Gold nanoparticles are widely used in biomedical imaging and diagnostic tests. Based on their established use in the laboratory and the chemical stability of Au(0), gold nanoparticles were expected to be safe. The recent literature, however, contains conflicting data regarding the cytotoxicity of gold nanoparticles. Against this background a systematic study of water-soluble gold nanoparticles stabilized by triphenylphosphine derivatives ranging in size from 0.8 to 15 nm is made. The cytotoxicity of these particles in four cell lines representing major functional cell types with barrier and phagocyte function are tested. Connective tissue fibroblasts, epithelial cells, macrophages, and melanoma cells prove most sensitive to gold particles 1.4 nm in size, which results in IC(50) values ranging from 30 to 56 microM depending on the particular 1.4-nm Au compound-cell line combination. In contrast, gold particles 15 nm in size and Tauredon (gold thiomalate) are nontoxic at up to 60-fold and 100-fold higher concentrations, respectively. The cellular response is size dependent, in that 1.4-nm particles cause predominantly rapid cell death by necrosis within 12 h while closely related particles 1.2 nm in diameter effect predominantly programmed cell death by apoptosis.

Gold nanoparticles (AuNPs) are generally considered nontoxic, similar to bulk gold, which is inert and biocompatible. AuNPs of diameter 1.4 nm capped with triphenylphosphine monosulfonate (TPPMS), Au1.4MS, are much more cytotoxic than 15-nm nanoparticles (Au15MS) of similar chemical composition. Here, major cell-death pathways are studied and it is determined that the cytotoxicity is caused by oxidative stress. Indicators of oxidative stress, reactive oxygen species (ROS), mitochondrial potential and integrity, and mitochondrial substrate reduction are all compromised. Genome-wide expression profiling using DNA gene arrays indicates robust upregulation of stress-related genes after 6 and 12 h of incubation with a 2 x IC50 concentration of Au1.4MS but not with Au15MS nanoparticles. The caspase inhibitor Z-VAD-fmk does not rescue the cells, which suggests that necrosis, not apoptosis, is the predominant pathway at this concentration. Pretreatment of the nanoparticles with reducing agents/antioxidants N-acetylcysteine, glutathione, and TPPMS reduces the toxicity of Au1.4MS. AuNPs of similar size but capped with glutathione (Au1.1GSH) likewise do not induce oxidative stress. Besides the size dependency of AuNP toxicity, ligand chemistry is a critical parameter determining the degree of cytotoxicity. AuNP exposure most likely causes oxidative stress that is amplified by mitochondrial damage. Au1.4MS nanoparticle cytotoxicity is associated with oxidative stress, endogenous ROS production, and depletion of the intracellular antioxidant pool.

Gold nanoparticles (GNP) provide many opportunities in imaging, diagnostics, and therapies of nanomedicine. Hence, their biokinetics in the body are prerequisites for specific tailoring of nanomedicinal applications and for a comprehensive risk assessment.We administered 198 Au-radio-labelled monodisperse, negatively charged GNP of five different sizes (1.4, 5, 18, 80, 200nm) and 2.8nm GNP with opposite surface charges by intravenous injection into rats. After 24 h the biodistribution of the GNP was quantitatively measured by gamma-spectrometry.The size and surface charge of GNP strongly determine the biodistribution. Most GNP accumulated in the liver increased from 50% of 1.4nm GNP to > 99% of 200nm GNP. In contrast, there was little size dependent accumulation of 18nm to 200nm GNP in most other organs. However, for GNP between 1.4nm and 5nm the accumulation increased sharply with decreasing size; i.e. a linear increase with the volumetric specific surface area. The differently charged 2.8nm GNP led to significantly different accumulations in several organs.We conclude that the alterations of accumulation in the various organs and tissues, depending on GNP size and surface charge, are mediated by dynamic protein binding and exchange. A better understanding of these mechanisms will improve drug delivery and dose estimates used in risk assessment.

It is of urgent need to identify the exact physico-chemical characteristics which allow maximum uptake and accumulation in secondary target organs of nanoparticulate drug delivery systems after oral ingestion. We administered radiolabelled gold nanoparticles in different sizes (1.4-200 nm) with negative surface charge and 2.8 nm nanoparticles with opposite surface charges by intra-oesophageal instillation into healthy adult female rats. The quantitative amount of the particles in organs, tissues and excrements was measured after 24 h by gamma-spectroscopy. The highest accumulation in secondary organs was mostly found for 1.4 nm particles; the negatively charged particles were accumulated mostly more than positively charged particles. Importantly, 18 nm particles show a higher accumulation in brain and heart compared to other sized particles. No general rule accumulation can be made so far. Therefore, specialized drug delivery systems via the oral route have to be individually designed, depending on the respective target organ.

Ligand stabilized gold nanoparticles have attracted much attention in the search for new chemically designed compounds for a future information technology, based on single-electron devices. This article gives an overview about the strategies used to synthesize and to assemble uniform gold nanoparticles in different dimensions as well as about the present status of the electrical properties of these. Examples are given for three-dimensional organisations, for the formation of self-assembled monolayers as well as for one-dimensional assemblies.