The uptake of pristine single-walled carbon nanotubes into macrophage-like cells has been studied using the nanotubes' intrinsic near-infrared fluorescence. Macrophage samples that have been incubated in growth media containing suspended single-walled nanotubes show characteristic nanotube fluorescence spectra. The fluorescence intensities increase smoothly with incubation time and external nanotube concentration. Near-infrared fluorescence microscopy at wavelengths above 1100 nm provides high contrast images indicating localization of nanotubes in numerous intracellular vesicles. Nanotube uptake appears to occur through phagocytosis. Population growth of macrophage cultures is unaffected by exposure to single-walled nanotube concentrations of ca. 4 mug/mL for up to 96 h.

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...

Despite the use of hyperthermia to treat cancer for thousands of years, the challenge of only heating malignant cells remains daunting. In pre-clinical and early clinical trials, metal nanoparticles induce hyperthermic cytotoxicity when exposed to near-infrared radiation or radiofrequency fields. We discuss the emerging roles of nanoparticles, especially gold, in the hyperthermic treatment of cancer. In addition, we discuss the similarities of radiofrequency ablation and nanoparticle mediated cytotoxicity.

The dyeing properties of cationic cotton dyed with acid dyes are examined in this study. For comparison, nylon 6 and untreated cotton are dyed by the same acid dyes (Sandolan Red MF‐2BL, Sandolan Golden Yellow MF‐GL, and Sandolan Blue MF‐GL). A cationic agent, polyepichlorohydrin‐dimethylamine (PECH‐amine), is used to modify cotton fabric. Significant increase in color yield is observed for cationic cotton over untreated cotton because of the introduced positively charged sites by cationic modification. Deeper shades are obtained in all cases with cationic cotton. All of the acid dyes used in this study show significant hooking behavior with both cationic cotton and nylon. © 2006 Wiley Periodicals, Inc. J Appl Polym Polym Sci 100: 3302–3306, 2006

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.

Capacitively coupled shortwave radiofrequency fields (13.56 MHz) resistively heat low concentrations (~1 ppm) of gold nanoparticles with a thermal power dissipation of ~380 kW/g of gold. Smaller diameter gold nanoparticles (< 50 nm) heat at nearly twice the rate of larger diameter gold nanoparticles (≥50 nm), which is attributed to the higher resistivity of smaller gold nanostructures. A Joule heating model has been developed to explain this phenomenon and provides critical insights into the rational design and engineering of nanoscale materials for noninvasive thermal therapy of cancer.

Replacing the two Mn 2+ ions normally present in human Arginase I with Co 2+ resulted in a significantly lowered K M value without a concomitant reduction in k cat . In addition, the pH dependence of the reaction was shifted from a pK a of 8.5 to a pK a of 7.5. The combination of these effects lead to a 10-fold increase in overall catalytic activity (k cat /K M ) at pH 7.4, close to the pH of human serum. Just as important for therapeutic applications, Co 2+ substitution lead to significantly increased serum stability of the enzyme. Our data can be explained by direct coordination of L-Arg to one of the Co 2+ ions during reaction, consistent with previously reported model studies. In vitro cytotoxicity experiments verified that the Co 2+ substituted human Arg I displays an approximately 12-15-fold lower IC 50 value for the killing of human hepatocellular carcinoma and melanoma cell lines, and thus constitutes a promising new candidate for the treatment of L-Arg auxotrophic tumors. KeywordsArginase; Cancer; Cobalt; Therapeutic; Hepatocellular Carcinoma; Melanoma; Enzyme Therapy There is clearly a need for new or improved therapies for cancers such as hepatocellular carcinomas (HCCs) and melanomas that are refractile to currently used chemotherapy. Fortunately, some malignancies have underlying metabolic deficiencies that provide a unique chemotherapeutic opportunity. Many hepatocellular, prostate or renal carcinomas as well as metastatic melanomas have an impaired urea cycle and thus are auxotrophic for the nonessential amino acid L-Arginine (L-Arg), experiencing cell cycle arrest and apoptosis in its absence. Clinical trials with the L-Arg degrading enzyme arginine deiminase (ADI) from

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.