TY - JOUR
T1 - Cellular uptake mechanisms of functionalised multi-walled carbon nanotubes by 3D electron tomography imaging.
AU - Al-Jamal, Khuloud T.
AU - Nerl, Hannah
AU - Müller, Karin H.
AU - Ali-Boucetta, Hanene
AU - Li, Shouping
AU - Haynes, Peter D.
AU - Jinschek, Joerg R.
AU - Prato, Maurizio
AU - Bianco, Alberto
AU - Kostarelos, Kostas
AU - Porter, Alexandra E.
PY - 2011/6
Y1 - 2011/6
N2 - 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.
AB - 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.
U2 - 10.1039/c1nr10080g
DO - 10.1039/c1nr10080g
M3 - Article
C2 - 21603701
SN - 2040-3372
VL - 3
SP - 2627
EP - 2635
JO - Nanoscale
JF - Nanoscale
IS - 6
ER -