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.

Keywords:

• actin cytoskeleton
• cell elasticity
• AFM
• ion channels
• patch clamp
• TEVC

Supplementary materials

Figure S1 Patch clamp measurement of an MM6 cell.

Notes: Shown is the current against the time. Each measuring cycle takes 13 seconds to complete and generates 17 points.

Figure S2 Patch clamp measurement of an MM6 cell with addition of TEA in different concentrations to block voltage-gated potassium channels.

Notes: Shown is the current against the time. Each measuring cycle takes 13 seconds to complete and generates 17 points.

Abbreviation: TEA, tetraethylammonium.

Figure S3 Example currents of Kv channels with their corresponding pulse protocol.

Notes: Two-electrode voltage clamp example currents of (A) Kv1.3 and (C) Kv7.1 with the (B and D) corresponding pulse protocols.

Figure S4 Example curve for the atomic force microscopy measurements of a primary monocyte.

Note: The curve approaching the cell is indicated in red, and the one retracting from the cell in blue.

Acknowledgments

This work was financially supported by the German Ministry of Science and Education in context of the research projects MINAC (0315773A) and BioTraP for CCC (13N11390). The authors thank Judith Schmidt and Kathrin Hardes for perfect technical assistance.

Disclosure

The authors report no conflicts of interest in this work.