Rational Design of Gold Nanoparticle Toxicology Assays: A Question of Exposure Scenario, Dose and Experimental Setup

Ulrike Taylor; Christoph Rehbock; Carmen Streich; Detlef Rath; Stephan Barcikowski

Disclosures

Nanomedicine. 2014;9(13):1971-1989. 

In This Article

Abstract and Introduction

Abstract

Many studies have evaluated the toxicity of gold nanoparticles, although reliable predictions based on these results are rare. In order to overcome this problem, this article highlights strategies to improve comparability and standardization of nanotoxicological studies. To this end, it is proposed that we should adapt the nanomaterial to the addressed exposure scenario, using ligand-free nanoparticle references in order to differentiate ligand effects from size effects. Furthermore, surface-weighted particle dosing referenced to the biologically relevant parameter (e.g., cell number or organ mass) is proposed as the gold standard. In addition, it is recommended that we should shift the focus of toxicological experiments from 'live–dead' assays to the assessment of cell function, as this strategy allows observation of bioresponses at lower doses that are more relevant for in vivo scenarios.

Introduction

Exposure of humans and the environment to nanoparticles is not a 'new' scenario. Even when the discussion is limited to anthropogenic particles, these have existed for centuries (e.g., inhaled in the form of carbon and cerium particles derived from diesel fumes or platinum from automotive catalyst exhaust). The rise of nanotechnology in the past two decades has led to an exponential increase in products containing specifically engineered nanoparticles. Their use comprises industrial and biomedical applications, as well as consumer products. In response to this increasing exposure to nanoparticles, a multitude of studies into their potential toxicity has been published. In this context, gold toxicity warrants special attention, as gold nanoparticles (AuNPs) are widely applied in medical applications[1–3] and hence exposure is a highly relevant scenario. Furthermore, AuNPs exhibit some unique features that distinguish them from other nanoparticle species. Firstly, AuNPs are known to be noble metals with no significant dissolution and ion release under physiological conditions.[1] Furthermore, metal AuNPs lack the band gap structure generally found in semiconductor metal oxide nanoparticles. Consequently, the formation of reactive oxygen species related to the particle's band gap[4] is far less pronounced. Hence, AuNPs are generally considered to be relatively biocompatible reference materials in nanotoxicology, ideally suited for studying subtle nanoscopic effects.

However, while nanotoxicological investigations of AuNPs have increased tremendously over the last 10 years (Figure 1), there is still considerable uncertainty regarding AuNP toxicity. Even though many studies have been published attesting to them having a very high biocompatibility,[5–7] there are numerous reports documenting a range of toxic effects.[8–11] This apparent discrepancy is due to the fact that, in contrast to airborne particles,[12] standardized methods for toxicological assays with colloidal nanoparticles are not widely applied, which is a rather surprising fact considering that these standards have already been documented (e.g., in recommendations released by the Organisation for Economic Co-operation and Development [OECD]).[13] Hence, this article aims to provide general guidelines for nanotoxicological assays of AuNPs. In this context, it should be noted that even though the main emphasis of this article is on gold nanotoxicology, some general trends may be applicable to other nanoparticles as well.

Figure 1.

Studies and citations listed under the topics 'gold nanoparticle' and 'toxicity' in the Web of Science database.

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