Application of magnetic field hyperthermia and superparamagnetic iron oxide nanoparticles to HIV-1-specific T-cell cytotoxicity

James P Williams,1 Paul Southern,2 Anya Lissina,3 Helen C Christian,4 Andrew K Sewell,3 Rodney Phillips,1,5,6 Quentin Pankhurst,2 John Frater1,5,6 1Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, UK; 2Davy-Faraday Research Laboratory, Royal Institution of Great Britain, Lo...

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Autores principales:	Williams JP, Southern P, Lissina A, Christian HC, Sewell AK, Phillips R, Pankhurst Q, Frater J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/df6d81087b224836b1405ba50716a5c0
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spelling	oai:doaj.org-article:df6d81087b224836b1405ba50716a5c02021-12-02T07:21:25ZApplication of magnetic field hyperthermia and superparamagnetic iron oxide nanoparticles to HIV-1-specific T-cell cytotoxicity1176-91141178-2013https://doaj.org/article/df6d81087b224836b1405ba50716a5c02013-07-01T00:00:00Zhttp://www.dovepress.com/application-of-magnetic-field-hyperthermia-and-superparamagnetic-iron--a13742https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013James P Williams,1 Paul Southern,2 Anya Lissina,3 Helen C Christian,4 Andrew K Sewell,3 Rodney Phillips,1,5,6 Quentin Pankhurst,2 John Frater1,5,6 1Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, UK; 2Davy-Faraday Research Laboratory, Royal Institution of Great Britain, London, UK; 3Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK; 4Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK; 5James Martin 21st Century School, John Radcliffe Hospital, Oxford, UK; 6Oxford NIHR Biomedical Research Centre, Oxford, UK Abstract: The latent HIV-1 reservoir remains the major barrier to HIV-1 eradication. Although successful at limiting HIV replication, highly active antiretroviral therapy is unable to cure HIV infection, thus novel therapeutic strategies are needed to eliminate the virus. Magnetic field hyperthermia (MFH) generates thermoablative cytotoxic temperatures in target-cell populations, and has delivered promising outcomes in animal models, as well as in several cancer clinical trials. MFH has been proposed as a strategy to improve the killing of HIV-infected cells and for targeting the HIV latent reservoirs. We wished to determine whether MFH could be used to enhance cytotoxic T-lymphocyte (CTL) targeting of HIV-infected cells in a proof-of-concept study. Here, for the first time, we apply MFH to an infectious disease (HIV-1) using the superparamagnetic iron oxide nanoparticle FeraSpin R. We attempt to improve the cytotoxic potential of T-cell receptor-transfected HIV-specific CTLs using thermotherapy, and assess superparamagnetic iron oxide nanoparticle toxicity, uptake, and effect on cell function using more sensitive methods than previously described. FeraSpin R exhibited only limited toxicity, demonstrated efficient uptake and cell-surface attachment, and only modestly impacted T-cell function. In contrast to the cancer models, insufficient MFH was generated to enhance CTL killing of HIV-infected cells. MFH remains an exciting new technology in the field of cancer therapeutics, which, as technology improves, may have significant potential to enhance CTL function and act as an adjunctive therapy in the eradication of latently infected HIV-positive cells. Keywords: nanoparticles, HIV-1, thermotherapy, cytotoxic T-cellWilliams JPSouthern PLissina AChristian HCSewell AKPhillips RPankhurst QFrater JDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 2543-2554 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Williams JP Southern P Lissina A Christian HC Sewell AK Phillips R Pankhurst Q Frater J Application of magnetic field hyperthermia and superparamagnetic iron oxide nanoparticles to HIV-1-specific T-cell cytotoxicity
description	James P Williams,1 Paul Southern,2 Anya Lissina,3 Helen C Christian,4 Andrew K Sewell,3 Rodney Phillips,1,5,6 Quentin Pankhurst,2 John Frater1,5,6 1Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, UK; 2Davy-Faraday Research Laboratory, Royal Institution of Great Britain, London, UK; 3Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK; 4Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK; 5James Martin 21st Century School, John Radcliffe Hospital, Oxford, UK; 6Oxford NIHR Biomedical Research Centre, Oxford, UK Abstract: The latent HIV-1 reservoir remains the major barrier to HIV-1 eradication. Although successful at limiting HIV replication, highly active antiretroviral therapy is unable to cure HIV infection, thus novel therapeutic strategies are needed to eliminate the virus. Magnetic field hyperthermia (MFH) generates thermoablative cytotoxic temperatures in target-cell populations, and has delivered promising outcomes in animal models, as well as in several cancer clinical trials. MFH has been proposed as a strategy to improve the killing of HIV-infected cells and for targeting the HIV latent reservoirs. We wished to determine whether MFH could be used to enhance cytotoxic T-lymphocyte (CTL) targeting of HIV-infected cells in a proof-of-concept study. Here, for the first time, we apply MFH to an infectious disease (HIV-1) using the superparamagnetic iron oxide nanoparticle FeraSpin R. We attempt to improve the cytotoxic potential of T-cell receptor-transfected HIV-specific CTLs using thermotherapy, and assess superparamagnetic iron oxide nanoparticle toxicity, uptake, and effect on cell function using more sensitive methods than previously described. FeraSpin R exhibited only limited toxicity, demonstrated efficient uptake and cell-surface attachment, and only modestly impacted T-cell function. In contrast to the cancer models, insufficient MFH was generated to enhance CTL killing of HIV-infected cells. MFH remains an exciting new technology in the field of cancer therapeutics, which, as technology improves, may have significant potential to enhance CTL function and act as an adjunctive therapy in the eradication of latently infected HIV-positive cells. Keywords: nanoparticles, HIV-1, thermotherapy, cytotoxic T-cell
format	article
author	Williams JP Southern P Lissina A Christian HC Sewell AK Phillips R Pankhurst Q Frater J
author_facet	Williams JP Southern P Lissina A Christian HC Sewell AK Phillips R Pankhurst Q Frater J
author_sort	Williams JP
title	Application of magnetic field hyperthermia and superparamagnetic iron oxide nanoparticles to HIV-1-specific T-cell cytotoxicity
title_short	Application of magnetic field hyperthermia and superparamagnetic iron oxide nanoparticles to HIV-1-specific T-cell cytotoxicity
title_full	Application of magnetic field hyperthermia and superparamagnetic iron oxide nanoparticles to HIV-1-specific T-cell cytotoxicity
title_fullStr	Application of magnetic field hyperthermia and superparamagnetic iron oxide nanoparticles to HIV-1-specific T-cell cytotoxicity
title_full_unstemmed	Application of magnetic field hyperthermia and superparamagnetic iron oxide nanoparticles to HIV-1-specific T-cell cytotoxicity
title_sort	application of magnetic field hyperthermia and superparamagnetic iron oxide nanoparticles to hiv-1-specific t-cell cytotoxicity
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/df6d81087b224836b1405ba50716a5c0
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Application of magnetic field hyperthermia and superparamagnetic iron oxide nanoparticles to HIV-1-specific T-cell cytotoxicity

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