Analyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled penetrance of biological membranes
| Autor: | Cecilia Sahlgren, Eudald Casals, Jessica M. Rosenholm, Ilkka Paatero, Ezgi Özliseli, Rasmus Niemi |
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| Přispěvatelé: | Institute for Complex Molecular Systems, Soft Tissue Biomech. & Tissue Eng. |
| Rok vydání: | 2017 |
| Předmět: |
Pathology
medicine.medical_specialty Embryo Nonmammalian Surface Properties Science Danio 02 engineering and technology macromolecular substances 010402 general chemistry 01 natural sciences Cardiovascular System Permeability Article law.invention Confocal microscopy law PEG ratio medicine Cardiovascular System/drug effects Animals Membranes/metabolism Calcium Compounds/pharmacokinetics Zebrafish Nonmammalian Multidisciplinary Membranes biology Silicates technology industry and agriculture Biological membrane Calcium Compounds 021001 nanoscience & nanotechnology biology.organism_classification Survival Analysis 0104 chemical sciences Cell biology Embryo Nanotoxicology Toxicity Drug delivery Medicine Nanoparticles Silicates/pharmacokinetics 0210 nano-technology |
| Zdroj: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) Scientific Reports, 7(1):8423. Nature Publishing Group |
| ISSN: | 2045-2322 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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