Submitted Abstract
Abstract of the thesis:The aims of the PhD project were to understand the mechanisms of cellular uptake as well as the intracellular biostability of functionalised multi-walled carbon nanotubes (f-MWNTs).Firstly, high resolution transmission electron microscopy (HR TEM) imaging and 3-D electron tomography were applied to study the pathways of f-MWNTs into non- phagocytic cells, and more specifically, to study the interaction between the f-MWNTs and the cell membrane. After exposing epithelial cells to f-MWNTs for 24 hours, two distinct uptake processes by which amino f-MWNTs can enter epithelial cells, were observed.This study was complemented by use of coarse-grained molecular dynamics simulations, to provide insight into, the interaction of f-CNTs with cell membranes and the effect of surface charge on this interaction.Secondly, the question whether f-MWNTs can be degraded by the body’s own defence mechanisms was addressed. HR TEM techniques were used to assess the graphitic structure and morphology of f-MWNTs after exposure in vivo in the murine brain and after exposure to cells from culture; with the aim to understand the mechanisms underlying the degradation process. F-MWNTs were found to have a reduced biostability in the brain tissue and in the cells from culture. By using STEM electron energy loss spectroscopy (STEM EELS) to compare the near-edge structure of the carbon K-edge prior to and post injection, graphitic CNTs could be distinguished from the graphitic debris and the amorphous cell background. This provided information about the individual steps, leading to the degradation of the f-MWNTs, and the nature of the degradation debris. In order to study the effect of the functionalization on the biostability, the study was repeated using pristine MWNTs in cells from culture. No signs of degradation of the pristine MWNTs were observed after 14 days exposure to cells from culture.