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Phosphate-enhanced cytotoxicity of zinc oxide nanoparticles and agglomerates.
Toxicol Lett. 2014 Feb 10; 225(1):177-84.TL

Abstract

Zinc oxide (ZnO) nanoparticles (NPs) have been found to readily react with phosphate ions to form zinc phosphate (Zn3(PO4)2) crystallites. Because phosphates are ubiquitous in physiological fluids as well as waste water streams, it is important to examine the potential effects that the formation of Zn3(PO4)2 crystallites may have on cell viability. Thus, the cytotoxic response of NIH/3T3 fibroblast cells was assessed following 24h of exposure to ZnO NPs suspended in media with and without the standard phosphate salt supplement. Both particle dosage and size have been shown to impact the cytotoxic effects of ZnO NPs, so doses ranging from 5 to 50 μg/mL were examined and agglomerate size effects were investigated by using the bioinert amphiphilic polymer polyvinylpyrrolidone (PVP) to generate water-soluble ZnO ranging from individually dispersed 4 nm NPs up to micron-sized agglomerates. Cell metabolic activity measures indicated that the presence of phosphate in the suspension media can led to significantly reduced cell viability at all agglomerate sizes and at lower ZnO dosages. In addition, a reduction in cell viability was observed when agglomerate size was decreased, but only in the phosphate-containing media. These metabolic activity results were reflected in separate measures of cell death via the lactate dehydrogenase assay. Our results suggest that, while higher doses of water-soluble ZnO NPs are cytotoxic, the presence of phosphates in the surrounding fluid can lead to significantly elevated levels of cell death at lower ZnO NP doses. Moreover, the extent of this death can potentially be modulated or offset by tuning the agglomerate size. These findings underscore the importance of understanding how nanoscale materials can interact with the components of surrounding fluids so that potential adverse effects of such interactions can be controlled.

Authors+Show Affiliations

Mechanical Engineering, Texas A&M University, College Station, TX 77843, United States; Chemical Engineering, Texas A&M University, College Station, TX 77843, United States.Chemical Engineering, Texas A&M University, College Station, TX 77843, United States.Mechanical Engineering, Texas A&M University, College Station, TX 77843, United States.Chemical Engineering, Texas A&M University, College Station, TX 77843, United States.Mechanical Engineering, Texas A&M University, College Station, TX 77843, United States.Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center College of Medicine, Bryan, TX 77807, United States.Chemical Engineering, Texas A&M University, College Station, TX 77843, United States; Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, United States. Electronic address: hahnm@rpi.edu.Mechanical Engineering, Texas A&M University, College Station, TX 77843, United States. Electronic address: hjsue@tamu.edu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24362007

Citation

Everett, W Neil, et al. "Phosphate-enhanced Cytotoxicity of Zinc Oxide Nanoparticles and Agglomerates." Toxicology Letters, vol. 225, no. 1, 2014, pp. 177-84.
Everett WN, Chern C, Sun D, et al. Phosphate-enhanced cytotoxicity of zinc oxide nanoparticles and agglomerates. Toxicol Lett. 2014;225(1):177-84.
Everett, W. N., Chern, C., Sun, D., McMahon, R. E., Zhang, X., Chen, W. J., Hahn, M. S., & Sue, H. J. (2014). Phosphate-enhanced cytotoxicity of zinc oxide nanoparticles and agglomerates. Toxicology Letters, 225(1), 177-84. https://doi.org/10.1016/j.toxlet.2013.12.005
Everett WN, et al. Phosphate-enhanced Cytotoxicity of Zinc Oxide Nanoparticles and Agglomerates. Toxicol Lett. 2014 Feb 10;225(1):177-84. PubMed PMID: 24362007.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phosphate-enhanced cytotoxicity of zinc oxide nanoparticles and agglomerates. AU - Everett,W Neil, AU - Chern,Christina, AU - Sun,Dazhi, AU - McMahon,Rebecca E, AU - Zhang,Xi, AU - Chen,Wei-Jung A, AU - Hahn,Mariah S, AU - Sue,H-J, Y1 - 2013/12/18/ PY - 2013/10/29/received PY - 2013/12/05/revised PY - 2013/12/06/accepted PY - 2013/12/24/entrez PY - 2013/12/24/pubmed PY - 2014/3/7/medline KW - AAS KW - Aggregation KW - Culture media byproduct KW - DLS KW - DMEM without phosphates KW - DMEM(+phos) KW - DMEM(−phos) KW - Dulbecco's modified Eagle's medium (DMEM) with phosphates KW - FBS KW - HRTEM KW - ICP-MS KW - NP KW - Nanohazard KW - PBS KW - PS KW - PSG KW - PVP KW - X-ray diffraction KW - XRD KW - Zinc oxide toxicity KW - Zinc phosphate toxicity KW - atomic absorption spectrometry KW - dynamic light scattering KW - fetal bovine serum KW - high-resolution transmission electron microscopy KW - inductively coupled plasma-mass spectrometry KW - nanoparticle KW - penicillin streptomycin KW - penicillin streptomycin l-glutamine KW - phosphate buffered saline KW - polyvinylpyrrolidone SP - 177 EP - 84 JF - Toxicology letters JO - Toxicol Lett VL - 225 IS - 1 N2 - Zinc oxide (ZnO) nanoparticles (NPs) have been found to readily react with phosphate ions to form zinc phosphate (Zn3(PO4)2) crystallites. Because phosphates are ubiquitous in physiological fluids as well as waste water streams, it is important to examine the potential effects that the formation of Zn3(PO4)2 crystallites may have on cell viability. Thus, the cytotoxic response of NIH/3T3 fibroblast cells was assessed following 24h of exposure to ZnO NPs suspended in media with and without the standard phosphate salt supplement. Both particle dosage and size have been shown to impact the cytotoxic effects of ZnO NPs, so doses ranging from 5 to 50 μg/mL were examined and agglomerate size effects were investigated by using the bioinert amphiphilic polymer polyvinylpyrrolidone (PVP) to generate water-soluble ZnO ranging from individually dispersed 4 nm NPs up to micron-sized agglomerates. Cell metabolic activity measures indicated that the presence of phosphate in the suspension media can led to significantly reduced cell viability at all agglomerate sizes and at lower ZnO dosages. In addition, a reduction in cell viability was observed when agglomerate size was decreased, but only in the phosphate-containing media. These metabolic activity results were reflected in separate measures of cell death via the lactate dehydrogenase assay. Our results suggest that, while higher doses of water-soluble ZnO NPs are cytotoxic, the presence of phosphates in the surrounding fluid can lead to significantly elevated levels of cell death at lower ZnO NP doses. Moreover, the extent of this death can potentially be modulated or offset by tuning the agglomerate size. These findings underscore the importance of understanding how nanoscale materials can interact with the components of surrounding fluids so that potential adverse effects of such interactions can be controlled. SN - 1879-3169 UR - https://www.unboundmedicine.com/medline/citation/24362007/Phosphate_enhanced_cytotoxicity_of_zinc_oxide_nanoparticles_and_agglomerates_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-4274(13)01461-6 DB - PRIME DP - Unbound Medicine ER -