{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T19:45:32Z","timestamp":1785181532135,"version":"3.55.0"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,13]],"date-time":"2021-03-13T00:00:00Z","timestamp":1615593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ELAN funding of the Medical Faculty of the Universit\u00e4tsklinikum Erlangen","award":["18-03-07-1-Balk"],"award-info":[{"award-number":["18-03-07-1-Balk"]}]},{"name":"Manfred-Roth-Stiftung, F\u00fcrth, Germany","award":["-"],"award-info":[{"award-number":["-"]}]},{"name":"Forschungsstiftung Medizin at the University hospital Erlangen, Germany","award":["-"],"award-info":[{"award-number":["-"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG) and Friedrich-Alexander-Universit\u00e4t Erlan-gen-N\u00fcrnberg (FAU) within the funding program of Open Access Publishing","award":["-"],"award-info":[{"award-number":["-"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Superparamagnetic iron oxide nanoparticles (SPIONs) feature distinct magnetic properties that make them useful and effective tools for various diagnostic, therapeutic and theranostic applications. In particular, their use in magnetic drug targeting (MDT) promises to be an effective approach for the treatment of various diseases such as cancer. At the cellular level, SPION uptake, along with SPION-mediated toxicity, represents the most important prerequisite for successful application. Thus, the present study determines SPION uptake, toxicity and biocompatibility in human head and neck tumor cell lines of the tongue, pharynx and salivary gland. Using magnetic susceptibility measurements, microscopy, atomic emission spectroscopy, flow cytometry, and plasma coagulation, we analyzed the magnetic properties, cellular uptake and biocompatibility of two different SPION types in the presence and absence of external magnetic fields. Incubation of cells with lauric acid and human serum albumin-coated nanoparticles (SPIONLA-HSA) resulted in substantial particle uptake with low cytotoxicity. In contrast, uptake of lauric acid-coated nanoparticles (SPIONLA) was substantially increased but accompanied by higher toxicity. The presence of an external magnetic field significantly increased cellular uptake of both particles, although cytotoxicity was not significantly increased in any of the cell lines. SPIONs coated with lauric acid and\/or human serum albumin show different patterns of uptake and toxicity in response to an external magnetic field. Consequently, the results indicate the potential use of SPIONs as vehicles for MDT in head and neck cancer.<\/jats:p>","DOI":"10.3390\/nano11030726","type":"journal-article","created":{"date-parts":[[2021,3,14]],"date-time":"2021-03-14T23:52:06Z","timestamp":1615765926000},"page":"726","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Cellular SPION Uptake and Toxicity in Various Head and Neck Cancer Cell Lines"],"prefix":"10.3390","volume":"11","author":[{"given":"Matthias","family":"Balk","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kr\u00f6ner-Fresenius-Stiftung Professorship, Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Haus","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kr\u00f6ner-Fresenius-Stiftung Professorship, Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"},{"name":"Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Band","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kr\u00f6ner-Fresenius-Stiftung Professorship, Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Unterweger","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kr\u00f6ner-Fresenius-Stiftung Professorship, Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eveline","family":"Schreiber","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kr\u00f6ner-Fresenius-Stiftung Professorship, Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf P.","family":"Friedrich","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kr\u00f6ner-Fresenius-Stiftung Professorship, Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Alexiou","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kr\u00f6ner-Fresenius-Stiftung Professorship, Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9448-1882","authenticated-orcid":false,"given":"Antoniu-Oreste","family":"Gostian","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kr\u00f6ner-Fresenius-Stiftung Professorship, Universit\u00e4tsklinikum Erlangen, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/s41419-019-1769-9","article-title":"Clinical update on head and neck cancer: Molecular biology and ongoing challenges","volume":"10","author":"Alsahafi","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1093\/jnci\/djk179","article-title":"Alcohol drinking in never users of tobacco, cigarette smoking in never drinkers, and the risk of head and neck cancer: Pooled analysis in the International Head and Neck Cancer Epidemiology Consortium","volume":"99","author":"Hashibe","year":"2007","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1056\/NEJMra1715715","article-title":"Head and Neck Cancer","volume":"382","author":"Chow","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.drup.2018.09.001","article-title":"Precision medicine in head and neck cancer","volume":"40","author":"Gil","year":"2018","journal-title":"Drug Resist. Updat."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1016\/S0140-6736(19)32591-7","article-title":"Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): A randomised, open-label, phase 3 study","volume":"394","author":"Burtness","year":"2019","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1056\/NEJMoa1602252","article-title":"Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck","volume":"375","author":"Ferris","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.radonc.2009.04.014","article-title":"Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients","volume":"92","author":"Pignon","year":"2009","journal-title":"Radiother. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"967826","DOI":"10.1155\/2014\/967826","article-title":"Pathophysiology of cisplatin-induced acute kidney injury","volume":"2014","author":"Ozkok","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"E2151","DOI":"10.1002\/hed.24026","article-title":"Cumulative cisplatin dose in concurrent chemoradiotherapy for head and neck cancer: A systematic review","volume":"38","author":"Strojan","year":"2016","journal-title":"Head Neck"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"149","DOI":"10.2174\/1871526517666170606102623","article-title":"Targeted Drug Delivery Systems and Their Therapeutic Applications in Cancer and Immune Pathological Conditions","volume":"17","author":"Iqbal","year":"2017","journal-title":"Infect. Disord. Drug Targets"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1615\/CritRevTherDrugCarrierSyst.2017017845","article-title":"Recent Advances in Nanoparticle-Based Targeted Drug-Delivery Systems Against Cancer and Role of Tumor Microenvironment","volume":"34","author":"Ashfaq","year":"2017","journal-title":"Crit. Rev. Ther. Drug Carrier Syst."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5223","DOI":"10.2147\/IJN.S138108","article-title":"Non-immunogenic dextran-coated superparamagnetic iron oxide nanoparticles: A biocompatible, size-tunable contrast agent for magnetic resonance imaging","volume":"12","author":"Unterweger","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.2147\/IJN.S156528","article-title":"Dextran-coated superparamagnetic iron oxide nanoparticles for magnetic resonance imaging: Evaluation of size-dependent imaging properties, storage stability and safety","volume":"13","author":"Unterweger","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"204152","DOI":"10.1088\/0953-8984\/20\/20\/204152","article-title":"Microcomputed tomography analysis of ferrofluids used for cancer treatment","volume":"20","author":"Rahn","year":"2008","journal-title":"J. Phys. Condens. Matter"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2903","DOI":"10.1088\/0953-8984\/18\/38\/S25","article-title":"Determination of the magnetic particle distribution in tumour tissue by means of x-ray tomography","volume":"18","author":"Brunke","year":"2006","journal-title":"J. Phys. Condens. Matter"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jddst.2018.03.017","article-title":"Superparamagnetic iron oxide nanoparticles based cancer theranostics: A double edge sword to fight against cancer","volume":"45","author":"Ansari","year":"2018","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1080\/17425247.2019.1554647","article-title":"Magnetic iron oxide nanoparticles for drug delivery: Applications and characteristics","volume":"16","author":"Vangijzegem","year":"2019","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.bbrc.2015.08.022","article-title":"Magnetic nanoparticle-based drug delivery for cancer therapy","volume":"468","author":"Tietze","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3287","DOI":"10.2217\/nnm.15.159","article-title":"Nanomedical innovation: The SEON-concept for an improved cancer therapy with magnetic nanoparticles","volume":"10","author":"Lyer","year":"2015","journal-title":"Nanomedicine (Lond)"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.nano.2013.05.001","article-title":"Efficient drug-delivery using magnetic nanoparticles--biodistribution and therapeutic effects in tumour bearing rabbits","volume":"9","author":"Tietze","year":"2013","journal-title":"Nanomedicine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4847","DOI":"10.2147\/IJN.S68539","article-title":"Development of a lauric acid\/albumin hybrid iron oxide nanoparticle system with improved biocompatibility","volume":"9","author":"Zaloga","year":"2014","journal-title":"Int. J. Nanomed."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.ejpb.2016.01.017","article-title":"Pharmaceutical formulation of HSA hybrid coated iron oxide nanoparticles for magnetic drug targeting","volume":"101","author":"Zaloga","year":"2016","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"19291","DOI":"10.3390\/ijms160819291","article-title":"Tangential Flow Ultrafiltration Allows Purification and Concentration of Lauric Acid-\/Albumin-Coated Particles for Improved Magnetic Treatment","volume":"16","author":"Zaloga","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"336","DOI":"10.3109\/08916934.2012.755960","article-title":"Colourful death: Six-parameter classification of cell death by flow cytometry--dead cells tell tales","volume":"46","author":"Munoz","year":"2013","journal-title":"Autoimmunity"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4185","DOI":"10.2147\/IJN.S82714","article-title":"Flow cytometry for intracellular SPION quantification: Specificity and sensitivity in comparison with spectroscopic methods","volume":"10","author":"Friedrich","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"119","DOI":"10.2147\/NSA.S282204","article-title":"Intracellular Quantification and Localization of Label-Free Iron Oxide Nanoparticles by Holotomographic Microscopy","volume":"13","author":"Friedrich","year":"2020","journal-title":"Nanotechnol. Sci. Appl."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Le, T.A., Zhang, X., Hoshiar, A.K., and Yoon, J. (2017). Real-Time Two-Dimensional Magnetic Particle Imaging for Electromagnetic Navigation in Targeted Drug Delivery. Sensors, 17.","DOI":"10.3390\/s17092050"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"88","DOI":"10.21037\/qims.2017.02.09","article-title":"A comprehensive literatures update of clinical researches of superparamagnetic resonance iron oxide nanoparticles for magnetic resonance imaging","volume":"7","author":"Wang","year":"2017","journal-title":"Quant. Imaging Med. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"757","DOI":"10.2217\/rme.15.36","article-title":"Advanced cell therapies: Targeting, tracking and actuation of cells with magnetic particles","volume":"10","author":"Connell","year":"2015","journal-title":"Regen. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.bios.2014.11.036","article-title":"How does fluorescent labeling affect the binding kinetics of proteins with intact cells?","volume":"66","author":"Yin","year":"2015","journal-title":"Biosens. Bioelectron."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1177\/1091581816648906","article-title":"The MTT and Crystal Violet Assays: Potential Confounders in Nanoparticle Toxicity Testing","volume":"35","author":"Almutary","year":"2016","journal-title":"Int. J. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.fct.2015.06.012","article-title":"Flow cytometry evaluation of in vitro cellular necrosis and apoptosis induced by silver nanoparticles","volume":"85","author":"Kumar","year":"2015","journal-title":"Food Chem. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-62703-383-1_1","article-title":"Navigation to the graveyard-induction of various pathways of necrosis and their classification by flow cytometry","volume":"1004","author":"Janko","year":"2013","journal-title":"Methods Mol. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"451405","DOI":"10.1155\/2015\/451405","article-title":"Lipoamino Acid Coated Superparamagnetic Iron Oxide Nanoparticles Concentration and Time Dependently Enhanced Growth of Human Hepatocarcinoma Cell Line (Hep-G2)","volume":"2015","author":"Gholami","year":"2015","journal-title":"J. Nanomater."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.2147\/IJN.S132369","article-title":"Selection of potential iron oxide nanoparticles for breast cancer treatment based on in vitro cytotoxicity and cellular uptake","volume":"12","author":"Poller","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Nguyen, K., Nuss, B., Muhlberger, M., Unterweger, H., Friedrich, R.P., Alexiou, C., and Janko, C. (2020). Superparamagnetic Iron Oxide Nanoparticles Carrying Chemotherapeutics Improve Drug Efficacy in Monolayer and Spheroid Cell Culture by Enabling Active Accumulation. Nanomaterials (Basel), 10.","DOI":"10.3390\/nano10081577"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jconrel.2018.07.007","article-title":"Targeting of drug-loaded nanoparticles to tumor sites increases cell death and release of danger signals","volume":"285","author":"Alev","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5933","DOI":"10.2147\/IJN.S132162","article-title":"Establishment of a biophysical model to optimize endoscopic targeting of magnetic nanoparticles for cancer treatment","volume":"12","author":"Roeth","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s00418-011-0780-8","article-title":"Visualization of superparamagnetic nanoparticles in vascular tissue using XmuCT and histology","volume":"135","author":"Tietze","year":"2011","journal-title":"Histochem. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1166\/jbn.2012.1465","article-title":"Temperature-sensitive polymer-coated magnetic nanoparticles as a potential drug delivery system for targeted therapy of thyroid cancer","volume":"8","author":"Koppolu","year":"2012","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Rahman, M., Laurent, S., Tawil, N., Yahia, L.H., and Mahmoudi, M. (2013). Protein-Nanoparticle Interactions: The Bio-Nano Interface. Protein-Nanoparticle Interact., 21\u201344.","DOI":"10.1007\/978-3-642-37555-2_2"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/1743-8977-7-36","article-title":"ISDD: A computational model of particle sedimentation, diffusion and target cell dosimetry for in vitro toxicity studies","volume":"7","author":"Hinderliter","year":"2010","journal-title":"Part. Fibre Toxicol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/nnano.2011.58","article-title":"The effect of sedimentation and diffusion on cellular uptake of gold nanoparticles","volume":"6","author":"Cho","year":"2011","journal-title":"Nat. Nanotechnol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.colsurfb.2008.09.014","article-title":"Agglomeration and sedimentation of TiO2 nanoparticles in cell culture medium","volume":"68","author":"Allouni","year":"2009","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jcis.2015.01.056","article-title":"Measuring and modeling the magnetic settling of superparamagnetic nanoparticle dispersions","volume":"447","author":"Prigiobbe","year":"2015","journal-title":"J. Colloid Interface Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"18541","DOI":"10.1039\/C6NR06275J","article-title":"Field-induced self-assembly of iron oxide nanoparticles investigated using small-angle neutron scattering","volume":"8","author":"Fu","year":"2016","journal-title":"Nanoscale"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1021\/nn3057565","article-title":"Pulsed magnetic field improves the transport of iron oxide nanoparticles through cell barriers","volume":"7","author":"Min","year":"2013","journal-title":"ACS Nano"},{"key":"ref_48","first-page":"31","article-title":"The role of iron in cell cycle progression and the proliferation of neoplastic cells","volume":"1603","author":"Le","year":"2002","journal-title":"Biochim. Biophys. Acta"}],"container-title":["Nanomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4991\/11\/3\/726\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:35:22Z","timestamp":1760160922000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4991\/11\/3\/726"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,13]]},"references-count":48,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["nano11030726"],"URL":"https:\/\/doi.org\/10.3390\/nano11030726","relation":{},"ISSN":["2079-4991"],"issn-type":[{"value":"2079-4991","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,13]]}}}