapy, there is no doubt that anoplin has desirable feature to be developed as a novel and selective anticancer agent. PMID:23873700

  5. Comparative in vitro cytotoxicity study on uncoated magnetic nanoparticles: effects on cell viability, cell morphology, and cellular uptake.

    PubMed

    Li, L; Mak, K Y; Shi, J; Koon, H K; Leung, C H; Wong, C M; Leung, C W; Mak, C S K; Chan, N M M; Zhong, W; Lin, K W; Wu, E X; Pong, P W T

    2012-12-01

    Magnetic iron oxide nanoparticles (MIONPs) must be biocompatible, and a thorough knowledge on their potential cytotoxicity is crucial for their biomedical applications. However, the detailed study about the effects of iron oxide nanoparticles on cell viability, cell morphology, and cellular uptake of different mammalian cells is still insufficient. In this paper, comparative cytotoxicity study of uncoated magnetite nanoparticles at different concentrations was performed on human cervical cancer cell line (HeLa) and immortalized normal human retinal pigment epithelial cell line (RPE). The size, structure, and magnetic behavior of the MIONPs were characterized using transmission electron microscopy (TEM), X-ray diffractometry (XRD), and vibrating sample magnetometry (VSM) respectively. After 24-hour incubation with the MIONPs, the cell viability was determined by live/dead assay, the cell morphology at high magnification was observed under scanning electron microscopy (SEM), and the cellular uptake of MIONPs was measured under TEM and verified by energy-dispersive X-ray spectroscopy (EDX) analysis. Our results indicate that the uncoated MIONPs at a high concentration (0.40 mg/ml) were toxic to both HeLa and RPE cells. However, the cytotoxicity of uncoated MIONPs at low concentrations was cell-type specific, and RPE cells were more susceptible to these MIONPs than HeLa cells. The effects of the MIONPs on cell morphology and the nanoparticles uptake also showed different features between these two cell lines. Hence cell type should be taken into consideration in the in vitro cytotoxicity study of uncoated MIONPs. Additionally, it should be noticed that the cell morphological changes and the uptake of nanoparticles can take place even though no toxic effect of these MIONPs at low concentrations was reflected in the traditional cell viability assay. PMID:23447952

  6. An in vitro and in vivo study of gemcitabine-loaded albumin nanoparticles in a pancreatic cancer cell line

    PubMed Central

    Yu, Xinzhe; Di, Yang; Xie, Chao; Song, Yunlong; He, Hang; Li, Hengchao; Pu, Xinming; Lu, Weiyue; Fu, Deliang; Jin, Chen

    2015-01-01

    Background and objectives Gemcitabine (Gem) is far from satisfactory as the first-line regimen for pancreatic cancer, and the emergence of albumin nanoparticles offers new hope for the delivery of Gem. In this study, Gem-loaded human serum albumin nanoparticles (Gem-HSA-NPs) were successfully synthesized, characterized, and tested on a BxPC-3 cell line both in vitro and in vivo. Materials and methods 4-N-myristoyl-gemcitabine (Gem-C14) was obtained first by coupling myristoyl with the 4-amino group of Gem. The Gem-HSA-NPs were then prepared by nanoparticle albumin-bound technology and characterized for particle size, zeta potential, morphology, encapsulation efficiency, drug-loading efficiency, and release characteristics. Using both in vitro and in vivo studies, Gem-C14 and Gem-HSA-NPs were tested on the human pancreatic cancer cell line BxPC-3. Results Gem-HSA-NPs showed an average particle size of 150±27 nm, and with an encapsulation rate of 82.99%±3.5% and a drug-loading rate of 10.42%±3.5%, they exhibited a favorable controlled- and sustained-release nature. In in vitro, Gem-C14 was equivalent in cytotoxicity to Gem. In in vivo, the Gem-HSA-NPs exhibited the strongest inhibitory effect on tumor growth but the lowest toxicity among the four groups. Conclusion The enhanced in vivo efficacy of Gem-HSA-NPs toward the pancreatic cancer cell line suggests their potential role for use in the clinical field. PMID:26586944

  7. A Nanoparticle-based Sensor Platform for Cell Tracking and Status/Function Assessment

    NASA Astrophysics Data System (ADS)

    Yeo, David; Wiraja, Christian; Chuah, Yon Jin; Gao, Yu; Xu, Chenjie

    2015-10-01

    Nanoparticles are increasingly popular choices for labeling and tracking cells in biomedical applications such as cell therapy. However, all current types of nanoparticles fail to provide real-time, noninvasive monitoring of cell status and functions while often generating false positive signals. Herein, a nanosensor platform to track the real-time expression of specific biomarkers that correlate with cell status and functions is reported. Nanosensors are synthesized by encapsulating various sensor molecules within biodegradable polymeric nanoparticles. Upon intracellular entry, nanosensors reside within the cell cytoplasm, serving as a depot to continuously release sensor molecules for up to 30 days. In the absence of the target biomarkers, the released sensor molecules remain ‘Off’. When the biomarker(s) is expressed, a detectable signal is generated (On). As a proof-of-concept, three nanosensor formulations were synthesized to monitor cell viability, secretion of nitric oxide, and ?-actin mRNA expression.

  8. A Nanoparticle-based Sensor Platform for Cell Tracking and Status/Function Assessment

    PubMed Central

    Yeo, David; Wiraja, Christian; Chuah, Yon Jin; Gao, Yu; Xu, Chenjie

    2015-01-01

    Nanoparticles are increasingly popular choices for labeling and tracking cells in biomedical applications such as cell therapy. However, all current types of nanoparticles fail to provide real-time, noninvasive monitoring of cell status and functions while often generating false positive signals. Herein, a nanosensor platform to track the real-time expression of specific biomarkers that correlate with cell status and functions is reported. Nanosensors are synthesized by encapsulating various sensor molecules within biodegradable polymeric nanoparticles. Upon intracellular entry, nanosensors reside within the cell cytoplasm, serving as a depot to continuously release sensor molecules for up to 30 days. In the absence of the target biomarkers, the released sensor molecules remain ‘Off’. When the biomarker(s) is expressed, a detectable signal is generated (On). As a proof-of-concept, three nanosensor formulations were synthesized to monitor cell viability, secretion of nitric oxide, and ?-actin mRNA expression. PMID:26440504

  9. Growth of Pt nanoparticle for proton-exchange-membrane fuel cells by

    E-print Network

    PEMFC Growth of Pt nanoparticle for proton-exchange-membrane fuel cells at anode side of a polymer electrolyte membrane (PEM) fuel cell. With a Pt loading of 25 g-Pt/cm2 , current of the electrochemical test result and fuel cell performance agree with each other. Key word : Pulsed laser deposition

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

    PubMed Central

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

    2011-01-01

    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

  11. MicroRNA-21 Exhibits Antiangiogenic Function by Targeting RhoB Expression in Endothelial Cells

    PubMed Central

    Bovy, Nicolas; Deroanne, Christophe; Lambert, Vincent; Gonzalez, Maria-Luz Alvarez; Colige, Alain; Rakic, Jean-Marie; Noël, Agnès; Martial, Joseph A.; Struman, Ingrid

    2011-01-01

    Background MicroRNAs (miRNAs) are endogenously expressed small non-coding RNAs that regulate gene expression at post-transcriptional level. The recent discovery of the involvement of these RNAs in the control of angiogenesis renders them very attractive in the development of new approaches for restoring the angiogenic balance. Whereas miRNA-21 has been demonstrated to be highly expressed in endothelial cells, the potential function of this miRNA in angiogenesis has never been investigated. Methodology/Principal Findings We first observed in endothelial cells a negative regulation of miR-21 expression by serum and bFGF, two pro-angiogenic factors. Then using in vitro angiogenic assays, we observed that miR-21 acts as a negative modulator of angiogenesis. miR-21 overexpression reduced endothelial cell proliferation, migration and the ability of these cells to form tubes whereas miR-21 inhibition using a LNA-anti-miR led to opposite effects. Expression of miR-21 in endothelial cells also led to a reduction in the organization of actin into stress fibers, which may explain the decrease in cell migration. Further mechanistic studies showed that miR-21 targets RhoB, as revealed by a decrease in RhoB expression and activity in miR-21 overexpressing cells. RhoB silencing impairs endothelial cell migration and tubulogenesis, thus providing a possible mechanism for miR-21 to inhibit angiogenesis. Finally, the therapeutic potential of miR-21 as an angiogenesis inhibitor was demonstrated in vivo in a mouse model of choroidal neovascularization. Conclusions/Significance Our results identify miR-21 as a new angiogenesis inhibitor and suggest that inhibition of cell migration and tubulogenesis is mediated through repression of RhoB. PMID:21347332

  12. Piceatannol exhibits selective toxicity to multiple myeloma cells and influences the Wnt/ beta-catenin pathway.

    PubMed

    Schmeel, Frederic Carsten; Schmeel, Leonard Christopher; Kim, Young; Schmidt-Wolf, Ingo G H

    2014-12-01

    Aberrant activation of Wnt/?-catenin signaling promotes development and progression of various malignant neoplasms. Recent studies observed that the Wnt pathway is constitutively active in myeloma cells and promotes an exaggerated proliferation. Thus, the Wnt signaling pathway might be an attractive therapeutic target for multiple myeloma. In this study, we identified piceatannol as an inhibitor of the Wnt/?-catenin pathway and as a potent inducer of apoptosis in myeloma cells. Interestingly, healthy cells remained mainly unaffected. These results reveal a significant selective induction of apoptosis by piceatannol and suggest a significant in vivo effect against multiple myeloma. PMID:24470348

  13. Theranostic Mesoporous Silica Nanoparticles Biodegrade after Pro-Survival Drug Delivery and Ultrasound/Magnetic Resonance Imaging of Stem Cells

    PubMed Central

    Kempen, Paul J.; Greasley, Sarah; Parker, Kelly A.; Campbell, Jos L.; Chang, Huan-Yu; Jones, Julian R.; Sinclair, Robert; Gambhir, Sanjiv S.; Jokerst, Jesse V.

    2015-01-01

    Increasing cell survival in stem cell therapy is an important challenge for the field of regenerative medicine. Here, we report theranostic mesoporous silica nanoparticles that can increase cell survival through both diagnostic and therapeutic approaches. First, the nanoparticle offers ultrasound and MRI signal to guide implantation into the peri-infarct zone and away from the most necrotic tissue. Second, the nanoparticle serves as a slow release reservoir of insulin-like growth factor (IGF)—a protein shown to increase cell survival. Mesenchymal stem cells labeled with these nanoparticles had detection limits near 9000 cells with no cytotoxicity at the 250 µg/mL concentration required for labeling. We also studied the degradation of the nanoparticles and showed that they clear from cells in approximately 3 weeks. The presence of IGF increased cell survival up to 40% (p<0.05) versus unlabeled cells under in vitro serum-free culture conditions. PMID:25825602

  14. Different Drosophila cell types exhibit differences in mitotic centrosome assembly dynamics

    E-print Network

    Conduit, Paul T.; Raff, Jordan W.

    2015-08-03

    Centrosomes are major microtubule organising centres comprising a pair of centrioles surrounded by pericentriolar material (PCM). The PCM expands dramatically as cells enter mitosis, and we previously showed that two key PCM components, Centrosomin...

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

    E-print Network

    Thorburn, Rebecca Ruth

    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 ...

  16. Linker-free conjugation and specific cell targeting of antibody functionalized iron-oxide nanoparticles

    PubMed Central

    Xu, Yaolin; Baiu, Dana C.; Sherwood, Jennifer A.; McElreath, Meghan R.; Qin, Ying; Lackey, Kimberly H.; Otto, Mario; Bao, Yuping

    2015-01-01

    Specific targeting is a key step to realize the full potential of iron oxide nanoparticles in biomedical applications, especially tumor-associated diagnosis and therapy. Here, we developed anti-GD2 antibody conjugated iron oxide nanoparticles for highly efficient neuroblastoma cell targeting. The antibody conjugation was achieved through an easy, linker-free method based on catechol reactions. The targeting efficiency and specificity of the antibody-conjugated nanoparticles to GD2-positive neuroblastoma cells were confirmed by flow cytometry, fluorescence microscopy, Prussian blue staining and transmission electron microscopy. These detailed studies indicated that the receptor-recognition capability of the antibody was fully retained after conjugation and the conjugated nanoparticles quickly attached to GD2-positive cells within four hours. Interestingly, longer treatment (12 h) led the cell membrane-bound nanoparticles to be internalized into cytosol, either by directly penetrating the cell membrane or escaping from the endosomes. Last but importantly, the uniquely designed functional surfaces of the nanoparticles allow easy conjugation of other bioactive molecules.

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

    PubMed Central

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

    2013-01-01

    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

  18. Design of a TiO2 nanosheet/nanoparticle gradient film photoanode and its improved performance for dye-sensitized solar cells

    NASA Astrophysics Data System (ADS)

    Wang, Wenguang; Zhang, Haiyan; Wang, Rong; Feng, Ming; Chen, Yiming

    2014-01-01

    A TiO2 film photoanode with gradient structure in nanosheet/nanoparticle concentration on the fluorine-doped tin oxide glass from substrate to surface was prepared by a screen printing method. The as-prepared dye-sensitized solar cell (DSSC) based on the gradient film electrode exhibited an enhanced photoelectric conversion efficiency of 6.48%, exceeding that of a pure nanoparticle-based DSSC with the same film thickness by a factor of 2.6. The enhanced photovoltaic performance of the gradient film-based DSSC was attributed to the superior light scattering ability of TiO2 nanosheets within the gradient structure, which was beneficial to light harvesting. Furthermore, the TiO2 nanosheets with exposed {001} facets facilitated the electron transport from dye molecules to the conduction band of TiO2 and further to the conductive glass. Meanwhile, the high specific surface area of TiO2 nanosheets helped the adsorption of dye molecules, and the TiO2 nanoparticle underlayer ensured good electronic contact between the TiO2 film and the fluorine-doped tin oxide glass substrate. The electrochemical impedance spectroscopy measurements further confirmed the electron transport differences between DSSCs based on nanosheet/nanoparticle gradient film electrodes and DSSCs based on nanosheet/nanoparticle homogeneous mixtures, pure TiO2 nanoparticles and pure TiO2 nanosheets with the same film thickness.

  19. Design of a TiO2 nanosheet/nanoparticle gradient film photoanode and its improved performance for dye-sensitized solar cells.

    PubMed

    Wang, Wenguang; Zhang, Haiyan; Wang, Rong; Feng, Ming; Chen, Yiming

    2014-02-21

    A TiO2 film photoanode with gradient structure in nanosheet/nanoparticle concentration on the fluorine-doped tin oxide glass from substrate to surface was prepared by a screen printing method. The as-prepared dye-sensitized solar cell (DSSC) based on the gradient film electrode exhibited an enhanced photoelectric conversion efficiency of 6.48%, exceeding that of a pure nanoparticle-based DSSC with the same film thickness by a factor of 2.6. The enhanced photovoltaic performance of the gradient film-based DSSC was attributed to the superior light scattering ability of TiO2 nanosheets within the gradient structure, which was beneficial to light harvesting. Furthermore, the TiO2 nanosheets with exposed {001} facets facilitated the electron transport from dye molecules to the conduction band of TiO2 and further to the conductive glass. Meanwhile, the high specific surface area of TiO2 nanosheets helped the adsorption of dye molecules, and the TiO2 nanoparticle underlayer ensured good electronic contact between the TiO2 film and the fluorine-doped tin oxide glass substrate. The electrochemical impedance spectroscopy measurements further confirmed the electron transport differences between DSSCs based on nanosheet/nanoparticle gradient film electrodes and DSSCs based on nanosheet/nanoparticle homogeneous mixtures, pure TiO2 nanoparticles and pure TiO2 nanosheets with the same film thickness. PMID:24435106

  20. Stable self-assembled nanostructured hen egg white lysozyme exhibits strong anti-proliferative activity against breast cancer cells.

    PubMed

    Mahanta, Sailendra; Paul, Subhankar; Srivastava, Ankit; Pastor, Ashutosh; Kundu, Bishwajit; Chaudhuri, Tapan K

    2015-06-01

    Chemotherapy side effects have long been a matter of great concern. Here we describe a structurally stable self-assembled nanostructured lysozyme (snLYZ) synthesized using a simple desolvation technique that exhibited anticancer activity, as well as excellent hemocompatibility. Field emission scanning electron microscopy; atomic force microscopy and dynamic particle size analyzer were used for analyzing the synthesized snLYZ. The analysis revealed spherical shape with an average size of 300 nm. Circular dichroism and tryptophan fluorescence spectroscopic analysis revealed its gross change in secondary as well as the tertiary level of the structure. snLYZ also demonstrated excellent structural as well as the functional stability of LYZ in a wide range of pH and temperature with a fair level of protection against proteinase K digestion. When applied to MCF-7 breast cancer cells, it exhibited approximately 95% cell death within 24h, involving a reactive oxygen species (ROS) based mechanism, and showed excellent hemocompatibility. Fluorescence microscopy imaging revealed distinct cellular internalization of snLYZ and the formation of cytoplasmic granules, which initiated a cell-killing process through membrane damage. In order to mimic targeted therapy, we tagged folic acid with snLYZ, which further enhanced cytotoxicity against MCF-7 cells. Therefore, this is the first report of its kind where we demonstrated the preparation of a highly stable self-assembled nanostructured lysozyme with a strong anti-proliferative activity against breast cancer cells. PMID:25935265

  1. Statistical prediction of nanoparticle delivery: from culture media to cell

    NASA Astrophysics Data System (ADS)

    Rowan Brown, M.; Hondow, Nicole; Brydson, Rik; Rees, Paul; Brown, Andrew P.; Summers, Huw D.

    2015-04-01

    The application of nanoparticles (NPs) within medicine is of great interest; their innate physicochemical characteristics provide the potential to enhance current technology, diagnostics and therapeutics. Recently a number of NP-based diagnostic and therapeutic agents have been developed for treatment of various diseases, where judicious surface functionalization is exploited to increase efficacy of administered therapeutic dose. However, quantification of heterogeneity associated with absolute dose of a nanotherapeutic (NP number), how this is trafficked across biological barriers has proven difficult to achieve. The main issue being the quantitative assessment of NP number at the spatial scale of the individual NP, data which is essential for the continued growth and development of the next generation of nanotherapeutics. Recent advances in sample preparation and the imaging fidelity of transmission electron microscopy (TEM) platforms provide information at the required spatial scale, where individual NPs can be individually identified. High spatial resolution however reduces the sample frequency and as a result dynamic biological features or processes become opaque. However, the combination of TEM data with appropriate probabilistic models provide a means to extract biophysical information that imaging alone cannot. Previously, we demonstrated that limited cell sampling via TEM can be statistically coupled to large population flow cytometry measurements to quantify exact NP dose. Here we extended this concept to link TEM measurements of NP agglomerates in cell culture media to that encapsulated within vesicles in human osteosarcoma cells. By construction and validation of a data-driven transfer function, we are able to investigate the dynamic properties of NP agglomeration through endocytosis. In particular, we statistically predict how NP agglomerates may traverse a biological barrier, detailing inter-agglomerate merging events providing the basis for predictive modelling of nanopharmacology.

  2. Statistical prediction of nanoparticle delivery: from culture media to cell.

    PubMed

    Brown, M Rowan; Hondow, Nicole; Brydson, Rik; Rees, Paul; Brown, Andrew P; Summers, Huw D

    2015-04-17

    The application of nanoparticles (NPs) within medicine is of great interest; their innate physicochemical characteristics provide the potential to enhance current technology, diagnostics and therapeutics. Recently a number of NP-based diagnostic and therapeutic agents have been developed for treatment of various diseases, where judicious surface functionalization is exploited to increase efficacy of administered therapeutic dose. However, quantification of heterogeneity associated with absolute dose of a nanotherapeutic (NP number), how this is trafficked across biological barriers has proven difficult to achieve. The main issue being the quantitative assessment of NP number at the spatial scale of the individual NP, data which is essential for the continued growth and development of the next generation of nanotherapeutics. Recent advances in sample preparation and the imaging fidelity of transmission electron microscopy (TEM) platforms provide information at the required spatial scale, where individual NPs can be individually identified. High spatial resolution however reduces the sample frequency and as a result dynamic biological features or processes become opaque. However, the combination of TEM data with appropriate probabilistic models provide a means to extract biophysical information that imaging alone cannot. Previously, we demonstrated that limited cell sampling via TEM can be statistically coupled to large population flow cytometry measurements to quantify exact NP dose. Here we extended this concept to link TEM measurements of NP agglomerates in cell culture media to that encapsulated within vesicles in human osteosarcoma cells. By construction and validation of a data-driven transfer function, we are able to investigate the dynamic properties of NP agglomeration through endocytosis. In particular, we statistically predict how NP agglomerates may traverse a biological barrier, detailing inter-agglomerate merging events providing the basis for predictive modelling of nanopharmacology. PMID:25797791

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

    NASA Astrophysics Data System (ADS)

    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

    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

  4. NK cells differentiated from bone marrow, cord blood and peripheral blood stem cells exhibit similar phenotype and functions.

    PubMed

    Carayol, G; Robin, C; Bourhis, J H; Bennaceur-Griscelli, A; Chouaib, S; Coulombel, L; Caignard, A

    1998-06-01

    In the present study, we investigated the differentiation of human NK cells from bone marrow, cord blood and mobilized peripheral blood purified CD34+ stem cells using a potent culture system. Elutriated CD34+ stem cells were grown for several weeks in medium supplemented with stem cell factor (SCF) and IL-15 in the presence or absence of a murine stromal cell line (MS-5). Our data indicate that IL-15 induced the proliferation and maturation of highly positive CD56+ NK cells in both types of culture, although murine stromal cells slightly increased the proliferation of NK cells. NK cells differentiated in the presence of MS-5 were mostly CD56+ CD7 and a small subset expressed CD16. These in vitro differentiated CD56+ NK cells displayed cytolytic activity against the HLA class I- target K562. The CD56+ CD16+ subset also lysed NK-resistant Daudi cells. Neither of these NK subsets were shown to express Fas ligand. Total CD56+ cells expressed high amounts of transforming growth factor-beta and granulocyte-macrophage colony-stimulating factor, but no IFN-gamma. Investigation of NK receptor expression showed that most CD56+ cells expressed membrane CD94 and NKG2-A mRNA. PCR analysis revealed that p58 was also expressed in these cells. The role of CD94 in NK cell-mediated cytotoxicity was assessed on human HLA-B7-transfected murine L cells. While a low cytotoxic activity towards HLA-B7 cells was observed, the HLA-DR4 control cells were killed with high efficiency. These studies demonstrate that cytolytic and cytokine-producing NK cells may be derived from adult and fetal precursors by IL-15 and that these cells express a CD94 receptor which may influence their lytic potential. PMID:9645381

  5. Visualization of Carbon Nanoparticles Within Cells and Implications for Toxicity

    NASA Astrophysics Data System (ADS)

    Porter, Alexandra; Gass, Mhairi

    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.

  6. Targeting docetaxel-PLA nanoparticles simultaneously inhibit tumor growth and liver metastases of small cell lung cancer.

    PubMed

    Liang, Zhen; Yang, Nan; Jiang, Yao; Hou, Chunying; Zheng, Ji; Shi, Jiaojiao; Zhang, Rui; Li, Dongmei; Liu, Yanyong; Zuo, Pingping

    2015-10-15

    Small cell lung cancer (SCLC) is one of the most malignant cancers in the world and 5-year survival rate has not been significantly improved with conventional chemotherapy. Targeting treatment may be a promising alternative to enhance the antitumor efficacy. Present study was aimed at establishing a targeting nanodrug delivery system for SCLC therapy. A targeting peptide (AHSGMYP, named AP), screened in H446 cells by phage display technology, was conjugated to the docetaxel (DTX) encapsulated polylactic acid nanoparticles (DN) to prepare the targeting DTX nanoparticles (AP-DN). Cell cytotoxicity, cellular uptake, therapeutic efficacy and biodistribution of AP-DN were investigated in vitro and in vivo experiment. The mean particle size of AP-DN was 260nm with encapsulation efficiency >94% and a sustained release profile. Cytotoxicity of AP-DN against H446 cell was superior to that of DTX and DN. AP-DN exhibited excellent antitumor efficacy and particularly effectively inhibited the liver metastases with better tolerance. Results of cellular uptake and biodistribution indicated that the excellent antitumor efficacy of AP-DN was attributed to both the increased accumulation of drug and cellular uptake. To our knowledge, this is the first report on establishing SCLC targeting delivery system which offers a potential therapeutic alterative for SCLC therapy. PMID:26299762

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

    PubMed Central

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

    2013-01-01

    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

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

    PubMed

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

    2013-01-01

    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

  9. Endothelial, epithelial, and fibroblast cells exhibit specific splicing programs independently of their tissue of origin.

    PubMed

    Mallinjoud, Pierre; Villemin, Jean-Philippe; Mortada, Hussein; Polay Espinoza, Micaela; Desmet, François-Olivier; Samaan, Samaan; Chautard, Emilie; Tranchevent, Léon-Charles; Auboeuf, Didier

    2014-03-01

    Alternative splicing is the main mechanism of increasing the proteome diversity coded by a limited number of genes. It is well established that different tissues or organs express different splicing variants. However, organs are composed of common major cell types, including fibroblasts, epithelial, and endothelial cells. By analyzing large-scale data sets generated by The ENCODE Project Consortium and after extensive RT-PCR validation, we demonstrate that each of the three major cell types expresses a specific splicing program independently of its organ origin. Furthermore, by analyzing splicing factor expression across samples, publicly available splicing factor binding site data sets (CLIP-seq), and exon array data sets after splicing factor depletion, we identified several splicing factors, including ESRP1 and 2, MBNL1, NOVA1, PTBP1, and RBFOX2, that contribute to establishing these cell type-specific splicing programs. All of the analyzed data sets are freely available in a user-friendly web interface named FasterDB, which describes all known splicing variants of human and mouse genes and their splicing patterns across several dozens of normal and cancer cells as well as across tissues. Information regarding splicing factors that potentially contribute to individual exon regulation is also provided via a dedicated CLIP-seq and exon array data visualization interface. To the best of our knowledge, FasterDB is the first database integrating such a variety of large-scale data sets to enable functional genomics analyses at exon-level resolution. PMID:24307554

  10. Disruption of cell membranes via laser-activated, acoustically active, carbon nanoparticles

    NASA Astrophysics Data System (ADS)

    Holguin, Stefany; Prausnitz, Mark; Thadhani, Naresh

    2015-06-01

    Physical drug delivery methods provide an avenue to overcome the selectivity of the cell membrane via physical forces that disrupt cell membranes and drive drug molecules into the cytosol. When carbon black nanoparticles in suspension with cells and drug molecules are exposed to nanosecond-pulsed laser light, high uptake and cell viability are observed. This laser-carbon nanoparticle interaction causes thermal expansion and local vaporization that results in the release of acoustic waves into the surrounding medium. These combined energy transduction mechanisms, phenomena called transient nanoparticle energy transduction (TNET), are responsible for disruption of the cell membrane and subsequent efficient intracellular drug uptake while maintaining high cell viability. The overall objective of this work is to investigate TNET and the bioeffects associated with physical disruption of cell membranes for drug delivery via laser-carbon nanoparticle interactions. For example, varying and quantifying energy input to carbon nanoparticles by way of laser beam manipulation, assists in the understanding and assessment of subsequent bioeffects. Results of work performed to date will be presented. National Science Foundation Graduate Research Fellowship under Grant No. 0946809, Georgia Tech University Center of Exemplary Mentoring (UCEM) & the Alfred P. Sloan Foundation.

  11. Effect of TiO2 Nanoparticles on Polymer-Based Bulk Heterojunction Solar Cells

    NASA Astrophysics Data System (ADS)

    Guo, Tzung-Fang; Pakhomov, Georgi L'vovich; Wen, Ten-Chin; Chin, Xing-Guo; Liou, Siou-Hong

    2006-12-01

    This work addresses the enhanced power conversion efficiency ? of a hybrid organic solar cell in which the active layer comprises poly(3-hexylthiophene) (P3HT), [6,6]-phenyl-C61-butyric acid methyl ester (PCBM), and titanium dioxide (TiO2) nanoparticles. Under the illumination, the open circuit voltage increases, the fill factor is improved and the series resistance reduces as the concentration of TiO2 nanoparticles increases. Highly refractive TiO2 nanoparticles are assumed to promote the internal trapping of photons by scattering (redirecting) the light reflected from the metallic electrode in the active layer. The transport of charge carriers through the active layer is also improved due to the formation of TiO2 nanoparticles/Al interfaces. ? is doubled and the short circuit current is maximized by optimizing the blending concentration of TiO2 nanoparticles.

  12. A two-step route to planar perovskite cells exhibiting reduced hysteresis

    SciTech Connect

    Ip, Alexander H.; Adachi, Michael M.; McDowell, Jeffrey J.; Xu, Jixian; Sargent, Edward H.; Quan, Li Na; Kim, Dong Ha

    2015-04-06

    A simple two-step method was used to produce efficient planar organolead halide perovskite solar cells. Films produced using solely iodine containing precursors resulted in poor morphology and failed devices, whereas addition of chlorine to the process greatly improved morphology and resulted in dense, uniform perovskite films. This process was used to produce perovskite solar cells with a fullerene-based passivation layer. The hysteresis effect, to which planar perovskite devices are otherwise prone, was greatly suppressed through the use of this interface modifier. The combined techniques resulted in perovskite solar cells having a stable efficiency exceeding 11%. This straightforward fabrication procedure holds promise in development of various optoelectronic applications of planar perovskite films.

  13. The effect of laser irradiation on living cells incubated with gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Bibikova, Olga; Singh, Prateek; Popov, Alexey; Akchurin, Georgy; Skovorodkin, Ilya; Khanadeev, Vitaly; Kinnunen, Matti; Bogatyrev, Vladimir; Khlebtsov, Nikolai; Vainio, Seppo; Tuchin, Valery

    2015-03-01

    Plasmon-resonant nanoparticles attached to cell membranes, under laser treatment can temporarily increase membrane permeability. In this paper, the influence of continuous-wave and pulsed (nanosecond) laser irradiation on living cells incubated with gold nanoparticles was investigated. Gold nanospheres, nanostars, and nanorods with different functionalization were used as plasmonic agents. The dependence between increase of medium temperature on the irradiation time was showed for nanostars and nanorods with different surface properties. Cells samples incubated with gold nanorods showed the highest temperature increase. Feasibility of cell optoporation by the use of gold nanospheres with variable functionalization was demonstrated. The cell membrane permeability was successfully enhanced as shown by the uptake of the fluorescent dye upon nanosecond laser treatment. Toxicity of the nanoparticles was estimated by MTT assay.

  14. Proteomic study of human bronchial epithelial cells exposed to SiC nanoparticles

    NASA Astrophysics Data System (ADS)

    Tokarski, Caroline; Hirano, Seishiro; Rolando, Christian

    2011-07-01

    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.

  15. Targeted delivery of EV peptide to tumor cell cytoplasm using lipid coated calcium carbonate nanoparticles.

    PubMed

    Kim, Sang Kyoon; Foote, Michael B; Huang, Leaf

    2013-07-01

    Intracellular-acting peptide drugs are effective for inhibiting cytoplasmic protein targets, yet face challenges with penetrating the cancer cell membrane. We have developed a lipid nanoparticle formulation that utilizes a pH-sensitive calcium carbonate complexation mechanism to enable the targeted delivery of the intracellular-acting therapeutic peptide EEEEpYFELV (EV) into lung cancer cells. Lipid-calcium-carbonate (LCC) nanoparticles were conjugated with anisamide, a targeting ligand for the sigma receptor which is expressed on lung cancer cells. LCC EV nanoparticle treatment provoked severe apoptotic effects in H460 non-small cell lung cancer cells in vitro. LCC NPs also mediated the specific delivery of Alexa-488-EV peptide to tumor tissue in vivo, provoking a high tumor growth retardation effect with minimal uptake by external organs and no toxic effects. PMID:22796364

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

    E-print Network

    Kral, Kelly M., 1979-

    2005-01-01

    (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 ...

  17. Quantitative photoacoustics to measure single cell melanin production and nanoparticle attachment

    NASA Astrophysics Data System (ADS)

    Bhattacharyya, Kiran; Eshein, Adam; Chandrasekhar, Anand; Viator, John A.

    2015-04-01

    Photoacoustics can be used as a label-free spectroscopic method of identifying pigmented proteins and characterizing their intracellular concentration over time in a single living cell. The authors use a microscopic laser irradiation system with a 5 ns, Q-switched laser focused onto single cells in order to collect photoacoustic responses of melanoma cells from the HS936 cell line and gold nanoparticle labeled breast cancer cells from the T47D cell line. The volume averaged intracellular concentration of melanin is found to range from 29-270 mM for single melanoma cells and the number of gold nanoparticles (AuNP) is shown to range from 850-5900 AuNPs/cell. Additionally, the melanin production response to UV-A light stimulus is measured in four melanoma cells to find a mass production rate of 5.7 pg of melanin every 15 min.

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

    SciTech Connect

    Zhang, Wen; Chen, Yongsheng

    2011-01-01

    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.

  19. Enhanced antitumoral activity of doxorubicin against lung cancer cells using biodegradable poly(butylcyanoacrylate) nanoparticles

    PubMed Central

    Melguizo, Consolación; Cabeza, Laura; Prados, Jose; Ortiz, Raúl; Caba, Octavio; Rama, Ana R; Delgado, Ángel V; Arias, José L

    2015-01-01

    Doxorubicin (Dox) is widely used for the combined chemotherapy of solid tumors. However, the use of these drug associations in lung cancer has low antitumor efficacy. To improve its efficacious delivery and activity in lung adenocarcinoma cells, we developed a biodegradable and noncytotoxic nanoplatform based on biodegradable poly(butylcyanoacrylate) (PBCA). The reproducible formulation method was based on an anionic polymerization process of the PBCA monomer, with the antitumor drug being entrapped within the nanoparticle (NP) matrix during its formation. Improved drug-entrapment efficiencies and sustained (biphasic) drug-release properties were made possible by taking advantage of the synthesis conditions (drug, monomer, and surfactant-agent concentrations). Dox-loaded NPs significantly enhanced cellular uptake of the drug in the A549 and LL/2 lung cancer cell lines, leading to a significant improvement of the drug’s antitumoral activity. In vivo studies demonstrated that Dox-loaded NPs clearly reduced tumor volumes and increased mouse-survival rates compared to the free drug. These results demonstrated that PBCA NPs may be used to optimize the antitumor activity of Dox, thus exhibiting a potential application in chemotherapy against lung adenocarcinoma. PMID:26715840

  20. Small molecule PZL318: forming fluorescent nanoparticles capable of tracing their interactions with cancer cells and activated platelets, slowing tumor growth and inhibiting thrombosis

    PubMed Central

    Li, Shan; Wang, Yuji; Wang, Feng; Wang, Yaonan; Zhang, Xiaoyi; Zhao, Ming; Feng, Qiqi; Wu, Jianhui; Zhao, Shurui; Wu, Wei; Peng, Shiqi

    2015-01-01

    Low selectivity of chemotherapy correlates with poor outcomes of cancer patients. To improve this issue, a novel agent, N-(1-[3-methoxycarbonyl-4-hydroxyphenyl]-?-carboline-3-carbonyl)-Trp-Lys-OBzl (PZL318), was reported here. The transmission electron microscopy, scanning electron microscopy, and atomic force microscopy images demonstrated that PZL318 can form nanoparticles. Fluorescent and confocal images visualized that PZL318 formed fluorescent nanoparticles capable of targeting cancer cells and tracing their interactions with cancer cells. In vitro, 40 ?M of PZL318 inhibited the proliferation of tumorigenic cells, but not nontumorigenic cells. In vivo, 10 nmol/kg of PZL318 slowed the tumor growth of S180 mice and alleviated the thrombosis of ferric chloride-treated ICR mice, while 100 ?mol/kg of PZL318 did not injure healthy mice and they exhibited no liver toxicity. By analyzing Fourier transform–mass spectrometry and rotating-frame Overhauser spectroscopy (ROESY) two-dimensional nuclear magnetic resonance spectra, the chemical mechanism of PZL318-forming trimers and nanoparticles was explored. By using mesoscale simulation, a nanoparticle of 3.01 nm in diameter was predicted containing 13 trimers. Scavenging free radicals, downregulating sP-selectin expression and intercalating toward DNA were correlated with the antitumor mechanism of PZL318. PMID:26345234

  1. Enhanced Stability of Aluminum Nanoparticle-Doped Organic Solar Cells.

    PubMed

    Sygletou, Maria; Kakavelakis, George; Paci, Barbara; Generosi, Amanda; Kymakis, Emmanuel; Stratakis, Emmanuel

    2015-08-19

    Enhancement of the stability of bulk heterojunction (BHJ) organic photovoltaic (OPV) devices is reported by the addition of surfactant-free aluminum (Al) nanoparticles (NPs) into the photoactive layer. The universality of the effect is demonstrated for two different BHJ systems, namely, the well-studied poly(3-hexylthiophene-2,5-diyl):phenyl-C61-butyric acid methyl ester (P3HT:PCBM) as well as the high efficient poly[N-9'-heptadecanyl-2,7-carbazole-alt-5,5-(4',7'-di-2-thienyl-2',1',3'-benzothiadiazole)]:[6,6]-phenyl-C71-butyric acid methyl ester (PCDTBT:PC71BM). It is shown that the lifetime of the devices with Al NPs, operating under continuous one-sun illumination in ambient conditions, is more than three times longer compared to the reference devices. Using complementary analytical techniques for in situ studies, we have explored the underlying mechanisms behind the observed stability improvement in the case of the P3HT:PCBM system. In particular, laser-induced fluorescence (LIF), photoluminescence decay and Fourier transform infrared (FTIR) spectroscopy experiments were performed and complemented with device degradation electrical measurements. It is found that the embedded Al NPs act as performance stabilizers, giving rise to enhanced structural stability of the active blend. Furthermore, it is revealed that the observed improvement can also be ascribed to NP-mediated mitigation of the photo-oxidation effect. This study addresses a major issue in OPV devices, that is, photoinduced stability, indicating that the exploitation of Al NPs could be a successful approach toward fabricating OPVs exhibiting long-term operating lifetimes. PMID:26222681

  2. Controlled intracellular generation of reactive oxygen species in human mesenchymal stem cells using porphyrin conjugated nanoparticles

    NASA Astrophysics Data System (ADS)

    Lavado, Andrea S.; Chauhan, Veeren M.; Alhaj Zen, Amer; Giuntini, Francesca; Jones, D. Rhodri E.; Boyle, Ross W.; Beeby, Andrew; Chan, Weng C.; Aylott, Jonathan W.

    2015-08-01

    Nanoparticles capable of generating controlled amounts of intracellular reactive oxygen species (ROS), that advance the study of oxidative stress and cellular communication, were synthesized by functionalizing polyacrylamide nanoparticles with zinc(ii) porphyrin photosensitisers. Controlled ROS production was demonstrated in human mesenchymal stem cells (hMSCs) through (1) production of nanoparticles functionalized with varying percentages of Zn(ii) porphyrin and (2) modulating the number of doses of excitation light to internalized nanoparticles. hMSCs challenged with nanoparticles functionalized with increasing percentages of Zn(ii) porphyrin and high numbers of irradiations of excitation light were found to generate greater amounts of ROS. A novel dye, which is transformed into fluorescent 7-hydroxy-4-trifluoromethyl-coumarin in the presence of hydrogen peroxide, provided an indirect indicator for cumulative ROS production. The mitochondrial membrane potential was monitored to investigate the destructive effect of increased intracellular ROS production. Flow cytometric analysis of nanoparticle treated hMSCs suggested irradiation with excitation light signalled controlled apoptotic cell death, rather than uncontrolled necrotic cell death. Increased intracellular ROS production did not induce phenotypic changes in hMSC subcultures.Nanoparticles capable of generating controlled amounts of intracellular reactive oxygen species (ROS), that advance the study of oxidative stress and cellular communication, were synthesized by functionalizing polyacrylamide nanoparticles with zinc(ii) porphyrin photosensitisers. Controlled ROS production was demonstrated in human mesenchymal stem cells (hMSCs) through (1) production of nanoparticles functionalized with varying percentages of Zn(ii) porphyrin and (2) modulating the number of doses of excitation light to internalized nanoparticles. hMSCs challenged with nanoparticles functionalized with increasing percentages of Zn(ii) porphyrin and high numbers of irradiations of excitation light were found to generate greater amounts of ROS. A novel dye, which is transformed into fluorescent 7-hydroxy-4-trifluoromethyl-coumarin in the presence of hydrogen peroxide, provided an indirect indicator for cumulative ROS production. The mitochondrial membrane potential was monitored to investigate the destructive effect of increased intracellular ROS production. Flow cytometric analysis of nanoparticle treated hMSCs suggested irradiation with excitation light signalled controlled apoptotic cell death, rather than uncontrolled necrotic cell death. Increased intracellular ROS production did not induce phenotypic changes in hMSC subcultures. Electronic supplementary information (ESI) available: Materials and experimental methods for the synthesis of (1) positively charged alkyne functionalized nanoparticles (2) Zn(ii) and Cu(ii) centred porphyrin (3); conjugating porphyrins to alkyne-functionalized nanoparticles via click chemistry (4) nanoparticle characterisation (size charge and fluorescence), (5) synthesis of BPTFMC (6) hMSC collection, storage and preparation (7) delivery of porphyrin functionalized nanoparticles (8) staining mitochondria, cumulative ROS production and determination of nanoparticles subcellular localisation (9) fluorescence microscopy and controlled irradiation of hMSCs (10) flow cytometry and controlled irradiation using a custom built irradiator. In addition, results highlighting: (1) nanoparticles emission spectra, size and charge, (2) BPTFMC fluorescence response and (3) hMSCs following light irradiation using flow cytometry. See DOI: 10.1039/c5nr00795j

  3. Silver nanoparticles disrupt regulation of steroidogenesis in fish ovarian cells.

    PubMed

    Degger, Natalie; Tse, Anna C K; Wu, Rudolf S S

    2015-12-01

    Despite the influx of silver nanoparticles (nAg) into the marine environment, their effects on fish reproduction remain completely unexplored. Using ovarian primary cells from marine medaka (Oryzias melastigma), in vitro studies were carried out to evaluate the effects of two differently coated nAg particles (Oleic Acid, (OA) nAg and Polyvinylpyrrolidone, (PVP) nAg) on fish ovarian tissues, using AgNO3 as a positive control. Cytotoxicity was evaluated by MTT assay and expression of key genes regulating steroidogenesis (StAR, CYP 19a, CYP 11a, 3?HSD and 20?HSD) were determined by Q-RT-PCR. EC50 values for PVP nAg, OA nAg and AgNO3 were 7.25?gL(-1), 924.4?gL(-1), and 42.0?gL(-1) respectively, showing that toxicity of silver was greatly enhanced in the PVP coated nano-form. Down regulation of CYP 19a was observed in both nAg and AgNO3 treatments, while down regulation of 3?HSD was only found in the OA nAg and AgNO3 treatments. For the first time, our results demonstrated that nAg can affect specific genes regulating steroidogenesis, implicating nAg as a potential endocrine disruptor. PMID:26546908

  4. TiO2 nanoparticles and bulk material stimulate human peripheral blood mononuclear cells?

    PubMed Central

    Becker, Kathrin; Schroecksnadel, Sebastian; Geisler, Simon; Carriere, Marie; Gostner, Johanna M.; Schennach, Harald; Herlin, Nathalie; Fuchs, Dietmar

    2014-01-01

    Nanomaterials are increasingly produced and used throughout recent years. Consequently the probability of exposure to nanoparticles has risen. Because of their small 1–100 nm size, the physicochemical properties of nanomaterials may differ from standard bulk materials and may pose a threat to human health. Only little is known about the effects of nanoparticles on the human immune system. In this study, we investigated the effects of TiO2 nanoparticles and bulk material in the in vitro model of human peripheral blood mononuclear cells (PBMC) and cytokine-induced neopterin formation and tryptophan breakdown was monitored. Both biochemical processes are closely related to the course of diseases like infections, atherogenesis and neurodegeneration. OCTi60 (25 nm diameter) TiO2 nanoparticles and bulk material increased neopterin production in unstimulated PBMC and stimulated cells significantly, the effects were stronger for OCTi60 compared to bulk material, while P25 TiO2 (25 nm diameter) nanoparticles had only little influence. No effect of TiO2 nanoparticles on tryptophan breakdown was detected in unstimulated cells, whereas in stimulated cells, IDO activity and IFN-? production were suppressed but only at the highest concentrations tested. Because neopterin was stimulated and tryptophan breakdown was suppressed in parallel, data suggests that the total effect of particles would be strongly pro-inflammatory. PMID:24361406

  5. Dendrimer-like alpha-d-glucan nanoparticles activate dendritic cells and are effective vaccine adjuvants.

    PubMed

    Lu, Fangjia; Mencia, Alejandra; Bi, Lin; Taylor, Aaron; Yao, Yuan; HogenEsch, Harm

    2015-04-28

    The use of nanoparticles for delivery of vaccine antigens and as vaccine adjuvants is appealing because their size allows efficient uptake by dendritic cells and their biological properties can be tailored to the desired function. Here, we report the effect of chemically modified phytoglycogen, a dendrimer-like ?-d-glucan nanoparticle, on dendritic cells in vitro, and the utility of this type of nanoparticle as a vaccine adjuvant in vivo. The modified phytoglycogen nanoparticle, termed Nano-11, has a positive surface charge which enabled electrostatic adsorption of negatively charged protein antigens. The Nano-11-antigen complexes were efficiently phagocytized by dendritic cells. Nano-11 induced increased expression of costimulatory molecules and the secretion of IL-1? and IL-12p40 by dendritic cells. Intramuscular injection of Nano-11-antigen formulations induced a significantly enhanced immune response to two different protein antigens. Examination of the injection site revealed numerous monocytes and relatively few neutrophils at one day after injection. The inflammation had nearly completely disappeared by 2 weeks after injection. These studies indicate that Nano-11 is an effective vaccine delivery vehicle that significantly enhances the immune response. This type of plant based nanoparticle is considered highly cost-effective compared with fully synthetic nanoparticles and appears to have an excellent safety profile making them an attractive adjuvant candidate for prophylactic vaccines. PMID:25747143

  6. Platinum and platinum-alloy nanoparticle catalysts for oxygen reduction reaction in fuel cells: Understanding atomic-scale structural properties

    NASA Astrophysics Data System (ADS)

    Loukrakpam, Rameshwori

    The development of active, robust, and low-cost nanocatalysts, which is crucial for advancement in fuel cell technology for transportation and stationary powers, has often been hampered by the lack of clear understanding of the correlation between nanostructural parameters of the catalysts and their electrocatalytic activity and stability. This dissertation work focuses on the fundamental understanding of factors governing the precise control of the nanostructural parameters (size, composition, shape, phase, etc) of platinum and platinum-based multimetallic alloy nanoparticle catalysts and their enhancement of electrocatalytic activities for oxygen reduction reaction (ORR) in fuel cells. Examples of monometallic (Pt nanocubes, etc.), bimetallic (PtCo, PtNi, PtIr, etc.), and trimetallic (PtIrCo, PtNiCo, etc) nanoparticles and catalysts with controllable sizes, shapes and compositions will be described. To gain fundamental insights, an array of advanced techniques was utilized for the characterization of the atomic-scale structures. Pt nanocubes with dominant (200) faces were found to exhibit an enhanced Pt-specific activity towards ORR. PtNi/C and PtCo/C catalysts were found to have size dependence for ORR. A change in the coordination number around Pt was also found to affect their electrocatalytic activity. PtIrCo/C catalysts thermally treated under different thermochemical conditions were found to exhibit a clear trend of fcc-type lattice shrinking with increase in temperature which was correlated with the increase in activity. The trimetallic catalysts were also found to exhibit a higher electrocatalytic activity for ORR than the bimetallic counterparts (PtIr/C and PtCo/C). These results have allowed us to establish the correlation between the nanostructural parameters (e.g., size, shape, composition, alloying/lattice strain, metal coordination structure, etc) and the electrocatalytic properties (activity and stability) for a series of nanocatalysts. The findings have significant implications for the implementation of the nanocatalysts in real fuel cells.

  7. Antibody fragment-armed mesoporous silica nanoparticles for the targeted delivery of bevacizumab in ovarian cancer cells.

    PubMed

    Zhang, Ying; Guo, Jing; Zhang, Xiao-Ling; Li, Da-Peng; Zhang, Ting-Ting; Gao, Fu-Feng; Liu, Nai-Fu; Sheng, Xiu-Gui

    2015-12-30

    In order to enhance the therapeutic efficacy and intracellular concentration of bevacizumab (BVC), we have designed a novel tumor endothelial marker 1 (TEM1)/endosialin (Ab-/scFv)-conjugated mesoporous silica nanoparticles (MSN) to target ovarian cancer cell. The Ab-/scFv-conjugated MSN were prepared by the conjugation of amine functional group of antibody of the carboxyl group of MSN. The resultant MSN was nanosized, spherical shaped, and exhibited a controlled release phenomenon in pH 7.4 conditions. Furthermore, BMSN/Ab was found to increase the cellular uptake and intracellular distribution of BVC in OVCAR-5 cancer cells. The Ab- conjugated MSN exhibited a superior anticancer effect with profound apoptosis in cancer cells in a time- and concentration dependent manner. Consistently, BMSN/Ab effectively inhibited the colony formation in transwell plate. Finally, BMSN/Ab showed a notable increase in the proportion of cells in G2/M phase of cell cycle indicating promising anticancer efficacy profile. Overall, Ab-/scFv-conjugated MSN might provide an effective strategy for the therapeutic management of ovarian cancers. PMID:26541303

  8. DNAM-1-based chimeric antigen receptors enhance T cell effector function and exhibit in vivo efficacy against melanoma.

    PubMed

    Wu, Ming-Ru; Zhang, Tong; Alcon, Andre; Sentman, Charles L

    2015-04-01

    Chimeric antigen receptor (CAR) T cell therapies hold great potential for treating cancers, and new CARs that can target multiple tumor types and have the potential to target non-hematological malignancies are needed. In this study, the tumor recognition ability of a natural killer cell-activating receptor, DNAM-1 was harnessed to design CARs that target multiple tumor types. DNAM-1 ligands, PVR and nectin-2, are expressed on primary human leukemia, myeloma, ovarian cancer, melanoma, neuroblastoma, and Ewing sarcoma. DNAM-1 CARs exhibit high tumor cell cytotoxicity but low IFN-? secretion in vitro. In contrast to other CAR designs, co-stimulatory domains did not improve the expression and function of DNAM-1 CARs. A DNAM-1/CD3zeta CAR reduced tumor burden in a murine melanoma model in vivo. In conclusion, DNAM-1-based CARs may have the potential to treat PVR and nectin-2 expressing hematological and solid tumors. PMID:25549845

  9. Cell Membrane-Coated Nanoparticles As an Emerging Antibacterial Vaccine Platform

    PubMed Central

    Angsantikul, Pavimol; Thamphiwatana, Soracha; Gao, Weiwei; Zhang, Liangfang

    2015-01-01

    Nanoparticles have demonstrated unique advantages in enhancing immunotherapy potency and have drawn increasing interest in developing safe and effective vaccine formulations. Recent technological advancement has led to the discovery and development of cell membrane-coated nanoparticles, which combine the rich functionalities of cellular membranes and the engineering flexibility of synthetic nanomaterials. This new class of biomimetic nanoparticles has inspired novel vaccine design strategies with strong potential for modulating antibacterial immunity. This article will review recent progress on using cell membrane-coated nanoparticles for antibacterial vaccination. Specifically, two major development strategies will be discussed, namely (i) vaccination against virulence factors through bacterial toxin sequestration; and (ii) vaccination against pathogens through mimicking bacterial antigen presentation. PMID:26457720

  10. Effect of cerium oxide nanoparticles on inflammation in vascular endothelial cells

    PubMed Central

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

    2010-01-01

    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

  11. Cell Membrane-Coated Nanoparticles As an Emerging Antibacterial Vaccine Platform.

    PubMed

    Angsantikul, Pavimol; Thamphiwatana, Soracha; Gao, Weiwei; Zhang, Liangfang

    2015-01-01

    Nanoparticles have demonstrated unique advantages in enhancing immunotherapy potency and have drawn increasing interest in developing safe and effective vaccine formulations. Recent technological advancement has led to the discovery and development of cell membrane-coated nanoparticles, which combine the rich functionalities of cellular membranes and the engineering flexibility of synthetic nanomaterials. This new class of biomimetic nanoparticles has inspired novel vaccine design strategies with strong potential for modulating antibacterial immunity. This article will review recent progress on using cell membrane-coated nanoparticles for antibacterial vaccination. Specifically, two major development strategies will be discussed, namely (i) vaccination against virulence factors through bacterial toxin sequestration; and (ii) vaccination against pathogens through mimicking bacterial antigen presentation. PMID:26457720

  12. In vitro cytotoxicity and induction of apoptosis by silica nanoparticles in human HepG2 hepatoma cells

    PubMed Central

    Lu, Xun; Qian, Jiangchao; Zhou, Huanjun; Gan, Qi; Tang, Wei; Lu, Jingxiong; Yuan, Yuan; Liu, Changsheng

    2011-01-01

    Background Silica nanoparticles have been discovered to exert cytotoxicity and induce apoptosis in normal human cells. However, until now, few studies have investigated the cytotoxicity of silica nanoparticles in tumor cells. Methods This study investigated the cytotoxicity of 7–50 nm silica nanoparticles in human HepG2 hepatoma cells, using normal human L-02 hepatocytes as a control. Cell nucleus morphology changes, cellular uptake, and expression of procaspase-9, p53, Bcl-2, and Bax, as well as the activity of caspase-3, and intracellular reactive oxygen species and glutathione levels in the silica nanoparticle-treated cells, were analyzed. Results The antitumor activity of the silica nanoparticles was closely related to particle size, and the antiproliferation activity decreased in the order of 20 nm > 7 nm > 50 nm. The silica nanoparticles were also cytotoxic in a dose- and time-dependent manner. However, the silica nanoparticles showed only slight toxicity in the L-02 control cells, Moreover, in HepG2 cells, oxidative stress and apoptosis were induced after exposure to 7–20 nm silica nanoparticles. Expression of p53 and caspase-3 increased, and expression of Bcl-2 and procaspase-9 decreased in a dose-dependent manner, whereas the expression of Bax was not significantly changed. Conclusion A mitochondrial-dependent pathway triggered by oxidative stress mediated by reactive oxygen species may be involved in apoptosis induced by silica nanoparticles, and hence cytotoxicity in human HepG2 hepatic cancer cells. PMID:21931484

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

    SciTech Connect

    Niu, Lu; Li, Yang; Li, Xiaojie; Gao, Xue; Su, Xingguang

    2012-11-15

    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.

  14. Cells exposed to nanosecond electrical pulses exhibit biomarkers of mechanical stress

    NASA Astrophysics Data System (ADS)

    Roth, Caleb C.; Barnes, Ronald A.; Ibey, Bennett L.; Beier, Hope T.; Moen, Erick K.; Glickman, Randolph D.

    2015-03-01

    Exposure of cells to very short (<1 ?s) electric pulses in the megavolt/meter range have been shown to cause disruption of the plasma membrane. This disruption is often characterized by the formation of numerous small pores (<2 nm in diameter) in the plasma membrane that last for several minutes, allowing the flow of ions into the cell. These small pores are called nanopores and the resulting damage to the plasma membrane is referred to as nanoporation. Nanosecond electrical pulse (nsEP) exposure can impart many different stressors on a cell, including electrical, electro-chemical, and mechanical stress. Thus, nsEP exposure is not a "clean" insult, making determination of the mechanism of nanoporation quite difficult. We hypothesize that nsEP exposure creates acoustic shock waves capable of causing nanoporation. Microarray analysis of primary adult human dermal fibroblasts (HDFa) exposed to nsEP, indicated several genes associated with mechanical stress were selectively upregulated 4 h post exposure. The idea that nanoporation is caused by external mechanical force from acoustic shock waves has, to our knowledge, not been investigated. This work will critically challenge the existing paradigm that nanoporation is caused solely by an electric-field driven event and could provide the basis for a plausible explanation for electroporation.

  15. Anatase TiO2 Nanoparticles with Exposed {001} Facets for Efficient Dye-Sensitized Solar Cells

    NASA Astrophysics Data System (ADS)

    Chu, Liang; Qin, Zhengfei; Yang, Jianping; Li, Xing'Ao

    2015-07-01

    Anatase TiO2 nanoparticles with exposed {001} facets were synthesized from Ti powder via a sequential hydrothermal reaction process. At the first-step hydrothermal reaction, H-titanate nanowires were obtained in NaOH solution with Ti powder, and at second-step hydrothermal reaction, anatase TiO2 nanoparticles with exposed {001} facets were formed in NH4F solution. If the second-step hydrothermal reaction was carried out in pure water, the H-titanate nanowires were decomposed into random shape anatase-TiO2 nanostructures, as well as few impurity of H2Ti8O17 phase and rutile TiO2 phase. Then, the as-prepared TiO2 nanostructures synthesized in NH4F solution and pure water were applied to the photoanodes of dye-sensitized solar cells (DSSCs), which exhibited power conversion efficiency (PCE) of 7.06% (VOC of 0.756?V, JSC of 14.80?mA/cm2, FF of 0.631) and 3.47% (VOC of 0.764?V, JSC of 6.86?mA/cm2, FF of 0.662), respectively. The outstanding performance of DSSCs based on anatase TiO2 nanoparticles with exposed {001} facets was attributed to the high activity and large special surface area for excellent capacity of dye adsorption.

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

    PubMed Central

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

    2013-01-01

    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

  17. Anatase TiO2 Nanoparticles with Exposed {001} Facets for Efficient Dye-Sensitized Solar Cells

    PubMed Central

    Chu, Liang; Qin, Zhengfei; Yang, Jianping; Li, Xing’ao

    2015-01-01

    Anatase TiO2 nanoparticles with exposed {001} facets were synthesized from Ti powder via a sequential hydrothermal reaction process. At the first-step hydrothermal reaction, H-titanate nanowires were obtained in NaOH solution with Ti powder, and at second-step hydrothermal reaction, anatase TiO2 nanoparticles with exposed {001} facets were formed in NH4F solution. If the second-step hydrothermal reaction was carried out in pure water, the H-titanate nanowires were decomposed into random shape anatase-TiO2 nanostructures, as well as few impurity of H2Ti8O17 phase and rutile TiO2 phase. Then, the as-prepared TiO2 nanostructures synthesized in NH4F solution and pure water were applied to the photoanodes of dye-sensitized solar cells (DSSCs), which exhibited power conversion efficiency (PCE) of 7.06% (VOC of 0.756?V, JSC of 14.80?mA/cm2, FF of 0.631) and 3.47% (VOC of 0.764?V, JSC of 6.86?mA/cm2, FF of 0.662), respectively. The outstanding performance of DSSCs based on anatase TiO2 nanoparticles with exposed {001} facets was attributed to the high activity and large special surface area for excellent capacity of dye adsorption. PMID:26190140

  18. Anatase TiO2 Nanoparticles with Exposed {001} Facets for Efficient Dye-Sensitized Solar Cells.

    PubMed

    Chu, Liang; Qin, Zhengfei; Yang, Jianping; Li, Xing'ao

    2015-01-01

    Anatase TiO2 nanoparticles with exposed {001} facets were synthesized from Ti powder via a sequential hydrothermal reaction process. At the first-step hydrothermal reaction, H-titanate nanowires were obtained in NaOH solution with Ti powder, and at second-step hydrothermal reaction, anatase TiO2 nanoparticles with exposed {001} facets were formed in NH4F solution. If the second-step hydrothermal reaction was carried out in pure water, the H-titanate nanowires were decomposed into random shape anatase-TiO2 nanostructures, as well as few impurity of H2Ti8O17 phase and rutile TiO2 phase. Then, the as-prepared TiO2 nanostructures synthesized in NH4F solution and pure water were applied to the photoanodes of dye-sensitized solar cells (DSSCs), which exhibited power conversion efficiency (PCE) of 7.06% (VOC of 0.756 V, JSC of 14.80 mA/cm(2), FF of 0.631) and 3.47% (VOC of 0.764 V, JSC of 6.86 mA/cm(2), FF of 0.662), respectively. The outstanding performance of DSSCs based on anatase TiO2 nanoparticles with exposed {001} facets was attributed to the high activity and large special surface area for excellent capacity of dye adsorption. PMID:26190140

  19. Carbon nanoparticle induced cytotoxicity in human mesenchymal stem cells through upregulation of TNF3, NFKBIA and BCL2L1 genes.

    PubMed

    Periasamy, Vaiyapuri S; Athinarayanan, Jegan; Alfawaz, Mohammed A; Alshatwi, Ali A

    2016-02-01

    Carbon based nanomaterials, including carbon nanotubes, graphene, nanodiamond and carbon nanoparticles, have emerged as potential candidates for a wide variety of applications because of their unusual electrical, mechanical, thermal and optical properties. However, our understanding of how increased usage of carbon based nanomaterials could lead to harmful effects in humans and other biological systems is inadequate. Our present investigation is focused on the cellular toxicity of carbon nanoparticles (CNPs) on human mesenchymal stem cells (hMSCs). Following exposure to CNPs, cell viability, nuclear morphological changes, apoptosis and cell cycle progression were monitored. Furthermore, the expression of genes involved in both cell death (e.g., P53, TNF3, CDKN1A, TNFRSF1A, TNFSF10, NFKBIA, BCL2L1) and cell cycle regulation (e.g., PCNA, EGR1, E2F1, CCNG1, CCND1, CCNC, CYCD3) were assessed using qPCR. Our results indicated that CNPs reduce cell viability and cause chromatin condensation and DNA fragmentation. Cell cycle analysis indicated that CNPs affect the cell cycle progression. However, the gene expression measurements confirmed that CNPs significantly upregulated the P53, TNF3, CDKNIA, and NFKBIA genes and downregulated the EGR1 gene in hMSCs. Our findings suggest that CNPs reduce cell viability by disrupting the expression of cell death genes in human mesenchymal stem cell (hMSC). The results of this investigation revealed that CNPs exhibited moderate toxicity on hMSCs. PMID:26364217

  20. Interference-free Micro/nanoparticle Cell Engineering by Use of High-Throughput Microfluidic Separation.

    PubMed

    Yeo, David C; Wiraja, Christian; Zhou, Yingying; Tay, Hui Min; Xu, Chenjie; Hou, Han Wei

    2015-09-23

    Engineering cells with active-ingredient-loaded micro/nanoparticles is becoming increasingly popular for imaging and therapeutic applications. A critical yet inadequately addressed issue during its implementation concerns the significant number of particles that remain unbound following the engineering process, which inadvertently generate signals and impart transformative effects onto neighboring nontarget cells. Here we demonstrate that those unbound micro/nanoparticles remaining in solution can be efficiently separated from the particle-labeled cells by implementing a fast, continuous, and high-throughput Dean flow fractionation (DFF) microfluidic device. As proof-of-concept, we applied the DFF microfluidic device for buffer exchange to sort labeled suspension cells (THP-1) from unbound fluorescent dye and dye-loaded micro/nanoparticles. Compared to conventional centrifugation, the depletion efficiency of free dyes or particles was improved 20-fold and the mislabeling of nontarget bystander cells by free particles was minimized. The microfluidic device was adapted to further accommodate heterogeneous-sized mesenchymal stem cells (MSCs). Complete removal of unbound nanoparticles using DFF led to the usage of engineered MSCs without exerting off-target transformative effects on the functional properties of neighboring endothelial cells. Apart from its effectiveness in removing free particles, this strategy is also efficient and scalable. It could continuously process cell solutions with concentrations up to 10(7) cells·mL(-1) (cell densities commonly encountered during cell therapy) without observable loss of performance. Successful implementation of this technology is expected to pave the way for interference-free clinical application of micro/nanoparticle engineered cells. PMID:26355568

  1. Gold nanoparticles with different charge and moiety induce differential cell response on mesenchymal stem cell osteogenesis.

    PubMed

    Li, Jia'En Jasmine; Kawazoe, Naoki; Chen, Guoping

    2015-06-01

    Stem cells exist in an in vivo microenvironment that provides biological and physiochemical cues to direct cell fate decisions. How the stem cells sense and respond to these cues is still not clearly understood. Gold nanoparticles (AuNPs) have been widely used for manipulation of cell behavior due to their ease of synthesis and versatility in surface functionalization. In this study, AuNPs with amine (AuNP-NH2), carboxyl (AuNP-COOH) and hydroxyl (AuNP-OH) functional groups possessing different surface charge were synthesized. Human bone marrow-derived mesenchymal stem cells (hMSCs) were treated with the surface functionalized AuNPs and assessed for cell viability and osteogenic differentiation ability. The surface functionalized AuNPs were well tolerated by hMSCs and showed no acute toxicity. Positively charged AuNPs showed higher cellular uptake. AuNPs did not inhibit osteogenesis but ALP activity and calcium deposition were markedly reduced in AuNP-COOH treatment. Gene profiling revealed an upregulation of TGF-? and FGF-2 expression that promoted cell proliferation over osteogenic differentiation in hMSCs. These results provide some insight on the influence of surface functionalized AuNPs on hMSCs behavior and the use of these materials for strategic tissue engineering. PMID:25858865

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

    NASA Astrophysics Data System (ADS)

    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

    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.

  3. Normal and Cystic Fibrosis Human Bronchial Epithelial Cells Infected with Pseudomonas aeruginosa Exhibit Distinct Gene Activation Patterns

    PubMed Central

    Balloy, Viviane; Varet, Hugo; Dillies, Marie-Agnès; Proux, Caroline; Jagla, Bernd; Coppée, Jean-Yves; Tabary, Olivier; Corvol, Harriet; Chignard, Michel; Guillot, Loïc

    2015-01-01

    Background and Aims In cystic fibrosis (CF), Pseudomonas aeruginosa is not eradicated from the lower respiratory tract and is associated with epithelial inflammation that eventually causes tissue damage. To identify the molecular determinants of an effective response to P. aeruginosa infection, we performed a transcriptomic analysis of primary human bronchial epithelial cells from healthy donors (CTRL) 2, 4, and 6 h after induced P. aeruginosa infection. Compared to noninfected cells, infected cells showed changes in gene activity, which were most marked 6 h postinfection and usually consisted in upregulation. Results By comparing for each time point of infection, the transcriptomic response of epithelial cells from CF patients and healthy donors, we identified 851, 638, 667, and 980 differentially expressed genes 0, 2, 4, and 6 h postinfection, respectively. Gene selection followed by bioinformatic analysis showed that most of the differentially expressed genes, either up- or downregulated, were in the protein-binding and catalytic gene-ontology categories. Finally, we established that the protein products of the genes exhibiting the greatest differential upregulation (CSF2, CCL2, TNF, CSF3, MMP1, and MMP10) between CF patients and CTRL were produced in higher amounts by infected cells from CF patients versus CTRL. Conclusions The differentially expressed genes in CF patients may constitute a signature for a detrimental inflammatory response and for an inefficient P. aeruginosa host-cell response. PMID:26485688

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

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

    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

  5. Analysis of Solar Cells Efficacy with Imbedded Layer of Spherical Plasmonic Nanoparticles

    NASA Astrophysics Data System (ADS)

    Reshetov, S. A.; Vladimirova, Yu. V.; Zadkov, V. N.

    2015-09-01

    The scattered sunlight absorption efficacy by a solar cell with imbedded layer of spherical plasmonic nanoparticles is simulated versus the parameters of the imbedded particles, the material they are made of, their density and location in the polymeric buffer layer inclusive. It was shown that the embedded plasmonic nanoparticles cause an increase of the relative efficacy of an organic solar cell with the P3HT:PCBM photosensitive layer and the PEDOT buffer layer of up to 10-20%. This increase depends also on the angle at which the sunlight shines the solar cell, which was also studied in detail.

  6. The Effect of Scattering Layer on the Performance of Dye-Sensitized Solar Cells Using TiO2 Hollow Spheres/TiO2 Nanoparticles Films as Photoanodes.

    PubMed

    Park, Su Kyung; Suh, Soong-Hyuck; Lee, Min Woo; Yun, Tae Kwan; Bae, Jae Young

    2015-10-01

    TiO2 hollow spheres were successfully synthesized using poly styrene as the template. Dye-sensitized solar cells are fabricated based on double-layered composite films of TiO2 nanoparticles and TiO2 hollow spheres. The photoelectric conversion performances of Dye-sensitized solar cells based on TiO2 nanoparticles/TiO2 nanoparticles, TiO2 nanoparticles/TiO2 hollow spheres and TiO2 hollow spheres/TiO2 hollow spheres double-layered films are investigated, and their photoelectric conversion efficiencies were determined to 4.52, 7.10 and 5.48%, respectively. Dye-sensitized solar cells based on double layered composite films of TiO2 nanoparticles and TiO2 hollow spheres exhibit the highest photo-electric conversion efficiency mainly due to the combined effect of two factors, the high light scattering of over-layer hollow spheres that enhance harvesting light of the Dye-sensitized solar cells and the under-layer TiO2 nanoparticle layer that ensures good electronic contact between TiO2 film and FTO conducting glass. The double layered composite TiO2 film electrodes are a promising development in enhancing the performance of dye-sensitized solar cells. PMID:26726506

  7. Mesenchymal stromal cells derived from acute myeloid leukemia bone marrow exhibit aberrant cytogenetics and cytokine elaboration

    PubMed Central

    Huang, J C; Basu, S K; Zhao, X; Chien, S; Fang, M; Oehler, V G; Appelbaum, F R; Becker, P S

    2015-01-01

    Bone marrow-derived mesenchymal stromal cells (BM-MSCs) play a fundamental role in the BM microenvironment (BME) and abnormalities of these cells may contribute to acute myeloid leukemia (AML) pathogenesis. The aim of the study was to characterize the cytokine and gene expression profile, immunophenotype and cytogenetics of BM-MSCs from AML patients compared to normal BM-MSCs from healthy donors. AML BM-MSCs showed decreased monocyte chemoattractant protein-1 levels compared to normal BM-MSCs. AML BM-MSCs expressed similar ?1 integrin, CD44, CD73, CD90 and E-cadherin compared to normal BM-MSCs. Cytogenetic analysis revealed chromosomal aberrations in AML BM-MSCs, some overlapping with and others distinct from their corresponding AML blasts. No significant difference in gene expression was detected between AML BM-MSCs compared to normal BM-MSCs; however, comparing the differences between AML and MSCs from AML patients with the differences between normal hematopoietic cells and normal MSCs by Ingenuity pathway analysis showed key distinctions of the AML setting: (1) upstream gene regulation by transforming growth factor beta 1, tumor necrosis factor, tissue transglutaminase 2, CCAAT/enhancer binding protein alpha and SWItch/Sucrose NonFermentable related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4; (2) integrin and interleukin 8 signaling as overrepresented canonical pathways; and (3) upregulation of transcription factors FBJ murine osteosarcoma viral oncogene homolog and v-myb avian myeloblastosis viral oncogene homolog. Thus, phenotypic abnormalities of AML BM-MSCs highlight a dysfunctional BME that may impact AML survival and proliferation. PMID:25860293

  8. RGS2-deficient mice exhibit decreased intraocular pressure and increased retinal ganglion cell survival

    PubMed Central

    Inoue-Mochita, Miyuki; Inoue, Toshihiro; Epstein, David L.; Blumer, Kendall J.

    2009-01-01

    Purpose Contractile activity of the trabecular meshwork (TM) and ciliary muscle (CM) influences aqueous humor drainage; however, the mechanisms linking tissue contractility and regulation of aqueous humor drainage are not well understood. Regulator of G Protein Signaling 2 (RGS2), a GTPase-activating protein of the G?q family of proteins, plays a critical role in regulation of contractile activity of vascular smooth muscle and in blood pressure homeostasis. To explore a potential role for RGS2 in intraocular pressure (IOP) homeostasis, we evaluated RGS2 knockout (RGS2?/?) mice for changes in IOP. Methods IOP was measured using a rebound tonometer in awake male RGS2?/? and littermate wild-type mice. Histological and immunofluorescence analyses were performed to evaluate changes in the iridocorneal structure, actomyosin organization in CM and TM, and retinal ganglion cell survival in both central and peripheral retina. Results In repeated measurements, IOP was found to be consistently lower in the RGS2?/? mice compared to littermate wild-type mice. This change in IOP appears to be associated with increased actin filament assembly in the CM, and widening of the Schlemm’s canal in the aqueous humor drainage pathway. Furthermore, ganglion cell number in the central retina was found to be significantly higher in the RGS2?/? mice relative to wild-type mice. Conclusions The data suggest that the deficiency of RGS2 decreased IOP, presumably due to increased aqueous humor drainage in association with increased CM contraction. These data indicate a potentially critical role for RGS2 in homeostasis of IOP and for retinal ganglion cell survival. PMID:19262744

  9. Silicon nanoparticles: applications in cell biology and medicine

    PubMed Central

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

    2006-01-01

    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

  10. ZnO nanoparticles induced oxidative stress and apoptosis in HepG2 and MCF-7 cancer cells and their antibacterial activity.

    PubMed

    Wahab, Rizwan; Siddiqui, Maqsood A; Saquib, Quaiser; Dwivedi, Sourabh; Ahmad, Javed; Musarrat, Javed; Al-Khedhairy, Abdulaziz A; Shin, Hyung-Shik

    2014-05-01

    Liver and breast cancer are the most traumatic diseases because they affect the major organs of the body. Nanomedicine recently emerged as a better option for the treatment of these deadly diseases. As a result, many nanoparticles have been used to treat cancer cell lines. Of the various nanoparticles, zinc oxide exhibits biocompatibility. Therefore, the aim of the present study was to investigate the activity of zinc oxide nanoparticles (ZnO-NPs) against HepG2 and MCF-7 cells. The NPs (?13±2 nm) were prepared via a non-protonated chemical route and were well-characterized through standard techniques. The study showed that treatment with NPs is notably effective against the proliferation of HepG2 and MCF-7 cancer cells in a dose-dependent manner. The MTT (3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide, a tetrazole) assays revealed the concentration-dependent cytotoxic effects of NPs in range of 2.5-100 ?g/ml. HepG2 and MCF-7 cells were exposed to ZnO-NPs and exhibited a significant reduction in their cell viability (95% and 96%; p<0.05) in response to a very low concentration (25 ?g/ml) of the ZnO-NPs; this finding was confirmed with FACS (fluorescence-activated cell sorting) data. The reduction in cell viability in response to NP treatment induces cytotoxicity in the cultured cells. The quantitative RT-PCR (real-time polymerase chain reaction) results demonstrate that the exposure of HepG2 cells to ZnO-NPs results in significant upregulation of the mRNA expression level of Bax, p53, and caspase-3 and the down regulation of the anti-apoptotic gene Bcl-2. The NPs were also tested against five pathogenic bacteria through the disk diffusion method, and their antibacterial activities were compared with that of ZnO salt. PMID:24657613

  11. Cell death induced by application of time-varying magnetic fields on nanoparticle-loaded dendritic cells

    E-print Network

    Marcos-Campos, I; Torres, T E; Marquina, C; Tres, A; Ibarra, M R; Goya, G F

    2010-01-01

    Aim: To assess the capability of monocyte-derived dendritic cells (DCs) to take Fe3O4 magnetic nanoparticles (MNPs), keeping their viability. To provoke cell death on these MNPs-loaded DCs using an external alternating magnetic field (AMF). Material & methods: Peripheral blood mononuclear cells were isolated from normal blood and platelets removed by centrifugation. Immunoselected CD14+ cells were cultured for 5 days, and the resulting cell phenotype was determined against several markers using flow cytometry. Co-cultures of DCs and MNPs were done overnight. The amount of Fe3O4 nanoparticles incorporated by DCs was quantified by magnetization measurements. MNPs-loaded DCs were exposed to AMF for 30 min and then cell viability was measured using trypan blue and FACS (annexin-propidium iodide) protocols. Morphological changes were investigated using scanning electron microscopy. Results: No significant decrease in cell viability of MNP/loaded DCs was observed up to five days, as compared against control sam...

  12. A spiking network model of cerebellar Purkinje cells and molecular layer interneurons exhibiting irregular firing

    PubMed Central

    Lennon, William; Hecht-Nielsen, Robert; Yamazaki, Tadashi

    2014-01-01

    While the anatomy of the cerebellar microcircuit is well-studied, how it implements cerebellar function is not understood. A number of models have been proposed to describe this mechanism but few emphasize the role of the vast network Purkinje cells (PKJs) form with the molecular layer interneurons (MLIs)—the stellate and basket cells. We propose a model of the MLI-PKJ network composed of simple spiking neurons incorporating the major anatomical and physiological features. In computer simulations, the model reproduces the irregular firing patterns observed in PKJs and MLIs in vitro and a shift toward faster, more regular firing patterns when inhibitory synaptic currents are blocked. In the model, the time between PKJ spikes is shown to be proportional to the amount of feedforward inhibition from an MLI on average. The two key elements of the model are: (1) spontaneously active PKJs and MLIs due to an endogenous depolarizing current, and (2) adherence to known anatomical connectivity along a parasagittal strip of cerebellar cortex. We propose this model to extend previous spiking network models of the cerebellum and for further computational investigation into the role of irregular firing and MLIs in cerebellar learning and function. PMID:25520646

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

    PubMed

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

    2014-06-20

    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. PMID:24859743

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

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

    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.

  15. Tracking of adipose tissue-derived progenitor cells using two magnetic nanoparticle types

    NASA Astrophysics Data System (ADS)

    Kasten, Annika; Siegmund, Birte J.; Grüttner, Cordula; Kühn, Jens-Peter; Frerich, Bernhard

    2015-04-01

    Magnetic resonance imaging (MRI) is to be considered as an emerging detection technique for cell tracking experiments to evaluate the fate of transplanted progenitor cells and develop successful cell therapies for tissue engineering. Adipose tissue engineering using adipose tissue-derived progenitor cells has been advocated for the cure of soft tissue defects or for persistent soft tissue augmentation. Adipose tissue-derived progenitor cells were differentiated into the adipogenic lineage and labeled with two different types of magnetic iron oxide nanoparticles in varying concentrations which resulted in a concentration-dependent reduction of gene expression of adipogenic differentiation markers, adiponectin and fatty acid-binding protein 4 (FABP4), whereas the metabolic activity was not altered. As a result, only low nanoparticle concentrations for labeling were used for in vivo experiments. Cells were seeded onto collagen scaffolds and subcutaneously implanted into severe combined immunodeficient (SCID) mice. At 24 h as well as 28 days after implantation, MRI analyses were performed visualizing nanoparticle-labeled cells using T2-weighted sequences. The quantification of absolute volume of the scaffolds revealed a decrease of volume over time in all experimental groups. The distribution of nanoparticle-labeled cells within the scaffolds varied likewise over time.

  16. Characterization, Quantification, and Determination of the Toxicity of Iron Oxide Nanoparticles to the Bone Marrow Cells.

    PubMed

    Paik, Sae-Yeol-Rim; Kim, Jong-Seok; Shin, Sung Jae; Ko, Sanghoon

    2015-01-01

    Iron oxide nanoparticles (IONPs) have been used to develop iron supplements for improving the bioavailability of iron in patients with iron deficiency, which is one of the most serious nutritional deficiencies in the world. Accurate information about the characteristics, concentration, and cytotoxicity of IONPs to the developmental and reproductive cells enables safe use of IONPs in the supplement industry. The objective of this study was to analyze the physicochemical properties and cytotoxicity of IONPs in bone marrow cells. We prepared three different types of iron samples (surface-modified iron oxide nanoparticles (SMNPs), IONPs, and iron citrate) and analyzed their physicochemical properties such as particle size distribution, zeta potential, and morphology. In addition, we examined the cytotoxicity of the IONPs in various kinds of bone marrow cells. We analyzed particle size distribution, zeta potential, iron levels, and subcellular localization of the iron samples in bone marrow cells. Our results showed that the iron samples were not cytotoxic to the bone marrow cells and did not affect the expression of cell surface markers and lipopolysaccharide (LPS)-induced the secretion of cytokines by murine bone marrow-derived dendritic cells (BMDCs). Our results may be used to investigate the interactions between nanoparticles and cells and tissues and the developmental toxicity of nanoparticles. PMID:26389886

  17. Characterization, Quantification, and Determination of the Toxicity of Iron Oxide Nanoparticles to the Bone Marrow Cells

    PubMed Central

    Paik, Sae-Yeol-Rim; Kim, Jong-Seok; Shin, Sung Jae; Ko, Sanghoon

    2015-01-01

    Iron oxide nanoparticles (IONPs) have been used to develop iron supplements for improving the bioavailability of iron in patients with iron deficiency, which is one of the most serious nutritional deficiencies in the world. Accurate information about the characteristics, concentration, and cytotoxicity of IONPs to the developmental and reproductive cells enables safe use of IONPs in the supplement industry. The objective of this study was to analyze the physicochemical properties and cytotoxicity of IONPs in bone marrow cells. We prepared three different types of iron samples (surface-modified iron oxide nanoparticles (SMNPs), IONPs, and iron citrate) and analyzed their physicochemical properties such as particle size distribution, zeta potential, and morphology. In addition, we examined the cytotoxicity of the IONPs in various kinds of bone marrow cells. We analyzed particle size distribution, zeta potential, iron levels, and subcellular localization of the iron samples in bone marrow cells. Our results showed that the iron samples were not cytotoxic to the bone marrow cells and did not affect the expression of cell surface markers and lipopolysaccharide (LPS)-induced the secretion of cytokines by murine bone marrow-derived dendritic cells (BMDCs). Our results may be used to investigate the interactions between nanoparticles and cells and tissues and the developmental toxicity of nanoparticles. PMID:26389886

  18. Can plasmonic Al nanoparticles improve absorption in triple junction solar cells?

    NASA Astrophysics Data System (ADS)

    Yang, L.; Pillai, S.; Green, M. A.

    2015-07-01

    Plasmonic nanoparticles located on the illuminated surface of a solar cell can perform the function of an antireflection layer, as well as a scattering layer, facilitating light-trapping. Al nanoparticles have recently been proposed to aid photocurrent enhancements in GaAs photodiodes in the wavelength region of 400-900?nm by mitigating any parasitic absorption losses. Because this spectral region corresponds to the top and middle sub-cell of a typical GaInP/GaInAs/Ge triple junction solar cell, in this work, we investigated the potential of similar periodic Al nanoparticles placed on top of a thin SiO2 spacer layer that can also serve as an antireflection coating at larger thicknesses. The particle period, diameter and the thickness of the oxide layers were optimised for the sub-cells using simulations to achieve the lowest reflection and maximum external quantum efficiencies. Our results highlight the importance of proper reference comparison, and unlike previously published results, raise doubts regarding the effectiveness of Al plasmonic nanoparticles as a suitable front-side scattering medium for broadband efficiency enhancements when compared to standard single-layer antireflection coatings. However, by embedding the nanoparticles within the dielectric layer, they have the potential to perform better than an antireflection layer and provide enhanced response from both the sub-cells.

  19. Can plasmonic Al nanoparticles improve absorption in triple junction solar cells?

    PubMed Central

    Yang, L.; Pillai, S.; Green, M. A.

    2015-01-01

    Plasmonic nanoparticles located on the illuminated surface of a solar cell can perform the function of an antireflection layer, as well as a scattering layer, facilitating light-trapping. Al nanoparticles have recently been proposed to aid photocurrent enhancements in GaAs photodiodes in the wavelength region of 400–900?nm by mitigating any parasitic absorption losses. Because this spectral region corresponds to the top and middle sub-cell of a typical GaInP/GaInAs/Ge triple junction solar cell, in this work, we investigated the potential of similar periodic Al nanoparticles placed on top of a thin SiO2 spacer layer that can also serve as an antireflection coating at larger thicknesses. The particle period, diameter and the thickness of the oxide layers were optimised for the sub-cells using simulations to achieve the lowest reflection and maximum external quantum efficiencies. Our results highlight the importance of proper reference comparison, and unlike previously published results, raise doubts regarding the effectiveness of Al plasmonic nanoparticles as a suitable front-side scattering medium for broadband efficiency enhancements when compared to standard single-layer antireflection coatings. However, by embedding the nanoparticles within the dielectric layer, they have the potential to perform better than an antireflection layer and provide enhanced response from both the sub-cells. PMID:26138405

  20. Live Cell Imaging of the Endocytosis and the Intracellular Trafficking of Multifunctional Lipid Nanoparticles

    SciTech Connect

    Zhang, Tieqiao; Danthi, S. N.; Xie, Jianwu; Hu, Dehong; Lu, H. Peter; Li, King H.

    2006-12-01

    Artificial lipid nanoparticles have drawn great attention due to their potential in medicine. Linked with targeting ligands, they can be used as probes and/or gene delivery vectors for specific types of target cells. Therefore, they are very promising agents in early detection, diagnosis and treatment of cancers and other genetic diseases. However, there are several barriers blocking the applications. Controlling the cellular uptake of the lipid nanoparticles is an important technical challenge to overcome. Understanding the mechanism of the endocytosis and the following intracellular trafficking is very important for improving the design and therefore the efficiency as a drug delivery system. By using fluorescence microscopy methods, we studied the endocytosis of lipid nanoparticles by live M21 cells. The movements of the nanoparticles inside the cell were quantitatively characterized and classified based on the diffusion behavior. The trajectories of nanoparticles movement over the cell membrane revealed hop-diffusion behavior prior to the endocytosis. Fast movement in large steps is observed in intracellular trafficking and is attributed to active movement along microtubule. These observations help to understand the mechanism of the endocytosis and the pathway of the particles in cells.

  1. Can plasmonic Al nanoparticles improve absorption in triple junction solar cells?

    PubMed

    Yang, L; Pillai, S; Green, M A

    2015-01-01

    Plasmonic nanoparticles located on the illuminated surface of a solar cell can perform the function of an antireflection layer, as well as a scattering layer, facilitating light-trapping. Al nanoparticles have recently been proposed to aid photocurrent enhancements in GaAs photodiodes in the wavelength region of 400-900 nm by mitigating any parasitic absorption losses. Because this spectral region corresponds to the top and middle sub-cell of a typical GaInP/GaInAs/Ge triple junction solar cell, in this work, we investigated the potential of similar periodic Al nanoparticles placed on top of a thin SiO2 spacer layer that can also serve as an antireflection coating at larger thicknesses. The particle period, diameter and the thickness of the oxide layers were optimised for the sub-cells using simulations to achieve the lowest reflection and maximum external quantum efficiencies. Our results highlight the importance of proper reference comparison, and unlike previously published results, raise doubts regarding the effectiveness of Al plasmonic nanoparticles as a suitable front-side scattering medium for broadband efficiency enhancements when compared to standard single-layer antireflection coatings. However, by embedding the nanoparticles within the dielectric layer, they have the potential to perform better than an antireflection layer and provide enhanced response from both the sub-cells. PMID:26138405

  2. Silver Nanoparticle Protein Corona Composition in Cell Culture Media

    PubMed Central

    Shannahan, Jonathan H.; Lai, Xianyin; Ke, Pu Chun; Podila, Ramakrishna; Brown, Jared M.; Witzmann, Frank A.

    2013-01-01

    The potential applications of nanomaterials as drug delivery systems and in other products continue to expand. Upon introduction into physiological environments and driven by energetics, nanomaterials readily associate proteins forming a protein corona (PC) on their surface. This PC influences the nanomaterial’s surface characteristics and may impact their interaction with cells. To determine the biological impact of nanomaterial exposure as well as nanotherapeutic applications, it is necessary to understand PC formation. Utilizing a label-free mass spectrometry-based proteomics approach, we examined the composition of the PC for a set of four silver nanoparticles (AgNPs) including citrate-stabilized and polyvinlypyrrolidone-stabilized (PVP) colloidal silver (20 or 110 nm diameter). To simulate cell culture conditions, AgNPs were incubated for 1 h in Dulbecco’s Modified Eagle Medium supplemented with 10% fetal bovine serum, washed, coronal proteins solubilized, and proteins identified and quantified by label-free LC-MS/MS. To determine which attributes influence PC formation, the AgNPs were characterized in both water and cell culture media with 10% FBS. All AgNPs associated a common subset of 11 proteins including albumin, apolipoproteins, keratins, and other serum proteins. 110 nm citrate- and PVP-stabilized AgNPs were found to bind the greatest number of proteins (79 and 85 respectively) compared to 20 nm citrate- and PVP-stabilized AgNPs (45 and 48 respectively), suggesting a difference in PC formation based on surface curvature. While no relationships were found for other protein parameters (isoelectric point or aliphatic index), the PC on 20 nm AgNPs (PVP and citrate) consisted of more hydrophobic proteins compared to 110 nm AgNPs implying that this class of proteins are more receptive to curvature-induced folding and crowding in exchange for an increased hydration in the aqueous environment. These observations demonstrate the significance of electrostatic and hydrophobic interactions in the formation of the PC which may have broad biological and toxicological implications. PMID:24040142

  3. / www.sciencexpress.org /15 July 2010 / Page 1 / 10.1126/science.1191035 Freshly isolated muscle stem cells (MuSCs) exhibit robust

    E-print Network

    Kay, Mark A.

    in muscle stem cell self-renewal and function in muscle regeneration. We report that when MuSCs are cultured stem cells (MuSCs) exhibit robust regenerative capacity in vivo that is rapidly lost in culture. Using physiological tissue rigidity, propagation of adult muscle stem cells is possible, enabling future cell

  4. Ebola virus-like particles produced in insect cells exhibit dendritic cell stimulating activity and induce neutralizing antibodies

    SciTech Connect

    Ye Ling; Lin Jianguo; Sun Yuliang; Bennouna, Soumaya; Lo, Michael; Wu Qingyang; Bu Zhigao; Pulendran, Bali; Compans, Richard W. . E-mail: compans@microbio.emory.edu; Yang Chinglai . E-mail: chyang@emory.edu

    2006-08-01

    Recombinant baculoviruses (rBV) expressing Ebola virus VP40 (rBV-VP40) or GP (rBV-GP) proteins were generated. Infection of Sf9 insect cells by rBV-VP40 led to assembly and budding of filamentous particles from the cell surface as shown by electron microscopy. Ebola virus-like particles (VLPs) were produced by coinfection of Sf9 cells with rBV-VP40 and rBV-GP, and incorporation of Ebola GP into VLPs was demonstrated by SDS-PAGE and Western blot analysis. Recombinant baculovirus infection of insect cells yielded high levels of VLPs, which were shown to stimulate cytokine secretion from human dendritic cells similar to VLPs produced in mammalian cells. The immunogenicity of Ebola VLPs produced in insect cells was evaluated by immunization of mice. Analysis of antibody responses showed that most of the GP-specific antibodies were of the IgG2a subtype, while no significant level of IgG1 subtype antibodies specific for GP was induced, indicating the induction of a Th1-biased immune response. Furthermore, sera from Ebola VLP immunized mice were able to block infection by Ebola GP pseudotyped HIV virus in a single round infection assay, indicating that a neutralizing antibody against the Ebola GP protein was induced. These results show that production of Ebola VLPs in insect cells using recombinant baculoviruses represents a promising approach for vaccine development against Ebola virus infection.

  5. Encapsulation of selenium in chitosan nanoparticles improves selenium availability and protects cells from selenium-induced DNA damage response

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Selenium, an essential mineral, plays important roles in optimizing human health. Chitosan is an effective, naturally oriented material for synthesizing nanoparticles with polyanions and exhibit preferable properties such as biocompatibility, biodegradation and resistance to certain enzymes. We have...

  6. Multidrug-resistant hela cells overexpressing MRP1 exhibit sensitivity to cell killing by hyperthermia: Interactions with etoposide

    SciTech Connect

    Souslova, Tatiana; Averill-Bates, Diana A. . E-mail: averill.diana@uqam.ca

    2004-12-01

    Purpose: Multidrug resistance (MDR) remains one of the primary obstacles in cancer chemotherapy and often involves overexpression of drug efflux transporters such as P-glycoprotein and multidrug resistance protein 1 (MRP1). Regional hyperthermia is undergoing clinical investigation in combination with chemotherapy or radiotherapy. This study evaluates whether hyperthermia can reverse MDR mediated by MRP1 in human cervical adenocarcinoma (HeLa) cells. Methods and materials: Cytotoxicity of hyperthermia and/or etoposide was evaluated using sulforhodamine-B in HeLa cells overexpressing MRP1 and their drug-sensitive counterparts. Glutathione, glutathione peroxidase (GPx), and glutathione S-transferase (GST) were quantified by spectrophotometry. GST isoenzymes were quantified by immunodetection. Caspase activation was evaluated by fluorometry and chromatin condensation by fluorescence microscopy using Hoechst 33258. Necrosis was determined using propidium iodide. Results: The major finding is that HeLa and HeLaMRP cells are both sensitive to cytotoxicity of hyperthermia (41-45 deg C). Hyperthermia induced activation of caspase 3 and chromatin condensation. Although total levels of cell killing were similar, there was a switch from apoptotic to necrotic cell death in MDR cells. This could be explained by decreased glutathione and GPx in MDR cells. MDR cells also contained very low levels of GST and were resistant to etoposide-induced apoptosis. Hyperthermia caused a modest increase in etoposide-induced apoptosis in HeLa and HeLaMRP cells, which required appropriate heat-drug scheduling. Conclusions: Hyperthermia could be useful in eliminating MDR cells that overexpress MRP1.

  7. Improved Cellular Specificity of Plasmonic Nanobubbles versus Nanoparticles in Heterogeneous Cell Systems

    PubMed Central

    Lukianova-Hleb, Ekaterina Y.; Ren, Xiaoyang; Constantinou, Pamela E.; Danysh, Brian P.; Shenefelt, Derek L.; Carson, Daniel D.; Farach-Carson, Mary C.; Kulchitsky, Vladimir A.; Wu, Xiangwei; Wagner, Daniel S.; Lapotko, Dmitri O.

    2012-01-01

    The limited specificity of nanoparticle (NP) uptake by target cells associated with a disease is one of the principal challenges of nanomedicine. Using the threshold mechanism of plasmonic nanobubble (PNB) generation and enhanced accumulation and clustering of gold nanoparticles in target cells, we increased the specificity of PNB generation and detection in target versus non-target cells by more than one order of magnitude compared to the specificity of NP uptake by the same cells. This improved cellular specificity of PNBs was demonstrated in six different cell models representing diverse molecular targets such as epidermal growth factor receptor, CD3 receptor, prostate specific membrane antigen and mucin molecule MUC1. Thus PNBs may be a universal method and nano-agent that overcome the problem of non-specific uptake of NPs by non-target cells and improve the specificity of NP-based diagnostics, therapeutics and theranostics at the cell level. PMID:22509318

  8. Improved cellular specificity of plasmonic nanobubbles versus nanoparticles in heterogeneous cell systems.

    PubMed

    Lukianova-Hleb, Ekaterina Y; Ren, Xiaoyang; Constantinou, Pamela E; Danysh, Brian P; Shenefelt, Derek L; Carson, Daniel D; Farach-Carson, Mary C; Kulchitsky, Vladimir A; Wu, Xiangwei; Wagner, Daniel S; Lapotko, Dmitri O

    2012-01-01

    The limited specificity of nanoparticle (NP) uptake by target cells associated with a disease is one of the principal challenges of nanomedicine. Using the threshold mechanism of plasmonic nanobubble (PNB) generation and enhanced accumulation and clustering of gold nanoparticles in target cells, we increased the specificity of PNB generation and detection in target versus non-target cells by more than one order of magnitude compared to the specificity of NP uptake by the same cells. This improved cellular specificity of PNBs was demonstrated in six different cell models representing diverse molecular targets such as epidermal growth factor receptor, CD3 receptor, prostate specific membrane antigen and mucin molecule MUC1. Thus PNBs may be a universal method and nano-agent that overcome the problem of non-specific uptake of NPs by non-target cells and improve the specificity of NP-based diagnostics, therapeutics and theranostics at the cell level. PMID:22509318

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

    SciTech Connect

    Kunzmann, Andrea; Andersson, Britta; Vogt, Carmen; Feliu, Neus; Ye Fei; Gabrielsson, Susanne; Toprak, Muhammet S.; Buerki-Thurnherr, Tina; Laurent, Sophie; Vahter, Marie; Krug, Harald; Muhammed, Mamoun; Scheynius, Annika; Fadeel, Bengt

    2011-06-01

    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.

  10. CD33-specific chimeric antigen receptor T cells exhibit potent preclinical activity against human acute myeloid leukemia.

    PubMed

    Kenderian, S S; Ruella, M; Shestova, O; Klichinsky, M; Aikawa, V; Morrissette, J J D; Scholler, J; Song, D; Porter, D L; Carroll, M; June, C H; Gill, S

    2015-08-01

    Patients with chemo-refractory acute myeloid leukemia (AML) have a dismal prognosis. Chimeric antigen receptor T (CART) cell therapy has produced exciting results in CD19+ malignancies and may overcome many of the limitations of conventional leukemia therapies. We developed CART cells to target CD33 (CART33) using the anti-CD33 single chain variable fragment used in gemtuzumab ozogamicin (clone My96) and tested the activity and toxicity of these cells. CART33 exhibited significant effector functions in vitro and resulted in eradication of leukemia and prolonged survival in AML xenografts. CART33 also resulted in human lineage cytopenias and reduction of myeloid progenitors in xenograft models of hematopoietic toxicity, suggesting that permanently expressed CD33-specific CART cells would have unacceptable toxicity. To enhance the viability of CART33 as an option for AML, we designed a transiently expressed mRNA anti-CD33 CAR. Gene transfer was carried out by electroporation into T cells and resulted in high-level expression with potent but self-limited activity against AML. Thus our preclinical studies show potent activity of CART33 and indicate that transient expression of anti-CD33 CAR by RNA modification could be used in patients to avoid long-term myelosuppression. CART33 therapy could be used alone or as part of a preparative regimen prior to allogeneic transplantation in refractory AML. PMID:25721896

  11. Efficient nanoparticle mediated sustained RNA interference in human primary endothelial cells

    NASA Astrophysics Data System (ADS)

    Mukerjee, Anindita; Shankardas, Jwalitha; Ranjan, Amalendu P.; Vishwanatha, Jamboor K.

    2011-11-01

    Endothelium forms an important target for drug and/or gene therapy since endothelial cells play critical roles in angiogenesis and vascular functions and are associated with various pathophysiological conditions. RNA mediated gene silencing presents a new therapeutic approach to overcome many such diseases, but the major challenge of such an approach is to ensure minimal toxicity and effective transfection efficiency of short hairpin RNA (shRNA) to primary endothelial cells. In the present study, we formulated shAnnexin A2 loaded poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles which produced intracellular small interfering RNA (siRNA) against Annexin A2 and brought about the downregulation of Annexin A2. The per cent encapsulation of the plasmid within the nanoparticle was found to be 57.65%. We compared our nanoparticle based transfections with Lipofectamine mediated transfection, and our studies show that nanoparticle based transfection efficiency is very high (~97%) and is more sustained compared to conventional Lipofectamine mediated transfections in primary retinal microvascular endothelial cells and human cancer cell lines. Our findings also show that the shAnnexin A2 loaded PLGA nanoparticles had minimal toxicity with almost 95% of cells being viable 24 h post-transfection while Lipofectamine based transfections resulted in only 30% viable cells. Therefore, PLGA nanoparticle based transfection may be used for efficient siRNA transfection to human primary endothelial and cancer cells. This may serve as a potential adjuvant treatment option for diseases such as diabetic retinopathy, retinopathy of prematurity and age related macular degeneration besides various cancers.

  12. Mice lacking c-fos have normal hematopoietic stem cells but exhibit altered B-cell differentiation due to an impaired bone marrow environment.

    PubMed Central

    Okada, S; Wang, Z Q; Grigoriadis, A E; Wagner, E F; von Rüden, T

    1994-01-01

    Mice lacking c-fos develop severe osteopetrosis with deficiencies in bone remodeling and exhibit extramedullary hematopoiesis, thymic atrophy, and altered B-cell development. In this study, we have used these mice to characterize in detail the developmental potential of hematopoietic stem cells lacking c-fos and to analyze how the lymphoid differentiation is altered. In c-fos -/- mice, B-cell numbers are reduced in the spleen, lymph nodes, and the peripheral blood as a result of a marked reduction (> 90%) in the number of clonogenic B-cell precursors. In contrast, the number and lineage distribution of myeloid progenitor cells are not affected. The thymic defects observed in a large number of these mice correlate with their health status, suggesting that this may be an indirect effect of the c-fos mutation. In vitro differentiation and bone marrow reconstitution experiments demonstrated that hematopoietic stem cells lacking c-fos can give rise to all mature myeloid as well as lymphoid cells, suggesting that the observed B lymphopenia in the mutant mice is due to an altered environment. Transplantation of wild-type bone marrow cells into newborn mutant mice resulted in the establishment of a bone marrow space and subsequent correction of the B-cell defect. These results demonstrate that hematopoietic stem cells lacking Fos have full developmental potential and that the observed defect in B-cell development is most likely due to the impaired bone marrow environment as a consequence of osteopetrosis. Images PMID:8264605

  13. G protein-coupled receptors function as logic gates for nanoparticle binding and cell uptake

    PubMed Central

    Hild, Wolfgang; Pollinger, Klaus; Caporale, Andrea; Cabrele, Chiara; Keller, Max; Pluym, Nicola; Buschauer, Armin; Rachel, Reinhard; Tessmar, Joerg; Breunig, Miriam; Goepferich, Achim

    2010-01-01

    More selective interactions of nanoparticles with cells would substantially increase their potential for diagnostic and therapeutic applications. Thus, it would not only be highly desirable that nanoparticles can be addressed to any cell with high target specificity and affinity, but that we could unequivocally define whether they rest immobilized on the cell surface as a diagnostic tag, or if they are internalized to serve as a delivery vehicle for drugs. To date no class of targets is known that would allow direction of nanoparticle interactions with cells alternatively into one of these mutually exclusive events. Using MCF-7 breast cancer cells expressing the human Y1-receptor, we demonstrate that G protein-coupled receptors provide us with this option. We show that quantum dots carrying a surface-immobilized antagonist remain with nanomolar affinity on the cell surface, and particles carrying an agonist are internalized upon receptor binding. The receptor functions like a logic “and-gate” that grants cell access only to those particles that carry a receptor ligand “and” where the ligand is an agonist. We found that agonist- and antagonist-modified nanoparticles bind to several receptor molecules at a time. This multiligand binding leads to five orders of magnitude increased-receptor affinities, compared with free ligand, in displacement studies. More than 800 G protein-coupled receptors in humans provide us with the paramount advantage that targeting of a plethora of cells is possible, and that switching from cell recognition to cell uptake is simply a matter of nanoparticle surface modification with the appropriate choice of ligand type. PMID:20498042

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

    PubMed Central

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

    2012-01-01

    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

  15. Spatial modulation spectroscopy for imaging and quantitative analysis of single dye-doped organic nanoparticles inside cells

    NASA Astrophysics Data System (ADS)

    Devadas, Mary Sajini; Devkota, Tuphan; Guha, Samit; Shaw, Scott K.; Smith, Bradley D.; Hartland, Gregory V.

    2015-05-01

    Imaging of non-fluorescent nanoparticles in complex biological environments, such as the cell cytosol, is a challenging problem. For metal nanoparticles, Rayleigh scattering methods can be used, but for organic nanoparticles, such as dye-doped polymer beads or lipid nanoparticles, light scattering does not provide good contrast. In this paper, spatial modulation spectroscopy (SMS) is used to image single organic nanoparticles doped with non-fluorescent, near-IR croconaine dye. SMS is a quantitative imaging technique that yields the absolute extinction cross-section of the nanoparticles, which can be used to determine the number of dye molecules per particle. SMS images were recorded for particles within EMT-6 breast cancer cells. The measurements allowed mapping of the nanoparticle location and the amount of dye in a single cell. The results demonstrate how SMS can facilitate efforts to optimize dye-doped nanoparticles for effective photothermal therapy of cancer.Imaging of non-fluorescent nanoparticles in complex biological environments, such as the cell cytosol, is a challenging problem. For metal nanoparticles, Rayleigh scattering methods can be used, but for organic nanoparticles, such as dye-doped polymer beads or lipid nanoparticles, light scattering does not provide good contrast. In this paper, spatial modulation spectroscopy (SMS) is used to image single organic nanoparticles doped with non-fluorescent, near-IR croconaine dye. SMS is a quantitative imaging technique that yields the absolute extinction cross-section of the nanoparticles, which can be used to determine the number of dye molecules per particle. SMS images were recorded for particles within EMT-6 breast cancer cells. The measurements allowed mapping of the nanoparticle location and the amount of dye in a single cell. The results demonstrate how SMS can facilitate efforts to optimize dye-doped nanoparticles for effective photothermal therapy of cancer. Electronic supplementary information (ESI) available: TEM imaging, calibration experiments for the SMS instrument with gold nanoparticles, SMS images of dye doped polymer beads from a commercial source, evidence for endosome uptake, and additional SMS images of dye-doped LPNPs in EMT-6 cells, and spectra of SRfluor680/croconaine doped lipid-polymer nanoparticles. See DOI: 10.1039/C5NR01614B

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

    PubMed Central

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

    2014-01-01

    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

  17. Effective medium analysis of thermally evaporated Ag nanoparticle films for plasmonic enhancement in organic solar cell

    NASA Astrophysics Data System (ADS)

    Haidari, Gholamhosain; Hajimahmoodzadeh, Morteza; Fallah, Hamid Reza; Varnamkhasti, Mohsen Ghasemi

    2015-09-01

    Films of silver nanoparticles have optical properties that are useful for applications such as plasmonic light trapping in solar cells. We report on the simple fabrication of Ag nanoparticle films via thermal evaporation, with and without subsequent annealing. These films result in a random array of particles of various shapes and sizes. The modeling of such a vast collection of particles is still beyond reach of the modern computers. We show that it is possible to represent the silver island films by the Bergman effective mediums with the same optical properties. The effective medium method provides us with deep insight about the shape, the size and the distribution of nanoparticles. The far field simulations of solar cells, in which the silver island film is replaced with an effective medium layer, show a reduction in the absorption of active layer. Besides, the near field simulations based on finite-difference time-domain technique demonstrate that the near field effects on active layer absorption are negligible and this method highlights the importance of nanoparticles shapes. The PCPDTBT:PCBM solar cells with embedded silver island films are fabricated, and it is found that their performances show the similar trend. This insight can be used for the optical analysis of thermally evaporated Ag nanoparticle films for the improvement of organic solar cells.

  18. Protease degradable tethers for controlled and cell-mediated release of nanoparticles in 2- and 3-dimensions

    PubMed Central

    Tokatlian, Talar; Shrum, Chadwick T.; Kadoya, Warren M.; Segura, Tatiana

    2010-01-01

    Strategies to control the release rate of bioactive signals from tissue engineering scaffolds are essential for tissue regeneration and tissue engineering applications. Here we report on a strategy to achieve temporal control over nanoparticle release from biomaterials using cell-secreted proteases. This cell-triggered release approach utilizes peptides that are degraded by matrix metalloproteinases (MMPs) at different rates to immobilize nanoparticles directly to the biomaterial surface. Thus, the peptide-immobilized nanoparticles are released with temporal control through the action of cell-released MMPs. We found that release rates of peptide-immobilized nanoparticles were a function of peptide sensitivity to proteases, the number of tethers between the nanoparticle and the surface and the concentration of proteases used to induce release. Cellular internalization of the peptide-immobilized nanoparticles was also a function of the peptide sensitivity to proteases, the number of tethers between the nanoparticle and the surface and MMP expression profile of the cells. Similar trends were observed for peptide-immobilized nanoparticles inside micro-porous hydrogels, indicating protease sensitive tethers are effective in controlling release rate and internalization of nanoparticles. Such a temporal delivery strategy of nanoparticles loaded with therapeutic payloads (e.g. protein, DNA, siRNA) can be an ideal means to guide tissue formation. PMID:20688389

  19. Slaying the Trojan Horse: Natural Killer Cells Exhibit Robust Anti-HIV-1 Antibody-Dependent Activation and Cytolysis against Allogeneic T Cells

    PubMed Central

    Gooneratne, Shayarana L.; Richard, Jonathan; Lee, Wen Shi; Finzi, Andrés; Kent, Stephen J.

    2014-01-01

    ABSTRACT Many attempts to design prophylactic human immunodeficiency virus type 1 (HIV-1) vaccines have focused on the induction of neutralizing antibodies (Abs) that block infection by free virions. Despite the focus on viral particles, virus-infected cells, which can be found within mucosal secretions, are more infectious than free virus both in vitro and in vivo. Furthermore, assessment of human transmission couples suggests infected seminal lymphocytes might be responsible for a proportion of HIV-1 transmissions. Although vaccines that induce neutralizing Abs are sought, only some broadly neutralizing Abs efficiently block cell-to-cell transmission of HIV-1. As HIV-1 vaccines need to elicit immune responses capable of controlling both free and cell-associated virus, we evaluated the potential of natural killer (NK) cells to respond in an Ab-dependent manner to allogeneic T cells bearing HIV-1 antigens. This study presents data measuring Ab-dependent anti-HIV-1 NK cell responses to primary and transformed allogeneic T-cell targets. We found that NK cells are robustly activated in an anti-HIV-1 Ab-dependent manner against allogeneic targets and that tested target cells are subject to Ab-dependent cytolysis. Furthermore, the educated KIR3DL1+ NK cell subset from HLA-Bw4+ individuals exhibits an activation advantage over the KIR3DL1? subset that contains both NK cells educated through other receptor/ligand combinations and uneducated NK cells. These results are intriguing and important for understanding the regulation of Ab-dependent NK cell responses and are potentially valuable for designing Ab-dependent therapies and/or vaccines. IMPORTANCE NK cell-mediated anti-HIV-1 antibody-dependent functions have been associated with protection from infection and disease progression; however, their role in protecting from infection with allogeneic cells infected with HIV-1 is unknown. We found that HIV-1-specific ADCC antibodies bound to allogeneic cells infected with HIV-1 or coated with HIV-1 gp120 were capable of activating NK cells and/or trigging cytolysis of the allogeneic target cells. This suggests ADCC may be able to assist in preventing infection with cell-associated HIV-1. In order to fully utilize NK cell-mediated Ab-dependent effector functions, it might also be important that educated NK cells, which hold the highest activation potential, can become activated against targets bearing HIV-1 antigens and expressing the ligands for self-inhibitory receptors. Here, we show that with Ab-dependent stimulation, NK cells expressing inhibitory receptors can mediate robust activation against targets expressing the ligands for those receptors. PMID:25320293

  20. Functionalized iron oxide nanoparticles for controlling the movement of immune cells

    NASA Astrophysics Data System (ADS)

    White, Ethan E.; Pai, Alex; Weng, Yiming; Suresh, Anil K.; van Haute, Desiree; Pailevanian, Torkom; Alizadeh, Darya; Hajimiri, Ali; Badie, Behnam; Berlin, Jacob M.

    2015-04-01

    Immunotherapy is currently being investigated for the treatment of many diseases, including cancer. The ability to control the location of immune cells during or following activation would represent a powerful new technique for this field. Targeted magnetic delivery is emerging as a technique for controlling cell movement and localization. Here we show that this technique can be extended to microglia, the primary phagocytic immune cells in the central nervous system. The magnetized microglia were generated by loading the cells with iron oxide nanoparticles functionalized with CpG oligonucleotides, serving as a proof of principle that nanoparticles can be used to both deliver an immunostimulatory cargo to cells and to control the movement of the cells. The nanoparticle-oligonucleotide conjugates are efficiently internalized, non-toxic, and immunostimulatory. We demonstrate that the in vitro migration of the adherent, loaded microglia can be controlled by an external magnetic field and that magnetically-induced migration is non-cytotoxic. In order to capture video of this magnetically-induced migration of loaded cells, a novel 3D-printed ``cell box'' was designed to facilitate our imaging application. Analysis of cell movement velocities clearly demonstrate increased cell velocities toward the magnet. These studies represent the initial step towards our final goal of using nanoparticles to both activate immune cells and to control their trafficking within the diseased brain.Immunotherapy is currently being investigated for the treatment of many diseases, including cancer. The ability to control the location of immune cells during or following activation would represent a powerful new technique for this field. Targeted magnetic delivery is emerging as a technique for controlling cell movement and localization. Here we show that this technique can be extended to microglia, the primary phagocytic immune cells in the central nervous system. The magnetized microglia were generated by loading the cells with iron oxide nanoparticles functionalized with CpG oligonucleotides, serving as a proof of principle that nanoparticles can be used to both deliver an immunostimulatory cargo to cells and to control the movement of the cells. The nanoparticle-oligonucleotide conjugates are efficiently internalized, non-toxic, and immunostimulatory. We demonstrate that the in vitro migration of the adherent, loaded microglia can be controlled by an external magnetic field and that magnetically-induced migration is non-cytotoxic. In order to capture video of this magnetically-induced migration of loaded cells, a novel 3D-printed ``cell box'' was designed to facilitate our imaging application. Analysis of cell movement velocities clearly demonstrate increased cell velocities toward the magnet. These studies represent the initial step towards our final goal of using nanoparticles to both activate immune cells and to control their trafficking within the diseased brain. Electronic supplementary information (ESI) available: Transmission electron microscopy images of the particles, additional independent experiments for the NF?B activity and exocytosis assays, TEM images for the SPION untreated cells, bright field microscopy images of the cells alone in the presence and absence of magnet, images of the magnetic movement experiments at higher doses of SPION, full uncropped images of the post-migration LIVE/DEAD assay, and a video file of cell movement. See DOI: 10.1039/c3nr04421a

  1. The impact of sphingosine kinase inhibitor-loaded nanoparticles on bioelectrical and biomechanical properties of cancer cells.

    PubMed

    Babahosseini, Hesam; Srinivasaraghavan, Vaishnavi; Zhao, Zongmin; Gillam, Frank; Childress, Elizabeth; Strobl, Jeannine S; Santos, Webster L; Zhang, Chenming; Agah, Masoud

    2016-01-01

    Cancer progression and physiological changes within the cells are accompanied by alterations in the biophysical properties. Therefore, the cell biophysical properties can serve as promising markers for cancer detection and physiological activities. To aid in the investigation of the biophysical markers of cells, a microfluidic chip has been developed which consists of a constriction channel and embedded microelectrodes. Single-cell impedance magnitudes at four frequencies and entry and travel times are measured simultaneously during their transit through the constriction channel. This microchip provides a high-throughput, label-free, automated assay to identify biophysical signatures of malignant cells and monitor the therapeutic efficacy of drugs. Here, we monitored the dynamic cellular biophysical properties in response to sphingosine kinase inhibitors (SphKIs), and compared the effectiveness of drug delivery using poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) loaded with SphKIs versus conventional delivery. Cells treated with SphKIs showed significantly higher impedance magnitudes at all four frequencies. The bioelectrical parameters extracted using a model also revealed that the highly aggressive breast cells treated with SphKIs shifted electrically towards that of a less malignant phenotype; SphKI-treated cells exhibited an increase in cell-channel interface resistance and a significant decrease in specific membrane capacitance. Furthermore, SphKI-treated cells became slightly more deformable as measured by a decrease in their channel entry and travel times. We observed no significant difference in the bioelectrical changes produced by SphKI delivered conventionally or with NPs. However, NPs-packaged delivery of SphKI decreased the cell deformability. In summary, this study showed that while the bioelectrical properties of the cells were dominantly affected by SphKIs, the biomechanical properties were mainly changed by the NPs. PMID:26607223

  2. Nano-immunoengineering: Nanoparticle-Based Manipulation of Antigen-Presenting Cells for Cancer Immunotherapy (Small 41/2015).

    PubMed

    Fang, Ronnie H; Kroll, Ashley V; Zhang, Liangfang

    2015-11-01

    On page 5483, L. Zhang and co-workers describe the process of nanoparticle-mediated antigen presentation. A dendritic cell takes up cell membrane-coated nanoparticles that are loaded with an immunological adjuvant. After uptake, the tumor antigens on the nanoparticle-stabilized membrane are processed and presented on the surface of the dendritic cell. Meanwhile, the adjuvant is released and causes the dendritic cell to mature, ultimately enabling it to activate tumor antigen-specific T cells (shown here as green). PMID:26503182

  3. In situ High Throughput Scattering Light Analysis of Single Plasmonic Nanoparticles in Living Cells

    PubMed Central

    Gu, Zhen; Jing, Chao; Ying, Yi-Lun; He, Pingang; Long, Yi-Tao

    2015-01-01

    Plasmonic nanoparticles have been widely applied in cell imaging, disease diagnosis, and photothermal therapy owing to their unique scattering and absorption spectra based on localized surface plasmon resonance (LSPR) property. Recently, it is still a big challenge to study the detailed scattering properties of single plasmonic nanoparticles in living cells and tissues, which have dynamic and complicated environment. The conventional approach for measuring the scattering light is based on a spectrograph coupled to dark-field microscopy (DFM), which is time-consuming and limited by the small sample capacity. Alternatively, RGB-based method is promising in high-throughput analysis of single plasmonic nanoparticles in dark-field images, but the limitation in recognition of nanoparticles hinders its application for intracellular analysis. In this paper, we developed an automatic and robust method for recognizing the plasmonic nanoparticles in dark-field image for RGB-based analysis. The method involves a bias-modified fuzzy C-means algorithm, through which biased illumination in the image could be eliminated. Thus, nearly all of the gold nanoparticles in the recorded image were recognized both on glass slide and in living cells. As confirmed, the distribution of peak wavelength obtained by our method is well agreed to the result measured by conventional method. Furthermore, we demonstrated that our method is profound in cell imaging studies, where its advantages in fast and high-throughput analysis of the plasmonic nanoparticles could be applied to confirm the presence and location of important biological molecules and provide efficiency information for cancer drug selection. PMID:25553107

  4. Optimal energy for cell radiosensitivity enhancement by gold nanoparticles using synchrotron-based monoenergetic photon beams.

    PubMed

    Rahman, Wan Nordiana; Corde, Stéphanie; Yagi, Naoto; Abdul Aziz, Siti Aishah; Annabell, Nathan; Geso, Moshi

    2014-01-01

    Gold nanoparticles have been shown to enhance radiation doses delivered to biological targets due to the high absorption coefficient of gold atoms, stemming from their high atomic number (Z) and physical density. These properties significantly increase the likelihood of photoelectric effects and Compton scattering interactions. Gold nanoparticles are a novel radiosensitizing agent that can potentially be used to increase the effectiveness of current radiation therapy techniques and improve the diagnosis and treatment of cancer. However, the optimum radiosensitization effect of gold nanoparticles is strongly dependent on photon energy, which theoretically is predicted to occur in the kilovoltage range of energy. In this research, synchrotron-generated monoenergetic X-rays in the 30-100 keV range were used to investigate the energy dependence of radiosensitization by gold nanoparticles and also to determine the photon energy that produces optimum effects. This investigation was conducted using cells in culture to measure dose enhancement. Bovine aortic endothelial cells with and without gold nanoparticles were irradiated with X-rays at energies of 30, 40, 50, 60, 70, 81, and 100 keV. Trypan blue exclusion assays were performed after irradiation to determine cell viability. Cell radiosensitivity enhancement was indicated by the dose enhancement factor which was found to be maximum at 40 keV with a value of 3.47. The dose enhancement factor obtained at other energy levels followed the same direction as the theoretical calculations based on the ratio of the mass energy absorption coefficients of gold and water. This experimental evidence shows that the radiosensitization effect of gold nanoparticles varies with photon energy as predicted from theoretical calculations. However, prediction based on theoretical assumptions is sometimes difficult due to the complexity of biological systems, so further study at the cellular level is required to fully characterize the effects of gold nanoparticles with ionizing radiation. PMID:24899803

  5. Optimal energy for cell radiosensitivity enhancement by gold nanoparticles using synchrotron-based monoenergetic photon beams

    PubMed Central

    Rahman, Wan Nordiana; Corde, Stéphanie; Yagi, Naoto; Abdul Aziz, Siti Aishah; Annabell, Nathan; Geso, Moshi

    2014-01-01

    Gold nanoparticles have been shown to enhance radiation doses delivered to biological targets due to the high absorption coefficient of gold atoms, stemming from their high atomic number (Z) and physical density. These properties significantly increase the likelihood of photoelectric effects and Compton scattering interactions. Gold nanoparticles are a novel radiosensitizing agent that can potentially be used to increase the effectiveness of current radiation therapy techniques and improve the diagnosis and treatment of cancer. However, the optimum radiosensitization effect of gold nanoparticles is strongly dependent on photon energy, which theoretically is predicted to occur in the kilovoltage range of energy. In this research, synchrotron-generated monoenergetic X-rays in the 30–100 keV range were used to investigate the energy dependence of radiosensitization by gold nanoparticles and also to determine the photon energy that produces optimum effects. This investigation was conducted using cells in culture to measure dose enhancement. Bovine aortic endothelial cells with and without gold nanoparticles were irradiated with X-rays at energies of 30, 40, 50, 60, 70, 81, and 100 keV. Trypan blue exclusion assays were performed after irradiation to determine cell viability. Cell radiosensitivity enhancement was indicated by the dose enhancement factor which was found to be maximum at 40 keV with a value of 3.47. The dose enhancement factor obtained at other energy levels followed the same direction as the theoretical calculations based on the ratio of the mass energy absorption coefficients of gold and water. This experimental evidence shows that the radiosensitization effect of gold nanoparticles varies with photon energy as predicted from theoretical calculations. However, prediction based on theoretical assumptions is sometimes difficult due to the complexity of biological systems, so further study at the cellular level is required to fully characterize the effects of gold nanoparticles with ionizing radiation. PMID:24899803

  6. Detection of molecules and cells using nuclear magnetic resonance with magnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Rümenapp, Christine; Gleich, Bernhard; Mannherz, Hans Georg; Haase, Axel

    2015-04-01

    For the detection of small molecules, proteins or even cells in vitro, functionalised magnetic nanoparticles and nuclear magnetic resonance measurements can be applied. In this work, magnetic nanoparticles with the size of 5-7 nm were functionalised with antibodies to detect two model systems of different sizes, the protein avidin and Saccharomyces cerevisiae as the model organism. The synthesised magnetic nanoparticles showed a narrow size distribution, which was determined using transmission electron microscopy and dynamic light scattering. The magnetic nanoparticles were functionalised with the according antibodies via EDC/NHS chemistry. The binding of the antigen to magnetic nanoparticles was detected through the change in the NMR T2 relaxation time at 0.5 T (?21.7 MHz). In case of a specific binding the particles cluster and the T2 relaxation time of the sample changes. The detection limit in buffer for FITC-avidin was determined to be 1.35 nM and 107 cells/ml for S. cerevisiae. For fluorescent microscopy the avidin molecules were labelled with FITC and for the detection of S. cerevisiae the magnetic nanoparticles were additionally functionalised with rhodamine. The binding of the particles to S. cerevisiae and the resulting clustering was also seen by transmission electron microscopy.

  7. Photothermal raster image correlation spectroscopy of gold nanoparticles in solution and on live cells

    PubMed Central

    Nieves, D. J.; Li, Y.; Fernig, D. G.; Lévy, R.

    2015-01-01

    Raster image correlation spectroscopy (RICS) measures the diffusion of fluorescently labelled molecules from stacks of confocal microscopy images by analysing correlations within the image. RICS enables the observation of a greater and, thus, more representative area of a biological system as compared to other single molecule approaches. Photothermal microscopy of gold nanoparticles allows long-term imaging of the same labelled molecules without photobleaching. Here, we implement RICS analysis on a photothermal microscope. The imaging of single gold nanoparticles at pixel dwell times short enough for RICS (60??s) with a piezo-driven photothermal heterodyne microscope is demonstrated (photothermal raster image correlation spectroscopy, PhRICS). As a proof of principle, PhRICS is used to measure the diffusion coefficient of gold nanoparticles in glycerol?:?water solutions. The diffusion coefficients of the nanoparticles measured by PhRICS are consistent with their size, determined by transmission electron microscopy. PhRICS was then used to probe the diffusion speed of gold nanoparticle-labelled fibroblast growth factor 2 (FGF2) bound to heparan sulfate in the pericellular matrix of live fibroblast cells. The data are consistent with previous single nanoparticle tracking studies of the diffusion of FGF2 on these cells. Importantly, the data reveal faster FGF2 movement, previously inaccessible by photothermal tracking, and suggest that inhomogeneity in the distribution of bound FGF2 is dynamic. PMID:26543570

  8. Cell penetrating peptide-modified poly(lactic-co-glycolic acid) nanoparticles with enhanced cell internalization.

    PubMed

    Steinbach, Jill M; Seo, Young-Eun; Saltzman, W Mark

    2016-01-15

    The surface modification of nanoparticles (NPs) can enhance the intracellular delivery of drugs, proteins, and genetic agents. Here we studied the effect of different surface ligands, including cell penetrating peptides (CPPs), on the cell binding and internalization of poly(lactic-co-glycolic) (PLGA) NPs. Relative to unmodified NPs, we observed that surface-modified NPs greatly enhanced cell internalization. Using one CPP, MPG (unabbreviated notation), that achieved the highest degree of internalization at both low and high surface modification densities, we evaluated the effect of two different NP surface chemistries on cell internalization. After 2h, avidin-MPG NPs enhanced cellular internalization by 5 to 26-fold relative to DSPE-MPG NP formulations. Yet, despite a 5-fold increase in MPG density on DSPE compared to Avidin NPs, both formulations resulted in similar internalization levels (48 and 64-fold, respectively) after 24h. Regardless of surface modification, all NPs were internalized through an energy-dependent, clathrin-mediated process, and became dispersed throughout the cell. Overall both Avidin- and DSPE-CPP modified NPs significantly increased internalization and offer promising delivery options for applications in which internalization presents challenges to efficacious delivery. PMID:26602822

  9. Effect of Magnetic Nanoparticles on Tobacco BY-2 Cell Suspension Culture

    PubMed Central

    Krystofova, Olga; Sochor, Jiri; Zitka, Ondrej; Babula, Petr; Kudrle, Vit; Adam, Vojtech; Kizek, Rene

    2012-01-01

    Nanomaterials are structures whose exceptionality is based on their large surface, which is closely connected with reactivity and modification possibilities. Due to these properties nanomaterials are used in textile industry (antibacterial textiles with silver nanoparticles), electronics (high-resolution imaging, logical circuits on the molecular level) and medicine. Medicine represents one of the most important fields of application of nanomaterials. They are investigated in connection with targeted therapy (infectious diseases, malignant diseases) or imaging (contrast agents). Nanomaterials including nanoparticles have a great application potential in the targeted transport of pharmaceuticals. However, there are some negative properties of nanoparticles, which must be carefully solved, as hydrophobic properties leading to instability in aqueous environment, and especially their possible toxicity. Data about toxicity of nanomaterials are still scarce. Due to this fact, in this work we focused on studying of the effect of magnetic nanoparticles (NPs) and modified magnetic nanoparticles (MNPs) on tobacco BY-2 plant cell suspension culture. We aimed at examining the effect of NPs and MNPs on growth, proteosynthesis—total protein content, thiols—reduced (GSH) and oxidized (GSSG) glutathione, phytochelatins PC2-5, glutathione S-transferase (GST) activity and antioxidant activity of BY-2 cells. Whereas the effect of NPs and MNPs on growth of cell suspension culture was only moderate, significant changes were detected in all other biochemical parameters. Significant changes in protein content, phytochelatins levels and GST activity were observed in BY-2 cells treated with MNPs nanoparticles treatment. Changes were also clearly evident in the case of application of NPs. Our results demonstrate the ability of MNPs to negatively affect metabolism and induce biosynthesis of protective compounds in a plant cell model represented by BY-2 cell suspension culture. The obtained results are discussed, especially in connection with already published data. Possible mechanisms of NPs’ and MNPs’ toxicity are introduced. PMID:23343980

  10. Effect of magnetic nanoparticles on tobacco BY-2 cell suspension culture.

    PubMed

    Krystofova, Olga; Sochor, Jiri; Zitka, Ondrej; Babula, Petr; Kudrle, Vit; Adam, Vojtech; Kizek, Rene

    2013-01-01

    Nanomaterials are structures whose exceptionality is based on their large surface, which is closely connected with reactivity and modification possibilities. Due to these properties nanomaterials are used in textile industry (antibacterial textiles with silver nanoparticles), electronics (high-resolution imaging, logical circuits on the molecular level) and medicine. Medicine represents one of the most important fields of application of nanomaterials. They are investigated in connection with targeted therapy (infectious diseases, malignant diseases) or imaging (contrast agents). Nanomaterials including nanoparticles have a great application potential in the targeted transport of pharmaceuticals. However, there are some negative properties of nanoparticles, which must be carefully solved, as hydrophobic properties leading to instability in aqueous environment, and especially their possible toxicity. Data about toxicity of nanomaterials are still scarce. Due to this fact, in this work we focused on studying of the effect of magnetic nanoparticles (NPs) and modified magnetic nanoparticles (MNPs) on tobacco BY-2 plant cell suspension culture. We aimed at examining the effect of NPs and MNPs on growth, proteosynthesis - total protein content, thiols - reduced (GSH) and oxidized (GSSG) glutathione, phytochelatins PC2-5, glutathione S-transferase (GST) activity and antioxidant activity of BY-2 cells. Whereas the effect of NPs and MNPs on growth of cell suspension culture was only moderate, significant changes were detected in all other biochemical parameters. Significant changes in protein content, phytochelatins levels and GST activity were observed in BY-2 cells treated with MNPs nanoparticles treatment. Changes were also clearly evident in the case of application of NPs. Our results demonstrate the ability of MNPs to negatively affect metabolism and induce biosynthesis of protective compounds in a plant cell model represented by BY-2 cell suspension culture. The obtained results are discussed, especially in connection with already published data. Possible mechanisms of NPs' and MNPs' toxicity are introduced. PMID:23343980

  11. Radiosensitizing effect of gold nanoparticles in carbon ion irradiation of human cervical cancer cells

    SciTech Connect

    Kaur, Harminder; Avasthi, D. K.; Pujari, Geetanjali; Sarma, Asitikantha

    2013-07-18

    Noble metal nanoparticles have received considerable attention in biotechnology for their role in bio sensing due to surface plasmon resonance, medical diagnostics due to better imaging contrast and therapy. The radiosensitization effect of gold nanoparticles (AuNP) has been gaining popularity in radiation therapy of cancer cells. The better depth dose profile of energetic ion beam proves its superiority over gamma radiation for fighting against cancer. In the present work, the glucose capped gold nanoparticles (Glu-AuNP) were synthesised and internalized in the HeLa cells. Transmission electron microscopic analysis of ultrathin sections of Glu-AuNP treated HeLa cells confirmed the internalization of Glu-AuNPs. Control HeLa cells and Glu-AuNp treated HeLa cells were irradiated at different doses of 62 MeV 12C ion beam (LET - 290keV/{mu}m) at BIO beam line of using 15UD Pelletron accelerator at Inter University Accelerator Centre, New Delhi, India. The survival fraction was assessed by colony forming assay which revealed that the dose of carbon ion for 90% cell killing in Glu-AuNP treated HeLa cells and control HeLa cells are 2.3 and 3.2 Gy respectively. This observation shows {approx} 28% reduction of {sup 12}C{sup 6+} ion dose for Glu-AuNP treated HeLa cells as compared to control HeLa cells.

  12. Selective photothermal efficiency of citrate capped gold nanoparticles for destruction of cancer cells

    SciTech Connect

    Raji, V.; Kumar, Jatish; Rejiya, C.S.; Vibin, M.; Shenoi, Vinesh N.; Abraham, Annie

    2011-08-15

    Gold nanoparticles are recently having much attention because of their increased applications in biomedical fields. In this paper, we demonstrated the photothermal efficacy of citrate capped gold nanoparticles (AuNPs) for the destruction of A431 cancer cells. Citrate capped AuNPs were synthesized successfully and characterized by UV-visible-NIR spectrophotometry and High Resolution Transmission Electron Microscopy (HR-TEM). Further, AuNPs were conjugated with epidermal growth factor receptor antibody (anti-EGFR) and applied for the selective photothermal therapy (PTT) of human epithelial cancer cells, A431. PTT experiments were conducted in four groups, Group I-control cells, Group II-cells treated with laser light alone, Group III-cells treated with unconjugated AuNP and further laser irradiation and Group IV-anti-EGFR conjugated AuNP treated cells irradiated by laser light. After laser irradiation, cell morphology changes that were examined using phase contrast microscopy along with the relevant biochemical parameters like lactate dehydrogenase activity, reactive oxygen species generation and caspase-3 activity were studied for all the groups to determine whether cell death occurs due to necrosis or apoptosis. From these results we concluded that, these immunotargeted nanoparticles could selectively induce cell death via ROS mediated apoptosis when cells were exposed to a low power laser light.

  13. Visualization and detection of live and apoptotic cells with fluorescent carbon nanoparticles.

    PubMed

    Dekaliuk, Mariia; Pyrshev, Kyrylo; Demchenko, Alexander

    2015-01-01

    Apoptosis is a genetically encoded cell death program that involves different processes occurring on molecular and sub-cellular levels. Here we report on its new features-the increased accumulation of fluorescent carbon nanoparticles (CDots) in cells and their changed distribution within cell interior, which can witness on altered mechanisms of their translocation through the membrane. The comparative studies of living (intact) and apoptotic cells were provided with two cell lines (HeLa, Vero) using two types of fluorescent nanoparticles ("violet" and "blue" CDots). In all studied cases the images of living and apoptotic cells were different; the apoptotic cells incorporated larger number of CDots resulting in their much brighter images. These nanoparticles are distributed in cell cytoplasm, however, when the cells are fixed and treated with detergent, their nucleus is also labeled. Flow cytometry allows distinguishing the sub-populations of living and apoptotic cells in their cultures and suggests a very cheap and easy way to characterize them. PMID:26589358

  14. Radiosensitizing effect of gold nanoparticles in carbon ion irradiation of human cervical cancer cells

    NASA Astrophysics Data System (ADS)

    Kaur, Harminder; Avasthi, D. K.; Pujari, Geetanjali; Sarma, Asitikantha

    2013-07-01

    Noble metal nanoparticles have received considerable attention in biotechnology for their role in bio sensing due to surface plasmon resonance, medical diagnostics due to better imaging contrast and therapy. The radiosensitization effect of gold nanoparticles (AuNP) has been gaining popularity in radiation therapy of cancer cells. The better depth dose profile of energetic ion beam proves its superiority over gamma radiation for fighting against cancer. In the present work, the glucose capped gold nanoparticles (Glu-AuNP) were synthesised and internalized in the HeLa cells. Transmission electron microscopic analysis of ultrathin sections of Glu-AuNP treated HeLa cells confirmed the internalization of Glu-AuNPs. Control HeLa cells and Glu-AuNp treated HeLa cells were irradiated at different doses of 62 MeV 12C ion beam (LET - 290keV/?m) at BIO beam line of using 15UD Pelletron accelerator at Inter University Accelerator Centre, New Delhi, India. The survival fraction was assessed by colony forming assay which revealed that the dose of carbon ion for 90% cell killing in Glu-AuNP treated HeLa cells and control HeLa cells are 2.3 and 3.2 Gy respectively. This observation shows ˜ 28% reduction of 12C6+ ion dose for Glu-AuNP treated HeLa cells as compared to control HeLa cells.

  15. Silica nanoparticle-based dual imaging colloidal hybrids: cancer cell imaging and biodistribution

    PubMed Central

    Lee, Haisung; Sung, Dongkyung; Kim, Jinhoon; Kim, Byung-Tae; Wang, Tuntun; An, Seong Soo A; Seo, Soo-Won; Yi, Dong Kee

    2015-01-01

    In this study, fluorescent dye-conjugated magnetic resonance (MR) imaging agents were investigated in T mode. Gadolinium-conjugated silica nanoparticles were successfully synthesized for both MR imaging and fluorescence diagnostics. Polyamine and polycarboxyl functional groups were modified chemically on the surface of the silica nanoparticles for efficient conjugation of gadolinium ions. The derived gadolinium-conjugated silica nanoparticles were investigated by zeta potential analysis, transmission electron microscopy, inductively coupled plasma mass spectrometry, and energy dispersive x-ray spectroscopy. MR equipment was used to investigate their use as contrast-enhancing agents in T1 mode under a 9.4 T magnetic field. In addition, we tracked the distribution of the gadolinium-conjugated nanoparticles in both lung cancer cells and organs in mice. PMID:26357472

  16. Velocity valleys enable efficient capture and spatial sorting of nanoparticle-bound cancer cells

    NASA Astrophysics Data System (ADS)

    Besant, Justin D.; Mohamadi, Reza M.; Aldridge, Peter M.; Li, Yi; Sargent, Edward H.; Kelley, Shana O.

    2015-03-01

    The development of strategies for isolating rare cells from complex matrices like blood is important for a wide variety of applications including the analysis of bloodborne cancer cells, infectious pathogens, and prenatal testing. Due to their high colloidal stability and surface-to-volume ratio, antibody-coated magnetic nanoparticles are excellent labels for cellular surface markers. Unfortunately, capture of nanoparticle-bound cells at practical flow rates is challenging due to the small volume, and thus low magnetic susceptibility, of magnetic nanoparticles. We have developed a means to capture nanoparticle-labeled cells using microstructures which create pockets of locally low linear velocity, termed velocity valleys. Cells that enter a velocity valley slow down momentarily, allowing the magnetic f