Mechanochemical Stimulation of MCF7 Cells with Rod‐Shaped Fe–Au Janus Particles Induces Cell Death Through Paradoxical Hyperactivation of ERK

Kilinc, Devrim; Leśniak, Anna; Rashdan, Suad; Gandhi, Dhruv; Blasiak, Agata; Fannin, P.C.; Kriegsheim, Alex von; Kölch, Walter; G, Lee

doi:10.1002/adhm.201400391

Cited by 27 publications

(57 citation statements)

References 54 publications

(73 reference statements)

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“…[9] Mechanics plays important roles in numerous physiological and pathological processes and is particularly important for cancer, since metastatic cancer accounts for over 90% of cancer-related deaths and forces acting on cells can modulate the metastatic process. [10] Metastasizing cells detach from the primary tumor, migrate through the extracellular matrix, enter the vasculature by squeezing through the endothelial cells, adhere to the endothelial cells, and exit the vasculature once again by penetrating the endothelium to eventually form a secondary tumor.…”

Section: Introductionmentioning

confidence: 99%

“…[13] An alternative approach would be to use mechanical stimulation to selectively kill tumors and circulating tumor cells. This could be achieved either through damaging the target cell’s membrane or its intracellular structures, [9c] or through activating select mechanotransduction pathways to induce cell death. [9b] …”

Section: Introductionmentioning

confidence: 99%

“…This could be achieved either through damaging the target cell’s membrane or its intracellular structures, [9c] or through activating select mechanotransduction pathways to induce cell death. [9b] …”

Section: Introductionmentioning

confidence: 99%

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Bio‐Nano‐Magnetic Materials for Localized Mechanochemical Stimulation of Cell Growth and Death

Kilinc

Dennis

2016

Advanced Materials

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Magnetic nanoparticles are promising new tools for therapeutic applications, such as magnetic nanoparticle hyperthermia therapy and targeted drug delivery. Recent in vitro studies have demonstrated that a force application with magnetic tweezers can also affect cell fate, suggesting a therapeutic potential for magnetically modulated mechanical stimulation. The magnetic properties of nanoparticles that induce physical responses and the subtle responses that result from mechanically induced membrane damage and/or intracellular signaling are evaluated. Magnetic particles with various physical, geometric, and magnetic properties and specific functionalization can now be used to apply mechanical force to specific regions of cells, which permit the modulation of cellular behavior through the use of spatially and time controlled magnetic fields. On one hand, mechanochemical stimulation has been used to direct the outgrowth on neuronal growth cones, indicating a therapeutic potential for neural repair. On the other hand, it has been used to kill cancer cells that preferentially express specific receptors. Advances made in the synthesis and characterization of magnetic nanomaterials and a better understanding of cellular mechanotransduction mechanisms may support the translation of mechanochemical stimulation into the clinic as an emerging therapeutic approach.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bio‐Nano‐Magnetic Materials for Localized Mechanochemical Stimulation of Cell Growth and Death

Kilinc

Dennis

2016

Advanced Materials

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“…35 In the second approach, peptides with randomly mixed amino acid sequences are used to show decreased binding efficiency of nanoparticles. 36 40 The increase in ERK phosphorylation was associated to the existence of "active zones," i.e., dynamic regions in the cell periphery, exhibiting higher rates of nanoparticle binding compared to the rest of the cell, suggesting, therefore, a localized receptor activation.…”

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confidence: 99%

“…40 The authors showed that nanoparticle size between 40-50 nm is critical to be internalized via receptor- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 15 inside the cells by laser confocal scanning microscopy in scattering (reflective) mode, as reported by Rotello et al 41 Also, larger anisotropic gold nanoparticles can be detected in living cells and followed in their intracellular dynamics. 42 In our study, we applied this technique to investigate the internalization kinetics of NPY-conjugated AuNCs into PC3 cells.…”

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Theranostic Nanocages for Imaging and Photothermal Therapy of Prostate Cancer Cells by Active Targeting of Neuropeptide-Y Receptor

Avvakumova¹,

Galbiati²,

Sironi³

et al. 2016

Bioconjugate Chem.

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Gold nanocages (AuNCs) have been shown to be a useful tool for harnessing imaging and hyperthermia therapy of cancer, thanks to their unique optical properties, low toxicity and facile surface functionalization. Herein, we use AuNCs for selective targeting of prostate cancer cells (PC3) via specific interaction between neuropeptide Y (NPY) receptor and three different NPY analogs conjugated to AuNCs. Localized surface plasmon band of the nanoconjugates was set around 800 nm, which is appropriate for in vivo applications. Long-term stability of nanoconjugates in different media was confirmed by UV-vis and DLS studies. Active NPY receptor targeting was observed by confocal microscopy showing time-dependent AuNCs cellular uptake. Activation of ERK1/2 pathway was evaluated by Western blot to confirm the receptor-mediated specific interaction with PC3. Cellular uptake kinetics were compared as a function of peptide structure. Cytotoxicity of nanoconjugates was evaluated by MTS and Annexin V assays, confirming their safety within the concentration range explored.Hyperthermia studies were carried out irradiating the cells, previously incubated with AuNCs, with a pulsed laser at 800 nm wavelength, showing a heating enhancement ranging from 6 to 35 °C above the culture temperature dependent on the irradiation power (between 1.6 and 12.7 W/cm2). Only cells treated with AuNCs underwent morphological alterations in the cytoskeleton structure upon laser irradiation, leading to membrane blebbing and loss of microvilli associated to cell migration. This effect is promising in view of possible inhibition of proliferation and invasion of cancer cells. In summary, our Au-peptide NCs proved to be an efficient theranostic nanosystem for targeted detection and activatable killing of prostate cancer cells.

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Core–Shell Gold Nanorod@Metal–Organic Framework Nanoprobes for Multimodality Diagnosis of Glioma

et al. 2016

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One of the most significant challenges in the diagnosis of brain cancer is efficient in vivo imaging using nontoxic nanoprobes. Core-shell gold nanorod@MIL-88(Fe) nanostars are successfully constructed as triple-modality imaging (computed tomography/magnetic-resonance imaging/photoacoustic imaging) nanoprobes that show low cytotoxicity, high contrast, high penetration depth, and high spatial resolution for accurate and noninvasive imaging and diagnosis of gliomas.

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Mechanochemical Stimulation of MCF7 Cells with Rod‐Shaped Fe–Au Janus Particles Induces Cell Death Through Paradoxical Hyperactivation of ERK

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

Cited by 27 publications

References 54 publications

Bio‐Nano‐Magnetic Materials for Localized Mechanochemical Stimulation of Cell Growth and Death

Bio‐Nano‐Magnetic Materials for Localized Mechanochemical Stimulation of Cell Growth and Death

Theranostic Nanocages for Imaging and Photothermal Therapy of Prostate Cancer Cells by Active Targeting of Neuropeptide-Y Receptor

Core–Shell Gold Nanorod@Metal–Organic Framework Nanoprobes for Multimodality Diagnosis of Glioma

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