A Single-chain Antibody for One-pot Fabrication of Luminescent Gold Nanoclusters and Rabies Virus Imaging in Cells

The fragile antibody leads to a great challenge as a scaffold to fabricate the luminescent metal nanoclusters using one-pot method.This study presents a stable single-chain anti-body(scFv57R-ATS)for the fabrication of luminescent gold nanoclusters(AuNCs@scFv57R-ATS)and a quick,sensitive rabies virus detection in living cells.In this paper,AuNCs@scFv57R-ATS was designed to specifically recognize antigen RV in modified HeLa cells,which promoted the demonstration of metal nanocluster fluorescent probes for antigen targeting and therapy.

Ratiometric Fluorescence Detection of 6-Mercaptopurine Based on the Nanohybrid of Fluorescence Carbon Dots and Gold Nanoclusters

The development of a simple and accurate quantitative method for the determination of 6-mercaptopurine (6-MP) is of great importance because of its serious side effects. Ratiometric fluorescence (RF) sensors are not subject to interference from environmental factors, and exhibit enhanced precision and accuracy. Therefore, a novel RF sensor for the selective detection of 6-MP was developed. The present work reports a sensitive and selective RF sensor for the detection of 6-mercaptopurine, by hybridizing carbon nanodots (CDots) and gold nanoclusters (AuNCs) capped with bovine serum albumin (BSA). The CDots serve as the reference signal and the AuNCs as the reporter. On addition of the 6-MP, AuNCs formed aggregates, because the existing cross-links within the AuNCs and BSA structure were broken in favour of the Au-S bonds, which can enhance the fluorescence of AuNCs, while the fluorescence of CDots is stable against 6-MP, leading to distinct ratiometric fluorescence changes when exposed to 6-MP. 6-MP could be detected in the range of 0 - 30.22 μM with a detection limit of 54 nM. The developed sensor was applied for the determination of 6-MP in human serum samples and satisfactory results were obtained.

Oxygen Electroreduction Performance of Ultrasmall Gold Nanoclusters

Ultrasmall gold nanoclusters consisting of 2-4 Au atoms were synthesized and their per- formance in electrocatalytic oxygen reduction reactions （ORR） was examined. These clus- ters were synthesized by exposing AuPPh3Cl to the aqueous ammonia medium for one week. Electrospray ionization mass spectrometry （ESI-MS）, X-ray absorption fihe struc- ture （XAFS）, and X-ray photoelectron spectroscopy （XPS） analyses indicate that the as- synthesized gold clusters （abbreviated as Aux） consist of 2-4 Au atoms coordinated by the triphenylphosphine, hydroxyl, and adsorbed oxygen ligands. A glassy carbon disk electrode loaded with the Aux clusters （Aux/GC） was characterized by the cyclic and linear-sweep voltammetry for ORR. The cyclic voltammogram vs. RHE shows the onset potential of 0.87 V, and the kinetic parameters of JK at 0.47 V and the electron-transfer mmlber per oxygen molecule were calculated to be 14.28 mA/cm2 and 3.96 via the Koutecky-Levich equations, respectively.

Atomically precise gold nanoclusters for healthcare applications

The potential application of gold nanoparticles(GNPs)in biomedicine has been extensively reported.However,there is still too much puzzle about their real face and potential health risks in comparison with the commercial drug molecules.The emergence of atomically precise gold nanoclusters(APGNCs)provides the opportunity to address the puzzle due to their ultrasmall size,defined molecular formula,editable surface engineering,available structures and unique physicochemical properties including excellent biocompatibility,strong luminescence,enzyme-like activity and efficient renal clearance,et al.Recently,these advantages of APGNCs also endow them promising performances in healthcare such as bioimaging,drug delivery,antibacterial and cancer therapy.Especially,their clear composition and structures like the commercial drug molecules facilitate the study of their functions and the structure-activity relationship in healthcare,which is essential for the guided design of APGNC nanomedicine.Therefore,this review will focus the advantages and recent progress of APGNCs in health care and envision their prospects for the future.

Fabrication of High Color Rendering Index White Light Emitting Diodes from Gold Nanoclusters

We demonstrated gold nanoclusters as color tunable emissive light converters for the application of white light emitting diodes (WLEDs). A blue LED providing 460 nm to excite gold nanoclusters mixed with UV curable material generates broad bandwidth emission at the visible range. Increasing the amount of gold nanoclusters, the correlated color temperature of WLEDs tuned from cold white to warm white, and also results in the variation of color rendering index (CRI). The highest CRI in the experiment is 92.

Gold nanoclusters encapsulated microneedle patches with antibacterial and self-monitoring capacities for wound management

The management of infected wounds is always of great significance and urgency in clinical and biomedicalfields.Recent efforts in this area are focusing on the development of functional wound patches with effective antibacterial,drug delivery,and sensor properties.Here,we present novel hyaluronic acid(HA)microneedle patches with these features by encapsulating aminobenzeneboronic acid-modified gold nanoclusters(A-GNCs)for infected wound management.The A-GNCs loaded microneedle patches were derived from negative-mold replication and showed high mechanical strength to penetrate the skin.The release of the A-GNCs was realized by the degradation of HA,and the self-monitor of the released actives was based on the dynamic bright orangefluorescence emitted from A-GNCs under ultravio-let radiation.As the A-GNCs could destroy bacteria membranes,the microneedle patches were with excellent in vitro antibiosis ability.Based on these features,we have demonstrated the bacteria inhibition,residual drug self-monitoring,and wound healing promotion abilities of the microneedle patches in Escherichia coli-or Staphylococcus aureus-infected wound management.These results indicated the great potential of such A-GNCs loaded microneedle patches for clinical applications.

Transition metal-mediated catalytic properties of gold nanoclusters in aerobic alcohol oxidation

Heteroatom dopants can greatly modify the electronic and physical properties and catalytic performance of gold nanoclusters. In this study, we investigate the catalytic activity of [Au25-x（PET）18-xM]NH3 （PET = 2-phenylethanethiolate, and M = Cu, Co, Ni, and Zn） nanoclusters in aerobic alcohol oxidation. The [Au25-xPET）18-xM]NH3 nanoclusters are thoroughly characterized by matrix assisted laser desorption ionization （MALDI） mass spectrometry, X-ray photoelectron spectroscopy （XPS）, Fourier transform infrared spectroscopy （FT-IR）, and inductively coupled plasma-mass spectrometry （ICP-MS）. The XPS analyses suggest that the transition metals strongly interact with the gold atoms of the nanoclusters. The CeO2-supported nanoclusters show catalytic activity, based on the conversion of benzyl alcohol, in the order, [Au25-x（PET）18-xNi] 〉 [Au25-x（PET）18-xCu] 〉 [Au25-x（PET）18-xZn] 〉 [Au25-x（PET）18-xCo]. Regarding product selectivity, the [Au25-xPET）18-xZn] and [Au25-x（PET）18-xCo] catalysts preferably yield benzaldehyde, [Au25-x（PET）18-xCu] yields benzaldehyde and benzyl acid, and [Au25-x（PET）18-xNi] yields benzyl acid. The exposed metal atoms are considered as the catalytic active sites. Also, the catalytic performance （including activity and selectivity） of the [Au25-x（PET）18-xM] catalysts is greatly turned and mediated by the transition metal type.

Metal–Organic Frameworks-Mediated Assembly of Gold Nanoclusters for Sensing Applications

Gold nanoclusters(AuNCs)are an emerging type of ultrasmall nanomaterials possessing unique physicochemical characteristics.Metal–organic frameworks(MOFs),a singular kind of porous solid and crystalline material,have attracted tremendous attention in recent years.The combination of AuNCs and MOFs can integrate and improve the prominent properties of both components,such as high catalytic activities,tunable optical properties,good biocompatibility,surface functionality and stability,which make the composites of MOFs and AuNCs promising for sensing applications.This review systematically summarizes the recent progress on the sensing of various analytes via MOFs-mediated AuNCs assemblies based on strategies of luminescence sensing,colorimetric sensing,electrochemiluminescence sensing,and electrochemical and photoelectrochemical sensing.A brief outlook regarding the future development of MOFs-mediated AuNCs assemblies for sensing application is presented as well.

NIR-II light activated photodynamic therapy with proteincapped gold nanoclusters

The use of near-infrared （NIR） light for photodynamic therapy （PDT） is a promising strategy to circumvent the limitations of current PDT, in which visible light with limited tissue penetration depth is usually used. In the present stud~ alkyl thiolated gold nanoclusters （AuNCs） were co-modified with human serum albumin （HSA） and catalase （CAT）, and then employed as a multifunctional, optical, theranostic nano-agent. In the AuNC@HSA/CAT system, the AuNCs were able to produce singlet oxygen under excitation by a 1,064-nm laser, which locates in the second NIR window （NIR-II）, and featured much lower tissue absorption and scattering, enabling NIR-II-triggered PDT. The HSA coating greatly improved the physiological stability of the nanoparticles, which showed efficient tumor retention after intravenous injection, as revealed by detecting the AuNC fluorescence. Moreover, the presence of CAT in the nanoparticles triggered decomposition of tumor endogenous H202 to generate oxygen, thereby enhancing the efficacy of PDT by relieving tumor hypoxia. Compared with conventional PDT using visible light, NIR-II-triggered PDT exhibits remarkably increased tissue penetration. Thus, we developed a new type of photosensitizing nano-agent that simultaneously enables in vivo fluorescence imaging, tumor hypoxia relief, and NIR-II light-induced in vivo PDT in the treatment of cancer.

Emerging NIR-Ⅱ Luminescent Gold Nanoclusters for In Vivo Bioimaging

Gold nanoclusters(AuNCs)with near-infraredⅡ(NIR-Ⅱ)photoluminescence(PL)have emerged as novel bioimaging probes for in vivo disease diagnosis.So far,it still lacks a systematic review focusing on the synthesis,PL tuning,and in vivo imaging of NIR-Ⅱluminescent AuNCs.In this review,we briefly introduce the synthesis of NIR-Ⅱluminescent AuNCs using various surface ligands.We discuss the origins and properties of NIR-ⅡPL in AuNCs,and summarize the strategies for improving and/or tuning NIR-ⅡPL emissions.We also provide an overview of the recent progress in the application of AuNCs in tumor-targeted imaging,molecular imaging,and other areas(such as the sensitive imaging of bones,vessels,lymph nodes,etc.).Finally,we present the prospects and challenges in the field of NIR-Ⅱluminescent AuNCs and related imaging applications,expecting to offer comprehensive understanding of this field,and thereby deepening and broadening the biological application of AuNCs.

The density of surface ligands regulates the luminescence of thiolated gold nanoclusters and their metal ion response

The fascinating luminescence properties of gold nanoclusters(AuNCs) have drawn considerable research interests,and been widely harnessed for a wide range of applications.However,a fundamental understanding towards ligand density’s role in the luminescence properties of these ultrasmall AuNCs remains unclear yet.In this communication,through systematic investigation of surface chemistries of glutathione-protected Au NCs(GSH-Au NCs) with diffe rent density of GSH as well as other thiolates,it is discovered that the density of surface ligands can significantly regulate the luminescence properties of AuNCs.Fluorescence lifetime spectroscopy and X-ray photoelectron spectroscopy showed that AuNCs with a higher density of electron-rich ligands facilitate their luminescence generation.Moreover,differences in the surface coverage of AuNCs can also affect their interactions with foreign species,as illustrated by significantly different fluorescence quenching capability of GSH-AuNCs with different ligand density towards Hg^(2+).This study provides new insight into the intriguing luminescence properties of metal NCs,which is hoped to stimulate further research on the design of metal NCs with strong luminescence and sensitive/specific responses for promising optoelectronic,sensing and imaging applications.

Gold nanoclusters conjugated berberine reduce inflammation and alleviate neuronal apoptosis by mediating M2 polarization for spinal cord injury repair

Spinal cord injury(SCI)leads to nerve cell apoptosis and loss of motor function.Herein,excessive activation of the M1 phenotype macrophages/microglia is found to be the main reason for the poor prognosis of SCI,but the selective activation phenotype(M2)macrophages/microglia facilitates the recovery of SCI.Thereafter,we used gold nanoclusters loaded berberine(BRB-AuNCs)to reduce inflammation by inhibiting the activation of M1 phenotype macrophages/microglia,which simultaneously inhibited neuronal apoptosis after SCI.In vitro and in vivo experiments showed that BRB-AuNCs reduced M1 protein marker CD86,increased M2 protein marker CD206,reduced inflammation and apoptotic cytokines(IL-1β,IL-6,TNF-α,Cleaved Caspase-3 and Bax).These results indicate that BRB-AuNCs have excellent anti-inflammatory and anti-apoptotic effects by inducing the polarization of macrophages/microglia from M1 phenotype to M2 phenotype.Thereafter,the motor functions of SCI rats were significantly improved after treatment with BRB-AuNCs.This work not only provides a new way for the treatment of SCI but also broadens BRB utilization strategies.

Phase transferring luminescent gold nanoclusters via single-stranded DNA

Atomically precise gold nanoclusters(Au NCs) are an emerging class of quantum-sized nanomaterials with discrete electronic energy levels, which has led to a range of attractive electronic and optical applications. Nevertheless, the lack of general methods to transfer Au NCs protected with hydrophobic ligands to an aqueous solution hampers their use in physiological settings. Here,we developed a single-stranded DNA-based approach that could transfer ~90% hydrophobic Au NCs into an aqueous solution.We experimentally and theoretically established that multivalent electrostatic and hydrophobic interactions between DNA strands and the hydrophobic ligand layer on Au NCs resulted in monodispersed DNA-coated Au NCs with high physical integrity in an aqueous solution. The fluorescence quantum yield of Au NCs was increased by ~13 fold, and surface-constrained DNA retained the specific recognition ability for biosensing. We further demonstrated the versatility of this phase-transfer approach, which thus holds great potential to advance biological and medical applications of Au NCs.

Self-quenched gold nanoclusters for turn-on fluorescence imaging of intracellular glutathione

Activatable fluorescence nanoprobes with only one kind of nanomaterial that can act as both the energy donor and acceptor simultaneously are scarce, but highly desirable for biosensing and bioimaging. In the present study, we reveal the preparation of self-quenched gold nanoclusters as a simple fluorescent turn-on probe for imaging intraceUular glutathione. The self-quenched gold nanoclusters are prepared via disulfide bond-induced aggregation of gold nanodusters. Compared with monodisperse gold nanoclusters, the developed self-quenched gold nanoclusters exhibit weak emission at 735 nm with a 40-nm red shift and much lower quantum yield （0.69%）. The prepared self-quenched gold nanodusters also possess good sensitivity and selectivity for glutathione detection, and are applicable for fluorescent turn-on imaging of intracellular glutathione.

Microwave-assisted in situ synthesis of fluorescent gold nanoclusters with BSA/montmorillonite and application on latent fingermark imaging

A method for in situ preparation of fluorescent gold nanoclusters(Au NCs) with bovine serum albumin/montmorillonite composite powder(Au NC-BSA/MMT) was developed, and the products were used to detect latent fingermarks. In this work, Au NCs were "grown" both inside and on the surface of BSA/MMT clay using one-step reduction of HAu Cl4 by BSA. The as-prepared Au NC-BSA/MMT nanocomposites emit intensive red fluorescence under the excitation of UV-visible light and show stable chemical features and low toxicity. The obtained fluorescent powders were characterized by UV-visible absorption spectroscopy,fluorescence spectroscopy, infrared spectroscopy, transmission electron microscopy/high-resolution transmission electron microscopy, scanning electron microscopy, X-ray photoelectron spectroscopy and X-ray diffraction to depict their sizes, structural information and optical features. Given their environmentally friendly preparation, simple operation, low cost, efficient UVvisible radiation-dependent photoluminescence and good affinity with finger residues, the in situ synthesized Au NC-BSA/MMT nanocomposite powders were used as an alternative fluorescent developing reagent for developing latent fingermarks deposited on various object surfaces(such as glass, aluminum foil, painted metal, plastic products and weighing papers) for individual identification. As results, the developed fingermarks with clear patterns and satisfactory level-2(minutiae points) and level-3(sweat pores) ridge details were obtained. Notably, treated prints could be excited by red light and emitted near infrared fluorescence, which was beneficial to avoid background interference and reduce the damage caused by UV light. With the advantages of the simple preparation process and good enhancement performance for latent fingermarks, the proposed method might be used in the preparation of various fluorescent probes for detecting trace evidence in forensic sciences.

Fluorescent Gold Nanoclusters:Promising Fluorescent Probes for Sensors and Bioimaging

Fluorescent gold nanoclusters(AuNCs)have recently emerged as a novel kind of promising fluorescent probes for high-performance sensors and bioimaging because of their ultrasmall size(\3 nm),strong luminescence,good photostability,and excellent biocompatibility.Over the past decade,we have witnessed growing popularity of AuNCs in analytical applications and enormous efforts have been devoted to their development.In this review,we provide an update on recent advances in the development of AuNCs in terms of physicochemical properties,synthesis strategies,and bioapplications.The optical,electrochemical,catalytical,and solvatochromic properties of AuNCs are first summarized,which are followed by different ligands or template-assisted controllable synthetic methods.Afterwards functionalization of AuNCs is described in terms of ligand exchange,bioconjugation,and noncovalent interaction.We then focus on the applications of AuNCs as fluorescent probes for detection of metal ions,inorganic anions,small biomolecules,proteins,nucleic acids,drug molecules,pH,and temperature.We also summarize the usage of metal NCs in cellular and in vivo targeting and imaging.Finally,we conclude with a brief look at the future challenges and prospects of the development of AuNCs.

Overcoming bacterial physical defenses with molecule-like ultrasmall antimicrobial gold nanoclusters

The size of metal nanoparticles(NPs)is crucial in their biomedical applications.Although abundant studies on the size effects of metal NPs in the range of 2-100 nm have been conducted,the exploration of the ultrasmall metal nanoclusters(NCs)of~1 nm in size with unique features is quite limited.We synthesize three different sized gold(Au)NCs of different Au atom numbers and two bigger sized Au NPs protected by the same ligand to study the size influence on antimicrobial efficacy.The ultrasmall Au NCs can easily traverse the cell wall pores to be internalized inside bacteria,inducing reactive oxygen species generation to oxidize bacterial membrane and disturb bacterial metabolism.This explains why the Au NCs are antimicrobial while the Au NPs are non-antimicrobial,suggesting the key role of size in antimicrobial ability.Moreover,in contrast to the widely known size-dependent antimicrobial properties,the Au NCs of different atom numbers demonstrate molecule-like instead of size-dependent antimicrobial behavior with comparable effectiveness,indicating the unique molecule-like feature of ultrasmall Au NCs.Overcoming the bacterial defenses at the wall with ultrasmall Au NCs changes what was previously believed to harmless to the bacteria instead to a highly potent agent against the bacteria.

Ovalbumin-stabilized gold nanoclusters with ascorbic acid as reducing agent for detection of serum copper

Ovalbumin-stabilized gold nanoclusters （OVA@AuNCs） were prepared with ascorbic acid as a reducing agent. This strategy could realize the synthesis of water-soluble OVA@AuNCs within 20 min. The asprepared fluorescent probe showed a red fluorescence emission at 630 nm. Moreover, the properties of the OVA@AuNCs were characterized by transmission electron microscope, dynamic light scattering, ultraviolet-visible spectroscopy, fluorescent spectroscopy. Based on the surface electron density decrease-induced fluorescence quenching mechanism, the OVA@AuNCs provided high sensitivity and selectivity for sensing copper ions. A good linear relationship was obtained between the fluorescence intensity of OVA@AuNCs and the concentration of copper ions in the range of 5.0-100.0pumol/L （R2z0.999） with a detection limit of 640 nmol/L. Furthermore, the rat serum copper contents were determined by using the OVA@AuNCs based assay, indicating great potential of fluorescent probes for application in biological and clinical analysis.

11-Mercaptoundecanoic acid functionalized gold nanoclusters as fluorescent probes for the sensitive detection of Cu^(2＋) and Fe^(3＋) ions

Metal ions are physiologically essential,but excessive metal ions may cause severe risk to plants and animals.Here,we prepared gold nanoclusters（Au NCs） protected by 11-mercaptoundecanoic acid（11-MUA）,which have excellent fluorescence properties for the detection of metal ions.The results showed that the copper ions（Cu^（2＋）） and iron ions（Fe^（3＋）） in the solution have obvious quenching effect on the fluorescence intensity of Au NCs.The detection range of Fe^（3＋） was 0.8-4.5 mmol/L（R^2= 0.992） and 4.5-11.0 mmol/L（R^2= 0.997）.And Cu^（2＋） has a lower linear range（0.1-1.0 mmol/L,R2= 0.993）.When EDTA was added into the reaction system,it was observed that the quenching effect of Cu^（2＋） and Fe^（3＋）on Au NCs showed different phenomenon.Then,the effect of metal ions on the fluorescence of Au NCs was investigated.The selective detection of Cu（2＋） was achieved by EDTA masking of Fe^（3＋）.In addition,we realized the metal ions detection application of Au NCs in the serum

The aromatic peptide protected gold nanoclusters with significant Stokes shift:Ligand-mediated two-step FRET

During the last decade,a great variety of ligand protected gold nanoclusters(AuNCs)have been synthesized,and their broad applications have been intensively reported.Although the spectroscopic properties of AuNCs have been comprehensively explored,the mechanism of the significant Stokes shift(>200 nm)and the specific role played by surface ligands have not been clearly explained yet.In this study,a series of fluorescent AuNCs with huge Stokes shift(up to 530 nm)were successfully prepared by employing the rationally designed tri-peptides as the protecting ligands,and their spectroscopic properties were systematically investigated.The detailed measurements on the example product,YCY-AuNCs(Tyr-Cys-Tyr liganded AuNCs),showed that the energy absorbed by the tyrosine(~250 nm)can be effectively transferred through the ligand-mediated two-step Förster resonance energy transfer(FRET)process and released as fluorescence emission in the near-infrared fluorescence(NIR)range(~780 nm),which resulted in the significant apparent Stokes shift.The YCY ligands play a critical role by offering the tyrosine groups(donor of the first FRET pair),generating the dityrosine-like structure on the AuNCs surface(acceptor of the first FRET pair and donor of the second FRET pair),and protecting the cores(acceptor of the second acceptor).The additional ligand exchange experiments and the investigation on the other AuNCs further demonstrated that the sufficient high density of the aromatic groups is also essential to mediate the two-step FRET and achieve the remarkable Stokes shift.We believe that the aromatic ligand-mediated FRET mechanism not only offers a new theoretical explanation for the huge Stokes shift exhibited in AuNCs,but also provides a general strategy for the construction of new materials with large Stokes shift.