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

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...

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Autores principales:	Ilkka Paatero, Eudald Casals, Rasmus Niemi, Ezgi Özliseli, Jessica M. Rosenholm, Cecilia Sahlgren
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3030e357a6c242d8a8ea19a59c6cc4bc
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spelling	oai:doaj.org-article:3030e357a6c242d8a8ea19a59c6cc4bc2021-12-02T16:06:35ZAnalyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled penetrance of biological membranes10.1038/s41598-017-09312-z2045-2322https://doaj.org/article/3030e357a6c242d8a8ea19a59c6cc4bc2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09312-zhttps://doaj.org/toc/2045-2322Abstract 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 nanotherapiesIlkka PaateroEudald CasalsRasmus NiemiEzgi ÖzliseliJessica M. RosenholmCecilia SahlgrenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ilkka Paatero Eudald Casals Rasmus Niemi Ezgi Özliseli Jessica M. Rosenholm Cecilia Sahlgren Analyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled penetrance of biological membranes
description	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
format	article
author	Ilkka Paatero Eudald Casals Rasmus Niemi Ezgi Özliseli Jessica M. Rosenholm Cecilia Sahlgren
author_facet	Ilkka Paatero Eudald Casals Rasmus Niemi Ezgi Özliseli Jessica M. Rosenholm Cecilia Sahlgren
author_sort	Ilkka Paatero
title	Analyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled penetrance of biological membranes
title_short	Analyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled penetrance of biological membranes
title_full	Analyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled penetrance of biological membranes
title_fullStr	Analyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled penetrance of biological membranes
title_full_unstemmed	Analyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled penetrance of biological membranes
title_sort	analyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled penetrance of biological membranes
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3030e357a6c242d8a8ea19a59c6cc4bc
work_keys_str_mv	AT ilkkapaatero analysesinzebrafishembryosrevealthatnanotoxicityprofilesaredependentonsurfacefunctionalizationcontrolledpenetranceofbiologicalmembranes AT eudaldcasals analysesinzebrafishembryosrevealthatnanotoxicityprofilesaredependentonsurfacefunctionalizationcontrolledpenetranceofbiologicalmembranes AT rasmusniemi analysesinzebrafishembryosrevealthatnanotoxicityprofilesaredependentonsurfacefunctionalizationcontrolledpenetranceofbiologicalmembranes AT ezgiozliseli analysesinzebrafishembryosrevealthatnanotoxicityprofilesaredependentonsurfacefunctionalizationcontrolledpenetranceofbiologicalmembranes AT jessicamrosenholm analysesinzebrafishembryosrevealthatnanotoxicityprofilesaredependentonsurfacefunctionalizationcontrolledpenetranceofbiologicalmembranes AT ceciliasahlgren analysesinzebrafishembryosrevealthatnanotoxicityprofilesaredependentonsurfacefunctionalizationcontrolledpenetranceofbiologicalmembranes
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Analyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled penetrance of biological membranes

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