Now showing 1 - 5 of 5
  • Publication
    Mechanochemical Stimulation of MCF7 Cells with Rod-Shaped Fe-Au Janus Particles Induces Cell Death through Paradoxical Hyperactivation of ERK
    Multifunctional nanoparticles that actively target-specific tissues are studied for cancer diagnosis and treatment. Magnetically and optically active particles are of particular interest because they enable multiple imaging modalities and physically modulated therapies, such as magnetic hyperthermia. Fe–Au nanorods are synthesized that have a long iron segment, coated with polyethylene glycol, and a short gold tip functionalized with heregulin (HRG), a known ligand of ErbB family of receptors. HRG–nanorods preferentially target MCF7 cells relative to MDA-MB-231 cells, as demonstrated in a novel microfluidics device. Targeting rates of these classical breast cancer cells correlate with their differential expression of ErbB2/3 receptors. HRG–nanorod binding stimulates the extracellular signal-regulated kinase 1/2 (ERK) phosphorylation in MCF7 cells. The increase in ERK phosphorylation is linked to 'active zones,' dynamic regions in the cell periphery, which exhibit higher rates of particle binding than the rest of the cell. Periodically stretching cells using magnetic tweezers further activates ERK, which leads to cell death in cells co-treated with B-Raf inhibitors, through ERK hyperactivation. Although to a lesser extent, cell death is also achieved through magnetic hyperthermia. These results demonstrate nanoscale targeting and localized mechanochemical treatment of specific cancer cell lines based on their receptor expression using multifunctional nanoparticles.
      622Scopus© Citations 25
  • Publication
    Effects of the Presence or Absence of a Protein Corona on Silica Nanoparticle Uptake and Impact on Cells
    Nanoparticles enter cells through active processes, thanks to their capability of interacting with the cellular machinery. The protein layer (corona) that forms on their surface once nanoparticles are in contact with biological fluids, such as the cell serum, mediates the interactions with cells in situ. As a consequence of this, here we show that the same nanomaterial can lead to very different biological outcomes, when exposed to cells in the presence or absence of a preformed corona. In particular, silica nanoparticles exposed to cells in the absence of serum have a stronger adhesion to the cell membrane and higher internalization efficiency, in comparison to what is observed in medium containing serum, when a preformed corona is present on their surface. The different exposure conditions not only affect the uptake levels but also result in differences in the intracellular nanoparticle location and impact on cells. Interestingly, we also show that after only one hour of exposure, a corona of very different nature forms on the nanoparticles exposed to cells in the absence of serum. Evidence suggests that these different outcomes can all be connected to the different adhesion and surface properties in the two conditions.
      2302Scopus© Citations 827
  • Publication
    In vitro study of the interaction of heregulin-functionalized magnetic-optical nanorods with MCF7 and MDA-MB- 231 cells
    Multifunctional nanoparticles that actively target specific cells are promising tools for cancer diagnosis and therapy. In this article we review the synthesis and surface chemistry of Fe–Au nanorods and their characterization using microscopy. The diameter of the rods used in this study was selected to be 150–200 nm so that they did not enter the cells. The 80 nm-long Au tips of the nanorods were functionalized with heregulin (HRG), and the micron-long Fe portion was coated with a poly(ethylene glycol) monolayer to minimize non-specific interactions. Nanorods functionalized with HRG were found to preferentially bind to MCF7 cells that express high levels of the receptor tyrosine-protein kinase ErbB2/3. Magnetic tweezers measurements were used to characterize the kinetic properties of the bond between the HRG on the rods and ErbB2/3 on the surface of the cells. The strong magnetization of Fe–Au nanorods makes them excellent candidates for in-vitro and in-vivo imaging, and magnetic therapeutic applications targeting cancer cells in circulation.
      525Scopus© Citations 1
  • Publication
    Atmospheric ammonia and nitrogen deposition on Irish Natura 2000 sites: Implications for Irish agriculture
    With growing global demand for food, the agriculture sector worldwide is under pressure to intensify and expand, risking acceleration of existing negative biodiversity impacts. Agriculture is the dominant source of ammonia (NH3) emissions, which can impact biodiversity directly through dry deposition as NH3 and by wet deposition following conversion to ammonium (NH4) in the atmosphere. Nitrogen deposition is one of the leading causes of global decline in biodiversity alongside changing land use and climate. Natura 2000 sites which are intended to protect important habitats and species across Europe, require strict levels of protection to ensure designated features achieve favourable conservation status. Many of these sites are nitrogen-limited, and/or contain sensitive species such as lichens or mosses. This project carried out ambient NH3 monitoring on selected Irish Natura 2000 sites, in order to establish potential impacts from agricultural NH3. Monitoring on twelve Natura 2000 sites observed concentrations ranging from 0.47 to 4.59 μg NH3 m−3, from which dry deposition was calculated to be 1.22–11.92 kg N ha−1 yr−1. European Monitoring and Evaluation Programme (EMEP) was used to quantify wet deposited NH4 and nitrogen oxides (NOx), in addition to dry deposited NOx on monitored sites. Estimated total nitrogen deposition ranged between 5.93 and 17.78 kg N ha−1 yr−1. On average across all monitored sites, deposition was comprised of 50.4%, 31.7%, 7.5%, and 10.3% dry NH3, wet NH4, dry NOx and wet NOx respectively. Implications for Irish agriculture are discussed in the light of both this monitoring and the European Commission Dutch Nitrogen Case (C 293/17 & C 294/17), highlighting a number of recommendations to aid compliance with the EU Habitats Directive (92/43/EEC).
      163Scopus© Citations 4
  • Publication
    Nanoparticle Adhesion to the Cell Membrane and Its effect on Nanoparticle Uptake Efficiency
    The interactions between nanosized particles and living systems are commonly mediated by what adsorbs to the nanoparticle in the biological environment, its biomolecular corona, rather than the pristine surface. Here, we characterize the adhesion toward the cell membrane of nanoparticles of different material and size and study how this is modulated by the presence or absence of a corona on the nanoparticle surface. The results are corroborated with adsorption to simple model supported lipid bilayers using a quartz crystal microbalance. We conclude that the adsorption of proteins on the nanoparticle surface strongly reduces nanoparticle adhesion in comparison to what is observed for the bare material. Nanoparticle uptake is described as a two-step process, where the nanoparticles initially adhere to the cell membrane and subsequently are internalized by the cells via energy-dependent pathways. The lowered adhesion in the presence of proteins thereby causes a concomitant decrease in nanoparticle uptake efficiency. The presence of a biomolecular corona may confer specific interactions between the nanoparticle-corona complex and the cell surface including triggering of regulated cell uptake. An important effect of the corona is, however, a reduction in the purely unspecific interactions between the bare material and the cell membrane, which in itself disregarding specific interactions, causes a decrease in cellular uptake. We suggest that future nanoparticle-cell studies include, together with characterization of size, charge, and dispersion stability, an evaluation of the adhesion properties of the material to relevant membranes.
      1591Scopus© Citations 570