Gold Nanoparticles of Diameter 1.4 nm Trigger Necrosis by Oxidative Stress and Mitochondrial Damage

Gold nanoparticles (AuNPs) are generally considered nontoxic, similar to bulk gold, which is inert and biocompatible. AuNPs of diameter 1.4 nm capped with triphenylphosphine monosulfonate (TPPMS), Au1.4MS, are much more cytotoxic than 15‐nm nanoparticles (Au15MS) of similar chemical composition. Here, major cell‐death pathways are studied and it is determined that the cytotoxicity is caused by oxidative stress. Indicators of oxidative stress, reactive oxygen species (ROS), mitochondrial potential and integrity, and mitochondrial substrate reduction are all compromised. Genome‐wide expression profiling using DNA gene arrays indicates robust upregulation of stress‐related genes after 6 and 12 h of incubation with a 2 × IC50 concentration of Au1.4MS but not with Au15MS nanoparticles. The caspase inhibitor Z‐VAD‐fmk does not rescue the cells, which suggests that necrosis, not apoptosis, is the predominant pathway at this concentration. Pretreatment of the nanoparticles with reducing agents/antioxidants N‐acetylcysteine, glutathione, and TPPMS reduces the toxicity of Au1.4MS. AuNPs of similar size but capped with glutathione (Au1.1GSH) likewise do not induce oxidative stress. Besides the size dependency of AuNP toxicity, ligand chemistry is a critical parameter determining the degree of cytotoxicity. AuNP exposure most likely causes oxidative stress that is amplified by mitochondrial damage. Au1.4MS nanoparticle cytotoxicity is associated with oxidative stress, endogenous ROS production, and depletion of the intracellular antioxidant pool.     

Observation on growth process of gold Y- and phi-shaped nanoparticles in solutions

The morphological evolution of gold (Au) nanoparticles is demonstrated via TEM and UV-vis spectroscopy in a real-time basis. Y-shaped and phi-shaped Au nanoparticles were prepared by a seed mediated method at 0 degrees C. The evolution of shape ranging from spheres to Y- and phi-shapes was characterized by UV-vis spectroscopy. For the spherical particles, the corresponding transverse plasmon absorption (540 nm) was observed at the initial growth stage. As further growth proceeded, new peaks appeared at ca. 620 nm and ca. 700-1000 nm, which was to the characteristic peak of Y-shaped and phi-shaped nanoparticles, respectively. In addition, all intermediate steps were observed in the morphology change by TEM. At the initial step, spherical particles with 20 nm size were generated and the particles were gradually evolved from tiny triangular shape or I-shape to Y- and phi-shape. In this study, the growth mechanism of Au nanoparticles was investigated by the characterization of optical properties as well as morphologies with respect to reaction time.     

Cytotoxicity of versatile nano-micro-particles based on hierarchical flower-like ZnO

ZnO (nano)structures remain of great interest in biomedical applications due to their unique properties and possible morphologies. Biocompatibility of typically fabricated ZnO structures remains questionable and they still lack desired biological functions, whence their functionalization is of high interest. In this work, we fabricated micro-sized ZnO hierarchical flower-like structures using facile template-free hydrothermal method to act as carriers for the delivery of gold nanoparticles (Au) and/or Biotin (Vitamin B) to cells. Au nanoparticles (~24 nm), as well as Biotin molecules were successfully deposited on the ZnO surface due to non-covalent physical interactions. We have then cultured two cells lines: SH-SY5Y (human malignant neural) and HEK-293 (human non-malignant) and observed that ZnO hierarchical particles exhibited cell line-dependent cytotoxicity. It appeared that further functionalization of ZnO with Au nanoparticles and subsequently with Biotin led to lower discrepancy between the two cell lines response indicating that cytotoxic pathways of pure ZnO were masked by the available surface adsorbed particles (Au/Biotin). Two-photon immunocytochemistry microscopy further confirmed that Biotin decorated particles affected neuroblastoma cells cytoskeleton. These findings contribute to the understanding of cytotoxic pathways of surface-decorated nano-micro-structures made from ZnO with two molecules typically used in anticancer and regenerative medicine therapies.     

In vitro safety toxicology data for evaluation of gold nanoparticles-chronic cytotoxicity, genotoxicity and uptake

Safety and toxic effects of nanoparticles are still largely unexplored due to the multiple aspects that influence their behaviour toward biological systems. Here, we focus the attention on 12 nm spherical gold nanoparticle coated or not with hyaluronic acid compared to its precursor counterpart salt. Results ranging from the effects of a 10-days exposure in an in vitro model with BALB/c 3T3 fibroblast cells show how 12 nm spherical gold nanoparticles are internalized from 3T3 cells by endo-lysosomal pathway by an indirect measurement technique; and how gold nanoparticles, though not being a severe cytotoxicant, induce DNA damage probably through an indirect mechanism due to oxidative stress. While coating them with hyaluronic acid reduces gold nanoparticles cytotoxicity and slows their cell internalization. These results will be of great interest to medicine, since they indicate that gold nanoparticles (with or without coating) are suitable for therapeutic applications due to their tunable cell uptake and low toxicity.     

Periodic square-like gold nanoparticle arrays templated by self-assembled 2D DNA Nanogrids on a surface

We report the use of a self-assembled two-dimensional (2D) DNA nanogrid as a template to organize 5-nm gold nanoparticles (Au NPs) into periodic square lattices. Each particle sits on only a single DNA tile. The center-to-center interparticle spacing between neighboring particles is controlled to be approximately 38 nm. These evenly distributed Au NP arrangements with accurate control of interparticle spacing may find applications in nanoelectronic and nanophotonic devices.     

Light emission of gold nanoparticles induced by the reaction of bis(2,4,6-trichlorophenyl) oxalate and hydrogen peroxide

Light emission at approximately 415 nm was observed for gold particles with diameters of 2.6-6.0 nm dispersed in a solution containing bis(2,4,6-trichlorophenyl) oxalate and hydrogen peroxide. It was found that the light intensity was independent of the protecting reagents of the gold nanoparticles with similar size, the light intensity with gold nanoparticles of 5.0 and 6.0 nm in diameter was stronger than that with gold nanoparticles of 2.6 and 2.8 nm in diameter, and the light intensity increased linearly with the concentration of the gold nanoparticles using 6.0-nm gold nanoparticles. The gold nanoparticles were identified as emitting species, and the quantum yield was determined to be (2.8 +/- 0.3) x 10(-5) using 6.0-nm gold nanoparticles. The light emission is suggested to involve a sequence of steps: the oxidation reaction of bis(2,4,6-trichlorophenyl) oxalate with hydrogen peroxide yielding an energy-rich intermediate 1,2-dioxetanedione, the energy transfer from this intermediate to gold nanoparticles, and the radiative relaxation of the as-formed exited-state gold nanoparticles. The observed luminescence is expected to find applications in the field of bioanalysis owing to the excellent biocompatibility and relatively high stability of gold nanoparticles.     

Photochemical synthesis of biopolymer coated Aucore-Agshell type bimetallic nanoparticles

Spherical Au nanoparticles have been prepared in the presence of a biopolymer, sodium alginate using UV-photoactivation technique. The particles are sodium alginate coated and are extremely stable. These Au nanoparticles have been used as seed for the synthesis of Aucore-Agshell type bimetallic nanoparticles. Sodium alginate is a carbohydrate-based biopolymer. In this synthesis it acts both as a reducing agent and a stabilizer for the evolved particles. Therefore, no extra capping agent is required from outside to make the generated particle stable. By varying the seed to silver ion ratios and using photoactivation technique Aucore-Agshell type bimetallic nanoparticles with various sizes and compositions have been synthesized. The method is very simple and reproducible and does not need any manipulative skill. Characterizations of these bimetallic nanoparticles have been done from their UV-visible spectroscopy, TEM/EDX, and AFM results. UV-visible extinction spectra reveal that the seed particles have an absorption maxima approximately 527 nm, attributed to the surface plasmon of the pure gold nanoparticles. From the TEM images the particle size of the gold seed particles was calculated to be 8.6 nm. The growth of bimetallic nanoparticles with time has been monitored. The finally evolved bimetallic Aucore-Agshell nanoparticles have a size in the range between approximately 10-14 nm. The particles are very stable and may have the potential for biological and catalytic applications.     

Magnesia supported Au and Ag catalysts for the preparation of few-layer graphene–metal nanocomposites: relationship between catalyst structure and the properties of graphene composites

Magnesia supported Au, Ag, and Au–Ag nanostructured catalysts were prepared, characterized, and used to synthesize few-layer graphene–metal nanoparticle (Gr–MeNP) composites. The catalysts have a mezoporous structure and a mixture of MgO and MgO·H₂O as support. The gold nanoparticles (AuNPs) are uniformly dispersed on the surface of the Au/MgO catalysts, and have a uniform round shape with a medium size of ~8 nm. On the other hand, the silver nanoparticles (AgNPs) present on the Ag/MgO catalyst have an irregular shape, larger diameters, and less uniform dispersion. The Au–Ag/MgO catalyst contains large Au–Ag bimetallic particles of ~20–30 nm surrounded by small (5 nm) AuNPs. Following the RF-CCVD process and the dissolution of the magnesia support, relative large, few-layer, wrinkled graphene sheets decorated with metal nanoparticles (MeNPs) are observed. Graphene–gold (Gr–Au) and graphene–silver (Gr–Ag) composites had 4–7 graphitic layers with a relatively large area and similar crystallinity for samples prepared in similar experimental conditions. Graphene–gold–silver composites (Gr–Au–Ag) presented graphitic rectangles with round, bent edges, higher crystallinity, and a higher number of layers (8–14). The MeNPs are encased in the graphitic layers of all the different samples. Their size, shape, and distribution depend on the nature of the catalyst. The AuNPs were uniformly distributed, had a size of about 15 nm, and a round shape similar to those from Au/MgO catalyst. In Gr–Ag, the AgNPs have a round shape, very different from that of the Ag/MgO catalyst, large size distribution and are not uniformly distributed on the surface. Agglomerations of AgNPs together with large areas of pristine few-layer graphene were observed. In Gr–Au–Ag composites, almost exclusively large bimetallic particles of about 25–30 nm, situated at the edge of graphene rectangles have been found.     

Open bridge-structured gold nanoparticle array for label-free DNA detection

We focused on changes in the electrical property of the open bridge-structured gold nanoparticles array consisting of 46-nm parent and 12-nm son gold nanoparticles by hybridization and applied it for a simple electrical DNA detection. Since a target DNA of a 24-mer oligonucleotide was added to the probe DNA modified 12-nm Au nanoparticles, which was arranged on the gap between the 46-nm Au particles, the response was read by an electrical readout system. Even in a simple measuring method, we obtained a rapid response to the cDNA with a high S/N ratio of 30 over a wide concentration range and a detection limit of 5.0 fmol. Moreover, the array discriminated 1-base mismatches, regardless of their location in the DNA sequence, which enabled us to detect single-nucleotide polymorphism, which is one of the important diagnoses, without any polymerase chain reaction amplification, sophisticated instrumentation, or fluorescent labeling through an easy-to-handle electrical readout system.     

Microstructural characterization of gold nanoparticles synthesized by solution plasma processing

Microstructural characteristics of gold nanoparticles (Au NPs) fabricated by solution plasma processing (SPP) in reverse micelle solutions have been studied by high-resolution transmission electron microscopy (HRTEM). The synthesized Au NPs, with an average size of 6.3 ± 1.4?nm, have different crystal characteristics; fcc single-crystalline particles, multiply twinned particles (MTPs), and incomplete MTPs (single-nanotwinned fcc configuration). The crystal structure characteristics of the Au NPs synthesized by the SPP method were analyzed and compared with similar-size Au NPs obtained by the conventional chemical reduction synthesis (CRS) method. The TEM analysis results show that the Au NPs synthesized by the CRS method have shapes and crystal structures similar to those nanoparticles obtained by the SPP method. However, from the detailed HRTEM analysis, the relative number of the Au MTPs and incomplete MTPs to the total number of the Au NPs synthesized by the SPP method was observed to be around 94%, whereas the relative number of these kinds of crystal structures fabricated by the CRS method was about 63%. It is most likely that the enhanced formation of the Au MTPs is due to the fact that the SPP method generates highly reaction-activated species under low environmental temperature conditions.     

A Comparative Study on the Selected Area Electron Diffraction Pattern of Fe Oxide/Au Core-shell Structured Nanoparticles

The selected area electron diffraction （SAED） pattern of magnetic iron oxide core/gold shell nanoparticles has been studied. For the composite particles with mean size less than 10 nm, their SAED pattern is found to be different from either the pattern of pure Fe oxide nanoparticles or that of pure Au particles. Based on the fact that the ring diameters of these composite particles fit the characteristic relation for the fcc structure, the Au atoms on surfaces of the concerned particles are supposed to pack in a way more tightly than they usually do in pure Au nanoparticles. The driving force for this is the coherency strain which enables the shell material at the heterostructured interface to adapt the lattice parameters of the core.     

Structural verification and optical characterization of SiO2–Au–Cu2O nanoparticles

In this paper, SiO₂–Au–Cu₂O core/shell/shell nanoparticles were synthesized by reducing gold chloride on 3-amino-propyl-triethoxysilane molecules attached silica nanoparticle cores for several stages. Cu₂O nanoparticles were synthesized readily with the size of 4–5 nm using a simple route of sol–gel method Then, they were clung to the surface of Au seeds. The morphology of the resultant particles was studied using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Transmission electron microscopy images demonstrate growth of monodispersed gold seeds and Cu₂O nanoparticles in narrow size up to 10 nm and 5 nm, respectively. The presence of gold and Cu₂O coating was confirmed by X-ray diffraction, Fourier transform infrared spectroscopy and UV–Vis spectroscopy. Absorption spectroscopy shows considerably 40 nm blue shift in absorption edge for SiO₂–Au–Cu₂O nanostructure rather than SiO₂–Au core/shell nanoparticles.     

Fabrication of conducting polymer micro/nanostructures coated with Au nanoparticles for electrochemical sensors

Polypyrrole (PPy) micro/nanostructures coated with Au nanoparticles were prepared by electropolymerization and electro-deposition. Two types of PPy structures, micro-embossed and nanowire forest, were synthesized on patterned gold electrodes using different aqueous solutions, and Au nanoparticles were coated onto the PPy micro/nanostructure surface. The size of the Au nanoparticles ranged from 10 to 100 nm, and the maximum density of the nanoparticles was 73 particles/microm2. The small size and high density of the Au nanoparticles were achieved by optimizing the deposition time and chloroauric acid (HAuCl4) concentration. Cyclic voltammograms of ferrocyanide oxidation showed that the PPy micro/nanostructures coated with Au nanoparticles exhibit good electrochemical activity. These high-performance electrodes can be used in electrochemical sensors because the Au nanoparticles enhance electron transfer and provide a binding site for biomarker molecules, such as DNA, protein, and aptamers.     

Au/LaVO4 Nanocomposite: Preparation, characterization, and catalytic activity for CO oxidation

The size of the gold particles is a very important parameter to get active catalysts. This paper reports a novel colloidal deposition method to prepare Au/LaVO₄ nanocomposite catalyst with monodispersed Au colloids and uniform LaVO₄ nanoplates in nonpolar solvent. Monodispersed Au colloids with tunable size (such as 2, 5, 7, 11, 13, and 16 nm) and LaVO₄ nanocrystals with well-defi ned shapes were pre-synthesized assisted with oleic acid/amine. During the following immobilization process, the particle size and shape of Au and LaVO₄ were nearly preserved. As-prepared Au/LaVO₄ nanocomposite showed high catalytic activity for CO oxidation at room temperature. Since sizes of gold particles were well-defi ned before the immobilization process, size effect of gold particles was easy to be investigated and the results show that 5-nm Au/LaVO₄ nanocomposite has the highest activity for CO oxidation. This synthetic method can be extended further for the preparation of other composite nanomaterials.     

Chemical solution approaches to YBa2Cu3O7_delta-Au nanocomposite superconducting thin films

We explore the feasibility of preparing YBa2CU3O7-Au (YBCO-Au) nanocomposite thin films by chemical solution deposition (CSD). Two approaches were used: (i) A standard in-situ methodology where Au metallorganic salts are added into the precursor solution of YBCO trifluoroacetate (TFA) salts and (ii) a novel approach where stable colloidal solutions of preformed gold nanoparticles (5-15 nm) were homogeneously mixed with TFA-YBCO solutions. A detailed analysis of the microstructure of the films showed that in both cases, there is a strong tendency of gold nanoparticles to migrate to the film surface. However the kinetics of this migration evidences important differences and in the case of preformed nanoparticles their size remains unchanged (a few nanometers) whereas for the in-situ nanocomposites gold ripening leads to large particles (hundreds of nanometers). The grown YBCO-Au films showed good superconducting characteristics (J(c) 2 MA/cm2 at 77 K) but the absence of Au inclusions inside the YBCO matrix explains the fact that no enhancement of vortex pinning was observed.     

Electrochemiluminescent metallopolymer-nanoparticle composites: nanoparticle size effects

Metallopolymer-gold nanocomposites have been synthesized in which the metal complex-Au nanoparticle (NP) mole ratio is systematically varied by mixing solutions of 4-(dimethylamino) pyridine protected gold nanoparticles and a [Ru(bpy)(2)PVP(10)](2+) metallopolymer; bpy is 2,2'-bipyridyl and PVP is poly-(4-vinylpyridine). The impact of changing the gold nanoparticle diameter ranging from 4.0 ± 0.5 to 12.5 ± 1 nm has been investigated. The photo induced emission of the metallopolymer undergoes static quenching by the metal nanoparticles irrespective of their size. When the volume ratio of Au NP-Ru is 1, the quenching efficiency increases from 38% to 93% on going from 4.0 ± 0.5 to 12.5 ± 1 nm diameter nanoparticles while the radius of the quenching sphere remains unaffected at 75 ± 5 ?. The conductivity of thin films is initially unaffected by nanoparticle incorporation until a percolation threshold is reached at a mole ratio of 4.95 × 10(-2) after which the conductivity increases before reaching a maximum. For thin films of the nanocomposites on electrodes, the electrochemiluminescence intensity of the nanocomposite initially increases as nanoparticles are added before decreasing for the highest loadings. The electrochemiluminescence intensity increases with increasing nanoparticle diameter. The electrochemiluminescence (ECL) emission intensity of the nanocomposite formed using 12.5 nm particles at mole ratios between 5 × 10(-3) and 10 × 10(-3) is approximately 7-fold higher than that found for the parent metallopolymer. The application of these materials for low cost ECL-based point of care devices is discussed.     

Nanoparticle-mediated cellular response is size-dependent

Nanostructures of different sizes, shapes and material properties have many applications in biomedical imaging, clinical diagnostics and therapeutics. In spite of what has been achieved so far, a complete understanding of how cells interact with nanostructures of well-defined sizes, at the molecular level, remains poorly understood. Here we show that gold and silver nanoparticles coated with antibodies can regulate the process of membrane receptor internalization. The binding and activation of membrane receptors and subsequent protein expression strongly depend on nanoparticle size. Although all nanoparticles within the 2-100 nm size range were found to alter signalling processes essential for basic cell functions (including cell death), 40- and 50-nm nanoparticles demonstrated the greatest effect. These results show that nanoparticles should no longer be viewed as simple carriers for biomedical applications, but can also play an active role in mediating biological effects. The findings presented here may assist in the design of nanoscale delivery and therapeutic systems and provide insights into nanotoxicity.     

Assemblies of carbon nanotubes and unencapsulated sub-10-nm gold nanoparticles

The development of assemblies consisting of unencapsulated, sub-10-nm gold particles attached to individual carbon nanotubes (CNTs) with diameters of 2 nm is described. The assemblies are formed on the surface of a porous anodic alumina (PAA) template on which the CNTs (single- or double-walled) are grown by plasma-enhanced chemical vapor deposition. The Au nanoparticles are formed through an indirect evaporation technique using a silicon nitride membrane mask, and diffuse along the PAA surface into the regions containing CNTs. The nanoparticles bind relatively strongly to the CNTs, as indicated by observations of nanoparticles that are suspended over pores or that move along with the CNTs. This approach may provide a new method to functionalize CNTs for chemical or biological sensing and fundamental studies of nanoscale contacts to CNTs.     

Synthesis and agglomeration of gold nanoparticles in reverse micelles

Reverse micelles prepared in the system water, sodium bis-(2-ethylhexyl) sulfoccinate (AOT), and isooctane were investigated as a templating system for the production of gold nanoparticles from Au(III) and the reducing agent sulfite. A core-shell Mie model was used to describe the optical properties of gold nanoparticles in the reverse micelles. Dynamic light scattering of gold colloids in aqueous media and in reverse micelle solution indicated agglomeration of micelles containing particles. This was verified theoretically with an analysis of the total interaction energy between pairs of particles as a function of particle size. The analysis indicated that particles larger than about 8?nm in diameter should reversibly flocculate. Transmission electron microscopy measurements of gold nanoparticles produced in our reverse micelles showed diameters of 8-10?nm. Evidence of cluster formation was also observed. Time-correlated UV-vis absorption measurements showed a red shift for the peak wavelength. This was interpreted as the result of multiple scattering and plasmon interaction between particles due to agglomeration of micelles with particles larger than 8?nm.     

Core/shell structured NaYF4:Yb3+/Er3+/Gd+3 nanorods with Au nanoparticles or shells for flexible amorphous silicon solar cells

A simple approach for preparing near-infrared (NIR) to visible upconversion (UC) NaYF4:Yb/Er/Gd nanorods in combination with gold nanostructures has been reported. The grown UC nanomaterials with Au nanostructures have been applied to flexible amorphous silicon solar cells on the steel substrates to investigate their responses to sub-bandgap infrared irradiation. Photocurrent–voltage measurements were performed on the solar cells. It was demonstrated that UC of NIR light led to a 16-fold to 72-fold improvement of the short-circuit current under 980 nm illumination compared to a cell without upconverters. A maximum current of 1.16 mA was obtained for the cell using UC nanorods coated with Au nanoparticles under 980 nm laser illumination. This result corresponds to an external quantum efficiency of 0.14% of the solar cell. Mechanisms of erbium luminescence in the grown UC nanorods were analyzed and discussed.