Spatially-resolved profiling of carbon nanotube uptake across cell lines.

The internalisation and intra-cellular distribution of carbon nanotubes (CNT) has been quantitatively assessed using imaging flow cytometry. Spatial analysis of the bright field images indicates the presence of a small sub-population (5% of cells) in which the internalised CNTs are packed into pronounced clusters, visible as dark spots due to strong optical scattering by the nanotubes. The area of these spots can be used as a label-free metric of CNT dose and we assess the relative uptake of charge-neutral CNTs, over a 24 hours exposure period across four cell types: J774 mouse macrophage cells, A549 and Calu-6 human lung cancer cells, and MCF-7 human breast cells. The relative dose as indicated by the spot-area metric closely correlates to results using the same CNT preparation, conjugated to a FITC-label and shows pronounced uptake by the J774 cells leading to a mean dose that is >60% higher than for the other cell types. Spatial evaluation of dosing clusters is also used to quantify differences in uptake by J774 cells of CNTs with different surface functionalisation. While the percentage of CNT-cluster positive cells increases from 5% to 19% when switching from charge-neutral CNTs to poly-cationic, dendron functionalised CNTs, the single cell level analysis of internalised clusters indicates a lower dose per cell of poly-cationic CNTs relative to the charge-neutral CNTs. We concluded that there is dose homeostasis i.e., the population-averaged cellular dose of CNTs remained unchanged.

Current Perspective of Carbon Nanotubes Application in Neurology.

The recent advances in nanotechnology have allowed new fields of research to investigate cutting edge brain-specific therapies and to tackle the complex brain-related disorders. The blood-brain barrier (BBB) is a major obstacle for drug delivery to the brain resulting in only few drugs reaching the market to tackle brain disorders. Nanoparticles (NPs) provide a flexible platform for conjugating drugs and targeting ligands and have been extensively researched to facilitate BBB crossing and effective delivery to the brain. In addition, the inherent properties of NPs are being utilized to facilitate other therapeutic possibilities. One example is carbon nanotubes (CNTs), which exhibit several attractive characteristics allowing their use in the brain environment. The properties include a high aspect ratio, the ability to penetrate biological membranes due to their tubular shape and their infrared absorption properties. In this chapter, we review major advances in using CNTs for treating brain tumor and degenerative diseases with special focus on their abilities to cross the BBB following systemic administration, which is the major obstacle for most other NPs.

Multiphoton luminescence imaging of chemically functionalized multi-walled carbon nanotubes in cells and solid tumors.

The intrinsic nonlinear photoluminescence (PL) property of chemically functionalized multi-walled nanotubes MWNTs (f-MWNTs) is reported in this study. f-MWNTs are imaged in fixed lung epithelial cancer cells (A549) and Kupffer cells in vitro, and in subcutaneously implanted solid tumors in vivo, for the first time, using multiphoton PL and fluorescence lifetime imaging (FLIM). Multiphoton imaging in the near-infrared excitation region (∼750-950 nm), employed in this study in a label-free manner, provides sensitivity and resolution optimal to track f-MWNTs within intra-cellular compartments and facilitates tumour imaging and sentinel lymph node tracking in vivo. Wider applications include employing this technique in live imaging of f-MWNTs in biological milieu to facilitate image-guided drug delivery.