Potential of magnetic hyperthermia to stimulate localized immune activation
Potential of magnetic hyperthermia to stimulate localized immune activation
Magnetic hyperthermia (MH) harnesses the heat-releasing properties of superparamagnetic iron oxide nanoparticles (SPIONs) and has potential to stimulate immune activation in the tumor microenvironment whilst sparing surrounding normal tissues. To assess feasibility of localized MH in vivo, SPIONs are injected intratumorally and their fate tracked by Zirconium-89-positron emission tomography, histological analysis, and electron microscopy. Experiments show that an average of 49% (21–87%, n = 9) of SPIONs are retained within the tumor or immediately surrounding tissue. In situ heating is subsequently generated by exposure to an externally applied alternating magnetic field and monitored by thermal imaging. Tissue response to hyperthermia, measured by immunohistochemical image analysis, reveals specific and localized heat-shock protein expression following treatment. Tumor growth inhibition is also observed. To evaluate the potential effects of MH on the immune landscape, flow cytometry is used to characterize immune cells from excised tumors and draining lymph nodes. Results show an influx of activated cytotoxic T cells, alongside an increase in proliferating regulatory T cells, following treatment. Complementary changes are found in draining lymph nodes. In conclusion, results indicate that biologically reactive MH is achievable in vivo and can generate localized changes consistent with an anti-tumor immune response.
biological response, heat-shock protein 70, immune stimulation, magnetic hyperthermia, superparamagnetic iron oxide nanoparticles
e2005241
Carter, Thomas J.
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Agliardi, Giulia
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Lin, Fang Yu
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Ellis, Matthew
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Jones, Clare
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Robson, Mathew
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Richard-Londt, Angela
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Southern, Paul
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Lythgoe, Mark
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Zaw Thin, May
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Ryzhov, Vyacheslav
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de Rosales, Rafael T.M.
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Gruettner, Cordula
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Abdollah, Maha R.A.
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Pedley, R. Barbara
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Pankhurst, Quentin A.
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Kalber, Tammy L.
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Brandner, Sebastian
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Quezada, Sergio
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Mulholland, Paul
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Shevtsov, Maxim
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Chester, Kerry
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8 April 2021
Carter, Thomas J.
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Agliardi, Giulia
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Lin, Fang Yu
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Ellis, Matthew
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Jones, Clare
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Robson, Mathew
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Richard-Londt, Angela
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Southern, Paul
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Lythgoe, Mark
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Zaw Thin, May
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Ryzhov, Vyacheslav
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de Rosales, Rafael T.M.
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Gruettner, Cordula
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Abdollah, Maha R.A.
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Pedley, R. Barbara
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Pankhurst, Quentin A.
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Kalber, Tammy L.
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Brandner, Sebastian
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Quezada, Sergio
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Mulholland, Paul
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Shevtsov, Maxim
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Chester, Kerry
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Carter, Thomas J., Agliardi, Giulia, Lin, Fang Yu, Ellis, Matthew, Jones, Clare, Robson, Mathew, Richard-Londt, Angela, Southern, Paul, Lythgoe, Mark, Zaw Thin, May, Ryzhov, Vyacheslav, de Rosales, Rafael T.M., Gruettner, Cordula, Abdollah, Maha R.A., Pedley, R. Barbara, Pankhurst, Quentin A., Kalber, Tammy L., Brandner, Sebastian, Quezada, Sergio, Mulholland, Paul, Shevtsov, Maxim and Chester, Kerry
(2021)
Potential of magnetic hyperthermia to stimulate localized immune activation.
Small, 17 (14), , [2005241].
(doi:10.1002/smll.202005241).
Abstract
Magnetic hyperthermia (MH) harnesses the heat-releasing properties of superparamagnetic iron oxide nanoparticles (SPIONs) and has potential to stimulate immune activation in the tumor microenvironment whilst sparing surrounding normal tissues. To assess feasibility of localized MH in vivo, SPIONs are injected intratumorally and their fate tracked by Zirconium-89-positron emission tomography, histological analysis, and electron microscopy. Experiments show that an average of 49% (21–87%, n = 9) of SPIONs are retained within the tumor or immediately surrounding tissue. In situ heating is subsequently generated by exposure to an externally applied alternating magnetic field and monitored by thermal imaging. Tissue response to hyperthermia, measured by immunohistochemical image analysis, reveals specific and localized heat-shock protein expression following treatment. Tumor growth inhibition is also observed. To evaluate the potential effects of MH on the immune landscape, flow cytometry is used to characterize immune cells from excised tumors and draining lymph nodes. Results show an influx of activated cytotoxic T cells, alongside an increase in proliferating regulatory T cells, following treatment. Complementary changes are found in draining lymph nodes. In conclusion, results indicate that biologically reactive MH is achievable in vivo and can generate localized changes consistent with an anti-tumor immune response.
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smll.202005241
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Accepted/In Press date: 20 January 2021
e-pub ahead of print date: 18 March 2021
Published date: 8 April 2021
Additional Information:
Funding Information:
The authors would like to thank micromod GmbH (Rostock, Germany) for providing perimag SPIONs. The authors acknowledge financial support from the EU Framework 7 Programme DARTRIX project contract no. 234870; the King's College London and UCL Comprehensive Cancer Imaging Centre funded by the CRUK and EPSRC in association with the MRC and DoH (England); British Council Institutional Links grant (ID: 277386067) under the Russia-UK partnership; King's Health Partners (KHP) Research and Development Challenge Fund award (R160402); The Centre of Excellence in Medical Engineering funded by the Wellcome Trust and EPSRC under Grant No. WT 088641/Z/09/Z; Russian Foundation for Basic Research 19-08-00024, Department of Health via the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas? NHS Foundation Trust and King's College London; EPSRC Early Cancer Fellowship (EP/L006472/1); Celia Abrahams and the Mothers and Daughters Committee; the National Brain Appeal, Cancer Research UK (CR-UK); Department of Health (ECMC, Experimental Cancer Medicine Network Centre); NIHR University College London Hospitals Biomedical Research Centre (SB) and Cancer Research UK Accelerator Grant (Cl 15121 A 20256) (ME) EPSRC Programme Grants EP/S032789/1 and EP/R045046/1 (RMTR). The views expressed are those of the authors and not necessarily those of the NHS, NIHR, or the Department of Health. Thanks to Kerrie Venner (UCL ION) for her assistance in producing TEM images and also to Tia Kulanthaivadivel (UCL Cancer Institute) for her helpful contribution to generation of Figure?1.
Publisher Copyright:
© 2021 The Authors. Small published by Wiley-VCH GmbH
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
Keywords:
biological response, heat-shock protein 70, immune stimulation, magnetic hyperthermia, superparamagnetic iron oxide nanoparticles
Identifiers
Local EPrints ID: 450373
URI: http://eprints.soton.ac.uk/id/eprint/450373
ISSN: 1613-6810
PURE UUID: 1e89d655-d31b-4069-ae57-1f29feccbd39
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Date deposited: 26 Jul 2021 16:31
Last modified: 17 Mar 2024 12:46
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Contributors
Author:
Thomas J. Carter
Author:
Giulia Agliardi
Author:
Fang Yu Lin
Author:
Matthew Ellis
Author:
Clare Jones
Author:
Mathew Robson
Author:
Angela Richard-Londt
Author:
Paul Southern
Author:
Mark Lythgoe
Author:
May Zaw Thin
Author:
Vyacheslav Ryzhov
Author:
Rafael T.M. de Rosales
Author:
Cordula Gruettner
Author:
Maha R.A. Abdollah
Author:
R. Barbara Pedley
Author:
Quentin A. Pankhurst
Author:
Tammy L. Kalber
Author:
Sebastian Brandner
Author:
Sergio Quezada
Author:
Paul Mulholland
Author:
Maxim Shevtsov
Author:
Kerry Chester
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