Mammalian pharmacokinetics of carbon nanotubes using intrinsic near-infrared fluorescence

Abstract

Individualized, chemically pristine single-walled carbon nanotubes have been intravenously administered to rabbits and monitored through their characteristic near-infrared fluorescence. Spectra indicated that blood proteins displaced the nanotube coating of synthetic surfactant molecules within seconds. The nanotube concentration in the blood serum decreased exponentially with a half-life of 1.0 +/- 0.1 h. No adverse effects from low-level nanotube exposure could be detected from behavior or pathological examination. At 24 h after i.v. administration, significant concentrations of nanotubes were found only in the liver. These results demonstrate that debundled single-walled carbon nanotubes are high-contrast near-infrared fluorophores that can be sensitively and selectively tracked in mammalian tissues using optical methods. In addition, the absence of acute toxicity and promising circulation persistence suggest the potential of carbon nanotubes in future pharmaceutical applications.

Fig. 1.

Normalized emission spectra (using 658 nm excitation) of samples of SWNTs prepared as suspensions in aqueous Pluronic (thin blue curve), in rabbit serum (dotted curve), and in blood serum sampled 30 min after i.v. injection (thick red curve).

Fig. 2.

Measured fluorescence intensity (symbols) for a sample of Pluronic-suspended SWNTs mixed with rabbit serum, as a function of time from mixing. The solid curve shows a best fit to a biexponential kinetic model.

Fig. 3.

Time dependence of blood serum SWNT concentration after injection, as measured for four rabbits. Each data point is the averaged emission intensity spectrally integrated above a linear baseline connecting the minima at 1,100 and 1,250 nm. This baseline construction captures a major SWNT fluorescence feature while avoiding systematic errors from an underlying background of weak autofluorescence. Error bars show standard errors of the mean. The solid curve is a first-order kinetic fit to the data.

Fig. 4.

Micrographs at two magnifications of liver tissue from rabbits killed 24 h after i.v. administration of suspended SWNTs. (A and B) Near-IR SWNT fluorescence images with field widths of 390 μm (A) and 83 μm (B). Scattered isolated bright pixels are artifacts from defective sensor elements in the near-IR camera; all larger features represent emission from SWNTs. In C and D, the SWNT fluorescence from A and B is shown overlaid as false-color green onto visible bright-field images from adjacent 3-μm-thick specimen slices that had been stained with hematoxylin and eosin.