Surface functionalities of gold nanoparticles impact embryonic gene expression responses

Abstract Incorporation of gold nanoparticles (AuNPs) into consumer products is increasing; however, there is a gap in available toxicological data to determine the safety of AuNPs. In this study, we utilised the embryonic zebrafish to investigate how surface functionalisation and charge influence molecular responses. Precisely engineered AuNPs with 1.5 nm cores were synthesised and functionalized with three ligands: 2-mercaptoethanesulfonic acid (MES), N,N,N-trimethylammoniumethanethiol (TMAT), or 2-(2-(2-mercaptoethoxy)ethoxy)ethanol. Developmental assessments revealed differential biological responses when embryos were exposed to the functionalised AuNPs at the same concentration. Using inductively coupled plasma–mass spectrometry, AuNP uptake was confirmed in exposed embryos. Following exposure to MES- and TMAT-AuNPs from 6 to 24 or 6 to 48 h post fertilisation, pathways involved in inflammation and immune response were perturbed. Additionally, transport mechanisms were misregulated after exposure to TMAT and MES-AuNPs, demonstrating that surface functionalisation influences many molecular pathways.

[1]  Robert L. Tanguay,et al.  Differential stability of lead sulfide nanoparticles influences biological responses in embryonic zebrafish , 2011, Archives of Toxicology.

[2]  R. Albrecht,et al.  Toxicity assessments of multisized gold and silver nanoparticles in zebrafish embryos. , 2009, Small.

[3]  J. West,et al.  Correlating nanoscale titania structure with toxicity: a cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[4]  Ting Li,et al.  Comparative toxicity study of Ag, Au, and Ag–Au bimetallic nanoparticles on Daphnia magna , 2010, Analytical and bioanalytical chemistry.

[5]  Lisa Truong,et al.  Media ionic strength impacts embryonic responses to engineered nanoparticle exposure , 2012, Nanotoxicology.

[6]  Vincent M. Rotello,et al.  Multimodal drug delivery using gold nanoparticles. , 2009, Nanoscale.

[7]  S. Sheikpranbabu,et al.  Gold nanoparticles downregulate VEGF-and IL-1β-induced cell proliferation through Src kinase in retinal pigment epithelial cells. , 2010, Experimental eye research.

[8]  W. Liu,et al.  Impact of silver nanoparticles on human cells: Effect of particle size , 2010, Nanotoxicology.

[9]  A. Dodd,et al.  Zebrafish: bridging the gap between development and disease. , 2000, Human molecular genetics.

[10]  J. McPherson,et al.  The syntenic relationship of the zebrafish and human genomes. , 2000, Genome research.

[11]  R. Klaper,et al.  Electron microscopy of gold nanoparticle intake in the gut of Daphnia magna , 2008 .

[12]  A. Rubinstein,et al.  Zebrafish: from disease modeling to drug discovery. , 2003, Current opinion in drug discovery & development.

[13]  Robert L. Tanguay,et al.  In vivo evaluation of carbon fullerene toxicity using embryonic zebrafish. , 2007, Carbon.

[14]  Brad T. Sherman,et al.  The DAVID Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally analyze large gene lists , 2007, Genome Biology.

[15]  Stacey L. Harper,et al.  Systematic Evaluation of Nanomaterial Toxicity: Utility of Standardized Materials and Rapid Assays , 2011, ACS nano.

[16]  T. Speed,et al.  Summaries of Affymetrix GeneChip probe level data. , 2003, Nucleic acids research.

[17]  Rafael A Irizarry,et al.  Exploration, normalization, and summaries of high density oligonucleotide array probe level data. , 2003, Biostatistics.

[18]  Leif O. Brown,et al.  Thiol-functionalized, 1.5-nm gold nanoparticles through ligand exchange reactions: scope and mechanism of ligand exchange. , 2005, Journal of the American Chemical Society.

[19]  J. Hertog Chemical Genetics: Drug Screens in Zebrafish , 2005 .

[20]  Markus Reischl,et al.  Zebrafish embryos as models for embryotoxic and teratological effects of chemicals. , 2009, Reproductive toxicology.

[21]  Sabine Neuss,et al.  Size-dependent cytotoxicity of gold nanoparticles. , 2007, Small.

[22]  James E Hutchison,et al.  Linear assemblies of nanoparticles electrostatically organized on DNA scaffolds , 2003, Nature materials.

[23]  Vincent M Rotello,et al.  Surface properties dictate uptake, distribution, excretion, and toxicity of nanoparticles in fish. , 2010, Small.

[24]  James E Hutchison,et al.  Toward greener nanosynthesis. , 2007, Chemical reviews.

[25]  K. Paigen One hundred years of mouse genetics: an intellectual history. I. The classical period (1902-1980). , 2003, Genetics.

[26]  James E Hutchison,et al.  Molecular-level control of feature separation in one-dimensional nanostructure assemblies formed by biomolecular nanolithography. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[27]  C. Mirkin,et al.  Nanoparticle-Based Bio-Bar Codes for the Ultrasensitive Detection of Proteins , 2003, Science.

[28]  Mitsuhiro Murayama,et al.  Influence of size and aggregation on the reactivity of an environmentally and industrially relevant nanomaterial (PbS). , 2009, Environmental science & technology.

[29]  Terence P. Speed,et al.  A comparison of normalization methods for high density oligonucleotide array data based on variance and bias , 2003, Bioinform..

[30]  Lisa Truong,et al.  Evaluation of embryotoxicity using the zebrafish model. , 2011, Methods in molecular biology.

[31]  S. Joo,et al.  Control of gold nanoparticle aggregates by manipulation of interparticle interaction. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[32]  C. Kimmel,et al.  Stages of embryonic development of the zebrafish , 1995, Developmental dynamics : an official publication of the American Association of Anatomists.

[33]  U. Simon,et al.  On the application potential of gold nanoparticles in nanoelectronics and biomedicine , 2010, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[34]  A I Saeed,et al.  TM4: a free, open-source system for microarray data management and analysis. , 2003, BioTechniques.

[35]  Krzysztof Matyjaszewski,et al.  Ionic strength and composition affect the mobility of surface-modified Fe0 nanoparticles in water-saturated sand columns. , 2008, Environmental science & technology.

[36]  Michal Lahav,et al.  Investigations into the Electrostatically Induced Aggregation of Au Nanoparticles , 2000 .

[37]  R. Shukla,et al.  Biocompatibility of gold nanoparticles and their endocytotic fate inside the cellular compartment: a microscopic overview. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[38]  Jennifer A. Dahl,et al.  Toward Greener Nanosynthesis , 2007 .

[39]  Brad T. Sherman,et al.  DAVID: Database for Annotation, Visualization, and Integrated Discovery , 2003, Genome Biology.

[40]  Kyunghee Choi,et al.  Repeated-dose toxicity and inflammatory responses in mice by oral administration of silver nanoparticles. , 2010, Environmental toxicology and pharmacology.

[41]  J. Pounds,et al.  Macrophage responses to silica nanoparticles are highly conserved across particle sizes. , 2009, Toxicological sciences : an official journal of the Society of Toxicology.

[42]  Zhongping Chen,et al.  Enhanced detection of early-stage oral cancer in vivo by optical coherence tomography using multimodal delivery of gold nanoparticles. , 2009, Journal of biomedical optics.

[43]  Marcelo O. Magnasco,et al.  Enhancement of Transport Selectivity through Nano-Channels by Non-Specific Competition , 2010, PLoS Comput. Biol..

[44]  Wu Dong,et al.  Zebrafish as a novel experimental model for developmental toxicology , 2003, Congenital anomalies.