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  4. Hyperthermia treatment of tumors by mesenchymal stem cell-delivered superparamagnetic iron oxide nanoparticles.
 
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Hyperthermia treatment of tumors by mesenchymal stem cell-delivered superparamagnetic iron oxide nanoparticles.
File(s)
Hyperthermia treatment of tumors by mesenchymal stem cell-delivered superparamagnetic iron oxide nanoparticles.pdf (2.28 MB)
Published version
Author(s)
Kalber, TL
Ordidge, KL
Southern, P
Loebinger, MR
Kyrtatos, PG
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Type
Journal Article
Abstract
Magnetic hyperthermia - a potential cancer treatment in which superparamagnetic iron oxide nanoparticles (SPIONs) are made to resonantly respond to an alternating magnetic field (AMF) and thereby produce heat - is of significant current interest. We have previously shown that mesenchymal stem cells (MSCs) can be labeled with SPIONs with no effect on cell proliferation or survival and that within an hour of systemic administration, they migrate to and integrate into tumors in vivo. Here, we report on some longer term (up to 3 weeks) post-integration characteristics of magnetically labeled human MSCs in an immunocompromized mouse model. We initially assessed how the size and coating of SPIONs dictated the loading capacity and cellular heating of MSCs. Ferucarbotran(®) was the best of those tested, having the best like-for-like heating capability and being the only one to retain that capability after cell internalization. A mouse model was created by subcutaneous flank injection of a combination of 0.5 million Ferucarbotran-loaded MSCs and 1.0 million OVCAR-3 ovarian tumor cells. After 2 weeks, the tumors reached ~100 µL in volume and then entered a rapid growth phase over the third week to reach ~300 µL. In the control mice that received no AMF treatment, magnetic resonance imaging (MRI) data showed that the labeled MSCs were both incorporated into and retained within the tumors over the entire 3-week period. In the AMF-treated mice, heat increases of ~4°C were observed during the first application, after which MRI indicated a loss of negative contrast, suggesting that the MSCs had died and been cleared from the tumor. This post-AMF removal of cells was confirmed by histological examination and also by a reduced level of subsequent magnetic heating effect. Despite this evidence for an AMF-elicited response in the SPION-loaded MSCs, and in contrast to previous reports on tumor remission in immunocompetent mouse models, in this case, no significant differences were measured regarding the overall tumor size or growth characteristics. We discuss the implications of these results on the clinical delivery of hyperthermia therapy to tumors and on the possibility that a preferred therapeutic route may involve AMF as an adjuvant to an autologous immune response.
Date Issued
2016-05-09
Date Acceptance
2015-10-23
Citation
International Journal of Nanomedicine, 2016, 2016 (11), pp.1973-1983
URI
http://hdl.handle.net/10044/1/37536
DOI
https://www.dx.doi.org/10.2147/IJN.S94255
ISSN
1178-2013
Publisher
Dove Medical Press
Start Page
1973
End Page
1983
Journal / Book Title
International Journal of Nanomedicine
Volume
2016
Issue
11
Copyright Statement
This work is published by Dove Medical Press Limited, and licensed under a Creative Commons Attribution License. The full terms of the License are available at http://creativecommons.org/licenses/by/4.0/. The license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URL
http://creativecommons.org/licenses/by/4.0/
Identifier
PII: ijn-11-1973
Subjects
MRI
SPIONs
hyperthermia
mesenchymal stem cells
tumor therapy
Publication Status
Published
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