Gold Nanostars Research Articles

Synthesis and Characterization of Silver-Plated Gold Nanostars for Biomedical and Sensing Applications

The physiochemical and optical characteristics of nanoscale colloids rely on their chemical composition, shape, and size. Gold nanostars are anisotropic multibranched nanoparticles with a central core and several sharp delicate tips, command significant attention in nanodiagnostic, imaging and sensing applications. Anisotropic nanoparticle’s shape, size and tips are of a great importance dominating their properties and performance in biomedical applications and sensing strategies which require optimization. Several factors can affect these features. In this regard, silver seed mediated goldnanostars were synthesized and characterized using different characterization techniques. Furthermore, the effect of the gold solution concentration on the morphology of the synthesized gold nanostars was investigated. Result indicated successful synthesis of gold nanostars with high yield and multiple sharp branches. EDX line scanning profile of the gold nanostars showed that there is a thin coating of silver in the shell of the nanostructures. Moreover, further analysis of TEM images of AuNSs in atomic scale resolution demonstrated that there are no dislocations and defects in the structure of the synthesized gold nanostars. Positive zeta potential of 42.3 mV confirmed good stability against aggregation in terms of charge stabilization. Synthesized anisotropic gold nanostars with near-infrared surface plasmon resonance in which tissue absorption and autofluorescence are minimized, can be used for multiple purposes on the biomedical field and sensing assays.

Dual-layers Raman reporter-tagged Au@Ag combined with core-satellite assemblies for SERS detection of Zearalenone.

Zearalenone (ZEN) is a prevalent mycotoxin identified in corn. A SERS-based immunosensor by constructing core-satellite assemblies was developed for ZEN detection. ZEN monoclonal antibody modified gold nanostars (AuNSs) were fabricated as the capture probe (core). The Raman signal probes (satellites) utilized ZEN antigen linked to the core-shell structures loaded with two layers of Raman reporter molecules (AuMBA@AgMBANPs). The coupling between AuNSs and AuMBA@AgMBANPs can produce a poweful electromagnetic field, thus considerably amplifying the Raman signal. The detection range of ZEN for corn samples under the optimal conditions was 5∼400μg/kg with a LOD of 3μg/kg, which completely satisfying the requirement of maximum residual level (60μg/kg). Moreover, the proposed SERS method was consistent with the HPLC-FLD method for the detection of ZEN in naturally contaminated corn samples (90.58% ∼ 105.29%). Conclusively, fabricated immunosensor with exceptional sensitivity and specificity broaden the application of SERS in mycotoxin detection.

Remodeling of tumor stroma combined with photothermal therapy in the treatment of triple-negative breast cancer

Objective: Polyethylene glycol-modified gold nanostar particles (GNS-PEG) were constructed to investigate whether the degradation of extracellular matrix in triple-negative breast cancer could improve the tumor delivery of GNS-PEG and enhance the efficacy of photothermal therapy. Methods: GNS-PEG were constructed and characterized for physicochemical properties as well as photothermal properties. At the cellular level, the cytotoxicity of halofuginone (HF) and the effect of photothermal therapy were detected. Mouse model of triple negative breast cancer was established by subcutaneous inoculation of 4T1 cells in BALB/c nude mice. Five injections of HF were given via tail vein (HF group), and tumor sections were stained with Masson stain and immunohistochemical staining for transforming growth factor β1 (TGFβ1), α-smooth muscle actin (α-SMA) and CD31 to observe the effect of tumor stromal degradation. Five injections of HF via tail vein followed by GNS-PEG (HF+ GNS-PEG group) were applied to determine the content of gold in tumor tissues by inductively coupled plasma mass spectrometry. The tumor sites of the mice in the GNS-PEG and HF+ GNS-PEG groups were irradiated with NIR laser and the temperature changes were recorded with an IR camera. The tumour growth and weight changes of mice in each group were observed. Ki-67 immunohistochemical staining, TdT-mediated dUTP nick-end labeling and HE staining were performed on tumor tissue sections from each group to observe tumor proliferation, apoptosis and necrosis. HE staining was performed on heart, liver, spleen, lung and kidney tissues from each group to observe the morphological changes of cells. Results: GNS-PEG nanoparticles showed a multi-branched structure with a particle size of 73.5±1.4 nm. The absorption peak of GNS was 810 nm, which is in the near infrared region. The photothermal conversion rate of GNS-PEG was up to 79.3%, and the photothermal effect could be controlled by the laser energy. HF has a concentration-dependent cytotoxicity, with a cell survival rate being as low as (22.8±2.6)% at HF concentration of up to 1 000 nmol/L. The photothermal effect of GNS-PEG was significant in killing tumor cells, with a cell survival rate of (32.7±5.2)% at the concentration of 25 pmol/L. The collagen area fraction, TGFβ1 integrated optical density and α-SMA integrated optical density in the tumor tissues of mice in the HF group were (2.1±0.2)%, 3.1±0.4 and 5.2±1.9, respectively, which were lower than those of the control group (all P<0.01), and the vessel diameter was 8.6±2.9 μm, which was higher than that of the control group (P<0.05). In the HF+ GNS-PEG group, the concentration of gold in tissues was 52.4 μg/g, higher than that in the GNS-PEG group (15.9 μg/g, P<0.05). After laser irradiation, the temperature of the tumor site in the HF+ GNS-PEG group was significantly higher than that in the GNS-PEG group. At the 4th minute, the temperatures of the tumor site in the GNS-PEG and HF+ GNS-PEG groups were 51.5 ℃ and 57.7 ℃ respectively; the tumor volume in the HF+ GNS-PEG group was effectively suppressed. The body weights of the mice in each group did not change significantly during the monitoring period. No significant abnormalities were observed in the main organs of the mice in the GNS-PEG group, but some hepatocytes in the HF and HF+ GNS-PEG groups showed edema and degeneration. Conclusion: The remodeling of extracellular matrix in triple-negative breast cancer could significantly improve the intratumoral delivery of GNS-PEG and thus achieve better photothermal therapy effect.

EXTH-30. GOLD NANOSTARS OBVIATE LIMITATIONS TO LASER INTERSTITIAL THERMAL THERAPY (LITT) AND ENHANCE THE POST-LITT IMMUNE RESPONSE

Abstract Laser interstitial thermal therapy (LITT) is a minimally-invasive technique for the treatment of intracranial tumors that uses a stereotactically-guided laser and real-time magnetic resonance imaging (MRI) to monitor ablation progress. Previous applications of gold nanostars (GNS) in laser ablation of tumors have studied extracranial tumors only and utilized externally administered near infrared radiation that cannot penetrate the cranial compartment. Herein, we present a novel platform for employing GNS in intracranial tumors. We developed non-toxic GNS that exhibit maximum photothermal effects at the 1064 nm laser wavelength used in the FDA-approved clinical Neuroblate® LITT system. Monte Carlo simulations demonstrate that our GNS can accelerate and focus thermal energy distributions. Using ex vivo tumor phantom models, we found that GNS-infused phantoms demonstrate more rapid heating and improved spatial conformation of thermal energy, with neighboring material exposed to lower temperatures than controls. In our intracranial CT-2A glioma model, we quantified accumulation of radiolabeled GNS in tumor tissue via PET/CT. As further validation of tumor-selective GNS accumulation, we used two-photon luminescence to show that GNS selectively accumulate and are retained in intracranial tumors at 24 and 72 hours post-injection. We then utilized our in vivo heterotopic CT-2A model to assess the capacity of systemically-delivered GNS to augment laser ablation; we were able to achieve higher ablation temperatures and more efficient temperature ramping with LITT+GNS. Finally, we explored the potential of LITT+GNS to synergize with immunotherapy to further enhance the post-ablation immune response and found that combination therapy resulted in improved tumor control and immunologic memory that was protective against tumor rechallenge. These results support the ability of GNS to optimize LITT for the treatment of intracranial tumors by improving efficiency and safety, and illustrate the potential of this platform to synergize with immunotherapy.

Quantitative Galactose Colorimetric Competitive Assay Based on Galactose Dehydrogenase and Plasmonic Gold Nanostars.

We describe a competitive colorimetric assay that enables rapid and sensitive detection of galactose and reduced nicotinamide adenine dinucleotide (NADH) via colorimetric readouts and demonstrate its usefulness for monitoring NAD+-driven enzymatic reactions. We present a sensitive plasmonic sensing approach for assessing galactose concentration and the presence of NADH using galactose dehydrogenase-immobilized gold nanostars (AuNS-PVP-GalDH). The AuNS-PVP-GalDH assay remains turquoise blue in the absence of galactose and NADH; however, as galactose and NADH concentrations grow, the reaction well color changes to a characteristic red color in the presence of an alkaline environment and a metal ion catalyst (detection solution). As a result, when galactose is sensed in the presence of H2O2, the colored response of the AuNS-PVP-GalDH assay transforms from turquoise blue to light pink, and then to wine red in a concentration-dependent manner discernible to the human eye. This competitive AuNS-PVP-GalDH assay could be a viable analytical tool for rapid and convenient galactose quantification in resource-limited areas.

3D SERS and Raman imaging of protective microcapsules containing bio‐active terpenoids

AbstractTerpenoids play a major role in agriculture, given their fungicidal and herbicidal actions, as well as their favorable toxicological, ecotoxicological, and environmental profiles. Despite all these advantages, terpenoids are reported to be unstable in direct sunlight and atmospheric conditions, so both commercial suppliers and scientific literature foresee their protection by encapsulation. The so‐called microcapsules (μCaps) are therefore of high relevance as drug‐delivery vectors, but very few techniques focus on their surface as well as on their morphological characterization. Indeed, these aspects are of great importance, given that their surface chemistry governs both their colloidal stability and mechanism of action. Common analysis techniques, such as chromatographic and mass‐spectrometric ones, are destructive, require sample preparation, and do not result in the complete morphological characterization of the microcapsules. Micro‐Raman spectroscopy, in conjunction with the surface‐enhanced Raman spectroscopy (SERS) effect, offers a valuable alternative method of investigation capable of achieving a complete and non‐destructive morphological characterization of the terpenoid‐encapsulating systems, the dimensions of which fall within the micrometric range. In addition, the SERS effect can be exploited by fabricating the microcapsules with gold nanostars (AuNSs) modified with chitosan and a SERS reporter (Nile Blue A). Thanks to the high contrast provided by the SERS signals of this tag, it was possible to localize and confirm the chitosan in the morphology of the microcapsules. The results of this study shed new light on the possibility of analyzing terpenoid‐encapsulating microcapsules and possibly other kinds of encapsulates brought by using Raman spectroscopy and by exploiting the SERS effect.

Composites of Gold Nanostars and Nitrogen- and Sulfur-Codoped Graphene Quantum Dots as Plasmon-Enhanced Immunosensors for Cancer Prognosis

Composites of Gold Nanostars and Nitrogen- and Sulfur-Codoped Graphene Quantum Dots as Plasmon-Enhanced Immunosensors for Cancer Prognosis

Synthesis of tunable gold nanostars via 3D-printed microfluidic device with vibrating sharp-tip acoustic mixing

Synthesis of tunable gold nanostars via 3D-printed microfluidic device with vibrating sharp-tip acoustic mixing

Hyper-Branched Gold Nanoconstructs for Photoacoustic Imaging in the Near-Infrared Optical Window.

In plasmonic nanoconstructs (NCs), fine-tuning interparticle interactions at the subnanoscale offer enhanced electromagnetic and thermal responses in the near-infrared (NIR) wavelength range. Due to tunable electromagnetic and thermal characteristics, NCs can be excellent photoacoustic (PA) imaging contrast agents. However, engineering plasmonic NCs that maximize light absorption efficiency across multiple polarization directions, i.e., exhibiting blackbody absorption behavior, remains challenging. Herein, we present the synthesis, computational simulation, and characterization of hyper-branched gold nanoconstructs (HBGNCs) as a highly efficient PA contrast agent. HBGNCs exhibit remarkable optical properties, including strong NIR absorption, high absorption efficiency across various polarization angles, and superior photostability compared to conventional standard plasmonic NC-based contrast agents such as gold nanorods and gold nanostars. In vitro and in vivo experiments confirm the suitability of HBGNCs for cancer imaging, showcasing their potential as reliable PA contrast agents and addressing the need for enhanced imaging contrast and stability in bioimaging applications.

Feasibility of NAD(P)/NAD(P)H as redox agents in enzymatic plasmonic gold nanostar assays for galactose quantification.

Plasmonic colorimetric sensors have emerged as powerful analytical tools in biochemistry due to their localized surface plasmon resonance extinction in the visible range. Here, we describe the feasibility of NAD(P)/NAD(P)H as redox agents in enzymatic plasmonic gold nanostar (AuNS) assays for galactose quantification using three model enzymes, GalDH, AR and GalOx, immobilized separately on polyvinylpyrrolidone-capped AuNS scaffolds. These highly specific, sensitive and selective bioassays induce the transformation of AuNS into quasi-spherical nanoparticles during the biorecognition of galactose in water and synthetic blood matrices. As a result, using our inexpensive and simple AuNS plasmon bioassays, the presence of galactose may be detected spectrophotometrically and by the naked eye.

A SERS-based immune-nanoprobe for ultrasensitive detection of glycinin via a lateral flow assay

Glycinin is one of the most nutritious ingredients in soybean, but it is also an allergen that can cause allergic reactions in humans and animals, and even endanger life in severe cases. Therefore, it is imperative to develop a rapid and ultrasensitive detection method for glycinin. In order to achieve this goal, this experiment combined surface-enhanced Raman spectroscopy (SERS) technology with an economical, simple, fast and easy-to-carry immunochromatographic test strip, and successfully constructed an efficient sandwich immunochromatographic test strip. The immunoprobe of the test strip was covalently coupled by gold nanostars (AuNSs), Raman molecule 4-aminothiophenol (4-PATP) and rabbit polyclonal antibody. In this experiment, a gold nanostar immunochromatographic test strip for detecting glycinin was established. The detection limit of the test strip was 0.23 ng / mL, the recovery rate was 91.5–96.6 %, and the coefficient of variation was 1.61–6.15 %. In addition, the test strip had no cross reaction with whey protein, wheat protein, peanut protein, sesame protein and β-conglycinin, indicating that the detection method had good specificity and the ability to avoid false positive results. Hence, this experiment successfully prepared a rapid and sensitive test strip for glycinin.

An electrochemical sensing platform based on gold nanostars for the detection of Alzheimer's disease marker Aβ oligomers (Aβo)

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ) peptides in the brain. Among the different forms of Aβ, oligomers (Aβo) are considered the most toxic and have been implicated in AD pathology. However, the accurate detection of Aβo remains challenging due to their low abundance and structural complexity. In this study, we propose an electrochemical sensing platform based on gold nanostars (AuS) for the detection of Aβo in AD. The AuS were functionalized with a peptide probe (PrPc) that specifically interacts with Aβo. The PrPc-AuS sensing platform exhibited high sensitivity and selectivity for Aβo detection. The electrochemical impedance spectroscopy (EIS) analysis showed significant changes in impedance upon binding of Aβo to the PrPc-AuS surface, providing quantitative information about the Aβo concentration. The platform demonstrated a linear detection range of 5–200 pM with a detection limit of 2 pM, meeting the requirements for clinical detection. This electrochemical sensing platform offers a promising approach for the early diagnosis and monitoring of AD, contributing to the development of point-of-care diagnostics for neurodegenerative diseases.

Improving Lyophilization and Long-Term Stability of Gold Nanostars for Photothermal Applications

Improving Lyophilization and Long-Term Stability of Gold Nanostars for Photothermal Applications

A surface-enhanced Raman scattering sensor for the detection of benzo[a]pyrene in foods based on a gold nanostars@reduced graphene oxide substrate.

In this study, a simple and sensitive surface-enhanced Raman scattering (SERS) sensor based on gold nanostars@reduced graphene oxide (AuNS@rGO) was successfully developed for the detection of benzo[a]pyrene in foods. The detection strategy involved benzo[a]pyrene adsorption on reduced graphene oxide, followed SERS detection of adsorbed molecules. Owing to the large electric fields generated by the gold nanostars under laser irradiation, which greatly amplified the Raman signals of benzo[a]pyrene, very high sensitivity for the target analyte was achieved. Under optimized conditions, the SERS sensor exhibited a wide linear detection range for benzo[a]pyrene (from 0.1μgL-1 to 10000μgL-1), with a low limit of detection of 0.0028μgL-1. Chicken samples spiked with benzo[a]pyrene were assayed using the sensor, with recoveries ranging from 89.20% to 100.80%. The benzo[a]pyrene content in roasted mutton sample was quantified using the SERS sensor and a reversed-phase high-performance liquid chromatography method, with similar results being obtained.

Ascorbic acid-mediated in situ growth of gold nanostars for photothermal immunoassay of ochratoxin A.

Currently, the development of efficient mycotoxins detection methods, particularly using portable devices as readout devices, remains a great challenge. Herein, a photothermal enzyme-linked immunosorbent assay (ELISA) based on gold nanostars (AuNSs) for the detection of ochratoxin A (OTA) using a "thermometer" was proposed for the first time. AuNSs with photothermal conversion capacity were parepared using an ascorbic acid (AA)-mediated in situ growth methd. Quantification was based on the alkaline phosphatase catalyzing the dephosphorylation of ascorbic acid 2-phosphoate to AA, thereby converting OTA concentration to the amount of in situ synthesized AuNSs, thus achieving straightforward readout by temperature. Benefiting from the classical tyramine signal amplification strategy, a detection limit of 0.39ngmL-1 was obtained. The recoveries of grape juice and maize samples spiked with 10ngmL-1 and 30ngmL-1 OTA ranged from 86.53% to 116.9%. Our method has great potential in on-site OTA detection for food safety.

Colorimetric and photothermal immunosensor for sensitive detection of cancer biomarkers based on enzyme-mediated growth of gold nanostars on polydopamine

BackgroundDetecting cancer biomarker levels in body fluids is essential for medical diagnosis. Enzyme-linked immunosorbent assay (ELISA) has been broadly used to detect cancer biomarkers. However, colorimetric ELISA based solely on nanoparticles (NPs) are susceptible to environmental influences, which often results in the detection inaccuracy, being limited in clinical applications. In this regard, the dual-mode approach would add signal diversity to the detection, making the results more reliable. ResultsWe present colorimetric and photothermal immunosensor that enables direct reading of the color and temperature of the solution. A core-satellite nanoprobe constructed by polydopamine (PDA) as the core and gold seeds as satellites is rationally designed as the signal reporter. When ascorbic acid is present in the solution, PDA can cooperate with ascorbic acid to reduce chloroauric acid and mediate the growth of gold seeds on the PDA surface, inducing a redshift of the localized surface plasmon resonance peak of the nanosensor and the change in photothermal conversion efficiency. The method is further combined with the sandwiched immunoassay to construct an alkaline phosphatase based colorimetric and photothermal ELISA for the highly sensitive and accurate evaluation and detection of prostate-specific antigen (PSA). The linear range was from 0.05 to 100 ng mL−1 with a detection limit of 6.71 pg mL−1 for the colorimetric detection, while the linear range was from 0.5 to 90 ng mL−1 with a detection limit of 0.13 ng mL−1 in the photothermal analysis. The accurate detection of PSA levels in serum samples was well demonstrated with the dual-mode approach. SignificanceThe presented immunoassay allows straightforward, sensitive, and selective readout by color and temperature without advanced instrumentation. Particularly, the LOD was much lower than the threshold in clinical trials for PSA. Therefore, this method has a great prospect in the early diagnosis of cancer biomarkers based on a dual-mode multifunctional platform.

Qualitative and quantitative studies of phthalates in extra virgin olive oil (EVOO) by surface-enhanced Raman spectroscopy (SERS) combined with long short term memory (LSTM) neural network

Phthalates are commonly used plasticizers in the plastics industry, and have received extensive attention due to their reproductive toxicity. Since phthalates are lipophilic solutions, phthalates can easily migrate from packaging to edible oils. This study synthesized stable and sensitive Gold Nanostars as SERS substrates to conduct qualitative and quantitative analysis of two common phthalates, dibutyl phthalate and di(2-ethylhexyl) phthalate. Two ethanol standard solutions and actual oil solutions of phthalates at different concentrations (10, 5, 1, 0.5, 0.1, 0.02 mg/kg) were prepared. After dimension reduction, LSTM achieved the accuracy of 98% for pure EVOO and EVOO adulterated with different types of phthalates. In terms of quantification, LSTM demonstrates great predictive performance with Rp2 greater than 0.97 and the ratio of performance to deviation greater than 5. These results have certain guiding significance for the analysis of plasticizers in edible oil.

Optimizing Surface-Enhanced Raman Spectroscopy Substrates with Gold Nanospheres, Nanorods and Nanostars

Surface-Enhanced Raman Spectroscopy is a powerful technique that boosts the distinctive fingerprint signals of molecules, making them more accessible for analysis. It utilizes metallic nanoparticles, acting as amplifiers, to greatly enhance the signals emitted by the molecules. This study aimed to explore the SERS potential of gold nanoparticles (AuNPs) with different geometries using a non-resonant molecule, 4-MBA. Nanospheres (14±2 nm), nanorods (11±2 nm x 50±7 nm) and nanostars (38±4 nm) were synthesized via the HAuCl4 reduction method. All three AuNP geometries exhibited a remarkable enhancement of the Raman signal of 4-MBA by a magnitude of 104. Notably, only gold nanorods and nanostars displayed localized surface plasmon within the biological window, making them highly suitable for biological sample analysis. Meanwhile, the application of gold nanospheres should be limited to chemical SERS detection. These findings confirm the potential use of these nanostructures as SERS substrates for studying molecules with low molar...

Near-Infrared-Driven Nanorocket for Rapid and Ultrasensitive Detection of MicroRNA.

Herein, by introducing gold nanostars (AuNSs) as fuel core, a near-infrared-driven nanorocket (NIDNR) with pretty fast walking was exploited for ultrasensitive miRNA detection. Compared with traditional nanomaterials-comprised nanomachines (NMs), the NIDNR possesses much better kinetic and thermodynamic performance owing to the extra photothermal driving force from localized surface plasmon (LSP). Impressively, the whole reaction time of NIDNR down to 15 min was realized, which is almost more than 8 times beyond those of conventional DNA-based NMs. This way, the inherent obstacle of traditional NMs, including long reaction time and low efficiency, could be easily addressed. As a proof of concept, the NIDNR was successfully applied to develop an electrochemical biosensing platform for rapid and sensitive detection of miRNA with an LOD down to 2.95 aM and achieved the real-time assay of real biological samples from human hepatocellular carcinoma cells (MHCC97L) and HeLa, thus providing an innovative insight to design more versatile DNA nanomachines for ultimate application in biosensing platform construction and clinical sample detection.

Glass supported SERS chips for emerging pollutant analyses

The dramatic increase of environmental pollution leads to the demand of new sampling strategies that could perform in-situ monitoring and rapid identification. In this regard, Surface Enhanced Raman Spectroscopy is a good candidate among the possible analytical techniques. Thus, enormous efforts are in course to select best nanoplatforms able to maximize the SERS effect and in turn to reach the lowest limit of pollutant detection. In this work, we investigated the SERS response of colloidal gold nanostars (GNS) coated with a layer of silver with increasing thickness. In particular, we observed a maximum in the SERS signal at a precise silver thickness. The so-optimized GNS@Ag were used to prepare glass supported SERS substrates, displaying good enhancement factor and high homogeneity intra sample. We also evaluate the reproducibility on large-scale production, demonstrating again a good homogeneity of the response and the overall goodness of the substrates. Our glassy SERS-active chips were fruitfully used to detect norfloxacin and thiram, as representative of harmful and toxic pollutants.