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 highcontrast 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.nanoparticle biodistribution ͉ nanoparticle toxicity ͉ luminescence spectroscopy ͉ single-walled carbon nanotubes S ingle-walled carbon nanotubes (SWNTs) are an important class of artificial nanomaterials with remarkable mechanical, thermal, electronic, and optical properties. These properties suggest diverse future biomedical uses in areas such as targeted chemotherapeutics, in vitro cell markers, diagnostic imaging contrast agents, biochemical sensors, and photoablative therapy agents (1-9). Before medical applications can be developed, it is necessary to explore the behavior and fate of SWNTs in mammals. However, little is currently known in this area, in part because of the challenge of detecting and tracking these allcarbon nanoparticles in complex biological environments.SWNTs can be envisioned as sections of graphene sheets rolled up to form seamless cylindrical tubes with a variety of structures (10). Each of these structures has a well defined diameter and chiral angle and shows either semiconducting or metallic behavior. The nanotube preparations used for this study contain several dozen structural types that are Ϸ1 nm in diameter and Ϸ300 nm long. After excitation with visible light, each type of semiconducting SWNT fluoresces at a near-infrared (near-IR) wavelength between Ϸ900 and 1,600 nm that is characteristic of its specific structure (11, 12). We have previously exploited this fluorescence emission to study the active ingestion of SWNTs by macrophage cells in vitro (13).Here we report the use of the intrinsic near-IR fluorescence, which is a property only of individualized SWNTs, to measure their blood elimination kinetics in rabbits and to identify the organs in which they concentrate. These methods and results provide a foundation for developing the targeted delivery of nanotubes to specific tissues for diagnostic and therapeutic uses. In contrast to alternative methods that track carbon nanotubes by linking them covalently or noncovalently to external fluorophores or chelated radioisotopes (1,8,14), the near-IR fluor...

The ability of near-infrared fluorescence imaging to detect single-walled carbon nanotubes (SWNTs) in organisms and biological tissues has been explored using Drosophila melanogaster (fruit flies). Drosophila larvae were raised on food containing ∼10 ppm of disaggregated SWNTs. Their viability and growth were not reduced by nanotube ingestion. Near-IR nanotube fluorescence was imaged from intact living larvae, and individual nanotubes in dissected tissue specimens were imaged, structurally identified, and counted to estimate a biodistribution.

The fluorescence spectra of individual semiconducting single-walled carbon nanotubes embedded in polymer films were measured during the application of controlled stretching and compressive strains. Nanotube band gaps were found to shift in systematic patterns that depend on the (n,m) structural type and are in excellent agreement with the predictions of theoretical models. Loss of nanotube-host adhesion was revealed by abrupt irregularities in plots of spectral shift vs strain.

A new approach is described for delivering small interfering RNA (siRNA) into cancer cells by noncovalently complexing unmodifi ed siRNA with pristine single-walled carbon nanotubes (SWCNTs). The complexes were prepared by simple sonication of pristine SWCNTs in a solution of siRNA, which then served both as the cargo and as the suspending agent for the SWCNTs. When complexes containing siRNA targeted to hypoxiainducible factor 1 alpha (HIF-1 ) were added to cells growing in serum containing culture media, there was strong specific inhibition of cellular HIF-1 activity. The ability to obtain a biological response to SWCNT / siRNA complexes was seen in a wide variety of cancer cell types. Moreover, intratumoral administration of SWCNT-HIF-1 siRNA complexes in mice bearing MiaPaCa-2 / HRE tumors signifi cantly inhibited the activity of tumor HIF-1 . As elevated levels of HIF-1 are found in many human cancers and are associated with resistance to therapy and decreased patient survival, these results imply that SWCNT / siRNA complexes may have value as therapeutic agents.

No abstract

not Available.