Surface Of Gold Nanoparticles Research Articles

Ligation of Gold Nanoparticles with Self-Assembling, Coiled-Coil Peptides.

The surface of gold nanoparticles (AuNPs) can be conjugated with a wide range of highly functional biomolecules. A common pitfall when utilizing AuNPs is their tendency to aggregate, especially when their surface is functionalized with ligands of low molecular weight (no steric repulsion) or ligands of neutral charge (no electrostatic repulsion). For biomedical applications, AuNPs that are colloidally stable are desirable because they have a high surface area and thus reactivity, resist sedimentation, and exhibit uniform optical properties. Here, we engineer the surface of AuNPs so that they remain stable when decorated with coiled-coil (CC) peptides while preserving the native polypeptide properties. We achieve this by using a neutral, mixed ligand layer composed of lipoic acid poly(ethylene glycol) and lipoic acid poly(ethylene glycol) maleimide to attach the CCs. Tuning the surface fraction of each component within the mixed ligand layer also allowed us to control the degree of AuNP labeling with CCs. We demonstrate the dynamic surface properties of these CC-AuNPs by performing a place-exchange reaction and their utility by designing an energy-transfer-based caspase-3 sensor. Overall, this study optimizes the surface chemistry of AuNPs to quantitatively present functional biomolecules while maintaining colloid stability.

Surface plasmon-assisted catalytic reduction of p-nitrothiophenol for the detection of Fe2+ by surface-enhanced Raman spectroscopy

Herein, we developed a concise, time-efficient, and high selective assay for detecting Fe2+ through its triggered surface plasmon-assisted reduction reaction of p-nitrothiophenol (PNTP) to p,p′-dimercaptoazobenzene (DMAB) on the surface of gold nanoparticles (AuNPs) based on surface-enhanced Raman scattering (SERS) spectroscopy. When Fe2+ was added to the PNTP-AuNPs system, the appearance of three characteristic peaks at 1142, 1392, and 1440 cm−1 attributed to DMAB demonstrated that Fe2+ induced the catalytic coupling reaction of PNTP. The Raman intensity ratio of the peak at 1142 cm−1 to the peak at 1336 cm−1 and the concentration of Fe2+ presented a good linear response from 10 to 100 μM with a limit of detection (LOD) of 0.35 μM. More importantly, the entire detection process can be completed within 2 min and further successfully used for the detection of Fe2+ in river water.

Theoretical study of the binding mechanism between anticancerous drug mercaptopurine and gold nanoparticles using a cluster model.

Mercaptopurine is an effective anticancer medicine yet known with serious adverse reactions, thus requiring further attempts to enhance its biological targeting. Small gold clusters Aun (n = 2-10) were used as model reactants to simulate the surface of gold nanoparticles. The computed results show that the drug molecules tend to anchor on the gold clusters at the S atom with the associated binding energies varying from -50 to -34 kcal mol-1 (in vacuum) and from -42 to -28 kcal mol-1 (in aqueous solution). Furthermore, the adsorption of the drug onto the gold surface is considered as a reversible process, and the mechanism of drug releasing was found to be triggerable by internal factors, such as a pH change or the concentrated presence of thiol amino acids in cancerous protein structures. Calculations based on density functional theory (DFT) were performed to probe the nature of interactions between the drug and gold nanoparticles. Structural features, thermodynamic parameters, bonding characteristics, and electronic properties of the resulting complexes were investigated at the PBE//cc-pVTZ/cc-pVDZ-PP level.

Inferring the Interfacial Reactivity of Gold Nanoparticles by Surface Plasmon Resonance Measurements.

Gold nanoparticles (GNPs) require a functionalization step in most cases to be suitable for applications. Optimizing this step in order to maintain both the stability and the plasmonic properties of the GNPs is a demanding process. Indeed, multiple analyses are required to get sufficient information on the grafting rate and the stability of the obtained suspension, leading to material and time waste. In this study, we propose to investigate ligand reactivity on a gold surface with surface plasmon resonance (SPR) measurements as a way to simulate the reactivity in GNP suspensions. We consider two thiolated ligands in this work: thioglycolic acid (TA) and 6-mercaptohexanoic acid (MHA). These thiols are grafted using different conditions on GNPs (monitored by optical absorption) and on a gold surface (monitored by SPR) and the grafting efficiency and stability are compared. The same conclusions are reached in both cases regarding the best protocol to implement, namely, the thiol molecules should be introduced in a water solution at a low concentration. This demonstrates the suitability of SPR to predict the reactivity on a GNP surface.

Building of a three-dimensional apta-nano interface using silver nanoflower for photoelectrochemical detection of carcinoembryonic antigen

Enhancing the sensitivity of photoelectrochemical (PEC) assays poses a challenging task. This study proposes a method to improve the sensitivity of PEC assays by creating a three-dimensional (3D) apta-nano interface using silver nanoflowers (AgNFs) with a 3D flower-like structure as a substrate. The aptamer (Apt) was immobilized on the surface of the AgNF-loaded gold nanoparticles (AuNPs) through the dual action of polyA blocking and Au-S bonding. Despite using cadmium sulfide quantum dots (CdS QDs) as the sole photoactive material, the as-prepared photoelectrode still showed excellent sensitivity. Using carcinoembryonic antigen (CEA) as a model target, the variation value of photocurrent (ΔI) exhibited good linear correlation (R2 = 0.9974) with the logarithm of CEA concentration in a wide detection range from 0.001 to 100 ng mL−1, and the detection limit was as low as 0.64 pg mL−1. In the assay of CEA in 1% serum, the recoveries reached 98.70 ∼ 99.63% with a low relative standard derivation (RSD) ranging from 1.11% to 2.05%. This study introduces novel concepts for the development of PEC sensors, potentially enhancing their utility in the clinical detection of disease markers.

Polyhedral Colloidal Clusters Assembled from Amphiphilic Nanoparticles in Deformable Droplets.

Polyhedral colloidal clusters assembled from functional inorganic nanoparticles have attracted great interest in both scientific research and applications. However, the spontaneous assembly of colloidal nanoparticles into polyhedral clusters with regular shape and tunable structures remains a grand challenges. Here, we successfully construct Mackay icosahedral and regular tetrahedral colloidal clusters assembled from gold nanoparticles grafted with a mixture of polystyrene (PS) and poly(2-vinylpyridine) (P2VP) homopolymers by precisely tuning the interfacial interaction between the nanoparticles and the oil/water interface. By increasing the proportion of hydrophilic P2VP ligands on the surface of gold nanoparticles, the Mackay icosahedral clusters can transform into regular tetrahedral clusters in order to maximize the surface area of the polyhedral assembly. Furthermore, we reveal the formation mechanism of these regular polyhedral colloidal clusters. The formation of polyhedral colloidal clusters is not only dependent on the entropy but also determined by the interfacial free energy. This finding demonstrates an effective approach to organize nanoparticles into polyhedral colloidal clusters with potential applications in various fields.

Microfluidic chip and chiroptical gold nanoparticle-based colorimetric sensor for enantioselective detection of L-tryptophan

Herein, we introduce a novel integrated system that merges an enantio-discriminative bio-MOF-packed centrifugal microfluidic chip made from PDMS with a user-friendly on-site colorimetric sensor. This innovative approach enables the precise enantioselective recognition of L-tryptophane (L-Trp). This chiral recognition probe was successfully synthesized through meticulous control of nano-ovals-shaped gold nanoparticles morphology and surface passivation. The operational factor of this methodology was optimized to ensure simplicity, practicality, and efficiency. This optimization led to reduced reagent consumption and instantaneous analytical feedback. The integrated system was effectively applied for enantioselective separation and quantification of L-Trp across an extensive linear range of 50 μM-1.5 mM, impressive limit of detection as low as 15 μM. It is noteworthy that this integrated system demonstrated desirable selectivity even in the presence of similar biomolecules, showcasing its robust performance and rapid detection capability. Further extended the application of this strategy to exceptional performance across enantioselective sensing of L-Trp in various sample matrices, comprising bovine serum albumin, bovine milk, blood plasma and urine samples. This integrated microfluidic sample pretreatment, chiroptical sensing, and on-site signal recording with a smartphone hold tremendous potential for widespread implementation, practical applications engaging healthcare and environmental, food safety, and point-of-needs analysis, facilitating successive solution mixing and colorimetric detection.

Construction of aptamer sensor based on Au nanozymes for ultrasensitive SERS detection of tobramycin

Tobramycin aptamer was adsorbed on the surface of gold nanoparticles (Au NPs) by van der Waals forces, hydrogen bonds, and other factors, limiting nanozyme peroxidase activity. Because tobramycin has a higher affinity for the tobramycin aptamer, including tobramycin in Au@Apts nanozymes was able to dislodge the aptamer from the surface of Au NPs and restore the catalytic activity of nanozymes. Raman spectroscopy of the enzyme-catalyzed product TMBox can detect this shift in enzyme activity. The restored value of nanozyme activity increased with tobramycin concentration and had a good linear correlation in the concentration range of 10−10∼10−1 M with a detection limit of 2.04 × 10−11 M. Aptamer biosensors are built using the SERS platform, which has the advantages of high sensitivity, high precision, and a wide detection range. It is prospectively employed in food safety and the detection of antibiotic residues.

A colorimetric aptasensor for detecting ochratoxin A based on label-free aptamer and gold nanozyme.

In this study, the aptamer of ochratoxin A (OTA) increased the negative charge density on the surface of gold nanoparticles (AuNPs) and promoted the release of hydroxyl radicals and Au3+ to enhance the peroxidase-like activity of the AuNPs. The OTA bound only to the aptamer and did not adsorb non-specifically to the AuNPs. Based on these two conclusions, a label-free colorimetric aptasensor was successfully developed, enabling the precise detection of OTA within the concentration range of 10-600nM, with a remarkably low detection limit of 6.20nM. The colorimetric aptasensor was applied to detect OTA in oats, corn, soybeans, rice, and glutinous rice.

Emission Onset Time-Adjustable Chemiluminescent Gold Nanoparticles with Ultrastrong Emission for Smartphone-Based Immunoassay of Severe Acute Respiratory Syndrome Coronavirus 2 Antigen.

Recently, our group reported a chemical timer approach to manipulate the onset time of chemiluminescence (CL) emission. However, it is still in the proof-of-concept stage, and its analytical applications have not been explored yet. Nanomaterials have merits of good catalytic effect, large specific surface area, good biocompatibility, and ease of self-assembly, which are ideal for constructing analytical-interfaces for bioassays. Herein, an emission onset time-adjustable chemiluminescent L012-Au/Mn2+ was synthesized for the first time by modifying Mn2+ on the surface of L012-protected gold nanoparticle. By using H2O2 and NaHCO3 as coreactants, L012-Au/Mn2+ could not only generate an ultrastrong and long-time CL emission but also its CL emission onset time could be adjusted by the addition of thiourea, which could effectively eliminate interference from the addition of coreactants, shorten the exposure time, reduce the detection background, and finally achieve high sensitivity CL imaging analysis. On this basis, a label-free CL immunoassay was constructed with a smartphone-based imaging system for high-throughput and sensitive determination of severe acute respiratory syndrome coronavirus 2 nucleocapsid (N) protein. The CL image of the immunoassay with different concentrations of N proteins was captured in one photograph 100 s after the injection of H2O2 with a short exposure time of 0.5 s. The immunoassay showed good linearity over the concentration range of 1 pg/mL to 10 ng/mL with a detection limit of 0.13 pg/mL, which was much lower than the reported CCD imaging detection method. In addition, it showed good selectivity and stability and was successfully applied in serum samples from healthy individuals and COVID-19 rehabilitation patients.

Engineering of functional nanosnowflakes from gold nanocarriers capped with amino-modified DNA oligonucleotides.

The design, engineering and electron microscopic characterization of anisotropic nanosized snowflake-like structural assemblies (nanosnowflakes) is reported. They were fabricated through immobilization of double stranded amine-modified and thiol-terminated DNA oligonucleotides on the surface of ultra-small isotropic gold nanoparticles used as nanocarriers. The transmission electron microscopy images combined with spectrophotometric data revealed the formation of self-assembled structural aggregation between individual ligands-coated nanoparticles. They act as seeds for the further spontaneous dendritic growth in different directions. Their anisotropic morphology is formed due to the occurrence of facilitated electrostatic interactions between positive charged amino-groups and the negative sugar-phosphate backbone of oligonucleotides. Thus, nanosnowflakes with size distribution between 40 and 80 nm were obtained. The microscopic analysis demonstrated also that the stable nanosnowflakes structure was highly dependent on the solution ionic strength, which effect the charge fluctuation within the assembly. The reported DNA functionalized nanostructures have potential to be applied as a platform for development of therapeutic materials, as well as drug delivery nanosystems. RESEARCH HIGHLIGHTS: The engineering, fabrication, and microscopic characterization of DNA nanosnowflakes is reported. The electron microscopy analysis revealed formation of self-assemblies with anisotropic morphology. The nanosnowflakes size distribution was between 40 and 80 nm.

Dual-layer 3D DNA nanostructure: The next generation of ultrafast DNA nanomachine for microRNA sensing and intracellular imaging

The working efficiency of traditional 3D DNA nanomachines is extremely restricted due to the complex DNA components modified on nanoparticles in the same spatial height. Herein, an ultrafast dual-layer 3D DNA nanomachine (UDDNM) based on catalytic hairpin assembly (CHA) was developed by assembling two different lengths of hairpin DNA on the surface of gold nanoparticles, the long hairpin 1 (H1), to capture the trigger, and the short hairpin 2 (H2), as the signal probe, to recycle the trigger. Compared to the traditional single-layer 3D DNA nanomachine, the dual-layer 3D DNA nanostructure greatly enhances the effective collision between trigger and targeted DNA probe, H1, since the H1 located in outer layer would react with the trigger, inhibiting the invalid collision between the trigger and residual DNA component, H2, and remarkably decreasing the steric hindrance associated with the nucleic acids layer around the nanoparticles. Especially, when the distance of two layers was fixed at 3 nm, the corresponding UDDNM could accomplish the overall reaction only in 3 min with a dramatically high initial rate of up to 5.93 × 10−7 M s−1, which was at least 5-fold beyond that of the typical single-layer 3D DNA nanomachines. As a proof of concept, the described UDDNM was successfully applied in ultrasensitive fluorescence detection and sensitive intracellular imaging of miRNA-21. Consequently, our strategy, based on the creation of dual-layer 3D DNA nanostructure, may create a new approach to designing the next generation of DNA nanomachine and has enormous potential for applications in bio-analysis, logic gate operations, and clinical diagnoses.

In Situ Activation of the Receptor Aggregation for Cell Apoptosis by an AI-Au Intelligent Nanomachine via Tumor Extracellular Acidity.

Polyvalent ligand-induced cell receptor aggregation is closely related to cell behavior regulation. At present, most of the means to induce receptor aggregation rely on external stimuli such as light, heat, and magnetic fields, which may cause side effects to normal cells. How to achieve receptor aggregation on the cancer cell surface to achieve cell apoptosis selectively is still a challenge. Therefore, by taking advantage of the unique property of cancer cells' slightly acidic microenvironment, an easy-to-use apoptosis-inducing mode for the in situ activation of cell surface nucleolin clustering has been developed, which not only opened a new channel for nucleolin receptor aggregation to regulate cell function and further development but also avoided damage to normal cells, providing a new strategy for tumor treatment. Dual functional ssDNA (AS1411 aptamer and pH-responsive I-strand sequence) was modified on the surface of gold nanoparticles (AuNPs) to fabricate AI-Au intelligent nanomachines. Then, the specific binding on cancer cells and aggregation of the nucleolin receptors can be achieved via the formation of an i-Motif structure among adjacent AuNPs under the acidic microenvironment. The result showed that AI-Au nanomachines mediated nucleolin cross-linking on the cell surface, resulting in a cytotoxic effect of approximately 60%. Experiments such as calcein-AM/PI staining, nuclear dye staining, and flow cytometry demonstrated that cell apoptosis became more evident with the increase of acidity under the cell surface microenvironment. Immunofluorescence imaging further confirmed the Cyt-c/caspase-3 apoptosis pathway induced by AI-Au nanomachines. The proposed strategy used for specific cancer cell apoptosis by the in situ activation of tumor cell membrane receptor aggregation is inexpensive and simple to use, which not only provides a new means of nucleolin receptor aggregation for regulating cell function but also offers a new strategy for tumor treatment with reduced side effect to normal cells. This work is significant for comprehending the ligand-induced receptor aggregation process and can lead to the development of a promising anticancer drug.

Noncovalent Adsorption of Single-Stranded and Double-Stranded DNA on the Surface of Gold Nanoparticles

Understanding the patterns of noncovalent adsorption of double-stranded nucleic acids (dsDNA) on gold nanoparticles (GNPs) was the aim of this study. It was found that the high-affinity motifs in DNA can and do act as an “anchor” for the fixation of the whole molecule on the GNP (up to 98 ± 2 single-stranded (ss)DNA molecules per particle with diameter of 13 ± 2 nm). At the same time, the involvement of an “anchor” in the intramolecular DNA interaction can negatively affect the efficiency of the formation of ss(ds)DNA–GNP structures. It has been shown that the interaction of GNP with DNA duplexes is accompanied by their dissociation and competitive adsorption of ssDNAs on GNP, wherein the crucial factor of DNA adsorption efficiency is the intrinsic affinity of ssDNA to GNP. We propose a detailed scheme for the interaction of dsDNA with GNPs, which should be taken into account in studies of this type. Researchers focused on this field should accept the complicated nature of such objects and take into account the many competing processes, including the processes of adsorption and desorption of DNA on gold as well as the formation of secondary structures by individual DNA strands.

Functionalized carbon nanotube field-effect transistor biosensor for highly sensitive detection of exosomal protein

Since the exosomal protein level is related to many diseases, sensitive detection of exosomal protein is highly desirable. Here, we describe a polymer-sorted high-purity semiconducting carbon nanotubes (CNTs) films-based field-effect transistor (FET) biosensor for ultrasensitive and label-free detection of MUC1, a transmembrane protein highly expressed in breast cancer exosomes. Polymer-sorted semiconducting CNTs hold advantages including high purity (>99%), high CNT concentration, and short processing time (<1 h), but they are difficult to be stably functionalized with biomolecules because of lacking hanging bonds on their surface. To solve this issue, poly-lysine (PLL) was employed to modify the CNT films after they were deposited on the sensing channel surface of the fabricated FET chip. To specifically recognize the exosomal protein, sulfhydryl aptamer probes were immobilized on the gold nanoparticles (AuNPs) surface that was assembled on PLL substrate. The aptamer-modified CNT FET was capable of sensitively and selectively detecting exosomal MUC1 as high as 0.34 fg/mL. Moreover, the CNT FET biosensor was able to recognize breast cancer patients from healthy individuals by comparing the expression level of exosomal MUC1. The developed CNT FET biosensor is expected to be a novel assay for early diagnosis of cancer.

Evaluation of Radiosensitization and Cytokine Modulation by Differentially PEGylated Gold Nanoparticles in Glioblastoma Cells.

Glioblastoma (GBM) is known as the most aggressive type of malignant brain tumour, with an extremely poor prognosis of approximately 12 months following standard-of-care treatment with surgical resection, radiotherapy (RT), and temozolomide treatment. Novel RT-drug combinations are urgently needed to improve patient outcomes. Gold nanoparticles (GNPs) have demonstrated significant preclinical potential as radiosensitizers due to their unique physicochemical properties and their ability to pass the blood-brain barrier. The modification of GNP surface coatings with poly(ethylene) glycol (PEG) confers several therapeutic advantages including immune avoidance and improved cellular localisation. This study aimed to characterise both the radiosensitizing and immunomodulatory properties of differentially PEGylated GNPs in GBM cells in vitro. Two GBM cell lines were used, U-87 MG and U-251 MG. The radiobiological response was evaluated by clonogenic assay, immunofluorescent staining of 53BP1 foci, and flow cytometry. Changes in the cytokine expression levels were quantified by cytokine arrays. PEGylation improved the radiobiological efficacy, with double-strand break induction being identified as an underlying mechanism. PEGylated GNPs also caused the greatest boost in RT immunogenicity, with radiosensitization correlating with a greater upregulation of inflammatory cytokines. These findings demonstrate the radiosensitizing and immunostimulatory potential of ID11 and ID12 as candidates for RT-drug combination in future GBM preclinical investigations.

Monolayer protein adsorption on cationic gold nanoparticles: A thermodynamic study

The mechanism for adsorption of Lysozyme (Lyz) and cytochrome c (Cyt. c) proteins on cetyltrimethylammonium bromide (CTAB) capped cationic gold nanoparticles (GNPs) of 26, 46, and 68 nm at pH 6.8 were probed by second harmonic light scattering technique (SHLS). We found that both the proteins binds with cationic GNPs with surprisingly high binding constant of 109-1010 M−1. The nsat values clearly indicates that both the proteins form only monolayer on the GNP surface. Dynamic light scattering measurements validate the adsorption parameters obtained from SHLS. The temperature-dependent SHLS measurements revealed that the adsorption processes were favoured by huge entropic gain.

Fiber Optic Localized Surface Plasmon Resonance Sensor Based on Carboxymethylated Dextran Modified Gold Nanoparticles Surface for High Mobility Group Box 1 (HMGB1) Analysis

Rapid, sensitive, and reliable detection of high mobility group box 1 (HMGB1) is essential for medical and diagnostic applications due to its important role as a biomarker of chronic inflammation. Here, we report a facile method for the detection of HMGB1 using carboxymethyl dextran (CM-dextran) as a bridge molecule modified on the surface of gold nanoparticles combined with a fiber optic localized surface plasmon resonance (FOLSPR) biosensor. Under optimal conditions, the results showed that the FOLSPR sensor detected HMGB1 with a wide linear range (10-10 to 10-6 g/mL), fast response (less than 10 min), and a low detection limit of 43.4 pg/mL (1.7 pM) and high correlation coefficient values (>0.9928). Furthermore, the accurate quantification and reliable validation of kinetic binding events measured by the currently working biosensors are comparable to surface plasmon resonance sensing systems, providing new insights into direct biomarker detection for clinical applications.

A Quantitative Study of Thermal and Non-thermal Mechanisms in Ultrasound-Induced Nano-drug Delivery.

The primary objective of this study was to quantify the contributions to drug release for thermal and non-thermal mechanisms in ultrasound-induced release from gold nanoparticles (GNPs) for the first time. We studied doxorubicin (DOX) and curcumin release from the surface of GNPs using two different methods to induce drug release in an ex vivo tissue model: (i) localized tissue heating with a water bath and (ii) low-intensity pulsed ultrasound (LIPUS) exposure. Both methods have similar temperature profiles and can induce the release of both hydrophobic (curcumin) and hydrophilic (DOX) drugs from the surface of GNPs. Quantitative drug release in both cases was compared via fluorescence measurements. The water bath heating method induced drug release using thermal effects only, whereas LIPUS exposure induced drug release used a combination of thermal and non-thermal mechanisms. It was found that there were increases of 70 ± 16% (curcumin) and 127 ± 20% (DOX) in drug release when LIPUS was used to induce drug release (both thermal and non-thermal mechanisms) as compared with the water bath (thermal mechanisms only) mediated release. We determined that non-thermal mechanisms account for 41 ± 3% of curcumin release and 56 ± 4% of DOX release. It was concluded that in our ex vivo tissue model, the non-thermal mechanisms play a significant role in LIPUS-induced drug release from GNP drug carriers and that the contributions of non-thermal mechanisms to drug release depend on the type of anticancer drug loaded on the GNP surface.

The Interaction of Amines with Gold Nanoparticles.

Understanding the interactions between amines and the surface of gold nanoparticles is important because of their role in the stabilization of the nanosystems, in the formation of the protein corona, and in the preparation of semisynthetic nanozymes. By using fluorescence spectroscopy, electrochemistry, X-ray photoelectron spectroscopy, high-resolution transmission electron microscopy, and molecular simulation,a detailed picture of these interactions is obtained. Herein, it is shown that amines interact with surface Au(0) atoms of the nanoparticles with their lone electron pair with a strength linearly correlating with their basicity corrected for steric hindrance. The kinetics of binding depends on the position of the gold atoms (flat surfaces or edges) while the mode of binding involves a single Au(0) with nitrogen sitting on top of it. A small fraction of surface Au(I) atoms, still present, is reduced by the amines yielding a much stronger Au(0)-RN.+ (RN. , after the loss of a proton) interaction. In this case, the mode of binding involves two Au(0) atoms with a bridging nitrogen placed between them. Stable Au nanoparticles, as those required for robust semisynthetic nanozymes preparation, are better obtained when the protein is involved (at least in part) in the reduction of the gold ions.