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Size and shape tunability have been widely demonstrated for gold nanorods (AuNRs), but reproducible and reliable protocols for the synthesis of small nanocrystals with high yield are still needed for potential biomedical applications. Here, we present novel seed-mediated and seedless protocols for gold nanorods by incorporating bioadditives or small thiolated molecules during the growth stage. The bioadditives glutathione (GSH), oxidized glutathione (GSSG), l-cysteine (l-cys), and l-methionine (l-met) are utilized in nanomolar and micromolar concentrations to modify the aspect ratio of AuNRs in a reproducible form. Overall, smaller aspect ratios are achieved for both synthetic approaches due to reduction in length or increment in length and width depending on the method, type of bioadditive and the strength of its interaction with the nanorod surface. For the seeded synthesis, only GSSG produces large nanorods in high yield, whereas for the seedless method GSH and GSSG form small nanorods with higher quality when compared to controls.

Gold nanoprisms (AuNPRs) are anisotropic nanostructures that have gained great attention in recent years because of their interesting and unique optical properties that can be tailored for biomedical, energy, and sensing applications. At present, several protocols have reported the high yield synthesis of AuNPRs of different dimensions using a seed-mediated approach. However, there is a need to develop reproducible and scalable methods with the goal of a controllable synthesis. Here, we report an improved seed-mediated synthesis of small monodisperse AuNPRs of distinct sizes in high yield using poly(vinylpyrrolidone) (PVP) as an additive in nanomolar concentrations. We show optimal synthetic parameters for a blue-shifting of the surface plasmon resonance band which correlates with the reduction in the edge length (L) of AuNPRs from 75 to 35 nm. Using measured extinction coefficients for AuNPRs of different sizes, a linear equation is proposed to estimate the concentration of unknown samples by using Beer’s law. Interestingly, the use of nanomolar amounts of PVP during the growth of AuNPRs significantly improves the shape yield. The surface chemistry properties of AuNPRs were measured by X-ray photoelectron spectroscopy and attenuated total reflectance infrared spectroscopy and revealed that PVP chains interact with AuNPRs through the carbonyl oxygen. This method is reproducible and scalable and enables the synthesis of AuNPRs with long-term shape stability (1 year) in aqueous solution.

Using the method of 3D optoacoustic tomography, we studied changes in tissues of the whole body of nude mice as the changes manifested themselves from live to postmortem. The studies provided the necessary baseline for optoacoustic imaging of necrotizing tissue, acute and chronic hypoxia, and reperfusion. They also establish a new optoacoustic model of early postmortem conditions of the whole mouse body. Animals were scanned in a 37°C water bath using a three-dimensional optoacoustic tomography system previously shown to provide high contrast maps of vasculature and organs based on changes in the optical absorbance. The scans were performed right before, 5 minutes after, 2 hours and 1 day after a lethal injection of KCl. The near-infrared laser wavelength of 765 nm was used to evaluate physiological features of postmortem changes. Our data showed that optoacoustic imaging is well suited for visualization of both live and postmortem tissues. The images revealed changes of optical properties in mouse organs and tissues. Specifically, we observed improvements in contrast of the vascular network and organs after the death of the animal. We associated these with reduced optical scattering, loss of motion artifacts, and blood coagulation.

We used a three-dimensional optical tomogaphy system that was previously developed to create high contrast maps of optical absorbance of mice tissues. In this study, animals were scanned before and after injection of gold nanorods (GNRs) at different time periods. As-synthesized GNRs were purified from hexadecyltrimethylammonium bromide (CTAB) and coated with polyethylene glycol (PEG) to obtain GNR-PEG complexes suitable for in vivo applications. Intravenous administration of the purified GNR-PEG complexes to mice resulted in an enhanced contrast of normal tissues and blood vessels as compared to ordinary nude mice. In parallel with optoacoustic imaging we investigated the accumulation of GNRs in liver using invasive analytical techniques. Maximum levels of GNRs in liver macrophages were observed after 48-72 hours post-injection, followed by slow clearance trend after 8 days. Optoacoustic imaging revealed redistribution of GNR in mouse organ and tissues: in the initial hours, accumulation of GNRs is seen predominantly in the periphery of the mouse, while a gradual increase of GNR levels in liver, spleen and kidneys is seen in 1 and 24 hours.

Background : This study was designed to investigate the relationship between the ethanol‐oxidizing capacity of the brain, accumulation of acetaldehyde, and ethanol‐induced hypnosis in animals in vivo.

Background : To clarify the role of brain acetaldehyde in the hypnotic effect of ethanol, we compared the ethanol‐oxidizing capacity (rate of acetaldehyde accumulation) and catalase and aldehyde dehydrogenase activity in the brains of animals genetically selected for different sensitivities to the hypnotic effect of ethanol.

It was found that the accumulation of acetaldehyde produced from 50 mM ethanol in rat brain homogenates takes place in all major brain regions. The velocity varied between 3.5 to 7.1 nmol/mg of protein/hr. The rate increased in the following orderbrain hemispheres, striatum, brainstem, hypothalamus, and cerebellum. Significant regional differences in this process were found in the initial period of incubation (5 min), acetaldehyde accumulation was maximal in the brain hemispheres; but, in the 30‐ to 60‐min period, it became significantly higher in the cerebellum. Inhibition of this process by the catalase inhibitor, 3‐amino‐1,2,4‐triazole (8 mM), was minimal in the brainstem (27%) and maximal (57%) in the cerebellum, despite nearly complete inhibition of catalase. This would indicate that processes other than catalase activity must contribute to acetaldehyde accumulation.

Introduction:Our laboratories’ focus is synthesis of potential carbon nanoparticle (CNP) therapeutics for acute injury. To enhance the likelihood of regulatory approval, we tested whether medicinal grade activated charcoal (AC) could serve as the initial source. Taken up avidly and localizing to organelles, e.g. mitochondria, CNP’s broad redox potential could facilitate electron transfer. Here, we test whether CNPs from AC are cytoprotective in a brain endothelial cell line and their restoration of cerebral autoregulation in a traumatic brain injury model.Materials and Methods:5-30 nM oxidized AC (OAC) were synthesized from medicinal AC, treated with oleum and 90% nitric acid, then covalently PEGylated. Cell number was assessed in bEnd.3 cells incubated 18 hrs with 50 μM H2O2w/wo 8 mg/L PEG-OACs. An electron transport assay was performed with NADH (e-donor) and resazurin (e-acceptor) using kinetic UV-vis spectroscopy. 2 mg/kg PEG-OACs were administered IV to rats upon resuscitation and at 200 minutes after mild fluid percussion injury model with superimposed 80 minutes of hypotensive shock, a model known to impair reperfusion. Cerebral perfusion was monitored by laser doppler flowmetry.Results:PEG-OAC improved viability (Fig. 1a; 47% vs. 80%; p=.005). Oxidation of NADH was 3.8x faster than w/o OAC (Fig. 1b). Cerebral perfusion was restored by PEG-OAC after direct cortical injury compared to PBS vehicle (n=10; Fig. 1c; p=.0008).Conclusion:PEG-OACs protect cultured cells from oxidative stress caused by H2O2, a byproduct of ischemia, exhibit electron shuttle-like properties and restore cerebral reperfusion in-vivo when given at a clinically relevant time point.

Gold nanorods (GNR) with a peak absorption wavelength of 760 nm were prepared using a seed-mediated method. A novel protocol has been developed to replace hexadecyltrimethylammonium bromide (CTAB) on the surface of GNR with 16-mercaptohexadecanoic acid (MHDA) and metoxy-poly(ethylene glycol)-thiol (PEG), and the monoclonal antibodies: HER2 or CD33. The physical chemistry property of the conjugates was monitored through optical and zetapotential measurements to confirm surface chemistry. The plasmon resonance is kept in the near infrared area, and changes from strong positive charge for GNR-CTAB to slightly negative for GNR-PEG-mAb conjugates are observed. The conjugates were investigated for different cells lines: breast cancer cells and human leukemia lines in vivo applications. These results demonstrate successful tumor accumulation of our modified PEG-MHDA conjugates of GNR for HER2/neu in both overexpressed breast tumors in nude mice, and for thermolysis of human leukemia cells in vitro. The conjugates are non-toxic and can be used in pre-clinical applications, as well as molecular and optoacoustic imaging, and quantitative sensing of biological substrates.