Shape dependence of nonlinear optical behaviors of gold nanoparticles

Tetrahedral, icosahedral, and cubic gold nanoparticles have been synthesized in experiment by reducing chloroauric acid with ethylene glycol (EG) in the presence of poly(vinylpyrrolidone) (PVP). The nonlinear properties of the gold nanoparticles have been investigated by using the Open-aperture Z-scan technique with the nanosecond pulse at a wavelength of 532 nm. It shows out that all the gold nanoparticles possess strong optical nonlinearities when being excited at their surface plasmon resonances. It is identified that the nonlinear properties of the gold nanoparticles are dependent on their shapes, and the icosahedra gold nanoparticles show much better nonlinear optical properties than the tetrahedral and cubic ones. Moreover, the mechanism for the process of the nonlinear properties is also analyzed.     

Pharmacokinetic and toxicological evaluation of multi-functional thiol-6-fluoro-6-deoxy-d-glucose gold nanoparticles in vivo

We synthesized a novel, multi-functional, radiosensitizing agent by covalently linking 6-fluoro-6-deoxy-d-glucose (6-FDG) to gold nanoparticles (6-FDG-GNPs) via a thiol functional group. We then assessed the bio-distribution and pharmacokinetic properties of 6-FDG-GNPs in vivo using a murine model. At 2?h, following intravenous injection of 6-FDG-GNPs into the murine model, approximately 30% of the 6-FDG-GNPs were distributed to three major organs: the liver, the spleen and the kidney. PEGylation of the 6-FDG-GNPs was found to significantly improve the bio-distribution of 6-FDG-GNPs by avoiding unintentional uptake into these organs, while simultaneously doubling the cellular uptake of GNPs in implanted breast MCF-7 adenocarcinoma. When combined with radiation, PEG-6-FDG-GNPs were found to increase the apoptosis of the MCF-7 breast adenocarinoma cells by radiation both in vitro and in vivo. Pharmacokinetic data indicate that GNPs reach their maximal concentrations at a time window of two to four hours post-injection, during which optimal radiation efficiency can be achieved. PEG-6-FDG-GNPs are thus novel nanoparticles that preferentially accumulate in targeted cancer cells where they act as potent radiosensitizing agents. Future research will aim to substitute the (18)F atom into the 6-FDG molecule so that the PEG-6-FDG-GNPs can also function as radiotracers for use in positron emission tomography scanning to aid cancer diagnosis and image guided radiation therapy planning.     

In vivo biodistribution and urinary excretion of mesoporous silica nanoparticles: effects of particle size and PEGylation

The in vivo biodistribution and urinary excretion of spherical mesoporous silica nanoparticles (MSNs) are evaluated by tail-vein injection in ICR mice, and the effects of the particle size and PEGylation are investigated. The results indicate that both MSNs and PEGylated MSNs of different particle sizes (80-360 nm) distribute mainly in the liver and spleen, a minority of them in the lungs, and a few in the kidney and heart. The PEGylated MSNs of smaller particle size escape more easily from capture by liver, spleen, and lung tissues, possess longer blood-circulation lifetime, and are more slowly biodegraded and correspondingly have a lower excreted amount of degradation products in the urine. Neither MSNs nor PEGylated MSNs cause tissue toxicity after 1 month in vivo.     

Controlling in vivo stability and biodistribution in electrostatically assembled nanoparticles for systemic delivery

This paper demonstrates the generation of systemically deliverable layer-by-layer (LbL) nanoparticles for cancer applications. LbL-based nanoparticles designed to navigate the body and deliver therapeutics in a programmable fashion are promising new and alternative systems for drug delivery, but there have been very few demonstrations of their systemic delivery in vivo due to a lack of knowledge in building LbL nanofilms that mimic traditional nanoparticle design to optimize delivery. The key to the successful application of these nanocarriers in vivo requires a systematic analysis of the influence of film architecture and adsorbed polyelectrolyte outer layer on their pharmacokinetics, which has thus far not been examined for this new approach to nanoparticle delivery. Herein, we have taken the first steps in stabilizing and controlling the systemic distribution of multilayer nanoparticles. Our findings highlight the unique character of LbL systems; the electrostatically assembled nanoparticles gain increased stability in vivo with larger numbers of deposited layers, and the final layer adsorbed generates a critical surface cascade, which dictates the surface chemistry and biological properties of the nanoparticle. This outer polyelectrolyte layer dramatically affects not only the degree of nonspecific particle uptake, but also the nanoparticle biodistribution. For hyaluronic acid (HA) outer layers, a long blood elimination half-life (～9 h) and low accumulation (～10-15% recovered fluorescence/g) in the liver were observed, illustrating that these systems can be designed to be highly appropriate for clinical translation.     

Shape control of gold nanoparticles by silver underpotential deposition

Four different gold nanostructures: octahedra, rhombic dodecahedra, truncated ditetragonal prisms, and concave cubes, have been synthesized using a seed-mediated growth method by strategically varying the Ag(+) concentration in the reaction solution. Using X-ray photoelectron spectroscopy and inductively coupled plasma atomic emission spectroscopy, we provide quantitative evidence that Ag underpotential deposition is responsible for stabilizing the various surface facets that enclose the above nanoparticles. Increasing concentrations of Ag(+) in the growth solution stabilize more open surface facets, and experimental values for Ag coverage on the surface of the particles fit well with a calculated monolayer coverage of Ag, as expected via underpotential deposition.     

In vivo imaging and biodistribution of multimodal polymeric nanoparticles delivered to the optic nerve

The use of nanoparticles for targeted delivery of therapeutic agents to sites of injury or disease in the central nervous system (CNS) holds great promise. However, the biodistribution of nanoparticles following in vivo administration is often unknown, and concerns have been raised regarding potential toxicity. Using poly(glycidyl methacrylate) (PGMA) nanoparticles coated with polyethylenimine (PEI) and containing superparamagnetic iron oxide nanoparticles as a magnetic resonance imaging (MRI) contrast agent and rhodamine B as a fluorophore, whole animal MRI and fluorescence analyses are used to demonstrate that these nanoparticles (NP) remain close to the site of injection into a partial injury of the optic nerve, a CNS white matter tract. In addition, some of these NP enter axons and are transported to parent neuronal somata. NP also remain in the eye following intravitreal injection, a non-injury model. Considerable infiltration of activated microglia/macrophages occurs in both models. Using magnetic concentration and fluorescence visualization of tissue homogenates, no dissemination of the NP into peripheral tissues is observed. Histopathological analysis reveals no toxicity in organs other than at the injection sites. Multifunctional nanoparticles may be a useful mechanism to deliver therapeutic agents to the injury site and somata of injured CNS neurons and thus may be of therapeutic value following brain or spinal cord trauma.     

Bio-synthesis of gold nanoparticles by human epithelial cells, in vivo

Healthy epithelial cells, in vivo, have the ability to synthesize gold nanoparticles when aqueous tetrachloroauric acid is made to react with human skin. Neither a reducing agent nor a protecting chemical is needed for this bio-synthesis method. The first indication of gold nanoparticle formation is the staining of the skin, which turns deep purple. Stereoscopic optical micrographs of human skin tissue in contact with aqueous tetrachloroauric acid clearly show the staining of the epithelial cells. The UV-Vis spectrum of these epithelial cells shows an absorption band with a maximum at 553 nm. This absorption peak is within the wavelength region where the surface plasmon resonance (SPR) band of aqueous colloidal gold exhibits a maximum. Transmission electron micrographs show that gold nanoparticles synthesized by epithelial cells have sizes between 1 and 100 nm. The electron diffraction pattern of these nanoparticles reveals a crystalline structure whose interplanar distances correspond to fcc metallic gold. Transmission electron micrographs of ultra-thin (70 nm thick) slices of epithelial cells clearly and undoubtedly demonstrate that gold nanoparticles are inside the cell. According to high resolution transmission electron micrographs of intracellular single gold nanoparticles, they have the shape of a polyhedron.     

Preparation,characterization, in vivo biodistribution and pharmacokinetic studies of donepezil-loaded PLGA nanoparticles for brain targeting

Objective: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder manifested by cognitive, memory deterioration and variety of neuropsychiatric symptoms. Donepezil is a reversible cholinesterase inhibitor used for the treatment of AD. The purpose of this work is to prepare a nanoparticulate drug delivery system of donepezil using poly(lactic-co-glycolic acid) (PLGA) for sustained release and efficient brain targeting.

Materials and methods: PLGA nanoparticles (NPs) were prepared by the solvent emulsification diffusion–evaporation technique and characterized for particle size, particle-size distribution, zeta potential, entrapment efficiency, drug loading and interaction studies and in vivo studies using gamma scintigraphy techniques.

Results and discussion: The size of drug-loaded NPs (drug polymer ratio 1:1) was found to be 89.67?±?6.43?nm. The TEM and SEM images of the formulation suggested that particle size was within 20–100?nm and spherical in shape, smooth morphology and coating of Tween-80 on the NPs was clearly observed. The release behavior of donepezil exhibited a biphasic pattern characterized by an initial burst release followed by a slower and continuous sustained release. The biodistribution studies of donepezil-loaded PLGA NPs and drug solution via intravenous route revealed higher percentage of radioactivity per gram in the brain for the nanoparticulate formulation as compared with the drug solution (p?Conclusion: The high concentrations of donepezil uptake in brain due to coated NPs may help in a significant improvement for treating AD. But further, more extensive clinical studies are needed to check and confirm the efficacy of the prepared drug delivery system.     

Attenuated effects of chitosan-capped gold nanoparticles on LPS-induced toxicity in laboratory rats

The impact of nanoparticles in medicine and biology has increased rapidly in recent years. Gold nanoparticles (AuNP) have advantageous properties such as chemical stability, high electron density and affinity to biomolecules. However, the effects of AuNP on human body after repeated administration are still unclear. Therefore, the purpose of the present study was to evaluate the effects of gold-11.68 nm (AuNP1, 9.8 μg) and gold-22.22 nm (AuNP2, 19.7 μg) nanoparticles capped with chitosan on brain and liver tissue reactivity in male Wistar rats exposed to lipopolysaccharide (LPS from Escherichia coli serotype 0111:B4, 250 μg) upon 8 daily sessions of intraperitoneal administration. Our results suggest that the smaller size of chitosan-capped AuNP shows the protective effects against LPS-induced toxicity, suggesting a very high potential for biomedical applications.     

In vivo molecular probing of cellular compartments with gold nanoparticles and nanoaggregates

Surface-enhanced Raman (SERS) signatures were measured from single living cells at different times after the uptake of gold nanoparticles. The spectra are indicative of chemical changes in the environment of the nanostructures over time. The increase of the SERS signal strength and parallel TEM studies indicate the formation of nanoaggregates providing optimum SERS enhancement for ultrasensitive probing inside the endosomal compartment. The results have implications for medical and biotechnology applications of SERS nanosensors in cells.     

Adverse effects of citrate/gold nanoparticles on human dermal fibroblasts

Nanoscale engineering is one of the most dynamically growing areas at the interface between electronics, physics, biology, and medicine. As there are no safety regulations yet, concerns about future health problems are rising. We investigated the effects of citrate/gold nanoparticles at different concentrations and exposure times on human dermal fibroblasts. We found that, as a result of intracellular nanoparticle presence, actin stress fibers disappeared, thereby inducing major adverse effects on cell viability. Thus, properties such as cell spreading and adhesion, cell growth, and protein synthesis to form the extracellular matrix were altered dramatically. These results suggest that the internal cell activities have been damaged.     

Uptake and biological effects of chitosan-capped gold nanoparticles on Chinese Hamster Ovary cells

In this study we examine the cytotoxic effect of chitosan capped-gold nanoparticles on Chinese Hamster Ovary (CHO) cells in vitro. The particles were synthesized through a low cost and rapid method by the aqueous reduction of chloroauric acid (HAuCl₄) with ascorbic acid (C₆H₈O₆) at ambient temperature. High molecular weight chitosan biopolymer was used to stabilize the particles against aggregation. The conjugated particles were able to traverse the cell membrane and enter the cells by endocytic pathway, their intracellular presence being clearly revealed by dark field microscopy imaging and light scattering spectra. Gold nanoparticles cytotoxicity was measured and cells were found to be viable more than 85%, even after long time exposure. Our results suggest that chitosan-conjugated gold nanoparticles have minimal impact on cells viability and morphology during 19 h demonstrating great potential to be used in biomedical applications such as cellular imaging or photothermal therapy.     

Shape matters: intravital microscopy reveals surprising geometrical dependence for nanoparticles in tumor models of extravasation

Delivery is one of the most critical obstacles confronting nanoparticle use in cancer diagnosis and therapy. For most oncological applications, nanoparticles must extravasate in order to reach tumor cells and perform their designated task. However, little understanding exists regarding the effect of nanoparticle shape on extravasation. Herein we use real-time intravital microscopic imaging to meticulously examine how two different nanoparticles behave across three different murine tumor models. The study quantitatively demonstrates that high-aspect ratio single-walled carbon nanotubes (SWNTs) display extravasational behavior surprisingly different from, and counterintuitive to, spherical nanoparticles although the nanoparticles have similar surface coatings, area, and charge. This work quantitatively indicates that nanoscale extravasational competence is highly dependent on nanoparticle geometry and is heterogeneous.     

Biosynthesis of gold nanoparticles

Synthesis of nanoparticles with interesting physico-chemical properties using efficient as well as eco-friendly technology is one of the main objectives of nanotechnology. Biological systems have been reported to synthesize inorganic materials under certain circumstances. Exploiting the biosynthetic potential of different organisms, nanoparticles of varying morphologies and sizes have been synthesized. Among the nanomaterials, gold has received considerable attention owing to its varied applications in the fields of nano-medicine, catalysis, electronics, and optics. This review gives an account on the biosynthesis of gold nanoparticles from microorganisms, plants, and other biological sources, with particular emphasis on the probable mechanisms leading to the formation of gold nanoparticles and the extent of control over nanoparticle properties that has been achieved so far in the biosynthetic protocols. It has been speculated that enzymes and/or proteins secreted by the organisms are involved in the bio-reduction and stabilization of the nanoparticles. The biosynthetic procedures could compete with existing solvent-based chemical synthetic procedures in order to achieve stable and monodisperse gold nanoparticles in large scale.     

Observation of intrinsic size effects in the optical response of individual gold nanoparticles

The photothermal heterodyne imaging method is used to study for the first time the absorption spectra of individual gold nanoparticles with diameters down to 5 nm. Intrinsic size effects that result in a broadening of the surface plasmon resonance are unambiguously observed. Dispersions in the peak energies and homogeneous widths of the single-particle resonances are revealed. The experimental results are analyzed within the frame of Mie theory.     

Size dependence electrocatalytic activity of gold nanoparticles decorated reduced graphene oxide for hydrogen evolution reaction

It is promising for AuNPs/RGO composites to be exploited for hydrogen evolution reaction (HER), due to the collaborative effects between the electrocatalytic Au nanoparticles (AuNPs) and conductive reduced graphene oxide (RGO). In this work, we used a simple way to decorate AuNPs onto the RGO surface by one pot in situ reduction both HAuCl₄ and GO, for which the controlled average size of AuNPs (2.7, 11.5 and 45.7 nm) is adjusting with the mass ratio of HAuCl₄ and GO. The obtained materials, AuNPs/RGO composites, show excellent electrocatalytic activity for the HER that critical dependence on the particle size of AuNPs. The results show that AuNPs/RGO with AuNPs size of 11.5 nm exhibits superior electrochemical activity: low onset potential of 0.029 V versus the reversible hydrogen electrode as well as a small Tafel slope of 86 mV per decade.