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- Publisher Website: 10.1016/j.taap.2007.07.009
- Scopus: eid_2-s2.0-35549008795
- PMID: 17764713
- WOS: WOS:000250847200006
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Article: Developmental toxicity of low generation PAMAM dendrimers in zebrafish
Title | Developmental toxicity of low generation PAMAM dendrimers in zebrafish |
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Authors | |
Keywords | Zebrafish embryo Nanotoxicology Nanotherapeutics Developmental toxicity Dendrimer RGD |
Issue Date | 2007 |
Citation | Toxicology and Applied Pharmacology, 2007, v. 225, n. 1, p. 70-79 How to Cite? |
Abstract | Biological molecules and intracellular structures operate at the nanoscale; therefore, development of nanomedicines shows great promise for the treatment of disease by using targeted drug delivery and gene therapies. PAMAM dendrimers, which are highly branched polymers with low polydispersity and high functionality, provide an ideal architecture for construction of effective drug carriers, gene transfer devices and imaging of biological systems. For example, dendrimers bioconjugated with selective ligands such as Arg-Gly-Asp (RGD) would theoretically target cells that contain integrin receptors and show potential for use as drug delivery devices. While RGD-conjugated dendrimers are generally considered not to be cytotoxic, there currently exists little information on the risks that such materials pose to human health. In an effort to compliment and extend the knowledge gleaned from cell culture assays, we have used the zebrafish embryo as a rapid, medium throughput, cost-effective whole-animal model to provide a more comprehensive and predictive developmental toxicity screen for nanomaterials such as PAMAM dendrimers. Using the zebrafish embryo, we have assessed the developmental toxicity of low generation (G3.5 and G4) PAMAM dendrimers, as well as RGD-conjugated forms for comparison. Our results demonstrate that G4 dendrimers, which have amino functional groups, are toxic and attenuate growth and development of zebrafish embryos at sublethal concentrations; however, G3.5 dendrimers, with carboxylic acid terminal functional groups, are not toxic to zebrafish embryos. Furthermore, RGD-conjugated G4 dendrimers are less potent in causing embryo toxicity than G4 dendrimers. RGD-conjugated G3.5 dendrimers do not elicit toxicity at the highest concentrations tested and warrant further study for use as a drug delivery device. © 2007 Elsevier Inc. All rights reserved. |
Persistent Identifier | http://hdl.handle.net/10722/216190 |
ISSN | 2023 Impact Factor: 3.3 2023 SCImago Journal Rankings: 0.788 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | King Heiden, Tisha C. | - |
dc.contributor.author | Dengler, Emelyne | - |
dc.contributor.author | Kao, Weiyuan John | - |
dc.contributor.author | Heideman, Warren | - |
dc.contributor.author | Peterson, Richard E. | - |
dc.date.accessioned | 2015-08-25T10:22:19Z | - |
dc.date.available | 2015-08-25T10:22:19Z | - |
dc.date.issued | 2007 | - |
dc.identifier.citation | Toxicology and Applied Pharmacology, 2007, v. 225, n. 1, p. 70-79 | - |
dc.identifier.issn | 0041-008X | - |
dc.identifier.uri | http://hdl.handle.net/10722/216190 | - |
dc.description.abstract | Biological molecules and intracellular structures operate at the nanoscale; therefore, development of nanomedicines shows great promise for the treatment of disease by using targeted drug delivery and gene therapies. PAMAM dendrimers, which are highly branched polymers with low polydispersity and high functionality, provide an ideal architecture for construction of effective drug carriers, gene transfer devices and imaging of biological systems. For example, dendrimers bioconjugated with selective ligands such as Arg-Gly-Asp (RGD) would theoretically target cells that contain integrin receptors and show potential for use as drug delivery devices. While RGD-conjugated dendrimers are generally considered not to be cytotoxic, there currently exists little information on the risks that such materials pose to human health. In an effort to compliment and extend the knowledge gleaned from cell culture assays, we have used the zebrafish embryo as a rapid, medium throughput, cost-effective whole-animal model to provide a more comprehensive and predictive developmental toxicity screen for nanomaterials such as PAMAM dendrimers. Using the zebrafish embryo, we have assessed the developmental toxicity of low generation (G3.5 and G4) PAMAM dendrimers, as well as RGD-conjugated forms for comparison. Our results demonstrate that G4 dendrimers, which have amino functional groups, are toxic and attenuate growth and development of zebrafish embryos at sublethal concentrations; however, G3.5 dendrimers, with carboxylic acid terminal functional groups, are not toxic to zebrafish embryos. Furthermore, RGD-conjugated G4 dendrimers are less potent in causing embryo toxicity than G4 dendrimers. RGD-conjugated G3.5 dendrimers do not elicit toxicity at the highest concentrations tested and warrant further study for use as a drug delivery device. © 2007 Elsevier Inc. All rights reserved. | - |
dc.language | eng | - |
dc.relation.ispartof | Toxicology and Applied Pharmacology | - |
dc.subject | Zebrafish embryo | - |
dc.subject | Nanotoxicology | - |
dc.subject | Nanotherapeutics | - |
dc.subject | Developmental toxicity | - |
dc.subject | Dendrimer | - |
dc.subject | RGD | - |
dc.title | Developmental toxicity of low generation PAMAM dendrimers in zebrafish | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1016/j.taap.2007.07.009 | - |
dc.identifier.pmid | 17764713 | - |
dc.identifier.scopus | eid_2-s2.0-35549008795 | - |
dc.identifier.volume | 225 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | 70 | - |
dc.identifier.epage | 79 | - |
dc.identifier.eissn | 1096-0333 | - |
dc.identifier.isi | WOS:000250847200006 | - |
dc.identifier.issnl | 0041-008X | - |