Gold Core Research Articles

Quantification by Luminescence Tracking of Red Emissive Gold Nanoparticles in Cells.

Optical microscopy techniques are ideal for live cell imaging for real-time nanoparticle tracking of nanoparticle localization. However, the quantification of nanoparticle uptake is usually evaluated by analytical methods that require cell isolation. Luminescent labeling of gold nanoparticles with transition metal probes yields particles with attractive photophysical properties, enabling cellular tracking using confocal and time-resolved microscopies. In the current study, gold nanoparticles coated with a red-luminescent ruthenium transition metal complex are used to quantify and track particle uptake and localization. Analysis of the red-luminescence signal from particles is used as a metric of cellular uptake, which correlates to total cellular gold and ruthenium content, independently measured and correlated by inductively coupled plasma mass spectrometry. Tracking of the luminescence signal provides evidence of direct diffusion of the nanoparticles across the cytoplasmic membrane with particles observed in the cytoplasm and mitochondria as nonclustered “free” nanoparticles. Electron microscopy and inhibition studies identified macropinocytosis of clusters of particles into endosomes as the major mechanism of uptake. Nanoparticles were tracked inside GFP-tagged cells by following the red-luminescence signal of the ruthenium complex. Tracking of the particles demonstrates their initial location in early endosomes and, later, in lysosomes and autophagosomes. Colocalization was quantified by calculating the Pearson’s correlation coefficient between red and green luminescence signals and confirmed by electron microscopy. Accumulation of particles in autophagosomes correlated with biochemical evidence of active autophagy, but there was no evidence of detachment of the luminescent label or breakup of the gold core. Instead, accumulation of particles in autophagosomes caused organelle swelling, breakdown of the surrounding membranes, and endosomal release of the nanoparticles into the cytoplasm. The phenomenon of endosomal release has important consequences for the toxicity, cellular targeting, and therapeutic future applications of gold nanoparticles.

Experimental Confirmation of a Topological Isomer of the Ubiquitous Au25(SR)18 Cluster in the Gas Phase

High-resolution electrospray ionization ion mobility mass spectrometry has revealed a gas-phase isomer of the ubiquitous, extremely well-studied Au25(SR)18 cluster both in anionic and cationic form. The relative abundance of the isomeric structures can be controlled by in-source activation. The measured collision cross section of the new isomer agrees extremely well with a recent theoretical prediction (MatusM. F.; et al. Chem. Commun.2020, 56, 8087) corresponding to a Au25(SR)18– isomer that is energetically close and topologically connected to the known ground-state structure via a simple rotation of the gold core without breaking any Au–S bonds. The results imply that the structural dynamics leading to isomerization of thiolate-protected gold clusters may play an important role in their gas-phase reactions and that isomerization could be controlled by external stimuli.

Propagation of Surface Plasmon Waves along Multi Wall Carbon Nanotube with Gold Core

We have studied the propagation of surface plasmon waves along multiwalled carbon nanotube with gold core. We have modeled the shells of multiwalled carbon nanotube as impedance sheets with axially directed surface conductivity incorporating inter shell coupling in an integral equation approach. We have found that in low frequency regime optical interband transitions did not occur and guided waves propagated with low attenuation in an multiwalled carbon nanotube which has metallic shells. In the same frequency range the axial polarizability of a finite length multiwalled carbon nanotube has a resonant behavior due the antenna length matching effect. The shells with surface conductivity due to interband transitions suppressed guided wave propagation. Surface Plasmon wave propagation in a multiwalled carbon nanotube with gold core showed that in the near infrared and visible regime the shells behaved as lossy dielectric materials and suppressed surface wave propagation along the gold core. The electromagnetic characteristics of carbon nanotube based antennas have been examined in different frequency regime ranging from the microwave to the visible regime. Carbon nanotube has been demonstrated to play a crucial role connected electrically to planner periodic structures of single wall carbon nanotubes, carbon nanotube bundles and carbon nanotube arrays. The inter shells interaction leaded to inter shell electron tunneling or hopping. Fermi momentum of two incommensurable shells do not coincide within the first Brillouin zone and the inter shell tunneling vanished. In the presence of localized defects inter shell conduction increased and defectfree shells were managed by neglecting intershell conduction. We have used microscopic model for multiwalled carbon nanotube and radiation characteristics were determined by its waveguiding properties, the dispersion equation for guided wave propagation on an infinitely long multiwall carbon nanotube. We have found that the guided wave has strong retardation and high attenuation so that the frequency of a geometric resonance is not connected to the free space wave length but to a shorter effective wavelength that depends on the material properties. The obtained results were compared with the previously obtained results and were found in good agreement.

Determination of NADH by Surface Enhanced Raman Scattering Using Au@MB@Ag NPs

Nicotinamide adenine dinucleotide (NADH) is an important coenzyme involved in various metabolic processes of living cells. As an important biomarker, NADH is associated with breast cancer and Alzheimer’s disease. In this paper, silver plated gold core–shell nanoparticles containing Raman signal molecules were synthesised on the basis of bare gold. Using the Raman peak corresponding to the 4-mercaptobenzonitrile (MB) silent region C≡N vibration for quantification, while avoiding competition with the precious metal surface binding site to be measured, it can also be free from the interference of endogenous biomolecules. On the one hand, it can correct the working curve, on the other hand, it can avoid competing with the binding site. Compared with the core–shell structure prepared here, the limit of detection (LOD) for NADH was only 10−5 M for bare gold and the LOD for the core–shell structure prepared on the basis of bare gold was 3.3 × 10−7 M. In terms of correction, with Rhodamine 6G (R6G) as a Raman signalling molecule, the R2 value before SERS detection and correction is only 0.9405, and the R2 value after correction increases to 0.9853. The unique fingerprint peak of SERS was used to realise the quantitative detection of NADH, which realizes the detection of NADH in complex biological samples of serum and provides the possibility for expanding the early diagnosis of breast cancer.

Manganese-doped gold core mesoporous silica particles as a nanoplatform for dual-modality imaging and chemo-chemodynamic combination osteosarcoma therapy.

In this study, an effective and facile strategy is reported to construct a multifunctional nanoplatform by in situ doping metal manganese on gold core mesoporous silica nanoparticles (Au@MMSN). After further modification of alendronate (Ald) on Au@MMSN, the obtained Au@MMSN-Ald efficiently integrates bone targeted chemo-chemodynamic combination therapy and dual-modality computed tomography/magnetic resonance (CT/MR) imaging into a single platform. In particular, Au@MMSN-Ald exhibits excellent tumor microenvironment responsive drug release efficiency. The doxorubicin hydrochloride (DOX) loaded Au@MMSN-Ald (DOX@Au@MMSN-Ald) is demonstrated with excellent targeted ability toward osteosarcoma. Accordingly, in a specific tumor microenvironment, DOX@Au@MMSN-Ald also displays outstanding combined efficiency for killing cancer cells in vitro and suppressing the osteosarcoma growth in vivo. Benefiting from the Au nanoparticles confined in the core and manganese ions released from the shell, CT and MR dual-modality imaging were performed to verify the effective accumulation of Au@MMSN-Ald at the tumor site. Overall, the constructed DOX@Au@MMSN-Ald nanoparticles integrated imaging guide, responsive drug release and combination therapy, which may provide some insight for further biomedical applications in efficient osteosarcoma therapy.

Utilization of gold nanoparticles to detect formalin adulteration in milk

Despite the addition of formalin in milk or any food product is banned in most of the countries, its use continues because of capability to increase shelf life of food by several folds and cheap availability. An addition of small quantity of solution of gold nanoparticles enhanced the capability of Tollen’s reagent and produced visible change in color due to presence of trace amount of formalin in solution. In order to establish this new technique, various samples of milk with different quantities of formalin were prepared and color change after the reaction with gold nanoparticles suspended in Tollen’s reagent was visibly observed. This was also monitored by UV–Visible Spectrophotometry to confirm the formation of gold core silver shell particles. This paper presents an easy, cost effective way to detect formalin adulteration in milk at very low concentrations and could be adopted in the area of quality control and can be further modified for use in the testing of other food products.

Visible light active Au@g-C3N4 core-shell plasmonic photocatalyst

A core–shell structure of Au nanoparticle and graphitic carbon nitride (g-C3N4) is synthesized by sonication-assisted reduction, using sodium citrate as the reducing agent. Noble metal nanoparticles have low dispersion stability in solution and have tendency to aggregate which reduces their activity. Corrosion of noble metal nanoparticles also restricts practical use of noble metal. Keeping this in mind, a core–shell structure of gold core and semiconductor graphitic carbon nitride shell is developed. Core-shell structure formation is confirmed by structural and morphological characterizations. This nanocomposite Au@g-C3N4 degraded 41% and 94.2% Methylene Blue present in the simulated wastewater in just 60 min with 1 wt% and 5 wt% of Au salt, respectively. This faster degradation of Methylene Blue is due to the large surface area of 2D g-C3N4, surface plasmon resonance of Au nanoparticles, and the interface formed between the two components which increase the lifetime of photogenerated electron-hole pairs.

Drug resistance-free cytotoxic nanodrugs in composites for cancer therapy.

Drug resistance is a major cause of treatment failure for small-molecule cancer chemotherapies, despite the advances in combination therapies, drug delivery systems, epigenetic drugs, and proteolysis-targeting chimeras. Herein, we report the use of a drug resistance-free cytotoxic nanodrug as an alternative to small-molecule drugs. The present nanodrugs comprise 2 nm core gold nanoparticles (AuNPs) covered completely with multivalent hydrocarbon chains to a final diameter of ∼10 nm as single drug molecules. This hydrophobic drug-platform was delivered in composite form (∼35 nm) with block-copolymer like other small-molecular drugs. Upon uptake by cells, the nanodrugs enhanced the intracellular levels of reactive oxygen species and induced apoptosis, presumably reflecting multivalent interactions between aliphatic chains and intracellular biomolecules. No resistance to our novel nanodrug was observed following multiple treatment passages and the potential for use in cancer therapy was verified in a breast cancer patient-derived xenograft mouse model. These findings provide insight into the use of nano-scaled compounds as agents that evade drug resistance to cancer therapy.

Curcumin reduced gold nanoparticles synergistically induces ROS mediated apoptosis in MCF-7 cancer cells

Curcumin nanotechnologies have increased the therapeutic efficacy of curcumin by enhancing its bio-availability. We have previously reported on the synthesis of stable, uniform and biocompatible gold nanoparticles using curcumin (cAuNPs) alone as the reducing and stabilizing agent. Here, we provide evidence for the synergistic effect produced by both the gold core and curcumin against breast cancer cells. Spectroscopic and electron microscopic observations show that cAuNPs in biological medium get coated by proteins which aids in their endocytosis. Inside the cells, cAuNPs triggers the generation of reactive oxygen species (ROS) which then depletes mitochondrial membrane potential (MMP). Consequently, the pro-apoptotic protein Bax is released that activates PARP cleavage and DNA fragmentation. The final stages of apoptosis including chromatin condensation and loss of filopodia are visualized through microscopy. These findings provide insights into the mechanism of action of cAuNPs in inducing apoptosis and also suggest their promising candidature as a chemotherapeutic drug.

Integrated SERS Platform for Reliable Detection and Photothermal Elimination of Bacteria in Whole Blood Samples.

Herein, an interference-free surface-enhanced Raman scattering (SERS) platform with a "sandwich" structure has been developed for reliable detection and photothermal killing of bacteria with whole blood as the real sample. The multifunctional platform comprised a plasmonic gold film (pAu) functionalized with bacteria-capturing units of 4-mercaptophenylboronic acid and internal reference of 4-mercaptobenzonitrile as the SERS substrate and vancomycin-modified core (gold)-shell (Prussian blue) nanoparticles (Au@PB@Van NPs) as the SERS tag. The detected SERS signals were from the Raman-silent region where no background signals occurred from biological sources, eliminating the interference and improving the detection sensitivity and accuracy. As a proof-of-concept, model bacterial strain, Staphylococcus aureus, was captured and detected in the whole blood samples. Furthermore, high antibacterial efficiency of approximately 100% was reached under the synergistic photothermal effect from pAu and Au@PB@Van NPs. This study provides a new avenue for bacteria detection in real samples and their subsequent in situ elimination.

A polarization-independent highly sensitive hybrid plasmonic waveguide structure

In this paper, we proposed a novel design of a polarization-independent hybrid plasmonic waveguide. The transverse magnetic (TM) hybrid mode is confined in the low index material sandwiched between the silicon core and top gold layer whereas the transverse electric (TE) hybrid mode is supported in a narrow air gap on both sides between the silicon core and a gold layer. For sensing applications, two vital parameters such as the sensitivity of the hybrid mode (S mode ) and evanescent field ratio (EFR) are studied which depends on the geometric parameters of the waveguide. The geometric parameters of the waveguide are optimized using the finite element method. The highest S mode and EFR for both polarizations is greater than 0.91 and 0.6, respectively. This study shows that polarization-independent highly sensitive refractive index sensors or evanescent field absorption gas sensors can be realized by utilizing the proposed hybrid plasmonic waveguide design.

The nature of the Sulfur-Metallic bonds (Metal = Ni, Pd and Pt) in doped gold nanoclusters: A density functional approach

“Atomically precise gold nanoparticles” that constitute single guest atom doped gold cores besides being protected by ligands, have drawn much attention in the fields of biology, chemistry and physics. To investigate the foundation of organic-metallic interface, metallic alloy- H2S complexes are used to model the core-ligand interactions. In this work, simulation of platinum group doped gold dimers and triangular trimers bonded to H2S, are investigated. To simulate experimental results, features including bond lengths, vibrational frequencies and binding energies were calculated for the dimers of platinum group metals and gold, via DFT. The Au-M dimers have minimum magnetic dipole moments compared to the dimers of two platinum group metals. Among the three platinum group atoms simulated, the relativistic effect prevents Pd from being tightly bonded to other metallic atoms. The “donor-acceptor” model is put forward for the complexes of H2S molecules and dimer/trimers, to explain the interaction of sulfur-metal bonds. The possibility of neighboring metallic atoms affecting the acceptor, Au or platinum group metallic atoms is distinct. A neighboring acceptor may improve the S-M interaction such as S-Ni bond while a neighboring weak donor may reduce the S-M interactions such as S-Pd/Pt bonds. With the isosurface plot of densities of electrons/holes at binding, one can identify that such an interaction involves both electrostatic and covalent features. The complexes having H2S as ligand and cores of the real gold clusters verified the reliability of the donor-acceptor model qualitatively.

The Au25(SR)18 cluster carrying icosahedral dodecaborate and glutathione ligands: A spectroscopic view

The functionality of Au25(S-glutathione)18 clusters change when some of the ligands in the cluster shell are replaced for other species. In this study we report on the synthesis and characterisation of a new cluster in which undecahydro-closo-dodecaborate thiolates are introduced as constituents of the shell surrounding the gold core. This is the first reported example in which the Au13 core of the Au25(S-glutathione)18 cluster is covered with an Au–S–B linkage instead of an Au–S–C on the dimeric shell units using a ligand exchange reaction. The spectra of the new cluster species clearly indicate a successful ligand exchange while retaining the gold core with undisrupted semirings containing both thiolate species. The resulting clusters were identified as Au25 [(S-glutathione)18-x (S-closo-borate)x-)] (x = 3, 4). Despite the achiral character of the closo-borate thiolates entering the semiring, increased chirality traces were observed in the high-energy region. Circular dichroism (CD) responses are ligand dependent and provide a fingerprint characteristic of the ligands present in the cluster. The next generation of such surface functionalized clusters provides unique base for computational and application studies.

Gold Nanorods with Organosilica Shells as a Platform for Creating Multifunctional Nanostructures

The perspectives of using γ-mercaptopropyltrimethoxysilane as a precursor for creating multifunctional composite nanoparticles (CNPs) with a rodlike gold core and an organosilica shell have been analyzed. It is shown that the presence of thiol groups, which are capable of specific interactions with metal ions and atoms, in the shell makes it possible to “directly” (i.e., without any additional modification) load rather large amounts of an anticancer drug, cisplatin, into it. In addition, preliminary data have been obtained that indicate the possibility of nitrosation of the SH-groups of the shells, which is very important from the viewpoint of creating container CNPs for NO, with such containers providing not only its delivery to tumors, but also its controlled release under the action of laser radiation.

Enhanced cytotoxicity of highly water-soluble gold nanoparticle-cyclopeptide conjugates in cancer cells

Conjugation of cytostatic drugs to nanomaterials seeks to improve their low bioavailability and selectivity to overcome the important associated side effects. In this work, we aimed to synthesize water-soluble gold nanoparticles as transporters for synthetic cyclic peptides with a potential anticancer activity but with a limited bioavailability. The highly water-soluble nanoparticles (2.5 nm diameter gold core) are coated with a mixture of polyethylene glycol linkers, one bearing a terminal hydroxyl group for increasing dispersibility in water, and the second bearing a carboxylic acid group for peptide conjugation through amide bond formation. Peptide-functionalized particles have a 9.7 ± 1.8 nm hydrodynamic diameter and are highly water-soluble and stable in solution for at least one year. The morphology of the gold cores as well as their organic coating was studied using Transmission Electron Microscopy, showing that the attachment of a limited number of peptides per nanoparticle leads to a uneven organic coating of two different thicknesses, one of 2.0 ± 0.6 nm formed by polyethylene glycol linkers, and a second of 3.6 ± 0.5 nm which includes the peptide. GNP significantly enhance the internalization of the cyclic peptide BPC734 in cells as compared to peptide in solution, with improved uptake in cancerous HT29 cells. Cytotoxicity studies show that peptide BPC734 in solution is toxic in the micromolar range, whereas peptide-functionalized particles are toxic at nanomolar peptide concentrations and with a significantly higher toxicity for cancerous cells. All these results, besides the stability and expected passive tumor targeting, make these particles a promising option for improving the bioavailability, efficacy, and selectivity in cancer therapy.

Toward the Formation of N-Heterocyclic-Carbene-Protected Gold Clusters of Various Nuclearities. A Comparison with Their Phosphine-Protected Analogues from Density Functional Theory Calculations.

The structure and bonding of a series of selected phosphine-protected gold clusters (Aun-P) of nuclearity varying from n = 6 to 13 were investigated by density functional theory (DFT) calculations and compared to those of the hypothetical homologues in which phosphines were replaced by N-heterocyclic carbene (NHC) analogues (Aun-C). Both the Aun-P and Aun-C series exhibit similar stabilities and structural features, except for n = 6, where some differences are noted. The NHC ligands are found to be even slightly more strongly bonded to the gold core (by a few kilocalories per mole per ligand) than phosphines. Investigation of the optical properties of both series using time-dependent DFT calculations indicates similarities in the nature and energies of the UV-vis optical transitions and, consequently, relatively similar shapes of the simulated spectra, with a general blue-shift tendency when going from Aun-P to Aun-C. The fluorescence behavior observed experimentally for some of the Aun-P species is expected to occur also for their Aun-C analogues, which can be extended to other carbene-ligand-protected nanoclusters. Our results show that it should be possible to stabilize gold clusters with NHC ligands, in relation to the seminal Au13-ligand-protected core, offering novel building blocks for the design of nanostructured materials with various properties.

Hemoglobin-Conjugated Gold Nanoclusters for Qualitative Analysis of Haptoglobin Phenotypes.

Designing a facile and rapid detection method for haptoglobin (Hp) phenotypes in human blood plasma is urgently needed to meet clinic requirements in hemolysis theranostics. In this work, a novel approach to qualitatively analyze Hp phenotypes was developed using a fluorescent probe of gold nanoclusters (AuNCs). Hemoglobin-conjugated (Hb)-AuNCs were successfully synthesized with blue-green fluorescence and high biocompatibility via one-pot synthesis. The fluorescence of Hb-AuNCs comes from the ligand-metal charge transfer between surface ligands of Hb and the gold cores with high oxidation states. The biocompatibility assays including cell viability and fluorescence imaging, demonstrated high biocompatibility of Hb-AuNCs. For the qualitative analysis, three Hp phenotypes in plasma, Hp 1-1, Hp 2-1, and Hp 2-2, were successfully discriminated according to changes in the fluorescence intensity and peak position of the maximum intensity of Hb-AuNCs. Our work provides a practical method with facile and rapid properties for the qualitative analysis of three Hp phenotypes in human blood plasma.

Protecting Group Free Synthesis of Glyconanoparticles Using Amino-Oxy-Terminated Polymer Ligands.

Glycomaterials display enhanced binding affinity to carbohydrate-binding proteins due to the nonlinear enhancement associated with the cluster glycoside effect. Gold nanoparticles bearing glycans have attracted significant interest in particular. This is due to their versatility, their highly tunable gold cores (size and shape), and their application in biosensors and diagnostic tools. However, conjugating glycans onto these materials can be challenging, necessitating either multiple protecting group manipulations or the use of only simple glycans. This results in limited structural diversity compared to glycoarrays which can include hundreds of glycans. Here we report a method to generate glyconanoparticles from unprotected glycans by conjugation to polymer tethers bearing terminal amino-oxy groups, which are then immobilized onto gold nanoparticles. Using an isotope-labeled glycan, the efficiency of this reaction was probed in detail to confirm conjugation, with 25% of end-groups being functionalized, predominantly in the ring-closed form. Facile post-glycosylation purification is achieved by simple centrifugation/washing cycles to remove excess glycan and polymer. This streamlined synthetic approach may be particularly useful for the preparation of glyconanoparticle libraries using automation, to identify hits to be taken forward using more conventional synthetic methods. Exemplar lectin-binding studies were undertaken to confirm the availability of the glycans for binding and show this is a powerful tool for rapid assessment of multivalent glycan binding.

Terahertz Raman Spectroscopy of Ligand-Protected Au8 Clusters.

For ligand-protected gold clusters, geometrical differences of gold cores and/or the presence of secondary gold core-ligand interactions influence their unique optical and electronic properties and can, in principle, be detected by spectral changes of gold core vibrations (phonon modes) in ultralow-frequency Raman spectroscopy. We report experimental and theoretical Raman spectra of Au8 clusters protected by phosphine ligands particularly in the "gold cluster fingerprint" region from 50 to 150 cm-1 Raman shift (1.5 to 4.5 terahertz, THz). A characteristic core breathing mode observed at ca. 123 cm-1 was sensitive to differences of core geometries. A new band was found at ca. 150 cm-1, originating from a local strain on a polyhedral gold core caused by weak Au···π interactions. THz Raman spectroscopy can be utilized for metal nanoclusters to visualize core structural changes and Au···π interactions, which cannot be captured by single crystal X-ray analysis.

CO Total and Preferential Oxidation over Stable Au/TiO2 Catalysts Derived from Preformed Au Nanoparticles

CO preferential oxidation (PROX) is an effective method to clean reformate H2 streams to feed low-temperature fuel cells. In this work, the PROX and CO oxidation reactions were studied on preformed Au nanoparticles (NPs) supported on TiO2 anatase. Preformed Au NPs were obtained from gold cores stabilized by dodecanethiols or trimethylsilane-dendrons. A well-controlled size of ca. 2.6 nm and narrow size distributions were achieved by this procedure. The catalysts were characterized by high-resolution transmission electron microscopy and ex situ and in situ X-ray photoelectron spectroscopy (XPS). The XPS results showed that the preformed Au NPs exhibited high thermal stability. The different ligand-derived Au catalysts, as well as a conventional gold catalyst for comparison purposes, were loaded onto cordierite supports with 400 cells per square inch. The activity and selectivity of the samples were evaluated for various operation conditions. The catalyst prepared using dodecanethiol-capped Au NPs showed the best performance. In fact, CO conversions of up to 70% at 40% CO2 selectivity and 90% O2 conversion were observed operating at 363 K in H2-rich atmospheres. The performance of the best catalysts was subsequently tested on stainless steel microreactors. A 500-hour stability test was carried out under a real post-reformate stream, including 18 vol.% CO2 and 29 vol.% H2O. A mean CO conversion of ca. 24% was measured for the whole test operating at 453 K and a gas hourly space velocity (GHSV) of 1.3 × 104 h−1. These results reveal our dodecanethiol- and carbosilane-derived Au catalysts as extremely promising candidates to conduct a PROX reaction while avoiding deactivation, which is one of the major drawbacks of Au/TiO2 catalysts.