Journal
NANOSCALE
Volume 3, Issue 6, Pages 2627-2635Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c1nr10080g
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Funding
- European Union [HEALTH-2008-20157]
- Life Sciences Division FEI Company Eindhoven, The Netherlands
- Centre for Electron Nanoscopy
- Danish Technical University, Lynby, DK
- National Research Fund Luxembourg (FNR)
- Engineering and Physical Sciences Research Council
- EPSRC [EP/C51596X]
- CNRS
- Agence Nationale de la Recherche [ANR-05-JCJC-0031-01]
- University of Trieste MUR [2006035330]
- Regione Friuli Venezia-Giulia
- Ministere de l'Enseignement Superieur et de la Recherche Scientifique (Algeria)
- Medical Research Council [G0801056B] Funding Source: researchfish
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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-NH3+). 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-NH3+ 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-NH3+ were able to escape vesicular (phagosome) entrapment by translocating directly into the cytoplasm.
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