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Dynamic magnetic fields remote-control apoptosis via nanoparticle rotation.

作者信息

Zhang Enming, Kircher Moritz F, Koch Martin, Eliasson Lena, Goldberg S Nahum, Renström Erik

机构信息

Department of Clinical Sciences Malmö, Lund University , Malmö 205 02, Sweden.

出版信息

ACS Nano. 2014 Apr 22;8(4):3192-201. doi: 10.1021/nn406302j. Epub 2014 Mar 20.


DOI:10.1021/nn406302j
PMID:24597847
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4004315/
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.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0938/4004315/300f257b7160/nn-2013-06302j_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0938/4004315/99766458018a/nn-2013-06302j_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0938/4004315/73d1f87554f4/nn-2013-06302j_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0938/4004315/d0e7c975b723/nn-2013-06302j_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0938/4004315/fd7c5040ea4d/nn-2013-06302j_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0938/4004315/f116658f5c09/nn-2013-06302j_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0938/4004315/703854007900/nn-2013-06302j_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0938/4004315/300f257b7160/nn-2013-06302j_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0938/4004315/99766458018a/nn-2013-06302j_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0938/4004315/73d1f87554f4/nn-2013-06302j_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0938/4004315/d0e7c975b723/nn-2013-06302j_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0938/4004315/fd7c5040ea4d/nn-2013-06302j_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0938/4004315/f116658f5c09/nn-2013-06302j_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0938/4004315/703854007900/nn-2013-06302j_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0938/4004315/300f257b7160/nn-2013-06302j_0007.jpg

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本文引用的文献

[1]
Magnetic fluid hyperthermia: advances, challenges, and opportunity.

Int J Hyperthermia. 2013-10-9

[2]
Lysosomal membrane permeabilization by targeted magnetic nanoparticles in alternating magnetic fields.

ACS Nano. 2013-5-24

[3]
Magnetic nanoparticle-mediated massively parallel mechanical modulation of single-cell behavior.

Nat Methods. 2012-10-14

[4]
A magnetic switch for the control of cell death signalling in in vitro and in vivo systems.

Nat Mater. 2012-10-7

[5]
M13-templated magnetic nanoparticles for targeted in vivo imaging of prostate cancer.

Nat Nanotechnol. 2012-9-16

[6]
Superparamagnetic iron oxide nanoparticles: magnetic nanoplatforms as drug carriers.

Int J Nanomedicine. 2012-7-6

[7]
Molecular body imaging: MR imaging, CT, and US. Part II. Applications.

Radiology. 2012-8

[8]
Photothermal microscopy of the core of dextran-coated iron oxide nanoparticles during cell uptake.

ACS Nano. 2012-6-7

[9]
Molecular body imaging: MR imaging, CT, and US. part I. principles.

Radiology. 2012-6

[10]
Development of multifunctional hyaluronan-coated nanoparticles for imaging and drug delivery to cancer cells.

Biomacromolecules. 2012-3-13

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