Lesniak, Anna

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Lesniak, Anna
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Lesniak, Anna

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  • Publication
    Mechanochemical Stimulation of MCF7 Cells with Rod-Shaped Fe-Au Janus Particles Induces Cell Death through Paradoxical Hyperactivation of ERK
    (Wiley, 2015-02-18)
    Kilinc, Devrim 
    ;
    Lesniak, Anna 
    ;
    Rashdan, Suad Ahmed 
    ;
    Gandhi, Dhruv 
    ;
    Blasiak, Agata 
    ;
    Fannin, Paul C. 
    ;
    Kriegsheim, Alexander von 
    ;
    Kolch, Walter 
    ;
    Lee, Gil U. 
    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.
      803Scopus© Citations 28
  • Publication
    In vitro study of the interaction of heregulin-functionalized magnetic-optical nanorods with MCF7 and MDA-MB- 231 cells
    (Royal Society of Chemistry, 2014-09)
    Lesniak, Anna 
    ;
    Kilinc, Devrim 
    ;
    Rashdan, Suad Ahmed 
    ;
    Kriegsheim, Alexander von 
    ;
    Ashall, B. 
    ;
    Zerulla, Dominic 
    ;
    Kolch, Walter 
    ;
    Lee, Gil U. 
    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.
      652Scopus© Citations 2