Cytotoxicity of Poly(Alkyl Cyanoacrylate) Nanoparticles

Einar Sulheim; Tore-Geir Iversen; Vu To Nakstad; Geir Klinkenberg; Håvard Sletta; Ruth Schmid; Anne Rein Hatletveit; Ane Marit Wågbø; Anders Sundan; Tore Skotland; Kirsten Sandvig; Ýrr Mørch

doi:10.3390/ijms18112454

Cytotoxicity of Poly(Alkyl Cyanoacrylate) Nanoparticles

Int J Mol Sci. 2017 Nov 18;18(11):2454. doi: 10.3390/ijms18112454.

Authors

Einar Sulheim^{1

2}, Tore-Geir Iversen^{3

4}, Vu To Nakstad⁵, Geir Klinkenberg⁶, Håvard Sletta⁷, Ruth Schmid⁸, Anne Rein Hatletveit⁹, Ane Marit Wågbø¹⁰, Anders Sundan¹¹, Tore Skotland^{12

13}, Kirsten Sandvig^{14

15

16}, Ýrr Mørch¹⁷

Affiliations

¹ SINTEF Materials and Chemistry, Sem Sælands vei 2A, 7034 Trondheim, Norway. einar.sulheim@ntnu.no.
² Department of Physics, Norwegian University of Science and Technology, Høgskoleringen 5, 7491 Trondheim, Norway. einar.sulheim@ntnu.no.
³ Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, 0379 Oslo, Norway. Tore-Geir.Iversen@rr-research.no.
⁴ Center for Cancer Biomedicine, Faculty of Medicine, University of Oslo, 0379 Oslo, Norway. Tore-Geir.Iversen@rr-research.no.
⁵ SINTEF Materials and Chemistry, Sem Sælands vei 2A, 7034 Trondheim, Norway. vu.nakstad@sintef.no.
⁶ SINTEF Materials and Chemistry, Sem Sælands vei 2A, 7034 Trondheim, Norway. geir.klinkenberg@sintef.no.
⁷ SINTEF Materials and Chemistry, Sem Sælands vei 2A, 7034 Trondheim, Norway. havard.sletta@sintef.no.
⁸ SINTEF Materials and Chemistry, Sem Sælands vei 2A, 7034 Trondheim, Norway. ruth.b.schmid@sintef.no.
⁹ SINTEF Materials and Chemistry, Sem Sælands vei 2A, 7034 Trondheim, Norway. annerein.hatletveit@sintef.no.
¹⁰ SINTEF Materials and Chemistry, Sem Sælands vei 2A, 7034 Trondheim, Norway. ane.marit.wagbo@sintef.no.
¹¹ Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 8905 MH, 7491 Trondheim, Norway. anders.sundan@ntnu.no.
¹² Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, 0379 Oslo, Norway. tore.skotland@rr-research.no.
¹³ Center for Cancer Biomedicine, Faculty of Medicine, University of Oslo, 0379 Oslo, Norway. tore.skotland@rr-research.no.
¹⁴ Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, 0379 Oslo, Norway. kirsten.sandvig@ibv.uio.no.
¹⁵ Center for Cancer Biomedicine, Faculty of Medicine, University of Oslo, 0379 Oslo, Norway. kirsten.sandvig@ibv.uio.no.
¹⁶ Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, 0316 Oslo, Norway. kirsten.sandvig@ibv.uio.no.
¹⁷ SINTEF Materials and Chemistry, Sem Sælands vei 2A, 7034 Trondheim, Norway. yrr.morch@sintef.no.

Abstract

Although nanotoxicology has become a large research field, assessment of cytotoxicity is often reduced to analysis of one cell line only. Cytotoxicity of nanoparticles is complex and should, preferentially, be evaluated in several cell lines with different methods and on multiple nanoparticle batches. Here we report the toxicity of poly(alkyl cyanoacrylate) nanoparticles in 12 different cell lines after synthesizing and analyzing 19 different nanoparticle batches and report that large variations were obtained when using different cell lines or various toxicity assays. Surprisingly, we found that nanoparticles with intermediate degradation rates were less toxic than particles that were degraded faster or more slowly in a cell-free system. The toxicity did not vary significantly with either the three different combinations of polyethylene glycol surfactants or with particle size (range 100-200 nm). No acute pro- or anti-inflammatory activity on cells in whole blood was observed.

Keywords: PACA; cytotoxicity; high-throughput screening; nanoparticles; nanotoxicology.

MeSH terms

Animals
Cell Line
Cell Survival / drug effects
Chemistry, Pharmaceutical
Cyanoacrylates / chemistry
Cyanoacrylates / toxicity*
Female
Hep G2 Cells
Humans
Male
Nanoparticles / chemistry
Nanoparticles / toxicity*
Particle Size
Polyethylene Glycols
Surface-Active Agents

Substances

Cyanoacrylates
Surface-Active Agents
Polyethylene Glycols