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Open AccessArticle

Loading of Primary Human T Lymphocytes with Citrate-Coated Superparamagnetic Iron Oxide Nanoparticles Does Not Impair Their Activation after Polyclonal Stimulation

1
Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, Universitätsklinikum Erlangen, 91054 Erlangen, Germany
2
Department of Chemistry and Pharmacy, Division of Pharmaceutics, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91058 Erlangen, Germany
3
Department of Dermatology, Laboratory of Dendritic Cell Biology, Universitätsklinikum Erlangen, 91052 Erlangen, Germany
4
Medical Immunology Campus Erlangen (MICE), Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany
*
Author to whom correspondence should be addressed.
Cells 2020, 9(2), 342; https://doi.org/10.3390/cells9020342
Received: 6 December 2019 / Revised: 14 January 2020 / Accepted: 28 January 2020 / Published: 1 February 2020
(This article belongs to the Special Issue The Interaction of Biomedical Nanoparticles with the Immune System)
For the conversion of immunologically cold tumors, characterized by a low T cell infiltration, into hot tumors, it is necessary to enrich T cells in the tumor area. One possibility is the use of magnetic fields to direct T cells into the tumor. For this purpose, primary T cells that were freshly isolated from human whole blood were loaded with citrate-coated superparamagnetic iron oxide nanoparticles (SPIONCitrate). Cell toxicity and particle uptake were investigated by flow cytometry and atomic emission spectroscopy. The optimum loading of the T cells without any major effect on their viability was achieved with a particle concentration of 75 µg Fe/mL and a loading period of 24 h. The cellular content of SPIONCitrate was sufficient to attract these T cells with a magnet which was monitored by live-cell imaging. The functionality of the T cells was only slightly influenced by SPIONCitrate, as demonstrated by in vitro stimulation assays. The proliferation rate as well as the expression of co-stimulatory and inhibitory surface molecules (programmed cell death 1 (PD-1), lymphocyte activation gene 3 (LAG-3), T cell immunoglobulin and mucin domain containing 3 (Tim-3), C-C motif chemokine receptor 7 (CCR7), CD25, CD45RO, CD69) was investigated and found to be unchanged. Our results presented here demonstrate the feasibility of loading primary human T lymphocytes with superparamagnetic iron oxide nanoparticles without influencing their viability and functionality while achieving sufficient magnetizability for magnetically controlled targeting. Thus, the results provide a strong fundament for the transfer to tumor models and ultimately for new immunotherapeutic approaches for cancer treatment. View Full-Text
Keywords: SPION; T cells; nanomedicine; cancer; solid tumor; magnetic targeting; T cell activation; immune therapy SPION; T cells; nanomedicine; cancer; solid tumor; magnetic targeting; T cell activation; immune therapy
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MDPI and ACS Style

Mühlberger, M.; Unterweger, H.; Band, J.; Lehmann, C.; Heger, L.; Dudziak, D.; Alexiou, C.; Lee, G.; Janko, C. Loading of Primary Human T Lymphocytes with Citrate-Coated Superparamagnetic Iron Oxide Nanoparticles Does Not Impair Their Activation after Polyclonal Stimulation. Cells 2020, 9, 342. https://doi.org/10.3390/cells9020342

AMA Style

Mühlberger M, Unterweger H, Band J, Lehmann C, Heger L, Dudziak D, Alexiou C, Lee G, Janko C. Loading of Primary Human T Lymphocytes with Citrate-Coated Superparamagnetic Iron Oxide Nanoparticles Does Not Impair Their Activation after Polyclonal Stimulation. Cells. 2020; 9(2):342. https://doi.org/10.3390/cells9020342

Chicago/Turabian Style

Mühlberger, Marina; Unterweger, Harald; Band, Julia; Lehmann, Christian; Heger, Lukas; Dudziak, Diana; Alexiou, Christoph; Lee, Geoffrey; Janko, Christina. 2020. "Loading of Primary Human T Lymphocytes with Citrate-Coated Superparamagnetic Iron Oxide Nanoparticles Does Not Impair Their Activation after Polyclonal Stimulation" Cells 9, no. 2: 342. https://doi.org/10.3390/cells9020342

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