Functionalization Of T Lymphocytes With Citrate-Coated Superparamagnetic Iron Oxide Nanoparticles For Magnetically Controlled Immune Therapy

Marina Mühlberger,1,2 Christina Janko,1 Harald Unterweger,1 Ralf P Friedrich,1 Bernhard Friedrich,1 Julia Band,1 Nadine Cebulla,1 Christoph Alexiou,1 Diana Dudziak,3 Geoffrey Lee,2 Rainer Tietze1 1Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and...

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Autores principales:	Mühlberger M, Janko C, Unterweger H, Friedrich RP, Friedrich B, Band J, Cebulla N, Alexiou C, Dudziak D, Lee G, Tietze R
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	magnetic targeting biocompatibility immunoaffinitychromatography cold tumor T cell Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/428db3a9be0a4be890463a6e0cfee0af
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spelling	oai:doaj.org-article:428db3a9be0a4be890463a6e0cfee0af2021-12-02T11:38:20ZFunctionalization Of T Lymphocytes With Citrate-Coated Superparamagnetic Iron Oxide Nanoparticles For Magnetically Controlled Immune Therapy1178-2013https://doaj.org/article/428db3a9be0a4be890463a6e0cfee0af2019-10-01T00:00:00Zhttps://www.dovepress.com/functionalization-of-t-lymphocytes-with-citrate-coated-superparamagnet-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Marina Mühlberger,1,2 Christina Janko,1 Harald Unterweger,1 Ralf P Friedrich,1 Bernhard Friedrich,1 Julia Band,1 Nadine Cebulla,1 Christoph Alexiou,1 Diana Dudziak,3 Geoffrey Lee,2 Rainer Tietze1 1Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, Universitätsklinikum Erlangen, Erlangen, Germany; 2Department of Chemistry and Pharmacy, Division of Pharmaceutics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; 3Department of Dermatology, Laboratory of Dendritic Cell Biology, Universitätsklinikum Erlangen, Erlangen, GermanyCorrespondence: Rainer TietzeSection of Experimental Oncology and Nanomedicine, ENT Department, Universitätsklinikum Erlangen, Glückstr. 10a, Erlangen 91054, GermanyTel +49 9131 8533142Fax +49 9131 8534828Email rainer.tietze@uk-erlangen.dePurpose: Immune activation with T cell tumor infiltration is beneficial for the prognosis of patients suffering from solid cancer. Depending on their immune status, solid tumors can be immunologically classified into three groups: “hot” tumors are infiltrated with T lymphocytes, “cold” tumors are not infiltrated and “immune excluded” tumors are only infiltrated in the peripheral tumor tissue. Checkpoint inhibitors provide new therapeutic options for “hot” tumors by triggering the immune response of T cells. In order to enable this for cold tumors as well, T cells must be enriched in the tumor. Therefore, we use the principle of magnetic targeting to guide T cells loaded with citrate-coated superparamagnetic iron oxide nanoparticles (SPIONCitrate) to the tumor by an externally applied magnetic field.Methods: SPIONCitrate were produced by alkaline coprecipitation of iron(II) and iron(III) chloride and in situ coating with sodium citrate. The concentration-dependent cytocompatibility of the particles was determined by flow cytometry and blood stability assays. Atomic emission spectroscopy was used for the quantification of the particle uptake into T lymphocytes. The attractability of the loaded cells was observed by live-cell imaging in the presence of an externally applied magnetic field.Results: SPIONCitrate displayed good cytocompatibility to T cells and did not show any sign of aggregation in blood. Finally, SPIONCitrate-loaded T cells were strongly attracted by a small external magnet.Conclusion: T cells can be “magnetized” by incorporation of SPIONCitrate for magnetic targeting. The production of the particle-cell hybrid system is straightforward, as the loading process only requires basic laboratory devices and the loading efficiency is sufficient for cells being magnetically controllable. For these reasons, SPIONCitrate are potential suitable candidates for magnetic T cell targeting.Keywords: magnetic targeting, biocompatibility, immunoaffinity chromatography, cold tumor, T cellMühlberger MJanko CUnterweger HFriedrich RPFriedrich BBand JCebulla NAlexiou CDudziak DLee GTietze RDove Medical Pressarticlemagnetic targetingbiocompatibilityimmunoaffinitychromatographycold tumorT cellMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 8421-8432 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	magnetic targeting biocompatibility immunoaffinitychromatography cold tumor T cell Medicine (General) R5-920
spellingShingle	magnetic targeting biocompatibility immunoaffinitychromatography cold tumor T cell Medicine (General) R5-920 Mühlberger M Janko C Unterweger H Friedrich RP Friedrich B Band J Cebulla N Alexiou C Dudziak D Lee G Tietze R Functionalization Of T Lymphocytes With Citrate-Coated Superparamagnetic Iron Oxide Nanoparticles For Magnetically Controlled Immune Therapy
description	Marina Mühlberger,1,2 Christina Janko,1 Harald Unterweger,1 Ralf P Friedrich,1 Bernhard Friedrich,1 Julia Band,1 Nadine Cebulla,1 Christoph Alexiou,1 Diana Dudziak,3 Geoffrey Lee,2 Rainer Tietze1 1Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, Universitätsklinikum Erlangen, Erlangen, Germany; 2Department of Chemistry and Pharmacy, Division of Pharmaceutics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; 3Department of Dermatology, Laboratory of Dendritic Cell Biology, Universitätsklinikum Erlangen, Erlangen, GermanyCorrespondence: Rainer TietzeSection of Experimental Oncology and Nanomedicine, ENT Department, Universitätsklinikum Erlangen, Glückstr. 10a, Erlangen 91054, GermanyTel +49 9131 8533142Fax +49 9131 8534828Email rainer.tietze@uk-erlangen.dePurpose: Immune activation with T cell tumor infiltration is beneficial for the prognosis of patients suffering from solid cancer. Depending on their immune status, solid tumors can be immunologically classified into three groups: “hot” tumors are infiltrated with T lymphocytes, “cold” tumors are not infiltrated and “immune excluded” tumors are only infiltrated in the peripheral tumor tissue. Checkpoint inhibitors provide new therapeutic options for “hot” tumors by triggering the immune response of T cells. In order to enable this for cold tumors as well, T cells must be enriched in the tumor. Therefore, we use the principle of magnetic targeting to guide T cells loaded with citrate-coated superparamagnetic iron oxide nanoparticles (SPIONCitrate) to the tumor by an externally applied magnetic field.Methods: SPIONCitrate were produced by alkaline coprecipitation of iron(II) and iron(III) chloride and in situ coating with sodium citrate. The concentration-dependent cytocompatibility of the particles was determined by flow cytometry and blood stability assays. Atomic emission spectroscopy was used for the quantification of the particle uptake into T lymphocytes. The attractability of the loaded cells was observed by live-cell imaging in the presence of an externally applied magnetic field.Results: SPIONCitrate displayed good cytocompatibility to T cells and did not show any sign of aggregation in blood. Finally, SPIONCitrate-loaded T cells were strongly attracted by a small external magnet.Conclusion: T cells can be “magnetized” by incorporation of SPIONCitrate for magnetic targeting. The production of the particle-cell hybrid system is straightforward, as the loading process only requires basic laboratory devices and the loading efficiency is sufficient for cells being magnetically controllable. For these reasons, SPIONCitrate are potential suitable candidates for magnetic T cell targeting.Keywords: magnetic targeting, biocompatibility, immunoaffinity chromatography, cold tumor, T cell
format	article
author	Mühlberger M Janko C Unterweger H Friedrich RP Friedrich B Band J Cebulla N Alexiou C Dudziak D Lee G Tietze R
author_facet	Mühlberger M Janko C Unterweger H Friedrich RP Friedrich B Band J Cebulla N Alexiou C Dudziak D Lee G Tietze R
author_sort	Mühlberger M
title	Functionalization Of T Lymphocytes With Citrate-Coated Superparamagnetic Iron Oxide Nanoparticles For Magnetically Controlled Immune Therapy
title_short	Functionalization Of T Lymphocytes With Citrate-Coated Superparamagnetic Iron Oxide Nanoparticles For Magnetically Controlled Immune Therapy
title_full	Functionalization Of T Lymphocytes With Citrate-Coated Superparamagnetic Iron Oxide Nanoparticles For Magnetically Controlled Immune Therapy
title_fullStr	Functionalization Of T Lymphocytes With Citrate-Coated Superparamagnetic Iron Oxide Nanoparticles For Magnetically Controlled Immune Therapy
title_full_unstemmed	Functionalization Of T Lymphocytes With Citrate-Coated Superparamagnetic Iron Oxide Nanoparticles For Magnetically Controlled Immune Therapy
title_sort	functionalization of t lymphocytes with citrate-coated superparamagnetic iron oxide nanoparticles for magnetically controlled immune therapy
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/428db3a9be0a4be890463a6e0cfee0af
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Functionalization Of T Lymphocytes With Citrate-Coated Superparamagnetic Iron Oxide Nanoparticles For Magnetically Controlled Immune Therapy

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