Martin G. O'Toole

Release-Modulated Antioxidant Activity of a Composite Curcumin-Chitosan Polymer.

Curcumin is known to have immense therapeutic potential but is hindered by poor solubility and rapid degradation in solution. To overcome these shortcomings, curcumin has been conjugated to chitosan through a pendant glutaric anhydride linker using amide bond coupling chemistry. The hybrid polymer has been characterized by UV-visible, fluorescence, and infrared spectroscopies as well as zeta potential measurements and SEM imaging. The conjugation reactivity was confirmed through gel permeation chromatography and quantification of unconjugated curcumin. An analogous reaction of curcumin with glucosamine, a small molecule analogue for chitosan, was performed and the purified product characterized by mass spectrometry, UV-visible, fluorescence, and infrared spectroscopies. Conjugation of curcumin to chitosan has greatly improved curcumin aqueous solubility and stability, with no significant curcumin degradation detected after one month in solution. The absorbance and fluorescence properties of curcumin are minimally perturbed (λmax shifts of 2 and 5 nm, respectively) by the conjugation reaction. This conjugation strategy required use of one out of two curcumin phenols (one of the main antioxidant functional groups) for covalent linkage to chitosan, thus temporarily attenuating its antioxidant capacity. Hydrolysis-based release of curcumin from the polymer, however, is accompanied by full restoration of curcumins antioxidant potential. Antioxidant assays show that curcumin radical scavenging potential is reduced by 40% after conjugation, but that full antioxidant potential is restored upon hydrolytic release from chitosan. Release studies show that curcumin is released over 19 days from the polymer and maintains a concentration of 0.23 ± 0.12 μM curcumin/mg polymer/mL solution based on 1% curcumin loading on the polymer. Release studies in the presence of carbonic anhydrase, an enzyme with known phenolic esterase activity, show no significant difference from nonenzymatic release studies, implying that simple ester hydrolysis is the dominant release mechanism. Conjugation of curcumin to chitosan through a phenol ester modification provides improved stability and solubility to curcumin, with ester hydrolysis restoring the full antioxidant potential of curcumin.

Highly Specific, NIR Fluorescent Contrast Agent with Emission Controlled by Gold Nanoparticle

Nanoparticles are currently being intensively studied for in vivo molecular imaging because of their unique and beneficial properties. Among these particles, some metal particles possess strong surface plasmon fields that can effectively alter fluorescence. Using this fluorescence alteration, an NIR fluorophore based, nanosized contrast agent for breast cancer diagnosis is being developed. The fluorophore is conjugated to gold nanoparticles (GNP) via a short spacer whose length was specially adjusted to have the strong plasmon field to quench the fluorescence. The spacer also has a special molecular sequence that can be cleaved by an enzyme secreted by targeted cancer cells. Normally, the entity does not fluoresce. If it is delivered to the cancer site, the short spacer would be cleaved by the enzyme secreted by the cancer cell at which point the fluorescence would be restored. This entity can incorporate a cancer targeting molecule for a cancer specific delivery. The entity specifically targets cancer cells and fluoresce only when the spacer is cleaved by a specific cancer secreting biomolecule, providing dual specificity for cancer diagnosis. In the future, this entity will be combined with cancer drugs for seamless detection and personalized therapy.

A high yield, controllable process for producing tunable near infrared-absorbing gold nanoplates†

The purpose of this study was to optimize a new synthesis technique, “DiaSynth,” to produce near-infrared (nIR) absorbing gold nanoplates with prescribed localized surface plasmon resonance (LSPR) wavelengths in higher yields over conventional synthesis methods without the need for laborious purification steps. The molecular weight cut off (MWCO; 3.5, 8, 12, 15, 25 & 50 kDa) of the regenerated cellulose membranes (RCM), temperature (25, 37, 50 & 100 °C) and surface area to volume (SA/Vol) ratio (220, 340 & 470 mm2 ml−1) of the RCM to the gold nanoplate solution were varied during the synthesis process to determine the effect of each parameter on gold nanoplates yield, LSPR peak placement and stability. Results indicate the ability of the RCM to remove ∼99% of the contaminant small gold colloid (<10 nm) produced during the synthesis process, while producing a 72% higher yield of gold nanoplates compared to a conventional one-step fabrication process. Increasing the MWCO of the RCM from 3.5 kDa to 15 kDa was found to blue shift the LSPR peak down by 40 nm. Increasing the SA/Vol ratio and temperature blue shifted the LSPR peak wavelength by hundreds of nanometers with the nIR absorbing gold nanoplate LSPR peak occurring within the range of 650–1100 nm. It was also discovered that the gold nanoplates fabricated via the DiaSynth process with dialysis (Process 1) displayed an increase in stability over time without the need of a capping agent. With the increased gold nanoplate stability, further purification and isolation of gold nanoplates was possible through sedimentation over time. This study demonstrated that increasing the temperature, SA/Vol, and MWCO of the RCM allows production of gold nanoplates of increased purity compared to other methods and the ability to tailor the tunability of the LSPR peak to a desired wavelength.

Wavelength specific excitation of gold nanoparticle thin-films

Advances in microelectromechanical systems (MEMS) continue to empower researchers with the ability to sense and actuate at the micro scale. Thermally driven MEMS components are often used for their rapid response and ability to apply relatively high forces. However, thermally driven MEMS often have high power consumption and require physical wiring to the device. This work demonstrates a basis for designing light-powered MEMS with a wavelength specific response. This is accomplished by patterning surface regions with a thin film containing gold nanoparticles that are tuned to have an absorption peak at a particular wavelength. The heating behavior of these patterned surfaces is selected by the wavelength of laser directed at the sample. This method also eliminates the need for wires to power a device. The results demonstrate that gold nanoparticle films are effective wavelength-selective absorbers. This “hybrid” of infrared absorbent gold nanoparticles and MEMS fabrication technology has potential applications in light-actuated switches and other mechanical structures that must bend at specific regions. Deposition methods and surface chemistry will be integrated with three-dimensional MEMS structures in the next phase of this work. The long-term goal of this project is a system of light-powered microactuators for exploring cellular responses to mechanical stimuli, increasing our fundamental understanding of tissue response to everyday mechanical stresses at the molecular level.