Mercaptopyrimidine-templated gold nanoclusters for antithrombotic therapy.

Here we report for the first time that mercaptopyrimidine-templated gold nanoclusters (DAMP-AuNCs) can be used as a novel anticoagulant candidate for the design of antithrombotic drugs. Anticoagulant mechanisms revealed that DAMP-AuNCs significantly inhibited thrombus formation by interacting with fibrinogen. Carrageenan-induced mice tail thrombosis model experiments showed that DAMP-AuNCs had antithrombotic efficacy comparable to heparin in vivo. More importantly, these ultrasmall AuNCs possess excellent blood compatibility and only induce negligible bleeding side effects. Our study is a successful attempt at developing novel antithrombotic agents with high biosafety.

Glycation of fibronectin impairs angiopoietin-1/Tie-2 signaling through uncoupling Tie-2-α5ß1 integrin crosstalk.

The dysfunction of angiopoietin-1 (Ang-1)/Tie-2 signaling pathways has been implicated in diabetic complications. However, the underlying molecular mechanisms remain unclear. Fibronectin (FN) is thought to have an important role in regulating Ang-1/Tie-2 signaling activation. But no previous study has investigated the effects of FN glycation on Ang-1/Tie-2 signaling. In the present study, FN was glycated by methylglyoxal (MGO) to investigate whether the glycation of FN contributes to diabetes-induced Ang-1/Tie-2 signaling impairment and to understand the molecular mechanisms involved. The results demonstrated that MGO-glycated FN significantly impaired Ang-1-evoked phosphorylation of Tie-2 and Akt, Ang-1-induced endothelial cell migration and tube formation and Ang-1-mediated cell survival. The glycation of FN also inhibited the binding of α5ß1 integrin to Tie-2. Moreover, FN was remarkably modified by AGEs in aortae derived from db/db mice, indicating the glycation of FN in vivo. Ang-1-induced aortic ring vessel outgrowth and Ang-1-mediated cell survival were also both significantly inhibited in aortae from db/db mice compared to that from the wild type littermates. Moreover, FN, rather than glycated FN partly restored aortic ring angiogenesis in db/db mice, indicating that the angiogenesis defect in the db/db mice are due to FN glycation. Collectively, the results in the present study suggest that the glycation of FN impairs Ang-1/Tie-2 signaling pathway by uncoupling Tie-2-α5ß1 integrin crosstalk. This may provide a mechanism for Ang-1/Tie-2 signaling dysfunction and angiogenesis failure in diabetic ischaemic diseases.

Atomically precise Au nanocluster-embedded carrageenan for single near-infrared light-triggered photothermal and photodynamic antibacterial therapy.

In this study, we report atomically precise gold nanoclusters-embedded natural polysaccharide carrageenan as a novel hydrogel platform for single near-infrared light-triggered photothermal (PTT) and photodynamic (PDT) antibacterial therapy. Briefly, atomically precise captopril-capped Au nanoclusters (Au25Capt18) prepared by an alkaline NaBH4 reduction method and then embedded them into the biosafe carrageenan to achieve superior PTT and PDT dual-mode antibacterial effect. In this platform, the embedded Au25Capt18, as simple-component phototherapeutic agents, exhibit superior thermal effects and singlet oxygen generation under a single near-infrared (NIR, 808 nm) light irradiation, which enables rapid elimination of bacteria. Carrageenan endows the hydrogel platform with superior gelation characteristics and wound microenvironmental regulation. The Au25Capt18-embedded hydrogels exhibited good water retention, hemostasis, and breathability, providing a favorable niche environment for promoting wound healing. In vitro experiments confirmed the excellent antibacterial activity of the Au25Capt18 hydrogels against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. The antibacterial effect and promoting wound healing function were further validated in a S. aureus-infected wound model. Biosafety evaluation showed that the Au25Capt18 hydrogel has excellent biocompatibility. This PTT/PDT dual-mode therapy offers an alternative strategy for battling bacterial infections without antibiotics. More importantly, this hydrogel is facile to prepare which is helpful for expanding applications.

Glycation of Tie-2 Inhibits Angiopoietin-1 Signaling Activation and Angiopoietin-1-Induced Angiogenesis.

The impairment of the angiopoietin-1 (Ang-1)/Tie-2 signaling pathway has been thought to play a critical role in diabetic complications. However, the underlying mechanisms remain unclear. The present study aims to investigate the effects of Tie-2 glycation on Ang-1 signaling activation and Ang-1-induced angiogenesis. We identified that Tie-2 was modified by advanced glycation end products (AGEs) in aortae derived from high fat diet (HFD)-fed mice and in methylglyoxal (MGO)-treated human umbilical vein endothelial cells (HUVECs). MGO-induced Tie-2 glycation significantly inhibited Ang-1-evoked Tie-2 and Akt phosphorylation and Ang-1-regulated endothelial cell migration and tube formation, whereas the blockade of AGE formation by aminoguanidine remarkably rescued Ang-1 signaling activation and Ang-1-induced angiogenesis in vitro. Furthermore, MGO treatment markedly increased AGE cross-linking of Tie-2 in cultured aortae ex vivo and MGO-induced Tie-2 glycation also significantly decreased Ang-1-induced vessel outgrow from aortic rings. Collectively, these data suggest that Tie-2 may be modified by AGEs in diabetes mellitus and that Tie-2 glycation inhibits Ang-1 signaling activation and Ang-1-induced angiogenesis. This may provide a novel mechanism for Ang-1/Tie-2 signal dysfunction and angiogenesis failure in diabetic ischaemic diseases.

Antibacterial metal nanoclusters.

Combating bacterial infections is one of the most important applications of nanomedicine. In the past two decades, significant efforts have been committed to tune physicochemical properties of nanomaterials for the development of various novel nanoantibiotics. Among which, metal nanoclusters (NCs) with well-defined ultrasmall size and adjustable surface chemistry are emerging as the next-generation high performance nanoantibiotics. Metal NCs can penetrate bacterial cell envelope more easily than conventional nanomaterials due to their ultrasmall size. Meanwhile, the abundant active sites of the metal NCs help to catalyze the bacterial intracellular biochemical processes, resulting in enhanced antibacterial properties. In this review, we discuss the recent developments in metal NCs as a new generation of antimicrobial agents. Based on a brief introduction to the characteristics of metal NCs, we highlight the general working mechanisms by which metal NCs combating the bacterial infections. We also emphasize central roles of core size, element composition, oxidation state, and surface chemistry of metal NCs in their antimicrobial efficacy. Finally, we present a perspective on the remaining challenges and future developments of metal NCs for antibacterial therapeutics.

Metformin prevents methylglyoxal-induced apoptosis by suppressing oxidative stress in vitro and in vivo.

Methylglyoxal (MGO) is an active metabolite of glucose and plays a prominent role in the pathogenesis of diabetic vascular complications, including endothelial cell apoptosis induced by oxidative stress. Metformin (MET), a widely prescribed antidiabetic agent, appears to reduce excessive reactive oxygen species (ROS) generation and limit cell apoptosis. However, the molecular mechanisms underlying this process are still not fully elucidated. We reported here that MET prevents MGO-induced apoptosis by suppressing oxidative stress in vitro and in vivo. Protein expression and protein phosphorylation were investigated using western blotting, ELISA, and immunohistochemical staining, respectively. Cell viability and apoptosis were assessed by the MTT assay, TUNEL staining, and Annexin V-FITC and propidium iodide double staining. ROS generation and mitochondrial membrane potential (MMP) were measured with fluorescent probes. Our results revealed that MET prevented MGO-induced HUVEC apoptosis, inhibited apoptosis-associated biochemical changes such as loss of MMP, the elevation of the Bax/Bcl-2 ratio, and activation of cleaved caspase-3, and attenuated MGO-induced mitochondrial morphological alterations in a dose-dependent manner. MET pretreatment also significantly suppressed MGO-stimulated ROS production, increased signaling through the ROS-mediated PI3K/Akt and Nrf2/HO-1 pathways, and markedly elevated the levels of its downstream antioxidants. Finally, similar results were obtained in vivo, and we demonstrated that MET prevented MGO-induced oxidative damage, apoptosis, and inflammation. As expected, MET reversed MGO-induced downregulation of Nrf2 and p-Akt. In addition, a PI3K inhibitor (LY-294002) and a Nrf2 inhibitor (ML385) observably attenuated the protective effects of MET on MGO-induced apoptosis and ROS generation by inhibiting the Nrf2/HO-1 pathways, while a ROS scavenger (NAC) and a permeability transition pores inhibitor (CsA) completely reversed these effects. Collectively, these findings broaden our understanding of the mechanism by which MET regulates apoptosis induced by MGO under oxidative stress conditions, with important implications regarding the potential application of MET for the treatment of diabetic vascular complications.

MG53 inhibits angiogenesis through regulating focal adhesion kinase signalling.

Mitsugumin 53 (MG53), which is expressed predominantly in striated muscle, has been demonstrated to be a myokine/cardiokine secreted from striated muscle under specific conditions. The important roles of MG53 in non-striated muscle tissues have also been examined in multiple disease models. However, no previous study has implicated MG53 in the control of endothelial cell function. In order to explore the effects of MG53 on endothelial cells, human umbilical vein endothelial cells (HUVECs) were stimulated with recombinant human MG53 (rhMG53). Then, rhMG53 uptake, focal adhesion kinase (FAK)/Src/Akt/ERK1/2 signalling pathway activation, cell migration and tube formation were determined in vitro. The efficacy of rhMG53 in regulating angiogenesis was also detected in postnatal mouse retinas. The results demonstrated that rhMG53 directly entered into endothelial cells in a cholesterol-dependent manner. The uptake of rhMG53 directly bound to FAK in endothelial cells, which resulted in a significant decrease in FAK phosphorylation at Y397. Accompanied by the dephosphorylation of FAK, rhMG53 uncoupled FAK-Src interaction and reduced the phosphorylation of Src at Y416. Consequently, the activation of FAK/Src downstream signalling pathways, such as Akt and ERK1/2, was also significantly inhibited by rhMG53. Furthermore, rhMG53 remarkably decreased HUVEC migration and tube formation in vitro and postnatal mouse retinal angiogenesis in vivo. Taken together, these data indicate that rhMG53 inhibits angiogenesis through regulating FAK/Src/Akt/ERK1/2 signalling pathways. This may provide a novel molecular mechanism for the impaired angiogenesis in ischaemic diseases.

Gold nanoclusters treat intracellular bacterial infections: Eliminating phagocytic pathogens and regulating cellular immune response.

Intracellular bacterial infection is underlying many serious human disorders, leading to high morbidity and mortality. The development of safe and efficient therapeutic agents is the most effective solutions to combat intracellular bacterial infections. Recently, ultrasmall gold nanoclusters (AuNCs) have emerged as an innovative nanoantibiotics against multidrug-resistant bacterial infections due to their inherent antibacterial activity. However, the therapeutic effects of AuNCs on intracellular bacterial infections and their effects on host cells still remain unvisited. Here, we demonstrate the therapeutic potential of 4,6-diamino-2-mercaptopyrimidine-functionalized AuNCs (AuDAMP) for intracellular multidrug-resistant infections in a co-culture model of macrophages and methicillin-resistant Staphylococcus aureus (MRSA). The AuNCs were found to show a superior intracellular antibacterial capability, which can eliminate most of the MRSA phagocytosed by macrophages, and without exhibiting obvious cytotoxicity on host RAW 264.7 macrophages at tested concentrations. More importantly, treatment of AuDAMP exerts critical roles on enhancing the innate immune response to defend against pathogens invading inside the host cells and alleviating the bacterial infection-induced inflammatory response to avoid pyroptosis by up-regulating significantly xenophagy level in macrophages. Taken together, our results suggest that AuNCs hold great potential for the treatment of intracellular bacterial infections.

A novel turn-on fluorescent sensor for the sensitive detection of glutathione via gold nanocluster preparation based on controllable ligand-induced etching.

In this study, we report a facile one-pot chemical etching approach to simply and rapidly prepare gold nanoclusters capped with luminol (Lum-AuNCs) in an alkaline aqueous solution at room temperature. A series of characterization studies have been carried out to explore the morphology, the optical properties and chemical components of Lum-AuNCs. The average diameter of Lum-AuNCs is 1.8 ± 0.3 nm, exhibiting fluorescence near 510 nm upon excitation at 420 nm with a quantum yield of 14.29% and an average fluorescence lifetime of 9.47 ns. On the basis of the ligand-induced etching of glutathione (GSH) to the intermediate (luminol capped gold nanoparticles, abbreviated as Lum-AuNPs), a novel and simple method for the fluorescence determination of GSH has been established. The method displays a good linear response in the range of 0.05-300 µM toward GSH with a limit of detection of 35 nM. This detection strategy with high sensitivity and selectivity facilitates its practical application for the detection of GSH levels in cell extracts. The in vitro cell results illustrate that Lum-AuNCs have good cytocompatibility and can be used to readily differentiate normal cells and tumor cells.

Gold Nanoclusters for Bacterial Detection and Infection Therapy.

Infections caused by antibiotic-resistant bacteria have become one of the most serious global public health crises. Early detection and effective treatment can effectively prevent deterioration and further spreading of the bacterial infections. Therefore, there is an urgent need for time-saving diagnosis as well as therapeutically potent therapy approaches. Development of nanomedicine has provided more choices for detection and therapy of bacterial infections. Ultrasmall gold nanoclusters (Au NCs) are emerging as potential antibacterial agents and have drawn intense attention in the biomedical fields owing to their excellent biocompatibility and unusual physicochemical properties. Recent significant efforts have shown that these versatile Au NCs also have great application potential in the selective detection of bacteria and infection treatment. In this review, we will provide an overview of research progress on the development of versatile Au NCs for bacterial detection and infection treatment, and the mechanisms of action of designed diagnostic and therapeutic agents will be highlighted. Based on these cases, we have briefly discussed the current issues and perspective of Au NCs for bacterial detection and infection treatment applications.

Fluorescence light up detection of aluminium ion and imaging in live cells based on the aggregation-induced emission enhancement of thiolated gold nanoclusters.

In this paper, a new strategy was presented for fluorescence labeling and imaging Al3+ in live cells with excess aluminum ions using thiolated fluorescence gold nanoclusters (Au NCs). The glutathione (GSH)-capped Au NCs were prepared via a green, facile one-pot method in aqueous solution and displayed excellent stability, ultrasmall size, monodispersity, and larger Stokes shift, which exhibits a relatively weak fluorescence at 650 nm Al3+-induced fluorescence enhancement of the GSH-Au NCs can be observed due to Al3+-triggered aggregation-induced emission (AIE) effect, which allows the role of GSH-Au NCs as a fluorescence light-up probe for detection of Al3+. Moreover, it was demonstrated that the fluorescence probe for Al3+ showed a wide detection range from 100 to 600 µM and good selectivity against other metal ions and common biomolecule. Furthermore, due to the advantages of excellent biocompatibility, low toxicity, red emission and high specificity, the proposed GSH-Au NCs fluorescence probes are suitable for the imaging of high concentrations of aluminum ions in cells, which can be applied to the diagnosis of cellular aluminum poisoning.

Glutathione Induced Transformation of Partially Hollow Gold-Silver Nanocages for Cancer Diagnosis and Photothermal Therapy.

Gold-silver nanocages (GSNCs) are widely used in cancer imaging and therapy due to excellent biocompatibility, internal hollow structures, and tunable optical properties. However, their possible responses toward the tumor microenvironment are still not well understood. In this study, it is demonstrated that a kind of relatively small sized (35 nm) and partially hollow GSNCs (absorbance centered at 532 nm) can enhance the intrinsic photoacoustic imaging performances for blood vessels around tumor sites. More importantly, the high concentration of glutathione around the tumor cells' microenvironment may induce the aggregation, disintegration, and agglomeration of these GSNCs sequentially, allowing significant shifts in the absorbance spectrum of GSNCs to the near-infrared (NIR) region. This enhanced absorbance in the NIR region entails the significant photothermal therapy (PTT) effect. In vivo experiments, including photoacoustic microscopy (PAM) for cancer diagnosis and PTT in tumor model mice, also show coincident consequences. Taken together, the slightly hollow GSNCs may assist PAM-based tumor diagnosis and induce a tumor targeted PTT effect. This work paves a new avenue for the development of an alternative tumor diagnostic and therapeutic strategy.

Chromium(III)-doped carbon dots: fluorometric detection of p-nitrophenol via inner filter effect quenching.

We report on the synthesis of chromium(III)-doped carbon dots (Cr-CDs) by one-pot hydrothermal pathway using tris(2, 4-pentanedionato) chromium(III) and polyethyleneimine as precursors. The Cr-CDs have a graphene-analogous structure and display blue-green fluorescence with excitation/emission maxima at 350/466 nm, a 20% quantum yield, and excitation-independent emissions. Their cytotoxicity is low. The Cr-CDs were used as a fluorescence probe for p-nitrophenol (p-NP). The assay has a linear working range that extends from 0.8~150 µM and a 0.27 µM lower detection limit. The assay was applied to the detecting of p-NP in spiked human urine, and conceivably may be extended to a method for the determination of parathion. Graphical abstract Schematic presentation for the synthesis of Cr-CDs (chromium(III)-doped carbon dots) and their application to the fluorometric determination of p-NP (p-nitrophenol) based on an inner filter effect.

Aggregation-Induced Electrochemiluminescence by Metal-Binding Protein Responsive Hydrogel Scaffolds.

Functionalized hydrogels have aroused general interest due to their versatile applications in biomaterial fields. This work reports a hydrogel network composed of gold nanoclusters linked with bivalent cations such as Ca2+ , Mg2+ , and Zn2+ . The hydrogel exhibits both aggregation-induced emission (AIE) and aggregation-induced electrochemiluminescence (AIECL) effects. Most noteworthy, the AIECL effect (≈50-fold enhancement) is even more significant than the corresponding AIE effect (approximately fivefold enhancement). Calmodulin, a Ca2+ binding protein, may efficiently regulate the AIECL dynamics after specific binding of the Ca2+ linker, with the linear range from 0.3 to 50 µg mL-1 and a limit of detection of 0.1 µg mL-1 . Considering the important roles of bivalent cations in the life system, these results may pave a new avenue for the design of a biomolecule-responsive AIECL-type hydrogel with multifunctional biomedical purposes.

Conjugating gold nanoclusters and antimicrobial peptides: From aggregation-induced emission to antibacterial synergy.

Antimicrobial peptides and antibacterial nanostructures are two emerging classes of antimicrobial agents that differ from conventional small-molecule antibiotics. Combining these two types of antimicrobial agents into one entity may be an effective strategy to improve their antimicrobial efficiency. In this study, we demonstrated an effective antibacterial hybrid formed by covalently conjugating antibacterial gold nanoclusters (Au NCs, a novel antimicrobial nanostructure) and daptomycin (Dap, a cyclic lipopeptide antimicrobial peptide). The as-synthesized hybrid structure (Dap-Au NCs) not only inherits the intrinsic properties from both agents but also renders an enhanced synergistic effect. Compared with the physically mixed Au NCs and daptomycin (Dap+Au NCs), the Dap-Au NCs hybrid structure has a stronger bactericidal effect toward methicillin-resistant Staphylococcus aureus, a representative of multidrug-resistant bacteria. Dap-Au NCs could effectively disrupt bacterial membranes by creating more and/or larger holes in the membranes due to the localized daptomycin within the conjugated structure. These larger (and possibly more) holes motivate the entry of Dap-Au NCs into bacterial cells and lead to more serious damage of the bacteria at subcellular levels. Moreover, bacterial genomic DNA fragmentation was further quantified to show that Dap-Au NCs may induce severe DNA breaks. The strong DNA destruction benefited from localized high concentrations of reactive oxygen species (ROS) induced by the localization of Au NCs in the antimicrobial conjugation. The conjugated Au NCs could serve as a critical free radical generator to continuously produce ROS within the bacteria. The continuous ROS bombings also limit the capacity of the bacteria to develop drug resistance. In addition, a significant fluorescence enhancement of the hybrid structure was observed due to a novel aggregation-induced emission (AIE) pattern caused by the Au NCs and daptomycin conjugation. This conjugation strategy provides a new perspective for the synthesis of new antimicrobial agents as well as AIE-type fluorescence materials.

Mercaptopyrimidine-Conjugated Gold Nanoclusters as Nanoantibiotics for Combating Multidrug-Resistant Superbugs.

Widespread bacterial resistance induced by the abuse of antibiotics eagerly needs the exploitation of novel antimicrobial agents and strategies. Gold nanoclusters (Au NCs) have recently emerged as an innovative nanomedicine, but study on their antibacterial properties especially toward multidrug resistant (MDR) bacteria is scarce. Herein, we demonstrate that a novel class of Au NCs, mercaptopyrimidine conjugated Au NCs, can act as potent nanoantibiotics targeting these intractable superbugs in vitro and in vivo, without induction of bacterial antibiotic resistance and noticeable cytotoxicity to mammalian cells. The Au NCs kill these superbugs through a combined mechanism including cell membrane destruction, DNA damage, and reactive oxygen species (ROS) generation, and exhibit excellent treatment effects in both macrophages and animal infection models induced by methicillin-resistant Staphylococcus aureus as representative. Moreover, the induction of intracellular ROS production in bacterial cells mainly attributed to the Au NCs' intrinsic oxidase- and peroxidase-like catalytic activities has been demonstrated for the first time.

Mercaptopyrimidine-directed gold nanoclusters: a suitable fluorescent probe for intracellular glutathione imaging and selective cancer cell identification.

Herein, we demonstrate a novel, facile, and suitable strategy for imaging GSH based on mercaptopyrimidine-directed gold nanoclusters (Au NCs). GSH can specifically induce the fluorescence enhancement of Au NCs by attacking the surface of the NCs to form dual ligand stabilized Au NCs at the millimolar level. Very importantly, the Au NCs can selectively image cancer cells.

In Vivo Biosynthesized Zinc and Iron Oxide Nanoclusters for High Spatiotemporal Dual-Modality Bioimaging of Alzheimer's Disease.

Alzheimer's disease is still incurable and neurodegenerative, and there is a lack of detection methods with high sensitivity and specificity. In this study, by taking different month old Alzheimer's mice as models, we have explored the possibility of the target bioimaging of diseased sites through the initial injection of zinc gluconate solution into Alzheimer's model mice post-tail vein and then the combination of another injection of ferrous chloride (FeCl2) solution into the same Alzheimer's model mice post-stomach. Our observations indicate that both zinc gluconate solution and FeCl2 solution could cross the blood-brain barrier (BBB) to biosynthesize the fluorescent zinc oxide nanoclusters and magnetic iron oxide nanoclusters, respectively, in the lesion areas of the AD model mice, thus enabling high spatiotemporal dual-modality bioimaging (i.e., including fluorescence bioimaging (FL) and magnetic resonance imaging (MRI)) of Alzheimer's disease for the first time. The result presents a novel promising strategy for the rapid and early diagnosis of Alzheimer's disease.

Endophytic fungi harbored in Panax notoginseng: diversity and potential as biological control agents against host plant pathogens of root-rot disease.

BACKGROUND: Endophytic fungi play an important role in balancing the ecosystem and boosting host growth. In the present study, we investigated the endophytic fungal diversity of healthy Panax notoginseng and evaluated its potential antimicrobial activity against five major phytopathogens causing root-rot of P. notoginseng. METHODS: A culture-dependent technique, combining morphological and molecular methods, was used to analyze endophytic fungal diversity. A double-layer agar technique was used to challenge the phytopathogens of P. notoginseng. RESULTS: A total of 89 fungi were obtained from the roots, stems, leaves, and seeds of P. notoginseng, and 41 isolates representing different morphotypes were selected for taxonomic characterization. The fungal isolates belonged to Ascomycota (96.6%) and Zygomycota (3.4%). All isolates were classified to 23 genera and an unknown taxon belonging to Sordariomycetes. The number of isolates obtained from different tissues ranged from 12 to 42 for leaves and roots, respectively. The selected endophytic fungal isolates were challenged by the root-rot pathogens Alternaria panax, Fusarium oxysporum, Fusarium solani, Phoma herbarum, and Mycocentrospora acerina. Twenty-six of the 41 isolates (63.4%) exhibited activity against at least one of the pathogens tested. CONCLUSION: Our results suggested that P. notoginseng harbors diversified endophytic fungi that would provide a basis for the identification of new bioactive compounds, and for effective biocontrol of notoginseng root rot.

Recent advances in biomedical applications of fluorescent gold nanoclusters.

Fluorescent gold nanoclusters (AuNCs) are emerging as novel fluorescent materials and have attracted more and more attention in the field of biolabeling, biosensing, bioimaging and targeted cancer treatment because of their unusual physicochemical properties, such as long fluorescence lifetime, ultrasmall size, large Stokes shift, strong photoluminescence, as well as excellent biocompatibility and photostability. Recently, significant efforts have been committed to the preparation, functionalization and biomedical application studies of fluorescent AuNCs. In this review, we have summarized the strategies for preparation and surface functionalization of fluorescent AuNCs in the past several years, and highlighted recent advances in the biomedical applications of the relevant fluorescent AuNCs. Based on these observations, we also give a discussion on the current problems and future developments of the fluorescent AuNCs for biomedical applications.