Nancy J. Halas

Temperature-sensitive polymer/nanoshell composites for photothermally modulated drug delivery

Composites of thermally sensitive hydrogels and optically active nanoparticles have been developed for the purpose of photothermally modulated drug delivery. Copolymers of N-isopropylacrylamide (NIPAAm) and acrylamide (AAm) exhibit a lower critical solution temperature (LCST) that is slightly above body temperature. When the temperature of the copolymer exceeds the LCST, the hydrogel collapses, causing a burst release of any soluble material held within the hydrogel matrix. Gold-gold sulfide nanoshells, a new class of nanoparticles designed to strongly absorb near-infrared light, have been incorporated into poly(NIPAAm-co-AAm) hydrogels for the purpose of initiating a temperature change with light; light at wavelengths between 800 and 1200 nm is transmitted through tissue with relatively little attenuation, absorbed by the nanoparticles, and converted to heat. Significantly enhanced drug release from composite hydrogels has been achieved in response to irradiation by light at 1064 nm. We have investigated the release of methylene blue and proteins of varying molecular weight. Additionally, the nanoshell-composite hydrogels can release multiple bursts of protein in response to repeated near-IR irradiation.

Threefold Electron Scattering on Graphite Observed with C60-Adsorbed STM Tips

The scanning tunneling microscope (STM) has been used to observe threefold symmetric electron scattering from point defects on a graphite surface. These theoretically predicted electronic perturbations could not be observed with a bare metal tip but could only be imaged when a fullerene (C60) molecule was adsorbed onto the tunneling region (apex) of an STM tip. Functionalizing an STM tip with an appropriate molecular adsorbate alters the density of states near the Fermi level of the tip and changes its imaging characteristics.

Bethe-hole polarization analyser for the magnetic vector of light

The nature of light as an electromagnetic wave with transverse components has been confirmed using optical polarizers, which are sensitive to the orientation of the electric field. Recent advances in nanoscale optical technologies demand their magnetic counterpart, which can sense the orientation of the optical magnetic field. Here we report that subwavelength metallic apertures on infinite plane predominantly sense the magnetic field of light, establishing the orientation of the magnetic component of light as a separate entity from its electric counterpart. A subwavelength aperture combined with a tapered optical fibre probe can also serve as a nanoscale polarization analyser for the optical magnetic field, analogous to a nanoparticle sensing the local electric polarization. As proof of its functionality, we demonstrate the measurement of a magnetic field orientation that is parallel to the electric field, as well as a circularly polarized magnetic field in the presence of a linearly polarized electric field.

Nanoshell-mediated near infrared photothermal tumor therapy

A novel photothermal therapy of neoplastic tissue is described. The use of near infrared (NIR) absorbing nanoshells permits targeted photothermal ablation of tumor tissue via NIR heating of nanoshell-laden tumors using an extracorporeal near infrared source. Human breast carcinoma cells incubated with nanoshells in vitro were found to undergo photothermally induced morbitity upon exposure to NIR light (820 nm, 44 W/cm/sup 2/) as determined using a fluorescent viability stain. Cells without nanoshells displayed no loss in viability after the same periods and conditions of near infrared illumination. Likewise, in vivo studies under MR guidance revealed that exposure to low doses of near infrared light (820 nm, 4 W/cm/sup 2/) in solid tumors treated with metal nanoshells reached average temperatures capable of inducing irreversible tissue damage (/spl Delta/T=37.4/spl plusmn/6.6/spl deg/C) within 4-6 minutes. Controls treated without nanoshells demonstrated significantly less average temperatures upon exposure to near infrared light (/spl Delta/T<10/spl deg/C). These findings demonstrated good correlation with histological findings. Tissues heated above the thermal damage threshold displayed coagulation, cell shrinkage, and loss of nuclear staining-indicators of irreversible thermal damage. Control tissues did not display these indicators and appeared undamaged.

Nanoshell-polymer composites for photothermally modulated drug delivery

Summary form only given. Optically active gold nanoshells; have been incorporated into thermally, responsive copolymers of N-Isopropylacrylamide (NIPAAm) and acryl-amide (AAm) for the purpose of photothermally modulated drug delivery. The copolymer exhibits a lower critical solution temperature (LCST) that is slightly above body, temperature. When the temperature of the hydrogel exceeds its LCST, a rapid collapse occurs, expelling any material contained within the hydrogel. The gold nanoshells initiate a temperature increase, via targeted absorption of near IR light.

Optically controllable materials: potential valves and actuators in microfluidics and MEMS

Composite materials consisting of optically active nanoparticles embedded within a thermally sensitive polymer selectively collapse when irradiated by light that matches the peak absorbtion wavelength of the nanoparticles. A copolymer of N-isopropylacrylamide and acrylamide exhibits a lower critical solution temperature (LCST) that is dependent on the relative amounts of each monomer in the polymer. Raising the temperature of the copolymer above the LCST initiates a rapid, reversible collapse. Optically active nanoparticles have been incorporated into NIPAAm/AAm hydrogels for the purpose of initiating a temperature increase via targeted absorption of near IR and green light. Gold nanoshells consist of a thin layer of gold surrounding a silica core, and altering the core/shell ratio allows the absorption of the nanoshells to be tuned over the visible and near IR spectrum. Gold colloid absorbs green light strongly at 532 nm. Two sets of composite hydrogels were fabricated, each containing one of the two nanoparticles. The nanoshell-composite hydrogels collapse in response to near-infrared irradiation but do not react to green light. The opposite behavior occurs for the colloid-composite hydrogels. This independent optical addressability should prove useful in a wide range of applications such as microfluidics and MEMS.

Nanoscale plasmonics for molecular recognition and light-triggered molecular release

Metallic nanostructures designed to provide plasmon resonances at specific optical frequencies and strong yet uniform near-field electromagnetic enhancements are useful nanodevices for light-driven sensing and actuation. The large local fields on the surface of these structures support surface-enhanced spectroscopies such as surface enhanced Raman spectroscopy (SERS). To use plasmonic nanostructures for molecular recognition, their properties must be exploited in combination with molecular layers that provide an optical signature that corresponds to capture of a target molecule. DNA oligomers bound to the surface of plasmonic nanostructures provide an optical signal that is sensitive to the conformational changes in the DNA itself due to interaction with other molecules, as would occur in binding events. This type of optical detection is label-free and reporter-free, that is, it does not depend upon the presence of a dye molecule bound to the DNA to provide an optical signal. DNA-drug interactions can be directly detected in this manner: the binding kinetics of chemotherapy drugs such as cisplatin can be directly monitored by this method, providing a streamlined spectroscopic approach to drug discovery.

Effect of adsorbed molecules on hot electron relaxation in gold nanoshells

Summary form only given. The optical response of metal nanoparticles is dominated by the electrons and thus is extremely rapid. For bulk metals, the relaxation of hot electrons is understood as an electron-phonon interaction! The relaxation of hot electrons in nanoparticles is more complex and affected by size and embedding medium. Nanoshells are nanoparticles with a thin metal shell coating a dielectric core. For nanoshells, the excitation wavelength of the collective electron oscillation (plasmon resonance) depends on the core size and shell thickness. Nanoshells with gold sulfide core and a gold shell have a plasmon resonance tunable from 600-950 nm. When p-aminobenzoic acid aniline, n-propylamine, or p-mercaptobenzoic acid were added to an aqueous nanoshell solution, the molecules were bound to the gold surface by the amine or thiol groups. Enhanced Raman signals were detected from the bound molecules due to the large local electric fields at the metal nanoshell surface, confirming the binding of the molecules. The transient bleaching of the nanoshell solutions was measured in a degenerate pump-probe experiment. The induced change in transmission occurred because of the change in the dielectric function of the gold shell for a hot electron distribution. The mechanism by which the adsorbed molecules affect the electron relaxation could be energy transfer from the hot electrons to adsorbed molecules or perturbation of the electronic potential of the metal by the bound molecules. This perturbation could induce a decrease in Coulomb screening in the nanoshells.