Transition-metal-based nanozymes for biosensing and catalytic tumor therapy.

Nanozymes, as an emerging class of enzyme mimics, have attracted much attention due to their adjustable catalytic activity, low cost, easy modification, and good stability. Researchers have made great efforts in developing and applying high-performance nanozymes. Recently, transition-metal-based nanozymes have been designed and widely developed because they possess unique photoelectric properties and high enzyme-like catalytic activities. To highlight these achievements and help researchers to understand the research status of transition-metal-based nanozymes, the development of transition-metal-based nanozymes from material characteristics to biological applications is summarized. Herein, we focus on introducing six categories of transition-metal-based nanozymes and highlight their progress in biomarker sensing and catalytic therapy for tumors. We hope that this review can guide the further development of transition-metal-based nanozymes and promote their practical applications in cancer diagnosis and treatment.

Bimetal-organic framework/GOx-based hydrogel dressings with antibacterial and inflammatory modulation for wound healing.

Antibiotic resistance of bacteria and persistent inflammation are critical challenges in treating bacteria infected wounds. Thus, it is urgent to develop versatile wound dressings that possess high-efficiency antibacterial performance and inflammation regulation. Herein, we have successfully constructed a hydrogel wound dressing consisting of the bimetallic metal-organic framework (MOF) loaded with glucose oxidase (GOx), termed as MOF(Fe-Cu)/GOx-polyacrylamide (PAM) gel. Hydrogel dressings can provide an efficient cascade-catalyzed system to accelerate wound healing via synergistic antibacterial and inflammatory modulation. Importantly, the catalytic property of the bimetallic MOF(Fe-Cu) is about five times that of the monometallic MOF(Fe). Based on such a cascade-catalyzed system, the abundant gluconic acid and H2O2 can be continuously produced by decomposing glucose via GOx. Such gluconic acid can notably improve the peroxidase performance of MOF(Fe-Cu), which can further efficiently decompose H2O2 to achieve the antibacterial. Meanwhile, MOF (Fe Cu)/GOx PAM gel can induce macrophages to change into an M2 phenotype, which can accelerate the transformation of the wound microenvironment to a remodeling state and then accelerate angiogenesis and neurogenesis. This work provides multifunctional bioactive materials for accelerating wound healing and will have great potential in clinical applications. STATEMENT OF SIGNIFICANCE: Antibiotic resistance and persistent inflammation are still the critical reasons for the slow healing of bacteria infected wounds. Herein, we prepared a hydrogel wound dressing composed of bimetallic metal organic framework (MOF) loaded with glucose oxidase (GOx). The catalytic activity of the bimetallic MOF(Fe-Cu) is significantly enhanced due to doping of copper, which makes it possess outstanding antibacterial ability based on cascade catalysis. Such dressing can promote the remodeling of inflammatory immunity by regulating macrophage polarization to suppress over-reactive inflammation, further accelerating the healing of bacteria-infected wounds. This study provides an innovative and effective way to accelerate the healing of bacteria infected wound by combining bacteria killing and inflammation modulation.

Aggregation-induced emission (AIE)-Based nanocomposites for intracellular biological process monitoring and photodynamic therapy.

As a non-invasive visualization technique, photoluminescence imaging (PLI) has found its huge value in many biological applications associated with intracellular process monitoring and early and accurate diagnosis of diseases. PLI can also be combined with therapeutics to build imaging-guided theragnostic platforms for achieving early and precise treatment of diseases. Photodynamic therapy (PDT) as a quintessential phototheranostics technology has gained great benefits from the combination with PLI. Recently, aggregation-induced emission (AIE)-active materials have emerged as one of the most promising bioimaging and phototheranostic agents. Most of AIEgens, however, need to be chemically engineered to form versatile nanocomposites with improved their photophysical property, photochemical activity, biocompatibility, etc. In this review, we focus on three categories of AIE-active nanocomposites and highlight their application progresses in the intracellular biological process monitoring and PLI-guided PDT. We hope this review can guide further development of AIE-active nanocomposites and promote their practical applications for monitoring intracellular biological processes and imaging-guided PDT.

Using bimetallic Au/Cu nanoplatelets for construction of facile and label-free inner filter effect-based photoluminescence sensing platform for sarcosine detection.

Herein, we report a facile and label-free method for sensitive and specific determination of prostate cancer biomarker sarcosine via using photoluminescent bimetallic Au/Cu nanoplatelets (AuCu NPs) to construct an inner filter effect (IFE)-based photoluminescence (PL) sensing platform. The AuCu NPs were formed by the cysteine-induced co-reduction reaction, which displayed bright PL with an emission peak at 560 nm. Meanwhile, the Cu(I) doping caused a maximum 25-fold enhancement of quantum yield (QY), compared with the native Au(I) complexes, i.e., from 0.85 to 21.5%. By integrating the AuCu NPs with p-phenylenediamine (PPD) oxidation reaction, an IFE-based sensor for sarcosine detection was constructed. In this method, sarcosine is oxidized under the catalysis of sarcosine oxidase (SOx) to yield H2O2. The latter further oxidizes PPD to form 2,5-diamino-N,N'-bis(p-aminophenyl)-l,4-benzoquinone di-imine (PPDox) in the presence of horseradish peroxidase (HRP). The UV-vis absorption spectrum of the PPDox can overlap well with the excitation and emission spectra of the AuCu NPs, resulting in the efficient quenching of the AuCu NPs via the IFE effect. Therefore, this IFE-based AuCu NPs/SOx/PPD/HRP sensing platform can be used for highly sensitive and specific sensing of sarcosine. The sensing platform showed two linear regions of the PL intensity of the AuCu NPs versus the concentration of sarcosine in the range of 0.5-5 µM and 5-100 µM with a detection limit (LOD) of 0.12 µM (S/N = 3). Furthermore, this IFE-based sensing platform could be developed into a paper-based biosensor for simple, instrument-free, and visual detection of sarcosine.

Strongly phosphorescent and water-soluble gold(I)-silver(I)-cysteine nanoplatelets via versatile small biomolecule cysteine-assisted synthesis for intracellular hypochlorite detection.

In biological systems, abnormal levels of hypochlorite (ClO-) could result in cell dysfunctions. Herein, we report a facile, one-step and green approach based on the versatile small biomolecule cysteine both serving as reducing agent and ligand for synthesizing the strongly photoluminencent and water-soluble Au(I)-Ag(I)-cysteine complexes nanoplatelets (Au(I)-Ag(I)-Cys nanoplatelets) for intracellular hypochlorite detection. Multiple spectroscopic and microscopical tools have been used to characterize the resultant Au(I)-Ag(I)-Cys nanoplatelets. It was found that with the cysteine-assisted synthesis approach, the Ag(I) doping to the Au(I) complexes could form the supramolecular organometallic nanoplatelets. Inside, the Au(I)-Ag(I) metallophilic interactions showing an Au to Ag charge transfer property were formed, thereby enhancing the photoluminescence (PL) intensity via the charge transfer from the bioligand's S to the metal-metal center. The quantum yield (QY) was measured to show a maximum 16-fold enhancement (i.e., from 0.85 to 13.8%). Interestingly, in the presence of ClO-, the metal-thiolate ligand structure of the as-synthesized Au(I)-Ag(I)-Cys nanoplatelets could be oxidatively damaged, causing the PL quenching, thereby producing the effect of biorecognition towards ClO- anions. The ClO--induced PL quenching produced two linear regions at ClO- concentrations of 0.01-5.0 µM and 5.0-1000 µM with a limit of detection (LOD) of 8.0 nM (S/N = 3). The ClO--induced PL quenching was specific over the other typical reactive oxygen species (ROS) and the potential interfering substances in biological samples. In addition, the Au(I)-Ag(I)-Cys nanoplatelets had good biocompatibility. Thus, they could be further developed as a biosensor for detecting endogenous ClO- anions in living cells.

An Aggregation-Induced Phosphorescence-Active "Turn-Off" Nanosensor Based on Ferric-Specific Quenching of Luminescent and Water-Soluble Au(I)-Cysteine Nanocomplexes.

Recently, aggregation-induced emission (AIE) has attracted extensive attention. Herein we report an AIP-active "turn-off" nanosensor based on ferric-specific quenching of photoluminescence (PL) of water-soluble Au(I)-cysteine nanocomplexes. The Au(I)-cysteine nanocomplexes were AIP-active, showing a PL peak at 590 nm. Transmission electron microscopy (TEM) characterization revealed that they show the characteristic morphology of nanofibers. High-speed centrifugation characterization and zeta potential measurement indicated that they are highly water-soluble. Interestingly, their PL could be quenched specifically by ferric ions over the other common 18 metal ions. Further TEM characterizations revealed that the quenching process was accompanied by the ferric-specific dissociation of Au(I)-cysteine nanofibers. These observations have enabled the development of a water-soluble AIP-active "turn-off" nanosensor based on Au(I) nanocomplexes for selective and sensitive detection of ferric ions. This study indicates that specific quenching and disassociation of AIP-active nanocomplexes might be a promising route for development of novel luminescent nanosensors.

Rational Design of "Three-in-One" Ratiometric Nanoprobes: Protein-Caged Dityrosine, CdS Quantum Dots, and Gold Nanoclusters.

Recently, multiplexed ratiometric fluorescence sensors for detecting several analytes have received much interest because of their multifunctionality. Here, we fabricate a novel trinity fluorescent nanoprobe in which one small-molecule fluorophore, blue-emissive dityrosine (diTyr) residues, and two nanomaterial fluorophores, green-emissive CdS quantum dots (CdSQDs) and red-emissive gold nanoclusters (AuNCs), are cocaged in a bovine serum albumin (BSA) molecule. The large differences of Stokes shifts among diTyr residues, CdSQDs, and AuNCs ensure their emission at a single excitation wavelength. The nanoprobes can be facilely integrated using two-step synthetic reactions. DiTyr residues and AuNCs are formed and bound to the protein cage through the redox reaction between Au3+ and tyrosine residues of BSA, and the CdSQDs are followed to be conjugated to the modified BSA cage-templated CdS combination reaction. With established benign biocompatibility, the nanoprobes can ratiometrically detect intracellular glutathione by significantly enhancing the green emission of the conjugated CdSQDs. Likewise, the ratiometric sensing of solution alkalinity and tris(2-carboxyethyl)phosphine can be achieved using blue-emitted diTyr residues and red-emitted AuNCs as the responsive units, respectively, and the corresponding other two fluorophores as the reference signals. This study addresses a concept of trinity fluorescence ratiometric sensing system with multiple targets and optional references, which should be a promising pathway to meet the challenges from complexing biochemical environments and multivariate analysis.

Self-Assembly of Metal Nanoclusters for Aggregation-Induced Emission.

Aggregation-induced emission (AIE) is an intriguing strategy to enhance the luminescence of metal nanoclusters (NCs). However, the morphologies of aggregated NCs are often irregular and inhomogeneous, leading to instability and poor color purity of the aggregations, which greatly limit their further potential in optical applications. Inspired by self-assembly techniques, manipulating metal NCs into well-defined architectures has achieved success. The self-assembled metal NCs often exhibit enhancing emission stability and intensity compared to the individually or randomly aggregated ones. Meanwhile, the emission color of metal NCs becomes tunable. In this review, we summarize the synthetic strategies involved in self-assembly of metal NCs for the first time. For each synthetic strategy, we describe the self-assembly mechanisms involved and the dependence of optical properties on the self-assembly. Finally, we outline the current challenges to and perspectives on the development of this area.

Chemical etching of pH-sensitive aggregation-induced emission-active gold nanoclusters for ultra-sensitive detection of cysteine.

This study reports the utilization of thiol-induced chemical etching of aggregation-induced emission (AIE)-active Au nanoclusters (NCs) for the facile, sensitive, and selective detection of cysteine. The AIE-active Au NCs were formed in an acidic solution containing excess Au(i)-thiolate complexes. At an acidic pH (2.0), the emission of these Au NCs was enhanced by cysteine at a concentratioin below 1 mM. However, the emission was quenched by cysteine at a high concentration, e.g., 500 mM, via the thiol-induced etching of gold, although the process occurred very slowly. Interestingly, in the absence of cysteine, increasing the solution pH enhanced the emission, while the presence of cysteine remarkably accelerated the etching-induced quenching process. The complete quenching of the emission by excess cysteine at pH 2.0 and the enhancement of the emission by the increasing pH in the absence of cysteine indicated that aurophilicity might not be involved in the AIE of the Au NCs prepared using glutathione (GSH) both as the reducing and protecting reagent. On the other hand, the etching process involved the penetration of cysteine molecules through the Au(i)-thiolate complexes, which could assemble or disassemble around the embedded Au NCs in response to the solution pH to get access to the innermost Au(0) cores. Therefore, a facile, sensitive, and selective method for the detection of cysteine was established. This method exhibited an extremely wide linear range as wide as nine orders of magnitude above the cysteine concentration, including two linear regions of the relative emission intensity of the Au NCs versus the logarithm of cysteine concentration, from 10 pM to 150 µM (correlation coefficient, 0.99851) and from 150 µM to 2 mM (correlation coefficient, 0.99866). An ultra-low limit of detection of 6.3 pM (S/N = 3) was also achieved. The developed method showed superior selectivity for cysteine relative to the 19 other natural amino acids and GSH. The method was applied for the analysis of human serum samples spiked with cysteine with satisfactory results. This study demonstrates the potential of the thiol-induced chemical etching approach as a powerful tool for studying luminescent metal NCs.