title: Comparison of cellular effects of starch-coated SPIONs and poly(lactic-co-glycolic acid) matrix nanoparticles on human monocytes.
abstract: Within the last years, progress has been made in the knowledge of the properties of medically used nanoparticles and their toxic effects, but still, little is known about their influence on cellular processes of immune cells. The aim of our comparative study was to present the influence of two different nanoparticle types on subcellular processes of primary monocytes and the leukemic monocyte cell line MM6. We used core-shell starch-coated superparamagnetic iron oxide nanoparticles (SPIONs) and matrix poly(lactic-co-glycolic acid) (PLGA) nanoparticles for our experiments. In addition to typical biocompatibility testing like the detection of necrosis or secretion of interleukins (ILs), we investigated the impact of these nanoparticles on the actin cytoskeleton and the two voltage-gated potassium channels Kv1.3 and Kv7.1. Induction of necrosis was not seen for PLGA nanoparticles and SPIONs in primary monocytes and MM6 cells. Likewise, no alteration in secretion of IL-1β and IL-10 was detected under the same experimental conditions. In contrast, IL-6 secretion was exclusively downregulated in primary monocytes after contact with both nanoparticles. Two-electrode voltage clamp experiments revealed that both nanoparticles reduce currents of the aforementioned potassium channels. The two nanoparticles differed significantly in their impact on the actin cytoskeleton, demonstrated via atomic force microscopy elasticity measurement and phalloidin staining. While SPIONs led to the disruption of the respective cytoskeleton, PLGA did not show any influence in both experimental setups. The difference in the effects on ion channels and the actin cytoskeleton suggests that nanoparticles affect these subcellular components via different pathways. Our data indicate that the alteration of the cytoskeleton and the effect on ion channels are new parameters that describe the influence of nanoparticles on cells. The results are highly relevant for medical application and further evaluation of nanomaterial biosafety.
authors: Center for Nanotechnology, Institute of Physics, University of Münster, Münster, Germany.
authors: Dominik
authors: D
authors: Gonnissen
authors: Center for Nanotechnology, Institute of Physics, University of Münster, Münster, Germany; National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors: Ying
authors: Y
authors: Qu
authors: Institute of Pharmaceutical Technology and Biopharmacy, University of Münster, Münster.
authors: Klaus
authors: K
authors: Langer
authors: chemicell GmbH, Berlin.
authors: Cengiz
authors: C
authors: Öztürk
authors: National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors: Yuliang
authors: Y
authors: Zhao
authors: National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors: Chunying
authors: C
authors: Chen
authors: Department of Cardiovascular Medicine, Institute for Genetics of Heart Diseases, University Hospital Münster.
authors: Guiscard
authors: G
authors: Seebohm
authors: Department of Pharmacology, Institute of Pharmaceutical and Medicinal Chemistry.
authors: Martina
authors: M
authors: Düfer
authors: Center for Nanotechnology, Institute of Physics, University of Münster, Münster, Germany.
authors: Harald
authors: H
authors: Fuchs
authors: Department of Cell Biology/Biophysics, Institute of Biochemistry, University of Münster, Münster, Germany.
authors: Hans-Joachim
authors: HJ
authors: Galla
authors: Center for Nanotechnology, Institute of Physics, University of Münster, Münster, Germany.
authors: Kristina
authors: K
authors: Riehemann
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005290:Ferric Compounds / Q000737:chemistry*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013213:Starch / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D005290:Ferric Compounds; D015850:Interleukin-6; C000499:ferric oxide; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D013213:Starch
keywords: AFM; TEVC; actin cytoskeleton; cell elasticity; ion channels; patch clamp