Xueyun Gao

• Chinese Academy of Sciences

Acute lung injury (ALI) is one of the most common respiratory system diseases with high prevalence. However, there is still lacking of effective specialized medicines for the treatment of ALI....

Gold nanocluster GA acts as a docetaxel sensitizer to promote ER stress and microtubule dysregulation, leading to significant tumor cell death and promoting anti-tumor cytokine production in treating triple-negative breast cancer.

Drug nanocrystals have received significant attention in drug development due to their enhanced dissolution rate and improved water solubility, making them effective in overcoming issues related to drug hydrophobicity, thereby improving drug bioavailability and treatment effectiveness. Recent advances in preparation techniques have facilitated rese...

Glioblastoma multiforme (GBM) is the most aggressive brain tumor. There is a pressing need to develop novel treatment strategies due to the poor targeting effect of current therapeutics. Here, a gold cluster coated with optimized GBM-targeting peptide is engineered, namely NA. NA can efficiently target GBM both in vitro and in vivo. Interestingly,...

The precise localization of metastatic tumors with subtle growth is crucial for timely intervention and improvement of tumor prognosis but remains a paramount challenging. To date, site-specific activation of fluorogenic probes for single-stimulus-based diagnosis typically targets an occult molecular event in a complex biosystem with limited specif...

To date, earlier diagnosis of Alzheimer’s disease (AD) is still challenging. Recent studies revealed the elevated expression of connective tissue growth factor (CTGF) in AD brain is an upstream regulator of amyloid-beta (Aβ) plaque, thus CTGF could be an earlier diagnostic biomarker of AD than Aβ plaque. Herein, we develop a peptide-coated gold nan...

Hepatitis and arthritis are prevalent inflammatory diseases, and the utilization of fluorogenic probes incorporating hydrogen sulfide (H 2 S) as a crucial mediator of inflammation presents significant opportunities for early detection. However, the poor in vivo biodistribution and limited targeted efficacy of molecule probes for inflammation imagin...

Activatable near‐infrared (NIR) fluorogenic probes offer a potent tool for real‐time, in situ detection of hepatic biomarkers, significantly advancing the precision in diagnosing inflammatory liver disease (ILD). However, the limited distribution of small molecule fluorogenic probes in the liver and their rapid clearance impair the accuracy of fluo...

Peptide-protected gold nanoclusters (AuNCs), possessing exceptional biocompatibility and remarkable physicochemical properties, have demonstrated intrinsic pharmaceutical activity in immunomodulation, making them a highly attractive frontier in the field of nanomedicine exploration. Autoimmune hepatitis (AIH) is a serious autoimmune liver disease c...

Inflammatory bowel disease (IBD) is one of the main factors leading to colitis-associated colorectal cancer (CAC). Therefore, it is critical to develop an effective treatment for IBD to prevent secondary colorectal carcinogenesis. M2 macrophages play crucial roles in the resolution phase of intestinal inflammation. However, traditional drugs rarely...

Gliomas are histologically and genetically heterogeneous tumors. However, classical histopathological typing often ignores the high heterogeneity of tumors and thus cannot meet the requirements of precise pathological diagnosis. Here, proximity‐anchored in situ spectral coding amplification (ProxISCA) is proposed for multiplexed imaging of RNA muta...

α v β 3 is overexpressed in various tumor cells and plays a key role in tumor genesis, invasion, and metastasis. Therefore, it is of great significance to precisely detect the α v β 3 level in cells via a simple method. For this purpose, we have constructed a peptide-coated platinum (Pt) cluster. Due to its bright fluorescence, well-defined Pt atom...

Immune-mediated skin diseases have a high prevalence and seriously affect patients’ quality of life. Gold compounds have been considered promising therapeutic agents in dermatology, but the high incidence of adverse reactions have limited their clinical application. There is a great need to develop more effective and less toxic gold-based drugs. Go...

Early diagnosis of hepatic inflammation is the key to timely treatment and avoid the worsening of liver inflammation. Near-infrared fluorescence (NIRF) probes have high sensitivity but low spatial resolution in lesion imaging, while photoacoustic (PA) imaging has good spatial location information. Therefore, the development of a NIRF/PA dual-modal...

Identifying effective reversal agents overcoming multidrug resistance with causal mechanisms from an efflux pump protein is of vital importance for enhanced tumor chemotherapy in clinic. To achieve this end, we construct a metal cluster-based probe, named clusterbody, to develop flow sorting-assisted single-cell mass spectrometry analysis. This clu...

Activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is the most aggressive form of DLBCL, with a significantly inferior prognosis due to resistance to the standard R-CHOP immunochemotherapy. Survival of ABC-DLBCL cells addicted to the constitutive activations of both canonical and noncanonical NF-κB signaling makes them attractive thera...

Studies have shown that Au triggers tumor cell apoptosis by directly inhibiting human thioredoxin reductase (hTrxR), thus making Au potential drugs for cancer treatment. However, the exact molecular mechanism of Au inhibiting hTrxR has never been demonstrated via experimental and theoretical studies. Here, we synthesized an Au4 cluster coated by an...

Zn²⁺ is one of the most critical micronutrients involved in embryonic development and growth. In situ tracking of the metabolic distribution of Zn²⁺ during embryogenesis can help to understand its role. However, the lack of practical fluorescence imaging tools hinders the dynamic tracking of Zn²⁺ changes and distribution in vivo. Here, we report a...

In cyanobacteria and algae (but not plants), flavodoxin (Fld) replaces ferredoxin (Fd) under stress conditions to transfer electrons from photosystem I (PSI) to ferredoxin-NADP⁺ reductase (FNR) during photosynthesis. Fld constitutes a small electron carrier noncovalently bound to flavin mononucleotide (FMN), and also an ideal model for revealing th...

Characterizing interactions between microbial cells and their specific inhibitory drugs is essential for developing effective drugs and understanding the therapeutic mechanism. Functional metal nanoclusters can be effective inhibitory agents against microorganisms according to various characterization methods, but quantitative three-dimensional (3D...

Current therapeutic strategies for autoimmune diseases such as multiple sclerosis (MS) are directed towards nonspecific immunosuppression, which has severe side effects. The induction of antigen-specific tolerance has become an ideal therapy for autoimmune diseases. In this study, we have constructed a dual peptide nanoparticle platform, including...

Thioredoxin reductase (TrxR1) is over activity in tumor cell to maintain their redox balance. Although gold clusters have great potential in antitumor drug as they could well inhibit TrxR1, the molecular mechanism has not been disclosed yet. In this work, we revealed gold clusters can well inhibit the activity of TrxR1 in lung tumor cells and furth...

Triple-negative breast cancer (TNBC) accounts for nearly one-quarter of all breast cancer cases, but effective targeted therapies for this disease remain elusive because TNBC cells lack the expression of the most common three receptors seen in other subtypes of breast cancers. The medium-term diagnosis of breast cancers is essential for development...

The prevalence of positron emission tomography (PET) imaging has advanced biomedical applications for its ultrahigh sensitivity, deep tissue penetration and quantitative visualization of diseases in vivo. ⁶⁴Cu with ideal half-life and decay characteristics has been designed as radioactive probes for disease diagnosis. The currently reported ⁶⁴Cu-la...

While gold compound have been approved for Rheumatoid arthritis treatment as it well suppresses inflammatory cytokines of patients, no such treatment is currently available for COVID-19 treatment in vivo. We firstly disclose gold cluster yields better therapeutic outcome than Remdesivir in COVID-19 hamster treatments as it is armed with direct inhi...

We construct a peptide-conjugated metal cluster as an enzyme-like catalytic bioprobe to enhance quantitative analysis of a membrane protein biomarker and detect epithelial-to-mesenchymal transition of tumor cells. This bioprobe with atomically precise formula, termed clusterzyme, possesses selective recognition and intrinsic enzyme-like activity. T...

A simple but efficient fluorogenic probe is reported for accurate imaging of ulcerative colitis via hypoxia detection. The hypoxia produced by ulcerative colitis can lead to the upregulation of nitroreductase (NTR). NB-NO2 provides a unique response to NTR, enabling accurate imaging of Dextran sulphate sodium (DSS)-induced ulcerative colitis in viv...

Metastatic lung cancer is the leading cause of death for cancer patients. Although many chemical drugs were developed for cancer treatment, metastatic cancer mortality did not decrease significantly. In this article, we designed an Au clusters (AuCs) modified by cyclic RGD peptides which well target the integrin of human lung carcinoma cells (A549)...

High-performance near-infrared (NIR) probes can achieve rapid and effective imaging and tracking of tumor biomarkers, which has attracted extensive attention in tumor visualization and early diagnosis. Fast response speed and high contrast fluorogenic enhancement are important criteria for high-performance imaging probes. Here, by introducing two h...

Hepatotoxicity is a serious problem faced by thousands of clinical drugs, and drug-induced liver injury (DILI) caused by chronic administration or overdose has become a major biosafety issue. However, the near-infrared (NIR) fluorescent probes currently used for liver injury detection still suffer from poor liver targeting ability and low sensitivi...

Comprehensive Summary Metal nanoclusters have attracted much attention due to their ultra‐small size and unique properties. The integration of protein or peptide can bring a synergistic effect on the physicochemical and physiological properties of metal clusters. Metal nanoclusters protected by peptides or proteins exhibit excellent biocompatibilit...

Multifunctional bioimaging probes based on metal clusters have multiple characteristics of metal clusters and functional conjugates, and their development has broad application prospects in the fields of biomedical imaging and tumor diagnosis. However, current bioconjugation methods on metal clusters are time-consuming and have low reaction efficie...

Rheumatoid Arthritis (RA) is a chronic autoimmune disease, which mainly causes inflammation of the synovial joints and destruction of cartilage and bone tissue. At present, a variety of clinical drugs have been applied in the treatment of rheumatoid arthritis. With the development of nanotechnology, more and more nano-drugs have been applied in the...

The development of three-dimensional (3D) single-cell imaging and protein quantitative methods can provide more comprehensive information for diagnoses. We report the design and synthesis of a multisignal nanoprobe (AuGdNC@BSA-CV) for single-cell 3D imaging and quantifying the integrin αIIbβ3 using correlated synchrotron radiation soft X-ray tomogr...

NAD(P)H:quinone oxidoreductase-1 (NQO1) is attractive as a potential cancer biomarker because it is abnormally expressed in many solid tumors and is closely related to a variety of carcinogenic processes. Determining and evaluating the content/activity of NQO1 in tumors is of great significance for early cancer diagnosis and therapeutic effect eval...

The virus replication and lung inflammation are basic targets for COVID-19 treatment. To effectively treat COVID-19, the best chemical drug should combine inhibition of SARS-CoV-2 replication and direct suppression of inflammatory cytokine expression together. Our SARS-CoV-2 main protease (M pro ) crystal structure studies revealed Au(I), derived f...

Traditional photodynamic therapy requires external light excitation to produce reactive oxygen species (ROSs) for treatment of tumor. Due to problems of light penetration, traditional PDT is limited by location and depth of tumor. In this study, we rationally designed and constructed a novel strategy to amplify the therapeutic effect of PDT. We pre...

Metalloenzymes are promising anticancer candidates to overcome chemoresistance by involving unique mechanisms. To date, it is still a great challenge to obtain synthetic metalloenzymes with persistent catalytic performance for cancer-specific DNA cleavage and operando imaging. Here, an artificial metalloenzyme, copper cluster firmly anchored in bov...

Our studies implied the golden compounds may be more effective against COVID 19 as they synergy inhibit SARS COV 2 replication and down regulation inflammation cytokine level. Our crystal structure studies firstly revealed Au (I) ions, derived from auranofin (AF) or gold cluster (GA), covalently bind sulfur atom of Cys145 and Cys156 of Mpro of SARS...

Platinum (Pt) drugs are widely used in anti‐cancer treatment although many reports advocated that tumor cells could inactivate Pt drugs via glutathione‐Pt (GSH‐Pt) adducts formation. To date, GSH chelated Pt molecules have not been assessed in cancer treatment because GSH‐Pt adducts are not capable of killing cancer cells, which is widely accepted...

SARS-CoV-2 has emerged as a world public health threat. Herein, we report that the clinical approved auranofin could significantly inhibit the activity of 3-chymotrypsin-like cysteine protease (Mpro or 3CLpro) of SARS-CoV-2. Phenyl isothiocyanate and gold cluster could perfectly inhibit 3CLpro of SARS-COV-2. Vitamin K3 could well suppress the activ...

The biomedical features of metal clusters have been explored in the applications of tumor diagnosis in recent years. Peptide or protein protected metal clusters with low toxicity, ultra-small size and good biocompatibility, are ideal bioanalytical tools, and exhibit better cancer diagnostic properties that have been attracted to oncologists. This p...

Sepsis-induced acute kidney injury (AKI) with high incidence and mortality rates remains a great challenge in the clinic; thus, novel therapies need to be developed urgently. This complication is associated with an overwhelming systemic inflammatory response. The aim of this study was to evaluate the potential effects and possible mechanisms of gol...

Noble metal nanoclusters (< 2 nm) prepared using special molecules, such as proteins and peptides as templates are attracting increasing attention in biomedical applications and cell imaging due to their excellent biocompatibility, size-dependent fluorescence properties and relatively simple synthesis. While cell imaging using metal clusters has de...

Rationale: Bone is the most frequent site for breast cancer metastasis, which accounts for the leading cause of death in advanced breast cancer patients. Serious skeletal-related events (SREs) caused by bone metastasis have a decisive impact on the life expectancy of breast cancer patients, making breast cancer almost incurable. Metastatic breast c...

This work reports the synthesis, radiolabeling and imaging studies of iodine-124 labeled peptide modified gold nanoclusters (AuNCs) as positron emission tomography (PET) tracer for lung cancer. The novel modified Au nanoclusters were successfully synthesized by conjugation of tumortargeting peptide luteinizing hormone releasing hormone (LHRH) to hu...

Accurate diagnosis of cancer at an early stage is the key to reduce cancer mortality and improve survival. PET imaging has high sensitivity but low spatial resolution, while CT imaging has good spatial location information. Therefore, the combination of PET and CT imaging can provide complementary advantages to achieve accurate early diagnosis of t...

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and progressive cartilage and bone damage. In our previous studies, we found that Au clusters using glutathione as a template (GACs) produced profound anti-inflammatory effects in vitro on lipopolysaccharide (LPS)-induced inflammation in mouse macrophag...

Chronic inflammation and progressive bone damage in joints are two main pathological features of rheumatoid arthritis (RA). We have synthesized a gold cluster with glutathione (Au29SG27) (named GA) that can effectively suppress both inflammation and bone damage in collagen-induced arthritis (CIA) in rats. Thus, gold clusters showed great potential...

Recent experiments have found that fullerenols can inhibit coagulation factor X (FXa) activity and have the effects on anticoagulation. But the interactions between fullerene derivatives and FXa are still lacking which are crucial for the new inhibitors designs and applications. In this study, we investigated the interaction principle between FXa a...

Glutathione-coated small-sized gold nanocluster denoted as Au29(SG)27 has potential applications in bio therapeutics. Since it is difficult to obtain an accurate atomic structure experimentally, its structure is predicted by density functional theory. The atomic structure of Au29(SG)27 is speculated to contain a ring motif (for low Au/S ratio), the...

Neurodegenerative diseases have become a huge challenge to public health, such as Alzheimer's and Parkinson's diseases. Microglia driving inflammation in the central nervous system (CNS) has been involved in the pathological process of these disorders and could be novel therapy target. However, traditional anti-inflammatory drugs are not effective...

Nano-material-based tumor photothermal therapy (PTT) has attracted increasing attention and been a promising method for cancer treatment due to its low level of adverse effects and noninvasiveness. However, thermotherapy alone still cannot control tumor metastasis and recurrence. Here, we developed surface functionalized modified copper sulfide nan...

Inflammation-induced bone erosion is a major pathological factor in several chronic inflammatory diseases that often cause severe outcomes, such as rheumatoid arthritis and periodontitis. Plenty of evidences indicated that the inflammatory bone destruction was attributed to an increase in the number of bone-resorbing osteoclasts. However, anti-reso...

Supplementary figures and tables.

Super‐small nanoclusters may intrinsically trigger specific molecular pathway for disease treatment in vitro/vivo. To prove the hypothesis the super‐small nanoclusters, e.g., Au clusters, are directly used to treat rheumatoid arthritis (RA) in vitro/vivo. RA is a chronic autoimmune disease that is characterized by the inflammation of joints and the...

Anticancer metallodrugs that aim to physiological characters unique to tumor microenvironment are expected to combat drug tolerance and side-effects. Recently, owing to the fact that reactive oxygen species’ is closely related to the development of tumors, people are committed to developing metallodrugs with the capacity of improving the level of r...

Cancer invasion and metastasis remain the major causes of over 90% of patient deaths. Molecular imaging methods such as computed tomography (CT)/magnetic resonance imaging (MRI) can precisely assess primary regional lymph node invasion and distant organ metastasis via body scanning; however, such diagnostic methods are often utilized too late for c...

We reported two Au clusters with precisely controlled molecular size (Au5Peptide3 and Au22Peptide10) showing different anti-tumor effects. In vitro, both Au5Peptide3 and Au22Peptide10 were well taken up by human nasopharyngeal cancer cells (CNE1 cells). However, only Au5Peptide3 significantly induced CNE1 cell apoptosis. Further studies showed that...

Membrane type 1 matrix metalloproteinase (MT1-MMP) is expressed in most tumors and is believed to play a key role in the development, invasion and metastasis of tumors. There is an urgent need to develop a simple method to detect the MT1-MMP expression level on cells. In this current study, we demonstrated a red emission Au cluster probes with the...

Increasingly serious microbial infections call for the development of new simpler methods for the precise diagnosis and specific inhibition of such pathogens. In this work, a peptide mineralized Au cluster probe was applied as a new simplified strategy to both recognize and inhibit a single bacteria species of Staphylococcus aureus (S. aureus) simu...

The epidermal growth factor receptor (EGFR) has become an important target protein in anticancer drug development. Meanwhile, peptide-Au cluster has been proposed as potential targeted nano-drug assembled by targeting peptide. Here, we designed and synthesized a novel peptide-Au cluster as Au10Peptide5 to target to EGFR. We found Au10Peptide5 could...

The original motivation of the article is to give a systematic investigation on the protocol of combining computer simulation and accurate synthesis of serial peptide protected gold clusters for potent tumor targeting therapy. Glutathione peroxidase-1 (GPx-1) is a crucial antioxidant selenoenzyme that regulates cellular redox level, thus becomes a...

The facile method to synthesize ultrasmall size super-magnetic iron oxide nanoparticle with good mono-dispersity, high relaxivity is desired for magnetic resonance imaging (MRI) technology. Herein, we developed a one-step method to direct the formation of super-paramagnetic iron oxide nanoparticle (uBSPIO) using albumin at mild condition. The resul...

Radiotherapy is an important technology for the clinical treatment of cancer, but the patients suffer from the severe side effects after exposure to radiation. There is an urgent need to develop theranostic agents with excellent imaging capability and effective radiosensitization in order to minimize X-ray irradiation. Herein, we report an approach...

UTL-5g is a novel small-molecule TNF-alpha modulator. It reduces cisplatin-induced side effects by protecting kidney, liver, and platelets, thereby increasing tolerance for cisplatin. UTL-5g also reduces radiation-induced acute liver toxicity. The mechanism of action for UTL-5g is not clear at the present time. A phosphoproteomic analysis to a dept...

Au nanoclusters and Clorine 6 (Ce6) co-loaded spatio-temporal controllable pH-sensitive liposomal nanocomposites are internalized by tumor cells via endocytosis are described by Fuping Gao, Xueyun Gao, and co-workers in article number 1601453. Au nanoclusters and Ce6 are burst and quickly released into cytoplasm under the acidic environment of lyso...

Multi-modal imaging agents are desirable for tumor diagnosis because they can provide more information on the tumor than single-modal imaging agents. However, most reported multi-modal imaging agents are dual-modal agents rather than tri-modal agents; therefore, detailed information on the tumor may still be insufficient when such imaging agents ar...

To improve both the activity and stability of electrocatalyst in Hydrogen Evolution Reaction (HER) remains a challenge. In this work, a facile and friendly way to synthesis of CoSe2 hollow microspheres was reported by using organic selenium source. The growth mechanism of CoSe2 hollow microspheres attributed to the Kirkendall effect with the hydrot...

Photodynamic therapy (PDT) is a minimally invasive therapeutic procedure of tumors with high selectivity and low side effect. However, it is usually not efficient in long-lasting tumor control. One of the main reasons is tumor cells develop some protective mechanisms that help them to deal with oxidative stress in the environment. The thioredoxin s...

Chronic lymphocytic leukaemia (CLL) is a rare blood cancer that always relapses as refractory disease and eventually leads to death. To date, therapeutic options for CLL patients are scarce and there is an urgent need to develop novel chemotherapeutics that are both effective and safe. Gold-containing compounds induce a lethal oxidative and endopla...

Alterations in protein (e.g., biomarkers) expression levels have a significant correlation with tumor development and prognosis; therefore, it is desired to develop precise methods to differentiate the expression level of proteins in tumor cell lines, especially at the single-cell level. Here, we report a precise and versatile approach of quantifyi...

Albumin-stabilized Ag nanodots (ANDs) are prepared by a one-step biomineralisation method. The highly-crystallized nanodots have ultrasmall sizes (approximately 5.8 nm) and robust X-ray attenuation (5.7313 HU per mM Ag). The unlabeled ANDs are directly excreted from the body via the urine after in vivo X-ray computer tomography (CT) imaging applica...

Previously we have shown that the inhibition of proliferation and induction of apoptosis in pancreatic ductal adenocarcinoma (PDA) cells by pristimerin (PM), a quinonemethide triterpenoid, was associated with the inhibition of human telomerase reverse transcriptase (hTERT) mRNA and hTERT protein. Herein we show that PM inhibits transcription factor...

Two-dimensional (2D) materials have intrigued not only fundamental science study but also novel materials engineering due to the unique physical and chemical properties. However, the commonly used methods for preparing few layers have limitations of low yield and poor extendibility into large-area applications. In this paper, graphene-like MoSe2 na...

Trichothecenes are powerful mycotoxins that inhibit protein synthesis and induce ribotoxic stress response in mammalian cells. Verrucarin A (VC-A) is a Type D macrocyclic mycotoxin which inhibits cell proliferation and induces apoptosis in cancer cells. However, the antitumor activity of VC-A for prostate cancer cells has not been investigated. The...

High-resolution imaging offers one of the most promising approaches for exploring and understanding the structure and function of biomaterials and biological systems. X-ray free-electron lasers (XFELs) combined with coherent diffraction imaging can theoretically provide high-resolution spatial information regarding biological materials using a sing...