Comparison of cellular effects of starch-coated SPIONs and poly(lactic-co-glycolic acid) matrix nanoparticles on human monocytes

Dominik Gonnissen,1 Ying Qu,1,2 Klaus Langer,3 Cengiz Öztürk,4 Yuliang Zhao,2 Chunying Chen,2 Guiscard Seebohm,5 Martina Düfer,6 Harald Fuchs,1 Hans-Joachim Galla,7 Kristina Riehemann11Center for Nanotechnology, Institute of Physics, University of Münster, Münster, Germany; 2National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, People’s Republic of China; 3Institute of Pharmaceutical Technology and Biopharmacy, University of Münster, Münster, 4chemicell GmbH, Berlin, 5Department of Cardiovascular Medicine, Institute for Genetics of Heart Diseases, University Hospital Münster, 6Department of Pharmacology, Institute of Pharmaceutical and Medicinal Chemistry, 7Department of Cell Biology/Biophysics, Institute of Biochemistry, University of Münster, Münster, GermanyAbstract: 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. Keywords: actin cytoskeleton, cell elasticity, AFM, ion channels, patch clamp, TEV