Paul Cherukuri

Mammalian pharmacokinetics of carbon nanotubes using intrinsic near-infrared fluorescence

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.

Targeted hyperthermia using metal nanoparticles

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.

Replacing Mn2+ with Co2+ in Human Arginase I Enhances Cytotoxicity toward L-Arginine Auxotrophic Cancer Cell Lines

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 led 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- to 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.

Teslaphoresis of Carbon Nanotubes

This paper introduces Teslaphoresis, the directed motion and self-assembly of matter by a Tesla coil, and studies this electrokinetic phenomenon using single-walled carbon nanotubes (CNTs). Conventional directed self-assembly of matter using electric fields has been restricted to small scale structures, but with Teslaphoresis, we exceed this limitation by using the Tesla coils antenna to create a gradient high-voltage force field that projects into free space. CNTs placed within the Teslaphoretic (TEP) field polarize and self-assemble into wires that span from the nanoscale to the macroscale, the longest thus far being 15 cm. We show that the TEP field not only directs the self-assembly of long nanotube wires at remote distances (>30 cm) but can also wirelessly power nanotube-based LED circuits. Furthermore, individualized CNTs self-organize to form long parallel arrays with high fidelity alignment to the TEP field. Thus, Teslaphoresis is effective for directed self-assembly from the bottom-up to the macroscale.