Nanoparticle interactions on a cellular scale

Abstract

Nanoobjects are distinguished from other materials by their nanoscale size. The special physico-chemical properties of nanoobjects attributed to size-effects are the basis for their high application potential. Some of these properties are considered to be the basis for biologically relevant effects of nanoobjects. These are promoted by a) specific entry pathways and distribution within the body and tissues, b) uptake into single cells and specific intracellular distribution, and c) a high chemical reactivity, influencing dissolution, adsorption patterns and kinetics, or agglomeration. To take this even further, the composition and morphology of nanoobjects, their surface properties as well as the composition of the surrounding media influence the interactions of nanoobjects with molecules and living entities. Focussing on the intracellular location of nanoparticles, we are using well-defined and fluorescently labelled nanoparticles. In order to detect cell-associated 25 – 130nm silica particles, confocal and the recently developed STED (STimulated Emission Depletion) microscopy are applied. An introduction into the latter technique, allowing for sub-diffraction resolution, is given and results of microscopic studies are presented. Furthermore, the location of 3 – 15nm gold nanoparticles after uptake into A549 cells as model for type II alveolar cells was studied using light and correlative light and electron microscopy. The distribution pattern of 3nm gold nanoparticles seemed to be different compared with larger nanoparticles. At relevant concentrations, particles induced changes of the cellular morphology, involving the cytoskeleton. Biochemical assays are generally used to analyse nanoparticle effects. Nanotoxicity studies using conventional assays are prone to interference of the particles with the test systems. As an example for direct effects of nanoparticles on such assays, the interference of silica nanoparticles with the traditional Limulus amebocyte lysate gel clot assay was analysed. In the presence of particles, not only inhibition, but also enhancement of the test system was observed. The influence of nanoparticle properties on biological assays is discussed.