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Sci Rep. 2017 Aug 21;7(1):8423. doi: 10.1038/s41598-017-09312-z.

Analyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled penetrance of biological membranes.

Author information

1
Department of Cell Biology, Biozentrum, University of Basel, Basel, Switzerland. ilkka.paatero@utu.fi.
2
Turku Centre for Biotechnology, Åbo Akademi University and University of Turku, FI-20520, Turku, Finland. ilkka.paatero@utu.fi.
3
Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, FI-20520, Turku, Finland.
4
Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, FI-20520, Turku, Finland.
5
Turku Centre for Biotechnology, Åbo Akademi University and University of Turku, FI-20520, Turku, Finland.
6
Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, FI-20520, Turku, Finland. cecilia.sahlgren@abo.fi.
7
Turku Centre for Biotechnology, Åbo Akademi University and University of Turku, FI-20520, Turku, Finland. cecilia.sahlgren@abo.fi.
8
Department of Biomedical Engineering, Technical University of Eindhoven, 5613 DR, Eindhoven, The Netherlands. cecilia.sahlgren@abo.fi.
9
Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands. cecilia.sahlgren@abo.fi.

Abstract

Mesoporous silica nanoparticles (MSNs) are extensively explored as drug delivery systems, but in depth understanding of design-toxicity relationships is still scarce. We used zebrafish (Danio rerio) embryos to study toxicity profiles of differently surface functionalized MSNs. Embryos with the chorion membrane intact, or dechoroniated embryos, were incubated or microinjected with amino (NH2-MSNs), polyethyleneimine (PEI-MSNs), succinic acid (SUCC-MSNs) or polyethyleneglycol (PEG-MSNs) functionalized MSNs. Toxicity was assessed by viability and cardiovascular function. NH2-MSNs, SUCC-MSNs and PEG-MSNs were well tolerated, 50 µg/ml PEI-MSNs induced 100% lethality 48 hours post fertilization (hpf). Dechoroniated embryos were more sensitive and 10 µg/ml PEI-MSNs reduced viability to 5% at 96hpf. Sensitivity to PEG- and SUCC-, but not NH2-MSNs, was also enhanced. Typically cardiovascular toxicity was evident prior to lethality. Confocal microscopy revealed that PEI-MSNs penetrated into the embryos whereas PEG-, NH2- and SUCC-MSNs remained aggregated on the skin surface. Direct exposure of inner organs by microinjecting NH2-MSNs and PEI-MSNs demonstrated that the particles displayed similar toxicity indicating that functionalization affects the toxicity profile by influencing penetrance through biological barriers. The data emphasize the need for careful analyses of toxicity mechanisms in relevant models and constitute an important knowledge step towards the development of safer and sustainable nanotherapies.

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