共 83 条
Evaluation of toxicological and teratogenic effects of carbosilane glucose glycodendrimers in zebrafish embryos and model rodent cell lines
被引:16
作者:

Liegertova, Michaela
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Univ JE Purkyne, Fac Sci, Usti Nad Labem, Czech Republic Univ JE Purkyne, Fac Sci, Usti Nad Labem, Czech Republic

Wrobel, Dominika
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Univ JE Purkyne, Fac Sci, Usti Nad Labem, Czech Republic Univ JE Purkyne, Fac Sci, Usti Nad Labem, Czech Republic

Herma, Regina
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Univ JE Purkyne, Fac Sci, Usti Nad Labem, Czech Republic Univ JE Purkyne, Fac Sci, Usti Nad Labem, Czech Republic

Mullerova, Monika
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CAS, Inst Chem Proc Fundamentals, Prague, Czech Republic Univ JE Purkyne, Fac Sci, Usti Nad Labem, Czech Republic

Stastna, Lucie Cervenkova
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CAS, Inst Chem Proc Fundamentals, Prague, Czech Republic Univ JE Purkyne, Fac Sci, Usti Nad Labem, Czech Republic

Curinova, Petra
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CAS, Inst Chem Proc Fundamentals, Prague, Czech Republic Univ JE Purkyne, Fac Sci, Usti Nad Labem, Czech Republic

Strasak, Tomas
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CAS, Inst Chem Proc Fundamentals, Prague, Czech Republic Univ JE Purkyne, Fac Sci, Usti Nad Labem, Czech Republic

Maly, Marek
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Univ JE Purkyne, Fac Sci, Usti Nad Labem, Czech Republic Univ JE Purkyne, Fac Sci, Usti Nad Labem, Czech Republic

Cermak, Jan
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机构:
Univ JE Purkyne, Fac Sci, Usti Nad Labem, Czech Republic
CAS, Inst Chem Proc Fundamentals, Prague, Czech Republic Univ JE Purkyne, Fac Sci, Usti Nad Labem, Czech Republic

Smejkal, Jiri
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Univ JE Purkyne, Fac Sci, Usti Nad Labem, Czech Republic Univ JE Purkyne, Fac Sci, Usti Nad Labem, Czech Republic

Stofik, Marcel
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Univ JE Purkyne, Fac Sci, Usti Nad Labem, Czech Republic Univ JE Purkyne, Fac Sci, Usti Nad Labem, Czech Republic

Maly, Jan
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h-index: 0
机构:
Univ JE Purkyne, Fac Sci, Usti Nad Labem, Czech Republic Univ JE Purkyne, Fac Sci, Usti Nad Labem, Czech Republic
机构:
[1] Univ JE Purkyne, Fac Sci, Usti Nad Labem, Czech Republic
[2] CAS, Inst Chem Proc Fundamentals, Prague, Czech Republic
关键词:
Carbosilane dendrimers;
glycodendrimers;
zebrafish;
toxicity;
teratogenicity;
molecular modeling;
POLY(PROPYLENE IMINE) DENDRIMERS;
MODIFIED PPI DENDRIMERS;
DEVELOPMENTAL TOXICITY;
MOLECULAR-DYNAMICS;
IN-VITRO;
BIOLOGICAL-PROPERTIES;
PAMAM DENDRIMERS;
SURFACE GROUPS;
FORCE-FIELD;
TEST FET;
D O I:
10.1080/17435390.2018.1475582
中图分类号:
TB3 [工程材料学];
学科分类号:
0805 ;
080502 ;
摘要:
Glycodendrimers (Glyco-DDMs) represent a rapidly growing class of nanoparticles with promising properties for biomedical applications but concerns regarding the impact on human health and environment are still justified. Here we report, for the first time, the comparative study of in vivo developmental toxicity of carbosilane Glyco-DDMs and their cytotoxicity in vitro. Carbosilane Glyco-DDMs (generation 1-3) containing 4, 8, and 16 beta-d-glucopyranosyl units at the periphery (DDM(1)Glu, DDM(2)Glu, and DDM(3)Glu) were synthesized and characterized by H-1, C-13 and Si-29 NMR, mass spectrometry, dynamic light scattering, atomic force microscopy (AFM), and computer modeling. In vitro cytotoxicity assay (MTT) of DDM(1-3)Glu was performed on three different rodent cell lines (Cricetulus griseus) - B14 (ATCC, CCL-14.1), BRL 3A (ATCC, CRL-1442), and NRK 52E (ATCC, CRL-1571). Overall, very low cytotoxicity was observed with calculated IC50 in mM range with slight difference between each cell line and DDM generation investigated. Modified fish embryo test (FET) was further used for DDM(3)Glu developmental toxicity testing on zebrafish (Danio rerio) embryos. While seemingly harmless to intact embryos, adverse effects of DDMs on the embryonic development become evident after chorion removal (LD50=2.78 mu M at 96 hpe). We summarized that the modified FET test showed a two to three orders of magnitude difference between the in vitro cytotoxicity and in vivo developmental toxicity of DDM(3)Glu. While, in general, the Glyco-DDMs show great promises as efficient vectors in targeted drug delivery or as therapeutic molecules itself, we suggest that their developmental toxicity should be thoroughly investigated to exclude safety risks associated with their potential biomedical use.
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收藏
页码:797 / 818
页数:22
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European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, I-21027 Ispra, VA, Italy European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, I-21027 Ispra, VA, Italy

Knoebel, Melanie
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UFZ Helmholtz Ctr Environm Res, D-04318 Leipzig, Germany European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, I-21027 Ispra, VA, Italy

Kussatz, Carola
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Fed Environm Agcy UBA, D-12307 Berlin, Germany European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, I-21027 Ispra, VA, Italy

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Lillicrap, Adam
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Norwegian Inst Water Res NIVA, N-0349 Oslo, Norway European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, I-21027 Ispra, VA, Italy

Martinez-Jeronimo, Fernando
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Escuela Nacl Ciencias Biol, Inst Politecn Nacl, Lab Hidrobiol Expt, Mexico City 11340, DF, Mexico European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, I-21027 Ispra, VA, Italy

Polleichtner, Christian
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机构: European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, I-21027 Ispra, VA, Italy

Rzodeczko, Helena
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机构: European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, I-21027 Ispra, VA, Italy

Salinas, Edward
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机构:
BASF SE, D-67056 Ludwigshafen, Germany European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, I-21027 Ispra, VA, Italy

Schneider, Katharina E.
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BASF SE, D-67056 Ludwigshafen, Germany European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, I-21027 Ispra, VA, Italy

Scholz, Stefan
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机构: European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, I-21027 Ispra, VA, Italy

van den Brandhof, Evert-Jan
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机构:
Natl Inst Publ Hlth & Environm RIVM, Ctr Environm Qual, NL-3720 BA Bilthoven, Netherlands European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, I-21027 Ispra, VA, Italy

van der Ven, Leo T. M.
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Natl Inst Publ Hlth & Environm RIVM, Ctr Hlth Protect, NL-3720 BA Bilthoven, Netherlands European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, I-21027 Ispra, VA, Italy

Walter-Rohde, Susanne
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机构:
Fed Environm Agcy UBA, D-06813 Dessau Rosslau, Germany European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, I-21027 Ispra, VA, Italy

Weigt, Stefan
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机构: European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, I-21027 Ispra, VA, Italy

Witters, Hilda
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机构:
Environm Risk & Hlth, Flemish Inst Technol Res VITO, Team Appl Bio & Mol Syst ABS, B-2400 Mol, Belgium European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, I-21027 Ispra, VA, Italy

Haider, Marlies
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机构:
European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, I-21027 Ispra, VA, Italy European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, I-21027 Ispra, VA, Italy