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Dynamic Magnetic Fields Remote-Control Apoptosis via Nanoparticle Rotation.

Zhang, Enming LU ; Kircher, Moritz F; Koch, Martin; Eliasson, Lena LU ; Goldberg, S Nahum and Renström, Erik LU (2014) In ACS Nano 8(4). p.3192-3201
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
ACS Nano
volume
8
issue
4
pages
3192 - 3201
publisher
The American Chemical Society
external identifiers
  • pmid:24597847
  • wos:000334990600009
  • scopus:84899429310
ISSN
1936-086X
DOI
10.1021/nn406302j
language
English
LU publication?
yes
id
3c3633bb-3460-4297-b7cd-da477aaca813 (old id 4383849)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24597847?dopt=Abstract
date added to LUP
2014-04-02 19:01:39
date last changed
2017-10-22 03:01:33
@article{3c3633bb-3460-4297-b7cd-da477aaca813,
  abstract     = {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.},
  author       = {Zhang, Enming and Kircher, Moritz F and Koch, Martin and Eliasson, Lena and Goldberg, S Nahum and Renström, Erik},
  issn         = {1936-086X},
  language     = {eng},
  number       = {4},
  pages        = {3192--3201},
  publisher    = {The American Chemical Society},
  series       = {ACS Nano},
  title        = {Dynamic Magnetic Fields Remote-Control Apoptosis via Nanoparticle Rotation.},
  url          = {http://dx.doi.org/10.1021/nn406302j},
  volume       = {8},
  year         = {2014},
}