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Dynamic Magnetic Fields Remote-Control Apoptosis via Nanoparticle Rotation

[Image: see text] The ability to control the movement of nanoparticles remotely and with high precision would have far-reaching implications in many areas of nanotechnology. We have designed a unique dynamic magnetic field (DMF) generator that can induce rotational movements of superparamagnetic iro...

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Autores principales: Zhang, Enming, Kircher, Moritz F., Koch, Martin, Eliasson, Lena, Goldberg, S. Nahum, Renström, Erik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004315/
https://www.ncbi.nlm.nih.gov/pubmed/24597847
http://dx.doi.org/10.1021/nn406302j
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author Zhang, Enming
Kircher, Moritz F.
Koch, Martin
Eliasson, Lena
Goldberg, S. Nahum
Renström, Erik
author_facet Zhang, Enming
Kircher, Moritz F.
Koch, Martin
Eliasson, Lena
Goldberg, S. Nahum
Renström, Erik
author_sort Zhang, Enming
collection PubMed
description [Image: see text] The ability to control the movement of nanoparticles remotely and with high precision would have far-reaching implications in many areas of nanotechnology. We have designed a unique dynamic magnetic field (DMF) generator that can induce rotational movements of superparamagnetic iron oxide nanoparticles (SPIONs). We examined whether the rotational nanoparticle movement could be used for remote induction of cell death by injuring lysosomal membrane structures. We further hypothesized that the shear forces created by the generation of oscillatory torques (incomplete rotation) of SPIONs bound to lysosomal membranes would cause membrane permeabilization, lead to extravasation of lysosomal contents into the cytoplasm, and induce apoptosis. To this end, we covalently conjugated SPIONs with antibodies targeting the lysosomal protein marker LAMP1 (LAMP1-SPION). Remote activation of slow rotation of LAMP1-SPIONs significantly improved the efficacy of cellular internalization of the nanoparticles. LAMP1-SPIONs then preferentially accumulated along the membrane in lysosomes in both rat insulinoma tumor cells and human pancreatic beta cells due to binding of LAMP1-SPIONs to endogenous LAMP1. Further activation of torques by the LAMP1-SPIONs bound to lysosomes resulted in rapid decrease in size and number of lysosomes, attributable to tearing of the lysosomal membrane by the shear force of the rotationally activated LAMP1-SPIONs. This remote activation resulted in an increased expression of early and late apoptotic markers and impaired cell growth. Our findings suggest that DMF treatment of lysosome-targeted nanoparticles offers a noninvasive tool to induce apoptosis remotely and could serve as an important platform technology for a wide range of biomedical applications.
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spelling pubmed-40043152015-03-05 Dynamic Magnetic Fields Remote-Control Apoptosis via Nanoparticle Rotation Zhang, Enming Kircher, Moritz F. Koch, Martin Eliasson, Lena Goldberg, S. Nahum Renström, Erik ACS Nano [Image: see text] The ability to control the movement of nanoparticles remotely and with high precision would have far-reaching implications in many areas of nanotechnology. We have designed a unique dynamic magnetic field (DMF) generator that can induce rotational movements of superparamagnetic iron oxide nanoparticles (SPIONs). We examined whether the rotational nanoparticle movement could be used for remote induction of cell death by injuring lysosomal membrane structures. We further hypothesized that the shear forces created by the generation of oscillatory torques (incomplete rotation) of SPIONs bound to lysosomal membranes would cause membrane permeabilization, lead to extravasation of lysosomal contents into the cytoplasm, and induce apoptosis. To this end, we covalently conjugated SPIONs with antibodies targeting the lysosomal protein marker LAMP1 (LAMP1-SPION). Remote activation of slow rotation of LAMP1-SPIONs significantly improved the efficacy of cellular internalization of the nanoparticles. LAMP1-SPIONs then preferentially accumulated along the membrane in lysosomes in both rat insulinoma tumor cells and human pancreatic beta cells due to binding of LAMP1-SPIONs to endogenous LAMP1. Further activation of torques by the LAMP1-SPIONs bound to lysosomes resulted in rapid decrease in size and number of lysosomes, attributable to tearing of the lysosomal membrane by the shear force of the rotationally activated LAMP1-SPIONs. This remote activation resulted in an increased expression of early and late apoptotic markers and impaired cell growth. Our findings suggest that DMF treatment of lysosome-targeted nanoparticles offers a noninvasive tool to induce apoptosis remotely and could serve as an important platform technology for a wide range of biomedical applications. American Chemical Society 2014-03-05 2014-04-22 /pmc/articles/PMC4004315/ /pubmed/24597847 http://dx.doi.org/10.1021/nn406302j Text en Copyright © 2014 American Chemical Society
spellingShingle Zhang, Enming
Kircher, Moritz F.
Koch, Martin
Eliasson, Lena
Goldberg, S. Nahum
Renström, Erik
Dynamic Magnetic Fields Remote-Control Apoptosis via Nanoparticle Rotation
title Dynamic Magnetic Fields Remote-Control Apoptosis via Nanoparticle Rotation
title_full Dynamic Magnetic Fields Remote-Control Apoptosis via Nanoparticle Rotation
title_fullStr Dynamic Magnetic Fields Remote-Control Apoptosis via Nanoparticle Rotation
title_full_unstemmed Dynamic Magnetic Fields Remote-Control Apoptosis via Nanoparticle Rotation
title_short Dynamic Magnetic Fields Remote-Control Apoptosis via Nanoparticle Rotation
title_sort dynamic magnetic fields remote-control apoptosis via nanoparticle rotation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004315/
https://www.ncbi.nlm.nih.gov/pubmed/24597847
http://dx.doi.org/10.1021/nn406302j
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