Mechanochemical Stimulation of MCF7 Cells with Rod-Shaped Fe-Au Janus Particles Induces Cell Death through Paradoxical Hyperactivation of ERK

Title: Mechanochemical Stimulation of MCF7 Cells with Rod-Shaped Fe-Au Janus Particles Induces Cell Death through Paradoxical Hyperactivation of ERK
Authors: Kilinc, DevrimLesniak, AnnaRashdan, Suad AhmedGandhi, DhruvBlasiak, AgataFannin, Paul C.Kriegsheim, Alexander vonKolch, WalterLee, Gil U.
Permanent link: http://hdl.handle.net/10197/7553
Date: 18-Feb-2015
Online since: 2016-04-08T09:15:35Z
Abstract: 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.
Funding Details: Science Foundation Ireland
Funding Details: Nanoremedies Programme
Programme for Research in Third-Level Institutions
European Regional Development Fund
Erasmus Mundus Gulf Countries Postdoctoral Fellowship
Marie Curie Intra-European Fellowship
Type of material: Journal Article
Publisher: Wiley
Journal: Advanced Healthcare Materials
Volume: 4
Issue: 3
Start page: 395
End page: 404
Copyright (published version): 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Keywords: Active targetingCancerErbB receptorsHeregulinMagnetic hyperthermia
DOI: 10.1002/adhm.201400391
Language: en
Status of Item: Peer reviewed
This item is made available under a Creative Commons License: https://creativecommons.org/licenses/by-nc-nd/3.0/ie/
Appears in Collections:Conway Institute Research Collection
SBI Research Collection
Medicine Research Collection
Chemistry Research Collection

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