title: Cellular uptake mechanisms of functionalised multi-walled carbon nanotubes by 3D electron tomography imaging.
abstract: Carbon nanotubes (CNTs) are being investigated for a variety of biomedical applications. Despite numerous studies, the pathways by which carbon nanotubes enter cells and their subsequent intracellular trafficking and distribution remain poorly determined. Here, we use 3-D electron tomography techniques that offer optimum enhancement of contrast between carbon nanotubes and the plasma membrane to investigate the mechanisms involved in the cellular uptake of shortened, functionalised multi-walled carbon nanotubes (MWNT-NH(3)(+)). Both human lung epithelial (A549) cells, that are almost incapable of phagocytosis and primary macrophages, capable of extremely efficient phagocytosis, were used. We observed that MWNT-NH(3)(+) were internalised in both phagocytic and non-phagocytic cells by any one of three mechanisms: (a) individually via membrane wrapping; (b) individually by direct membrane translocation; and (c) in clusters within vesicular compartments. At early time points following intracellular translocation, we noticed accumulation of nanotube material within various intracellular compartments, while a long-term (14-day) study using primary human macrophages revealed that MWNT-NH(3)(+) were able to escape vesicular (phagosome) entrapment by translocating directly into the cytoplasm.
authors: Nanomedicine Laboratory, Centre for Drug Delivery Research, The School of Pharmacy, University of London, London, WC1N 1AX, UK.
authors: Khuloud T
authors: KT
authors: Al-Jamal
authors: Hannah
authors: H
authors: Nerl
authors: Karin H
authors: KH
authors: Müller
authors: Hanene
authors: H
authors: Ali-Boucetta
authors: Shouping
authors: S
authors: Li
authors: Peter D
authors: PD
authors: Haynes
authors: Joerg R
authors: JR
authors: Jinschek
authors: Maurizio
authors: M
authors: Prato
authors: Alberto
authors: A
authors: Bianco
authors: Kostas
authors: K
authors: Kostarelos
authors: Alexandra E
authors: AE
authors: Porter