Stability Of Gold Nanorods Research Articles

Development of pH-responsive porphyran-coated gold nanorods for tumor photothermal and immunotherapy

Cancer poses a significant threat to human health, and monotherapy frequently fails to achieve optimal therapeutic outcomes. Based on this premise, porphyran (PHP), a marine polysaccharide with immunomodulatory function, was used as a framework to coat gold nanorods and construct a novel nanomedicine (PHP-MPBA-GNRs) combining photothermal therapy and immunotherapy. In this design, PHP not only maintained the dispersion stability and photothermal stability of gold nanorods but also could be released under weakly acidic conditions to activate anti-tumor immunity. In vivo studies have shown that PHP-MPBA-GNRs can effectively inhibit tumor cell proliferation and reduce metastasis under near-infrared (NIR) light irradiation. Preliminary mechanistic investigations revealed that PHP-MPBA-GNRs could increase reactive oxygen species (ROS) and induce apoptosis in cancer cells. The PHP in PHP-MPBA-GNRs can also activate dendritic cells and up-regulate the expression of co-stimulatory molecules and antigen-presenting complexes. All biological experiments, including in vivo tests, demonstrated that PHP-MPBA-GNRs achieved a combination of photothermal therapy and immunotherapy for tumors.

Dispersion and stability of gold nanorods prepared by anodized aluminum oxide (AAO) templates in alkaline solution

Dispersion and stability of gold nanorods prepared by anodized aluminum oxide (AAO) templates in alkaline solution

Effective Distribution of Gold Nanorods in Ordered Thick Mesoporous Silica: A Choice of Noninvasive Theranostics.

Porous silica coated gold nanorod core-shell structures demonstrate a multifunctional role in bioimaging, drug delivery, and cancer therapeutics applications. Here, we address a new approach for effective distribution of gold nanorods (GNRs) in a mesoporous silica (MS) shell, viz., one nanorod in one silica particle (GMS). We have studied that silica coating presents major advantages for the better biocompatibility and stability of GNRs. In this study, two different thicknesses of silica shell over GNRs have been discussed as per the application's need; GNRs in thin silica (11 nm) are fit for phototherapy and bioimaging, whereas thick and porous silica (51 nm) coated gold nanorods are suitable for triggered drug delivery and theranostics. However, effective distribution of GNRs in ordered architecture of thick mesoporous silica (MS, more than 50 nm thickness) with high surface area (more than 1000 m2/g) is not well understood so far. Here, we present methodical investigations for uniform and highly ordered mesoporous silica coating over GNRs with tunable thickness (6 to 51 nm). Judicious identification and optimization of different reaction parameters like concentrations of silica precursor (TEOS, 1.85-43.9 mM), template (CTAB, 0.9-5.7 mM), effect of temperature, pH (8.6-10.8), stirring speed (100-400 rpm), and, most importantly, the mode of addition of TEOS with GNRs have been discussed. Studies with thick, porous silica coated GNRs simplify the highest ever reported surface area (1100 m2/g) and cargo capacity (57%) with better product yield (g/batch). First and foremost, we report a highly scalable (more than 500 mL) and rapid direct deposition of an ordered MS shell around GNRs. These engineered core-shell nanoparticles demonstrate X-ray contrast property, synergistic photothermal-chemotherapeutics, and imaging of tumor cell (96% cell death) due to released fluorescent anticancer drug molecules and photothermal effect (52 °C) of embedded GNRs. A deeper insight into their influence on the architectural features and superior theranostics performances has been illustrated in detail. Hence, these findings indicate the potential impact of individual GMS for image guided combination therapeutics of cancer.

Kinetic Model Evaluation of the Resilience of Plasmonic Nanoantennas for Laser-Induced Fusion

A kinetic model of the plasmonic response and stability of gold nanorods under high-intensity laser irradiation is used to evaluate their suitability as amplifiers for laser-induced inertial confinement fusion.

Correlation between Spectroscopic and Mechanical Properties of Gold Nanocrystals under Pressure

The effects of nonhydrostatic pressure on the morphology and stability of gold nanorods (AuNRs) and nanospheres (AuNSs) in 4:1 methanol–ethanol mixtures were studied by optical absorption spectroscopy and transmission electron microscopy at pressures of up to 23 and 30 GPa, respectively. Solvent solidification and associated nonhydrostatic stresses were found to have a negligible effect on the shape and size of AuNSs. On the contrary, while AuNRs maintained their initial morphology in the hydrostatic range, the uniaxial stress component induced under nonhydrostatic conditions had a shearing effect on the AuNRs, breaking them into smaller particles. Interestingly, colloidal stability was maintained in all cases, and the particles showed no sign of aggregation, despite the severe nonhydrostatic conditions to which both AuNR and AuNS colloids were subjected.

Tweaking homogeneity and stability of gold nanorods by synergistic action of pH and temperature

Commonly used seed-mediated method of gold nanorod synthesis has limitations like formation of by-products (stars, squares, dog-bones, platelets), slow but continuous growth during storage/ageing which adversely affects their homogeneity. Storage in the presence of cetyltrimethylammonium bromide (CTAB) is also essential to prevent their aggregation, which being toxic, needs to be removed before using them for biological applications. We herein, present a simple approach to overcome these limitations through synergistic action of low pH and high temperature. The proposed modifications synthesize highly homogeneous nanorods which are stable upto months even when stored in water. Copyright © 2018 VBRI Press.

The Effect of Chemical Structure of OEG Ligand Shells with Quaternary Ammonium Moiety on the Colloidal Stabilization, Cellular Uptake and Photothermal Stability of Gold Nanorods.

PurposePlasmonic photothermal cancer therapy by gold nanorods (GNRs) emerges as a promising tool for cancer treatment. The goal of this study was to design cationic oligoethylene glycol (OEG) compounds varying in hydrophobicity and molecular electrostatic potential as ligand shells of GNRs. Three series of ligands with different length of OEG chain (ethylene glycol units = 3, 4, 5) and variants of quaternary ammonium salts (QAS) as terminal functional group were synthesized and compared to a prototypical quaternary ammonium ligand with alkyl chain – (16-mercaptohexadecyl)trimethylammonium bromide (MTAB).MethodsStep-by-step research approach starting with the preparation of compounds characterized by NMR and HRMS spectra, GNRs ligand exchange evaluation through characterization of cytotoxicity and GNRs cellular uptake was used. A method quantifying the reshaping of GNRs was applied to determine the effect of ligand structure on the heat transport from GNRs under fs-laser irradiation.ResultsFourteen out of 18 synthesized OEG compounds successfully stabilized GNRs in the water. The colloidal stability of prepared GNRs in the cell culture medium decreased with the number of OEG units. In contrast, the cellular uptake of OEG+GNRs by HeLa cells increased with the length of OEG chain while the structure of the QAS group showed a minor role. Compared to MTAB, more hydrophilic OEG compounds exhibited nearly two order of magnitude lower cytotoxicity in free state and provided efficient cellular uptake of GNRs close to the level of MTAB. Regarding photothermal properties, OEG compounds evoked the photothermal reshaping of GNRs at lower peak fluence (14.8 mJ/cm2) of femtosecond laser irradiation than the alkanethiol MTAB.ConclusionOEG+GNRs appear to be optimal for clinical applications with systemic administration of NPs not-requiring irradiation at high laser intensity such as drug delivery and photothermal therapy inducing apoptosis.

Hydroxyethyl Starch-Based Functionalization of Gold Nanorods: A Possible Alternative to Polyethylene Glycol as a Surface Modifier

PEGylation refers to the process of functionalizing nanoparticles with polyethylene glycol (PEG) to avoid unspecific uptake by the mononuclear phagocyte system and prolong the circulation half-life of nanomedicines. Immunogenicity and nonbiodegradability are the major limitations in PEGylation that can be resolved by substituting PEG with biofriendly polymers, such as hydroxyethyl starch (HES). In the current study, thiolated hydroxyethyl starch (HES-SH, 130/0.4) was harnessed to stabilize gold nanorods (AuNRs) and compared with PEG-SH-coated AuNRs at different aspects of characterization and photothermal analysis. Our results confirm that AuNRs were functionalized successfully with both HES-SH and PEG-SH, where the initial spectra and colloidal stability of gold nanorods were restored after functionalization. In addition, the photothermal conversion stability of gold nanorods was maintained during both HESylation and PEGylation without affecting the heat generation. In summary, we presume that HES-SH can be used as a surface modifier to stabilize gold nanorods and might be used as a promising alternative to PEG.

Cellular Uptake and Cytotoxicity of Varying Aspect Ratios of Gold Nanorods in HeLa Cells.

Gold nanorods (GNRs) have received broad attention due to their tunable surface plasmonic resonance modes, which make them an attractive candidate for biomedical applications in drug and gene delivery, biological imaging, and cancer treatment. In this study, we highlight the interactions of four different aspect ratios (ARs), 2.6, 3.2, 5.4 and 11.5, of GNRs with HeLa cells with respect to cellular uptake and cellular viability while also considering the effects of other parameters such as the surface stabilizer, supernatant, and serum proteins present in the medium. From this work, it was determined that the cell viability depended on the chemical composition of the supernatant, especially the amount of excess surfactant, hexadecyltrimethylammonium bromide (CTAB), used for the synthesis of GNRs; thus, the effect of aspect ratio of GNRs on endocytosis could not be directly discerned. For example, when exposed to GNRs of aspect ratio 11.5, HeLa cells showed higher cellular uptake compared to the shorter aspect ratios and a lower cytotoxicity simply because of the lower concentration of CTAB used during the synthesis, and a gentler purification method, such as sedimentation, also appeared to be a factor. Overall, the synthesis protocols, functionalization, purification processes, and the stability of GNRs in media have a major effect on cellular uptake and viability. Our results suggest that perhaps AR does play a role in endocytosis although an overall trend could not be unequivocally established, and sedimentation, contact time, and internalization kinetics need to be probed further using more biocompatible ligands in future studies.

Electrodissolution Inhibition of Gold Nanorods with Oxoanions

The incorporation of metal nanoparticles into bulk electrochemical systems has resulted in technological advances in electronics, electrocatalysis, and sensing. Metal “nanoelectrodes” are exposed to varied chemical environments that can cause dissolution under applied potentials, often below bulk oxidation values. Gold nanorods are being developed as superior light harvesting nanoantennas in photoelectrocatalysis, and light scatterers for nanoscopic spectroelectrochemical sensing. However, dissolution poses a critical problem for gold nanoelectrode functionalized devices as the electrochemical and optical properties of nanoparticles are highly dependent on size and shape, and the cost of replacement can be prohibitive. We employed an analytical, single particle approach to monitor the chloride-mediated dissolution pathway of gold nanorods in the presence of oxoanion electrodissolution inhibitors. Hyperspectral dark-field imaging revealed that the morphological stability of gold nanorods at anodic potentials improved with the addition of low relative concentrations of oxoanions to aqueous halide electrolyte solutions. Single particle measurements were necessary to address the inter-particle heterogeneity of chemically synthesized gold nanorods. Direct correlation imaging of single gold nanorods with scanning electron microscopy supported the reaction pathway heterogeneity statistics and electrodissolution potentials obtained spectroscopically. We determined that the electrodissolution inhibition capacity of oxoanions in the presence of chloride ions for gold nanoparticles was governed primarily by the electroadsorption potential and ionicity of the oxoanion. Determining the factors for inhibition will assist in the expansion of the electrochemical stability window, opening new avenues for gold nanoelectrodes in diverse and harsh catalytic and sensing environments.

Freeze-drying of monoclonal antibody-conjugated gold nanorods: Colloidal stability and biological activity

Maintaining colloidal stability of nanoparticles in suspensions is a major challenge. Therefore, freeze-drying (lyophilization) is recently proposed to preserve colloidal stability of nanoparticles through maintaining them in a solid state. However, freeze-drying would itself induce nanoparticle aggregation unless proper formulation with a careful selection of cryoprotectants is considered. Herein, we evaluate the colloidal stability of gold nanorods (GNRs) conjugated with a rituximab as a model monoclonal antibody upon freeze-drying in the presence of various cryoprotectants (mannitol, trehalose and sucrose). Aggregation-induced optical responses of GNRs were used as a sensitive tool to follow nanoparticle aggregation. In the absence of cryoprotectants, rituximab-conjugated GNRs aggregate irreversibly while evaluated cryoprotectants exhibit a significant protective effect. Maximal colloidal stability of GNRs is observed in the presence of trehalose while mannitol results in best cake formation in terms of shape and integrity. A combination of trehalose and mannitol produces a lyophilized product with satisfactory GNR colloidal stability and cake shape. Moreover, we show that freeze-dried rituximab-conjugated GNRs in presence of proper cryoprotectants maintain typical binding to lymphoma tissues as confirmed via immunohistochemistry assay.

Impact of the electron beam on the thermal stability of gold nanorods studied by environmental transmission electron microscopy

In-situ transmission electron microscopy experiments are of great interest to nanoscience and nanotechnology. However, it is known that the electron beam can have a significant impact on the structure of the sample which makes it important to carefully interpret in-situ data. In this work, we studied the thermal stability of CTAB-stabilized gold nanorods under different gaseous environments in an environmental transmission electron microscope and compared the outcome to ex-situ heating experiments. We observed a remarkable influence of the electron beam: While the nanorods were stable under inert conditions when exposed to the electron beam even at 400°C, the same nanorods reshaped at temperatures as low as 100°C under ex-situ conditions. We ascribe the stabilizing effect to the transformation of the CTAB bi-layer into a thin carbon layer under electron beam irradiation, preventing the nanorods from deforming. When exposed to an oxidizing environment in the environmental transmission electron microscope, this carbon layer was gradually removed and the gold atoms became mobile allowing for the deformation of the rod. This work highlights the importance of understanding the phenomena taking place under electron beam irradiation, which can greatly affect in-situ experiments and conclusions drawn from these. It stresses that in-situ electron microscopy data, taken on measuring the temperature dependence of nanoparticle properties, should be carefully assessed and accompanied by ex-situ experiments if possible.

Effect of Colloidal Medium on the Shelf-Life and Stability of Gold Nanorods Prepared by Seed-Mediated Synthesis.

Gold nanorods (GNRs) owing to their tunable longitudinal surface plasmon resonance in tissue transparent near infrared region have potential applications (like cancer imaging, surface enhanced Raman spectroscopy, cancer targeting, drug delivery and optical hyperthermia) in nanomedicine. Success of these diagnosis/therapy options depends on the plasmonic properties of gold nanorods, which are influenced by the interaction of GNRs with the colloidal medium. In this article, a systematic study is performed to evaluate the effect of colloidal medium on shelf life and stability of gold GNRs. As-synthesized GNRs are preserved in four aqueous media (deionized water, pluronic F-127, CTAB solution and growth solution) and their stability is investigated by closely monitoring the changes in the plasmonic signatures by UV-Visible spectroscopy and variation in hydrodynamic size by photon correlation spectroscopy for 30 days. As-synthesized GNRs are most stable in deionized water followed by pluronic F-127, CTAB and growth solution. The vast difference in the colloidal stability of GNRs in different media is due to the differences in surface driven unzipping of gold in these aqueous media.

High colloidal stability of gold nanorods coated with a peptide-ethylene glycol: Analysis by cyanide-mediated etching and nanoparticle tracking analysis

The stability of gold nanorods was assessed following coating with various charged or uncharged ligands, mostly peptides. Highly stable monodispersed gold nanorods were obtained by coating CTAB-stabilized gold nanorods with a pentapeptide with C-terminal ethylene glycol units (peptide-EG). UV⿿vis spectroscopy of these nanorods suspended in saline solutions indicated no signs of aggregation, and they were easily purified using size-exclusion chromatography. A more stringent measure of nanorod stability involved observing changes in the UV⿿vis absorbance of gold nanorods subjected to etching with cyanide. The λmax absorbance of peptide-EG coated nanorods red-shifted in etchant solution. The hypothesis that changes in the nanorod aspect ratio led to this red-shift was confirmed by TEM analysis, which showed pit formation along the transverse axis. The etching process was followed in solution using nanoparticle tracking analysis. The red-shift was shown to occur while the particles remained mono-dispersed, and so was not due to aggregation. Adding both etchant solution and peptide-EG to the nanorods was further shown to allow modulation of the ολmax red-shift and increase the etchant resistance of peptide-EG nanorods. Thus, very stable gold nanorods can be produced using the peptide-EG coating approach and their optical properties modulated with etchant.

Colloidal stability of gold nanorod solution upon exposure to excised human skin: Effect of surface chemistry and protein adsorption

In this study, we evaluated the colloidal stability of gold nanorods (with positive, negative and neutral surface charge) in solution upon contact with excised human skin. UV–vis absorption, plasmon peak broadening index (PPBI%) and transmission electron microscope analysis were used to follow nanoparticles aggregation in solution. Our results show that positively charged gold nanorods aggregate extensively upon exposure to excised human skin compared to negatively and neutrally charged gold nanorods. Skin-induced aggregation of cationic gold nanorods was linked to the adsorption of proteins released from the dermis layer to the surface of gold nanorods. Protein adsorption significantly screen nanorod’s effective surface charge and induce their aggregation. Moreover, we demonstrate that the presence of polyethylene glycol polymer on the surface of cationic gold nanorods minimize this aggregation significantly by providing steric repulsion (non-electrostatic stabilization mechanism). This work highlights the importance of evaluating the colloidal stability of nanoparticles in solution upon contact with skin, which is a “usually overlooked” parameter when studying the nanoparticle-skin interaction.

Investigating the stability of gold nanorods modified with thiol molecules for biosensing

Studying the stability of centrifugated gold nanorods unmodified/modified with thiols.

Immobilized papain on gold nanorods as heterogeneous biocatalysts

Papain, a thiol protease present in the latex of Carica papaya, is an enzyme which exhibits broad proteolytic activity, and, for this reason, it is utilized in a variety of industrial applications. Immobilization of papain on gold nanoparticles highly preserves its activity and enhances the stability, allowing the reuse of the linked enzyme many times without any significant loss of its catalytic performance. In particular, kcat and KM values remain substantially unchanged, while immobilized form shows a higher activity on a wider pH range retains 80 % residual activity also at 90 °C and shows higher functionality than the free form when incubated for long time (1 h) at 90 °C and at extreme pH values (3 and 12). A higher activity of immobilized papain with respect to the free form in the presence of various bivalent metal ions, known as strong inhibitors of papain, was also found. The reasons of this enhanced stability of gold nanorods immobilized papain are discussed.

Stability of Gold Nanorods Passivated with Amphiphilic Ligands

The stability of gold nanorods (NRs) coated with amphiphilic ligands (ALs) was investigated. NRs coated with cetyltrimethylammonium bromide (CTAB) were ligand exchanged with polyoxyethylene [10] cetyl ether (Brij56), Oligofectamine (OF), and phosphatidylserine (PS). An aggregation index based on the longitudinal surface plasmon resonance peak broadening was used to measure stability of the NR-ALs under different conditions including the number of washes, pH, ionic concentration, and temperature. The aggregation index was also used to measure the stability of the NR-ALs under ultrafast laser irradiation and in the presence of proteins commonly used in cell culture. Differences in NR-AL stability were found, which were due to differences in the physical and chemical properties of the ALs. Apart from the charge on the AL headgroup, we suggest the Gibbs free energy of passivation (ΔG(p)) and enthalpy of passivation (ΔH(p)) of the AL could potentially aid in the selection of amphiphiles that can effectively passivate NRs for stability and optimize their properties and desired biological impact.

Thermal stability of gold nanorods in an aqueous solution

The thermal stability of the gold nanorods in an aqueous solution was investigated by UV–vis absorption spectroscopy and TEM technique. It was found that the longitudinal surface plasmon resonance absorption of the gold nanorods gradually moved to a shorter wavelength at high temperature, suggesting the decrease of the aspect ratio. The decrease of the aspect ratio could be attributed to the increase of the diameter and the decrease of the length, which was associated with Ostwald ripening in the solution. This shape deformation could be inhibited by reducing the concentration of cetyltrimethylammonium bromide or coating the surface of gold nanorods with poly(sodium styrenesulfonate). The results are very important to the future applications of the gold nanorods where they have to be heated to high temperature without change of their optical properties.

Enhanced photoacoustic stability of gold nanorods by silica matrix confinement

Photoacoustic tomography (PAT) has garnered much attention for its high contrast and excellent spatial resolution of perfused tissues. Gold nanorods (GNRs) have been employed to further enhance the imaging contrast of PAT. However, the photon fluences typically needed for PA wave induction often also result in GNR shape changes that significantly reduce the efficiency of acoustic wave generation. In this work, we propose, synthesize, and evaluate amorphous silica-coated gold nanorods (GNR-Si) in an effort to improve contrast agent stability and ameliorate efficiency loss during photoacoustic (PA) wave induction. TEM and optical absorption spectra measurements of GNR and GNR-Si show that encasing GNRs within amorphous silica provides substantial protection of nanorod conformation from thermal deformation. PA signals generated by GNR-Si demonstrate considerably greater resistance to degradation of signal intensity with repetitive pulsing than do uncoated GNRs, thereby enabling much longer, high-contrast imaging sessions than previously possible. The prolongation of high-contrast imaging, and biocompatibility and easy surface functionalization for targeting ligands afforded by amorphous silica, suggest GNR-Si to be potentially significant for the clinical translation of PAT.