Glutathione-protected Gold Nanoclusters Research Articles

Construction of logic gate computation for the assay of the nerve agent sarin based on an AChE-based dual-channel sensing system.

Nerve agents have posed a huge threat to national and human security, and their sensitive detection is crucial. Herein, based on the oxidation of Ce4+ and the aggregation-induced emission (AIE) of glutathione-protected gold nanoclusters (GSH-Au NCs), a cascade reaction was designed to prepare oxidized 3,3',5,5'-tetramethylbenzidine (oxTMB) and GSH-Au NCs crosslinked by Ce3+ (Ce3+-GSH-Au NCs). oxTMB had a broad UV-visible absorption range (500-700 nm) and was capable of quenching the fluorescence of Ce3+-GSH-Au NCs at 590 nm through the internal filtration effect (IFE). Thiocholine (TCh), the hydrolysis product of acetylthiocholine chloride (ATCl) catalyzed by acetylcholinesterase (AChE), reduced oxTMB completely, resulting in a decrease in the absorption of oxTMB and the recovery of IFE-quenched fluorescence of Ce3+-GSH-Au NCs. Nerve agent sarin (GB) hindered the production of TCh and the reduction of oxTMB by inhibiting the AChE activity, leading to the fluorescence of Ce3+-GSH-Au NCs being quenched again. The dual-output sensing system (AChE + ATCl + oxTMB + Ce3+-GSH-Au NCs) exhibited a low limit of detection to GB (2.46 nM for colorimetry and 1.18 nM for fluorimetry) and excellent selectivity toward common interferences being unable to inhibit AChE. Moreover, the intelligent logic gate constructed based on the sensing system showed promising applications in the field of smart sensing of nerve agents.

On-off-on switchable fluorescent chemosensor based on glutathione-protected gold nanoclusters for high-selective on-site Cr(VI) detection in complex biological samples

Given that Cr(VI) is highly carcinogenic and teratogenicity, its routine health monitoring is crucial to measuring Cr(VI)-induced health risk earlier. Despite being considered one of the most promising candidate tools for metal detection, the gold nanoclusters (AuNCs)-based fluorescent sensors have been widely applied due to their specialties (e.g., on-site conveniences, low toxicity, high stability, facile processability, and unique optical properties), while AuNCs are subjected to interference from the coexisted metals within complex mixtures, the specific detection of Cr(VI) remains a great challenge. A novel fluorescent “on-off-on” strategy (i.e., the switch of AuNCs, AuNCs-Cr(VI), and Cr(III)) is proposed for Cr(VI) measurement, based on core-shell structured Au(0)@Au(I)-SG NCs (2.5 nm) in the presence of L-glutathione (GSH, reductant of Cr(VI) to Cr(III)), providing enhanced Cr(VI)-selective, stability, and biocompatibility. In this context, this approach enables specific detection of Cr(VI) in complex biological samples without interference from coexisting metals, exhibits high anti-interference ability, can be lowered up to 3.0 min and down to 75.0 nmol/L (well below regulatory limits). Compared with the conventionally-used flame atomic absorption spectroscopy (FAAS), our proposed approach is better for avoiding sample digestion, convenience, easy operation, and suitable monitoring at home. Herein, the proposed method has been successfully applied to Cr(VI) measurement in complex biological fluid samples and offers high sensitivity and selectivity for pre-diagnosis and post-treatment monitoring.

A cellulosic gold nanocluster multi-emission fluorescence probe for assessing types and levels of hROS

The distinction of high reactive oxygen species (hROS) types has positive significance for disease diagnosis. Here, to visibly assess hROS types and levels, a cellulosic multi-emission fluorescence probe was designed by incorporating proline-protected gold nanoclusters (Em: 450 nm), glutathione-protected gold nanoclusters (Em: 680 nm) and o-phenylenediamine (Em: 565 nm) onto cellulose nanocrystal. Ingeniously, the probe displayed the stabilized, quenched and activated fluorescence signals corresponding to hROS at 450 nm, 680 nm, and 565 nm, respectively. The response time of the probe for hROS was greatly reduced from 29 min to 7 min through gold nanoclusters releasing Au(Ⅲ) during the fluorescence quenching process to accelerate the fluorescence opening of o-phenylenediamine. Therefore, the probe with long-term stability (12 months) possessed excellent sensitivity and selectivity to distinguish hROS types, and exhibited visually yellow, white, and green fluorescence for •OH, ClO−, and ONOO−, respectively, and the corresponding detection limits were 0.56 μM, 0.73 μM and 0.81 μM within 5 min, 6 min and 7 min, respectively. The design strategy provides the ideas for constructing multi-emission probe to distinguish multiple analytes at similar levels.

Fluorometric and colorimetric quantitative analysis platform for acid phosphatase by cerium ions-directed AIE and oxidase-like activity.

A facile and sensitive fluorescent and colorimetric dual-readout assay for detection of acid phosphatase (ACP) was developed via Ce(III) ions-directed aggregation-induced emission (AIE) of glutathione-protected gold nanoclusters (GSH-AuNCs) and oxidase-mimicking activity of Ce(IV) ions. Free Ce(IV) ions exhibited a strong oxidase-mimetic activity, catalytically oxidizing colorless 3,3',5,5'-tetramethylbenzidine (TMB) into its blue product oxTMB in the presence of dissolved O2, thus triggering a remarkable color reaction detectedvisually. ACP can hydrolyze L-ascorbic acid-2-phosphate (AAP) with the production of ascorbic acid (AA). The AA is able to reduce Ce(IV) ions to Ce(III) ions, thus quenching the oxidase-mimetic activity of Ce(IV) ions. Meanwhile, Ce(III) ions induce AIE of GSH-AuNCs, resulting in the enhancement of thefluorescence signal of GSH-AuNCs. Both the fluorescent and colorimetric dual-mode analysis platforms exhibit a sensitive response to ACP, providing detection limits as low as 0.101 U/L and 0.200 U/L, respectively. Besides, this fabricated dual-mode detection platform holds the potential for analysis of ACP in human serum samples and screening inhibitors for ACP. With good performance and practicability, this study shows promising application in the convenient and reliable determination of ACP activity.

A novel fluorescent sensor array to identify Baijiu based on the single gold nanocluster probe

Baijiu occupies a vital position in Chinese food and China's market. Strict evaluation of Baijiu is highly demanded. In this study, we constructed a novel fluorescent sensor array based on the single glutathione-protected gold nanoclusters (AuNCs) probe for the detection of organic acids and Baijiu. The fluorescence of AuNCs was simply modulated by three metal ions (Cu2+, Mn2+, and Ag+), and formed new complexes as sensing elements. These four sensing elements responded variously to nine organic acids, and further chemometric analysis results allowed for the classification and quantification of acids. Moreover, the sensor array successfully identified 21 Baijiu samples of different brands among 11 aroma types. It could also distinguish Baijiu of different qualities as well as pure Baijiu from its adulterations and showed high selectivity among multiple interfering drinks. The results demonstrated that the AuNCs-based sensor array has considerable potential for quality monitoring of Baijiu.

Gold nanocluster-based ratiometric fluorescent probe for biosensing of Hg2+ ions in living organisms.

Gold nanoclusters (Au NCs) have become a new alternative to conventional fluorescent probes in biosensing and imaging. Herein, a gold nanocluster-based nanocomplex displaying single-excitation and dual-emission fluorescence property was fabricated by the conjugation of red-emitting glutathione-protected gold nanoclusters (Au-GSH NCs) and green-emitting fluorescein isothiocyanate (FITC) molecules. The inorganic-organic nanocomplex possesses good ratiometric fluorescence sensing ability with one emission peak showing a sensitive fluorescence response towards Hg2+ ions and the other acting as the internal reference. The nanocomplex was demonstrated to have high stability, excellent biocompatibility, high intracellular penetrability and good biological imaging ability. It was employed as a sensitive nanosensor for rapid sensing and imaging of Hg2+ ions in living cells and zebrafish with high contrast.

Covalent anchoring of atomically precise glutathione-protected gold nanoclusters on graphene oxide nanosheets

This paper describes the development of a novel method of producing nanocomposites consisting of gold nanoclusters anchored on graphene oxide nanosheets in a cost-effective and reproducible manner. The novelty of the technique hinges on the covalent functionalization of atomically precise subnanometer gold clusters protected by glutathione (Au15SG13 and Au25SG18) on to graphene oxide (GO) nanosheets according to the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride crosslinking method, using the existing carboxylic groups present both at the surfaces of the nanoclusters and the GO nanosheets. The atomic precision of glutathione-protected gold nanoclusters was evidenced by electrospray ionization mass spectrometry. The formed hybrid nanocomposites were characterized by TEM measurements and exhibit nonlinear optical properties characteristic of GO, in particular a strong second harmonic scattering response as well as a multi-photon excited fluorescence spectrum characterized by a broad band in the visible range between 350 and 700 nm. Atomically precise nanoclusters covalently linked to GO nanosheets are therefore promising for new applications in the areas of optoelectronics and photovoltaics.

Novel Synthesis of Thiolated Gold Nanoclusters Induced by Lanthanides for Ultrasensitive and Luminescent Detection of the Potential Anthrax Spores' Biomarker.

In this study, we reported a facile, one-pot, and "green" synthesis of glutathione-protected gold nanoclusters (GSH@AuNCs) initiated by samarium (Sm3+) lanthanides for the first time. Sm3+ lanthanides more efficiently induced the formation of GSH@AuNCs with significantly enhanced luminescence than other lanthanides or heavy metal ions (Cd2+, Pb2+) did. Using this strategy, a detection for Sm3+ was made with a linearity range of (10.0-100.0 μM) and a limit of detection (LOD) of 0.5 μM. The Sm3+-based GSH@AuNCs were characterized by eco-friendliness, photostability, and low-cost synthesis with low biological toxicity and had great potential in the application for biosensing and bioimaging. They were successfully employed in the detection of dipicolinic acid (DPA), a well-reported biomarker for sensing potential infection by strongly hazardous anthrax spores. A good linear response was obtained for DPA detection ranging from 1.0 to 120.0 μM with a low LOD of 0.1 μM, which was much lower (600 times) than the infectious dosage of anthrax spores (6 × 10-5 M). The detection was due to the strong binding affinity and strong chelation capability of DPA to Sm3+ lanthanides, which caused the dissociation of the aggregates with an obvious decrease or even a turning-off effect of their luminescence.

Synthesis and Characterization of Highly Sensitive pH Probes Based on Fluorescein-Conjugated Gold Nanoclusters

Intracellular pH is a critical parameter that regulates the cellular metabolism. Thus, sensitive monitoring of the intracellular pH change is essential in understanding mechanisms governing drug delivery and cell apoptosis. In this work, we synthesized highly sensitive pH probes composed of fluorescein and glutathione-protected gold nanoclusters and characterized their optical properties. The fluorescein was conjugated to the gold nanocluster by using an amide coupling reaction. In steady-state photoluminescence (PL) measurements, fluorescein conjugated to gold nanocluster shows more than 160-fold pH-contrasting emission in the pH range of 4.3-7.8 while glutathione coupled fluorescein shows only 10-fold pH contrast in the same pH range. Transient absorption measurements confirmed that the enhanced PL was caused by the ultrafast energy transfer from the nonthermalized states of gold nanocluster to fluorescein. Furthermore, efficient nonthermalized energy transfer occurring in the fluorescein-conjugated gold nanocluster led to a dramatically pH-contrasting PL. In addition to the intrinsic advantages such as low toxicity and facile surface modification, fluorescein-conjugated gold nanoclusters exhibit high pH sensitivity with wide dynamic range, offering new opportunities for the study of intracellular processes.

Facile Hydrophobication of Glutathione-Protected Gold Nanoclusters and Encapsulation into Poly(lactide-co-glycolide) Nanocarriers

We report a simple surface functionalization of glutathione-capped gold nanoclusters by hydrophobic ion pairing with alkylamine followed by a complete phase transfer to various organic solvents with maintained colloidal stability and photoluminescence properties. The described surface hydrophobication enables efficient encapsulation of gold nanoclusters into PLGA nanocarriers allowing their visualization inside cultured cells using confocal fluorescent microscopy. The simplicity and efficiency of the described protocols should extend the biomedical applications of these metallic nanoclusters as a fluorescent platform to label hydrophobic polymeric nanocarriers beyond conventional organic dyes.

Size Characterization of Glutathione-Protected Gold Nanoclusters in the Solid, Liquid and Gas Phases

Monolayer-protected metal nanoclusters belonging to the size regime between two and a few hundred atoms represent unique building blocks for new materials. Because of the extremely tiny size of such clusters (smaller than ∼3 nm in diameter) and the stabilizing layer which varies in size and composition, traditional techniques used for characterizing the size of large metal nanoparticles are not very reliable. In this work, we compare solid, liquid and gas phase size characterization methods for selected glutathione- (SG-) protected gold clusters (namely Au15(SG)13, Au18(SG)14, and Au25(SG)18). We also investigate the effect of nanocluster ion-pairing with bulky counterions on their size characterization. We show that X-ray powder diffraction, ion mobility mass spectrometry, and time-resolved fluorescence anisotropy can be a useful addition to tools available for ultrasmall nanoparticle characterization.

Highly selective and sensitive detection of heparin based on competition-modulated assembly and disassembly of fluorescent gold nanoclusters

A simple and economical fluorescence assay for heparin using glutathione-protected gold nanoclusters via competitive binding was developed.

Cu2+-Mediated turn-on fluorescence assay for sulfide ions using glutathione-protected gold nanoclusters: enhanced sensitivity, good reusability, and cell imaging

Cu2+-Mediation enables turn-on fluorescence detection of S2−using GSH-Au NCs with good sensitivity, reusability, and applicability in cell imaging.

Fluorescence sensitization of gold-glutathione nanoclusters by aqueous solutions of sodium and potassium ions

Gold nanoclusters (Au-NCs) are powerful alternatives to commonly used dyes for use in fluorescent assays and in imaging. This is due to their high brightness and biocompatibility. Glutathione protected gold nanoclusters (Au-NCs@GSH) were used to investigate the effect of sodium and potassium ions (at 0.1 to 1 mM concentrations) on their fluorescence. It was found that addition of these alkali ions does not modify the emission wavelength of AuNCs@GSH, but fluorescence intensity undergoes a gradual increase (by ~130 %) until a plateau is reached. Fluorescence is particularly enhanced by KSCN. The effect is interpreted in terms of a decrease in the band gap of the AuNCs@GSH that depends on the nature of the anion. The results illustrate the role of anions and monovalent cations commonly used in buffers with respect to the tuning of the fluorescence of AuNCs@GSH. The findings should be taken into account when using AuNCs@GSH in assays based on fluorescence enhancement or quenching.

Ultrasmall glutathione-protected gold nanoclusters as next generation radiotherapy sensitizers with high tumor uptake and high renal clearance.

Radiotherapy is often the most straightforward first line cancer treatment for solid tumors. While it is highly effective against tumors, there is also collateral damage to healthy proximal tissues especially with high doses. The use of radiosensitizers is an effective way to boost the killing efficacy of radiotherapy against the tumor while drastically limiting the received dose and reducing the possible damage to normal tissues. Here, we report the design and application of a good radiosensitizer by using ultrasmall Au29–43(SG)27–37 nanoclusters (<2 nm) with a naturally-occurring peptide (e.g., glutathione or GSH) as the protecting shell. The GSH-coated Au29–43(SG)27–37 nanoclusters can escape the RES absorption, leading to a good tumor uptake (~8.1% ID/g at 24 h post injection). As a result, the as-designed Au nanoclusters led to a strong enhancement for radiotherapy, as well as a negligible damage to normal tissues. After the treatment, the ultrasmall Au29–43(SG)27–37 nanoclusters can be efficiently cleared by the kidney, thereby avoiding potential long-term side-effects caused by the accumulation of gold atoms in the body. Our data suggest that the ultrasmall peptide-protected Au nanoclusters are a promising radiosensitizer for cancer radiotherapy.

Novel theranostic DNA nanoscaffolds for the simultaneous detection and killing of Escherichia coli and Staphylococcus aureus.

A novel theranostic platform is made by utilizing a self-assembled DNA nanopyramid (DP) as scaffold for incorporation of both detection and therapeutic moieties to combat bacterial infection. Red-emissive glutathione-protected gold nanoclusters (GSH-Au NCs) were used for bacterial detection. Actinomycin D (AMD) that was intercalated on the DP scaffold was used as therapeutic agent. This results in the formation of theranostic DPAu/AMD. Model bacteria Escherichia coli and Staphylococcus aureus were found to be readily taken in the DPAu/AMD and be susceptible to its killing effect. In addition, DPAu/AMD was observed to outperform the free AMD in killing infectious bacteria. The degradation of the DP structure by DNase was found to be responsible for the release of AMD and the effective killing effect of the infectious bacteria. This novel strategy presents a basic platform for future improvements to detect infectious bacteria and treatment.

Excited-State Behavior of Luminescent Glutathione-Protected Gold Clusters

The excited-state behavior of luminescent gold clusters provides new insights in understanding their photocatalytic activity in the visible region. The excited state of glutathione-protected gold nanoclusters (AuGSH), which is characterized by the long-lived excited state (τ = 780 ns), arises from the ligand-to-metal type transition. These AuGSH clusters are in a partially oxidized state (Au(I)) and are readily reduced by chemical or electrochemical methods. Interestingly, a metal core transition with short-lived lifetime (τ < 3 ps) appears along with a longer lifetime in reduced AuGSH clusters. The role of the oxidation state of gold clusters in dictating the photocatalytic reduction of methyl viologen is discussed.