Toxic and teratogenic silica nanowires in developing vertebrate embryos.
Silica-based nanomaterials show promise for biomedical applications such as cell-selective drug delivery and bioimaging. They are easily functionalized, which allows for the conjugation or encapsulation of important biomolecules. Although recent in vitro studies suggested that silica-derived nanomaterials are nontoxic, in vivo studies of silica nanomaterial toxicity have not been performed. Using the embryonic zebrafish as a model system, we show that silica nanomaterials with aspect ratios greater than 1 are highly toxic (LD(50) = 110 pg/g embryo) and cause embryo deformities, whereas silica nanomaterials with an aspect ratio of 1 are neither toxic nor teratogenic at the same concentrations. Silica nanowires also interfere with neurulation and disrupt expression of sonic hedgehog, which encodes a key midline signaling factor. Our results demonstrate the need for further testing of nanomaterials before they can be used as platforms for drug delivery.


BACKGROUND
Silica-based nanomaterials show promise for biomedical applications such as cell-selective drug delivery and bioimaging. Using an embryonic zebrafish model system silica nanomaterials with aspect ratios greater than one were found to be highly toxic; whereas silica nanomaterials with an aspect ratio of one are neither toxic nor teratogenic. These results demonstrate the need for testing "nanomaterials" before they can be used as platforms for drug delivery.
Nelson
Steve M
SM
Department of Biological Sciences, University of Idaho, Moscow, Idaho, USA.
Mahmoud
Tarek
T
Beaux
Miles
M
Shapiro
Pamela
P
McIlroy
David N
DN
Stenkamp
Deborah L
DL
D000818:Animals; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000378:metabolism; D008845:Microinjections; D053758:Nanoparticles / Q000633:toxicity; D053770:Nanowires / Q000633:toxicity*; D012822:Silicon Dioxide / Q000493:pharmacokinetics / Q000633:toxicity*; D012996:Solutions; D013010:Sonication; D016019:Survival Analysis; D013723:Teratogens / Q000633:toxicity*; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000378:metabolism
D012996:Solutions; D013723:Teratogens; D029961:Zebrafish Proteins; D012822:Silicon Dioxide