International Journal of Nanomedicine (Oct 2019)
Functionalization Of T Lymphocytes With Citrate-Coated Superparamagnetic Iron Oxide Nanoparticles For Magnetically Controlled Immune Therapy
Abstract
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 [email protected]: 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
