Atomically precise Fluorescent Gold Nanocluster as a barrier-permeable and brain-specific imaging probe.

Photonic nanomaterials play a crucial role in facilitating the necessary signal for optical brain imaging, presenting a promising avenue for early diagnosis of brain-related disorders. However, the blood-brain barrier (BBB) presents a significant challenge, blocking the entry of most molecules or materials from the bloodstream into the brain. To overcome this, photonic nanocrystals in the form of gold clusters (LAuC) with size less than 3nm, have been developed, with Levodopa conjugated to LAuC (Dop@LAuC) for targeted brain imaging. Dop@LAuC crosses the BBB and emits in the near-infrared (NIR) wavelength, enabling real-time optical brain imaging. An in vitro BBB model using brain endothelial cells showed that 50% of Dop@LAuC crossed the barrier within 3 hours, compared to only 10% of LAuC, highlighting the enhanced ability of L-dopa-conjugated gold clusters to penetrate the BBB. In vivo optical imaging in healthy mice further confirmed the material's efficacy to cross BBB without compromising the barrier integrity.

Loading Lewis Acid/Base Pair on Metal Nanocluster for Catalytic Ugi Reaction.

Constructing structurally robust and catalytically active metal nanoclusters for catalyzing multi-component reactions is an interesting while challenging task. Inspired by Lewis acid and Lewis base catalysis, we realized the combination of both Lewis acid and Lewis base sites on the surface of a stable gold nanocluster Au35Cd2. The catalytic potential of Au35Cd2 in four-component Ugi reaction was explored, demonstrating high activity and exceptional recyclability. In-depth mechanism studies indicate that the catalytic synergy of the Lewis acid/base pair is crucial for the high efficiency of Au35Cd2-catalyzed Ugi reaction. Bearing the stable structure, multiple activation sites and hierarchical chirality, Au35Cd2 is expected to display further interesting catalytic performance such as asymmetric catalysis.

Levonorgestrel protected Au10 cluster for hypochlorite sensing in living organisms.

BACKGROUND: Highly reactive oxygen species (ROS) could lead to serious damage in living cells and are associated with many diseases like cancers. Metal cluster with strong fluorescence has great potential in biosensing and many thiolate ligands-protected clusters have been applied in ROS sensing. RESULTS: In this work, we synthesized levonorgestrel protected Au10 cluster with specific sensing ability for highly ROS via crystal transformation from Au8 cluster, demonstrating the significance of inner core structure on detecting performance. The detection limit of Au10 cluster for ClO- could reach as low as 0.1 µM. This fluorescent probe not only achieving detection of exogenous ClO- in living cells and zebrafish, but also successful imaging of endogenous ClO- in HeLa and HepG2 cells. SIGNIFICANCE: In comparison to previously reported cluster-based sensors for ROS, this work proposes a different reaction mechanism of metal nanoclusters for ROS detection (breakage of gold-alkynyl bond and oxidation of alkynyl group). This provides new directions for designing specific ROS probes and broadens the applications of metal clusters in disease diagnostics.

Developing a novel ultraselective and ultrasensitive label-free direct spectrofluorimetric nanobiosensor for direct highly fast field detection of explosive triacetone triperoxide.

BACKGROUND: Direct detection of the notorious explosive triacetone triperoxide (TATP) is very difficult because it lacks facile ionization and UV absorbance or fluorescence. Besides, the current indirect methods are time-consuming and need a pre-step for TATP cleavage to hydrogen peroxide. Moreover, they commonly show significant false-positive results in the presence of some camouflage which limits their field applications. Herein, for the first time, a novel label-free field-applicable spectrofluorimetric nanobiosensor was developed for direct TATP detection using a novel activated-protein protected gold nanocluster (ABSA-AuNCs; QY = 28.3 %) synthesized by a combined protein-assisted-ultrasonication procedure. RESULTS: The ABSA-AuNCs revealed a fluorescence spectrum centered at 330.0 nm which was significantly quenched by TATP (binding constant = 154.06 M-1; ΔG = -12.5 kJ mol-1; E(%) = 88.5 %). This phenomenon was used as a basis for direct TATP quantification, providing a working range of 0.01-40.0 mg L-1 and a detection limit of 6.7 µg L-1 which is the lowest LOD provided for TATP detection up to now. A %RSD of 0.9 % and 1.56 % was obtained for repeatability and inter-day reproducibility, respectively. The selectivity was checked against a variety of camouflages, revealing ultra-selectivity. Several synthetic samples prepared by several camouflages and real samples (clay soil and real water media) were analyzed, revealing quantitative recoveries of TATP. SIGNIFICANCE: During the production of the notorious explosive TATP, it can be discharged into water and soil. This novel method eliminated the false-positive results of traditional methods and is applicable for direct quantitative detection of camouflaged TATP and its residues in real soil and water samples in a highly short response time (2 min). The camouflaged TATP analysis is important for tracking the terrorist attacks in field conditions and analysis of soil and water can provide a first indication of the location of the production site.

Intracellular Gold Nanocluster/Organic Semiconductor Heterostructure for Enhancing Photosynthesis.

Photosynthetic microorganisms, which rely on light-driven electron transfer, store solar energy in self-energy carriers and convert it into bioenergy. Although these microorganisms can operate light-induced charge separation with nearly 100% quantum efficiency, their practical applications are inherently limited by the photosynthetic energy conversion efficiency. Artificial semiconductors can induce an electronic response to photoexcitation, providing additional excited electrons for natural photosynthesis to improve solar conversion efficiency. However, challenges remain in importing exogenous electrons across cell membranes. In this work, we have developed an engineered gold nanocluster/organic semiconductor heterostructure (AuNC@OFTF) to couple the intracellular electron transport chain of living cyanobacteria. AuNC@OFTF exhibits a prolonged excited state lifetime and effective charge separation. The internalized AuNC@OFTF permits its photogenerated electrons to participate in the downstream of photosystem II and construct an oriented electronic highway, which enables a five-fold increase in photocurrent in living cyanobacteria. Moreover, the binding events of AuNC@OFTF established an abiotic-biotic electronic interface at the thylakoid membrane to enhance electron flux and finally furnished nicotinamide adenine dinucleotide phosphate. Thus, AuNC@OFTF can be exploited to spatiotemporally manipulate and enhance the solar conversion of living cyanobacteria in cells, providing an extended nanotechnology for re-engineering photosynthetic pathways.

Adsorption and Distribution of Triplex-hybridizing Bioconjugated Gold Nanoclusters inside Spermatozoa- A Study using Confocal Microscopy and Fluorescence Lifetime Imaging.

The study of the interactions between biofunctionalized gold nanoclusters (Au NCs) and spermatozoa is highly relevant to evaluate the potential of Au NCs as imaging probes and transfection agents in the reproductive biology. In this work, confocal laser scanning microscopy (CLSM) was used to investigate the distribution of Au NCs bioconjugated with peptide (nuclear localisation sequence, NLS) and oligonucleotide (locked nucleic acid, LNA) ligands in bovine spermatozoa. Fluorescence lifetime imaging (FLIM) was employed to detect changes in the NC´s chemical environment. We observed a pronounced regio-selective accumulation of the bioconjugates in spermatozoa with high concentration at the equatorial segment. Furthermore, 3D-CLSM showed successful non-endosomal cellular uptake of the conjugates by intact sperm cells and the distribution of the bioconjugates was found to be influenced by the ligand types. Interestingly, the FLIM data showed differences in lifetime depending on membrane integrity. Furthermore, ligand-dependent changes in lifetime between NC bioconjugates carrying peptide and oligonucleotide ligands were found, probably attributed to specific interactions with sperm cell compartments.

Chiral Amphiphilic Au23 Cluster and Its Specific Recognition to Remote Di-amines.

The atomic precision of metal nanoclusters and variability of surface ligands pave the way for its rational design and functionalization, whereas the property strengthening in multiple ways has been long challenging. Herein, improved amphiphilicity, chirality, thermostability, and strong CPL (circularly polarized luminescence) properties have been accomplished by facile ligand exchange of [Au23(CHT)16]- with HCapt (HCHT and HCapt denote cyclohexanethiol and captopril). In addition, the obtained chiral [Au23(SR)16]- (short for [Au23(CHT)16-x(Capt)x]-) clusters show specific binding affinity to remote-diamines (such as arginine and single/double strand DNA), originating from the hydrogen bonding and Van der Walls interaction among the surface Capt ligands and the di-amine groups.

Gold Nanocluster: A Photoelectric Converter for X-Ray-Activated Chemotherapy.

Despite the promise of activatable chemotherapy, the development of a spatiotemporally controllable strategy for prodrug activation in deep tissues remains challenging. Herein, a proof-of-concept is proposed for a gold nanocluster-based strategy that utilizes X-ray irradiation to trigger the liberation of platinum (Pt)-based prodrug conjugates, thus enabling radiotherapy-directed chemotherapy. Mechanistically, the irradiated activation of prodrugs is achieved through direct photoelectron transfer from the excited-state gold nanoclusters to the Pt(IV) center, resulting in the release of cytotoxic Pt(II) agents. Compared to the traditional combination of chemotherapy and radiotherapy, this radiotherapy-directed chemotherapy strategy offers superior antitumor efficacy and safety benefits through spatiotemporal synergy at the tumor site. Additionally, this strategy elicits robust immunogenic cell death and yields profound outcomes for combined immunotherapy of breast cancer. This versatile strategy is ushering in a new era of radiation-mediated chemistry for controlled drug delivery and the precise regulation of biological processes.

Bioinspired Surface Ligand Engineering Regulates Electron Transfers in Gold Clusterzymes to Enhance the Catalytic Activity for Improving Sensing Performance.

Metal nanoclusters feature a hierarchical structure, facilitating their ability to mimic enzyme-catalyzed reactions. However, the lack of true catalytic centers, compounded by tightly bound surface ligands hindering electron transfers to substrates, underscores the need for universal rational design methodologies to emulate the structure and mechanisms of natural enzymes. Motivated by the electron transfer in active centers with specific chemical structures, by integrating the peroxidase cofactor Fe-TCPP onto the surface of glutathione-stabilized gold nanoclusters (AuSG), we engineered AuSG-Fe-TCPP clusterzymes with a remarkable 39.6-fold enhancement in peroxidase-like activity compared to AuSG. Fe-TCPP not only mimics the active center structure, enhancing affinity to H2O2, but also facilitates the electron transfer process, enabling efficient H2O2 activation. By exemplifying the establishment of a detecting platform for trace H2O2 produced by ultrasonic cleaners, we substantiate that the bioinspired surface-ligand-engineered electron transfer can improve sensing performance with a wider linear range and lower detection limit.

Photosynthetic bacteria-based whole-cell inorganic-biohybrid system for multimodal enhanced tumor radiotherapy.

The whole-cell inorganic-biohybrid systems show special functions and wide potential in biomedical application owing to the exceptional interactions between microbes and inorganic materials. However, the hybrid systems are still in stage of proof of concept. Here, we report a whole-cell inorganic-biohybrid system composed of Spirulina platensis and gold nanoclusters (SP-Au), which can enhance the cancer radiotherapy through multiple pathways, including cascade photocatalysis. Such systems can first produce oxygen under light irradiation, then convert some of the oxygen to superoxide anion (•O2-), and further oxidize the glutathione (GSH) in tumor cells. With the combination of hypoxic regulation, •O2- production, GSH oxidation, and the radiotherapy sensitization of gold nanoclusters, the final radiation is effectively enhanced, which show the best antitumor efficacy than other groups in both 4T1 and A549 tumor models. Moreover, in vivo distribution experiments show that the SP-Au can accumulate in the tumor and be rapidly metabolized through biodegradation, further indicating its application potential as a new multiway enhanced radiotherapy sensitizer.

Concomitant Near-Infrared Photothermy and Photoluminescence of Rod-Shaped Au52(PET)32 and Au66(PET)38 Synthesized Concurrently.

Gold nanoclusters exhibiting concomitant photothermy (PT) and photoluminescence (PL) under near-infrared (NIR) light irradiation are rarely reported, and some fundamental issues remain unresolved for such materials. Herein, we concurrently synthesized two novel rod-shaped Au nanoclusters, Au52(PET)32 and Au66(PET)38 (PET = 2-phenylethanethiolate), and precisely revealed that their kernels were 4 × 4 × 6 and 5 × 4 × 6 face-centered cubic (fcc) structures, respectively, based on the numbers of Au layers in the [100], [010], and [001] directions. Following the structural growth mode from Au52(PET)32 to Au66(PET)38, we predicted six more novel nanoclusters. The concurrent synthesis provides rational comparison of the two nanoclusters on the stability, absorption, emission and photothermy, and reveals the aspect ratio-related properties. An interesting finding is that the two nanoclusters exhibit concomitant PT and PL under 785 nm light irradiation, and the PT and PL are in balance, which was explained by the qualitative evaluation of the radiative and non-radiative rates. The ligand effects on PT and PL were also investigated.

Photofunctional Gold Nanocluster Composites for Bioapplications.

Gold nanoclusters (AuNCs), with customized structures and diverse optical properties, are promising optical materials. Constructing composite systems by the assembly and incorporation of AuNCs can utilize their optical properties to achieve diagnostic and therapeutic applications in the biological field. Therefore, the exploration of the assembly behaviors of AuNCs and the enhancement of their performance has attracted widespread interest. In this review, we introduce multiple interactions and assembly modes that are prevalent in nanocomposites and microcomposites based on AuNCs. Then, the functions of AuNC composites for bioapplications are demonstrated in detail. These composite systems have inherited and enhanced the inherent optical performances of the AuNCs to meet diverse requirements for biological sensing and optical treatments. Finally, we discuss the prospects of AuNC composites and highlight the challenges and opportunities in biomedical applications.

X-Ray-Triggered CO-Release from Gold Nanocluster: All-in-One Nanoplatforms for Cancer Targeted Gas and Radio Synergistic Therapy.

Glycolysis-dominant metabolic pathway in cancer cells can promote their therapeutic resistance against radiotherapy (RT). Carbon monoxide (CO) as a glycolysis inhibitor can enhance the efficiency of RT. Herein, an X-ray responsive CO-releasing nanocomposite (HA@AuNC@CO) based on strong host-guest interactions between the radiosensitizer and CO donor for enhanced RT is developed. The encapsulated gold nanoclusters (CD-AuNCs) can effectively generate cytotoxic reactive oxygen species (ROS) under X-ray radiation, which not only directly inactivate cancer cells but also induce in situ CO gas generation from adamantane modified metal carbonyl (Ada-CO) for glycolysis inhibition. Both in vitro and in vivo results demonstrate that HA@AuNC@CO exhibits active targeting toward CD44 overexpressed cancer cells, along with excellent inhibition of glycolysis and efficient RT against cancer. This study offers a new strategy for the combination of gas therapy and RT in tumor treatment.

Noncovalent Interaction Guided Precise Photoluminescence Regulation of Gold Nanoclusters in Both Isolate Species and Aggregate States.

Designing luminophores bright in both isolate species and aggregate states is of great importance in many emerging cutting-edge applications. However, the conventional luminophores either emit in isolate species but quench in aggregate state or emit in aggregate state but darken in isolate species. Here we demonstrate that the precise regulation of noncovalent interactions can realize luminophores bright in both isolate species and aggregate states. It is firstly discovered that the intra-cluster interaction enhances the emission of atomically precise Au25(pMBA)18 (pMBA=4-mercaptobenzoic acid), a nanoscale luminophore, while the inter-cluster interaction quenches the emission. The emission enhancing strategies are then well-designed by both introducing exogenous substances to block inter-cluster interaction and surface manipulation of Au25(pMBA)18 at the molecular level to enhance intra-cluster interaction, opening new possibilities to controllably enhance the luminophore's photoluminescence in both isolate species and aggregate states in different phases including aqueous solution, solid state and organic solvents.

Dual-emission ciprofloxacin-gold nanoclusters enable ratiometric sensing of Cu2+, Al3+, and Hg2.

An innovative triple optical sensor is presented that utilizes gold nanoclusters (GNCs) stabilized with ciprofloxacin (CIP) and bovine serum albumin (BSA). The sensor is designed to identify three critical metal ions, namely Cu2+, Al3+, and Hg2+. Under 360 nm excitation, the synthesized CIP-BSA-GNCs demonstrate dual fluorescence emission with peaks at 448 nm (blue) and 612 nm (red). The red emission is associated with the interior of the CIP-BSA-GNCs, whereas the blue emission results from the surface-bound CIP molecules. The sensitive and selective fluorescent nanosensor CIP-BSA-GNCs were employed to detect Cu2+, Al3+, and Hg2+ ions. Cu2+ effectively quenched the fluorescence intensity of the CIP-BSA-GNCs at both peaks via the internal charge transfer mechanism (ICT). Cu2+ could be detected within the concentration range 1.13 × 10-3 to 0.05 µM, with a detection limit of 0.34 nM. Al3+ increased the intensity of CIP fluorescence at 448 nm via the chelation-induced fluorescence enhancement mechanism. The fluorescence intensity of the core CIP-BSA-GNCs at 612 nm was utilized as a reference signal. Thus, the ratiometric detection of Al3+ succeeded with a limit of detection of 0.21 nM within the dynamic range 0.69 × 10-3 to 0.07 µM. Hg2+ effectively quenched the fluorescence intensity of the CIP-BSA-GNCs at 612 nm via the metallophilic interaction mechanism. The fluorescence intensity of CIP molecules at 448 nm was utilized as a reference signal. This allowed for the ratiometric detection of Hg2+ with a detection limit of 0.7 nM within the concentration range 2.3 × 10-3 to 0.1 µM.

Two-Orders-of-Magnitude Enhancement of Photoinitiation Activity via a Simple Surface Engineering of Metal Nanoclusters.

Development of high-performance photoinitiator is the key to enhance the printing speed, structure resolution and product quality in 3D laser printing. Here, to improve the printing efficiency of 3D laser nanoprinting, we investigate the underlying photochemistry of gold and silver nanocluster initiators under multiphoton laser excitation. Experimental results and DFT calculations reveal the high cleavage probability of the surface S-C bonds in gold and silver nanoclusters which generate multiple radicals. Based on this understanding, we design several alkyl-thiolated gold nanoclusters and achieve a more than two-orders-of-magnitude enhancement of photoinitiation activity, as well as a significant improvement in printing resolution and fabrication window. Overall, this work for the first time unveils the detailed radical formation pathways of gold and silver nanoclusters under multiphoton activation and substantially improves their photoinitiation sensitivity via surface engineering, which pushes the limit of the printing efficiency of 3D laser lithography.

Development of gold nanocluster complex for the detection of tumor necrosis factor-alpha based on immunoassay.

Tumor necrosis factor-alpha, TNF-α, a cytokine recognized as a key regulator of inflammatory responses, is primarily produced by activated monocytes and macrophages. Measuring TNF-α levels serves as a valuable indicator for tracking several diseases and pathological states. Gold nanotechnology has been identified as a highly effective catalyst with unique properties for measuring inflammatory cytokines. This study aimed to synthesize gold nanoclusters (AuNCs) and the AuNCs-streptavidin system, along with their characterizations and spherical morphology. The detection of TNF-α antigen with AuNCs was determined, and a new immunoassay-based AuNCs analytical platform was studied. In this study, it was demonstrated that the synthesized AuNCs and AuNCs-streptavidin showed a bright-yellow appearance with absorption peaks at A600 and A610 nm, respectively. The approximately spherical shape was observed by TEM analysis. The AuNCs demonstrated a sensitivity limit for the detection of the TNF-α antigen, with a linear dose-dependent detection range of less than 1.25 ng/mL. The products of the band sizes and band intensities were proportional to the amount of TNF-α in the range of ∼80 kDa, ∼55 kDa, and âˆ¼ 25 kDa in western blot analysis. The TNF-α in cell lysate was successfully detected using an immunoassay after the activation of RAW264.7 cells with lipopolysaccharide (LPS). This assay may serve as a viable alternative for TNF-α detection with high speed, sensitivity, and qualities, ensuring its broad applications.

Dual Catalysis of Gold Nanoclusters: Photocatalytic Cross-Dehydrogenative Coupling by Cooperation of Superatomic Core and Molecularly Modified Staples.

Thiolate-protected gold nanoclusters (AuNCs) have attracted significant attention as nano-catalysts, revealing a superatomic core and gold-thiolate staples as distinct structural units. Here, we demonstrate the unprecedented dual catalytic activity of thiolate-protected [Au25 (SR)18 ]- nanoclusters, involving both photosensitized 1 O2 generation by the Au13 superatomic core and catalytic carbon-carbon bond formation facilitated by Au2 (SR)3 staples. This synergistic combination of two different catalytic units enables efficient cross-dehydrogenative coupling of terminal alkynes and tertiary aliphatic amines to afford propargylamines in high yields of up to 93 %. Mixed-ligand AuNCs bearing both thiolate and alkynyl ligands revealed the intermediacy of the alkynyl-exchanged AuNCs toward both photosensitization and C-C bond-forming catalytic cycles. Density functional theory calculations also supported the intermediacy of the alkynyl-exchanged AuNCs. Thus, the use of ligand-protected metal nanoclusters has enabled the development of an exceptional multifunctional catalyst, wherein distinct nanocluster components facilitate cooperative photo- and chemo-catalysis.

The first solid-state route to luminescent Au(I)-glutathionate and its pH-controlled transformation into ultrasmall oligomeric Au10-12(SG)10-12 nanoclusters for application in cancer radiotheraphy.

There is still a need for synthetic approaches that are much faster, easier to scale up, more robust and efficient for generating gold(I)-thiolates that can be easily converted into gold-thiolate nanoclusters. Mechanochemical methods can offer significantly reduced reaction times, increased yields and straightforward recovery of the product, compared to the solution-based reactions. For the first time, a new simple, rapid and efficient mechanochemical redox method in a ball-mill was developed to produce the highly luminescent, pH-responsive Au(I)-glutathionate, [Au(SG)]n. The efficient productivity of the mechanochemical redox reaction afforded orange luminescent [Au(SG)]n in isolable amounts (mg scale), usually not achieved by more conventional methods in solution. Then, ultrasmall oligomeric Au10-12(SG)10-12 nanoclusters were prepared by pH-triggered dissociation of [Au(SG)]n. The pH-stimulated dissociation of the Au(I)-glutathionate complex provides a time-efficient synthesis of oligomeric Au10-12(SG)10-12 nanoclusters, it avoids high-temperature heating or the addition of harmful reducing agent (e.g., carbon monoxide). Therefore, we present herein a new and eco-friendly methodology to access oligomeric glutathione-based gold nanoclusters, already finding applications in biomedical field as efficient radiosensitizers in cancer radiotherapy.

Triple Ligand Engineered Gold Nanoclusters with Enhanced Fluorescence and Device Compatibility for Efficient Electroluminescence Light-Emitting Diodes.

Gold nanoclusters (Au NCs) are potential emitters for electroluminescent light-emitting diodes (EL-LEDs) but restricted by the limited photoluminescence quantum yield (PLQY) and poor device compatibility. Herein, triple ligand engineered Au NCs enable the fabrication of Au NC-based LEDs with improved EL efficiency. Rigidified triple ligand shells greatly reduce the nonradiative transition and thus increase the PLQY of Au NCs from 2.1 to 73.4%. Most importantly, this strategy significantly improves the compatibility between Au NCs and charge transport materials in EL-LED fabrication. As a result, the EL-LEDs reach a maximum brightness of 1104 cd/m2 and an external quantum efficiency of 5.1%, which is the highest recorded for any reported Au NC-based EL-LEDs.