Systematic evaluation of nanomaterial toxicity: utility of standardized materials and rapid assays.
Harper, S.L., J.L. Carriere, J.M. Miller, J.E. Hutchison, B.L.S. Maddux, and R.L. Tanguay
ACS Nano, 2011, 5 (6), pp 4688–4697
The challenge of optimizing both performance and safety in nanomaterials hinges on our ability to resolve which structural features lead to desired properties. It has been difficult to draw meaningful conclusions about biological impacts from many studies of nanomaterials due to the lack of nanomaterial characterization, unknown purity, and/or alteration of the nanomaterials by the biological environment. To investigate the relative influence of core size, surface chemistry, and charge on nanomaterial toxicity, we tested the biological response of whole animals exposed to a matrix of nine structurally diverse, precision-engineered gold nanoparticles (AuNPs) of high purity and known composition. Members of the matrix include three core sizes and four unique surface coatings that include positively and negatively charged headgroups. Mortality, malformations, uptake, and elimination of AuNPs were all dependent on these parameters, showing the need for tightly controlled experimental design and nanomaterial characterization. Results presented herein illustrate the value of an integrated approach to identify design rules that minimize potential hazard.
These uptake data imply that biological systems react to positively charged nanoparticles differently than other nanomaterials and suggest that AuNPs with MES and TMAT ligands act through fundamentally different mechanisms, since TMAT-AuNPs cause primarily mortality at low doses and are not readily eliminated by the organism, while MES can be tolerated at higher concentrations, is rapidly cleared from the animal, and manifests its biological effect through malformations rather than mortality.
The embryonic zebrafish assay revealed that gold nanoparticles with no charge do not adversely impact biological systems across a broad range of sizes. AuNPs with both positive and negative charges perturbed development significantly, with positively charged AuNPs primarily causing mortality and negatively charged particles inducing malformations. The zebrafish embryos took up all AuNP types tested, but TMAT-AuNP particles were not eliminated as rapidly as the MES-, MEE-, and MEEE-AuNP particles.
While the results demonstrate the importance of charge on AuNPs’ interactions with biological systems, the question of the importance of size raises many issues that require consideration. Most important to considerations of size is the metric used to quantify exposure concentrations. At least in the case of the TMAT AuNPs in this study, different metrics suggested different conclusions on the impact of size on toxicity.