Light-activated Nanocatalyst for Precise In-situ Antimicrobial Synthesis via Photoredox-Catalytic Click Reaction.

The excessive and prolonged use of antibiotics contributes to the emergence of drug-resistant S. aureus strains and potential dysbacteriosis-related diseases, necessitating the exploration of alternative therapeutic approaches. Herein, we present a light-activated nanocatalyst for synthesizing in-situ antimicrobials through photoredox-catalytic click reaction, achieving precise, site-directed elimination of S. aureus skin infections. Methylene blue (MB), a commercially available photosensitizer, was encapsulated within the CuII-based metal-organic framework, MOF-199, and further enveloped with Pluronic F-127 to create the light-responsive nanocatalyst MB@PMOF. Upon exposure to red light, MB participates in a photoredox-catalytic cycle, driven by the 1,3,5-benzenetricarboxylic carboxylate salts (BTC-) ligand presented in the structure of MOF-199. This light-activated MB then catalyzes the reduction of CuII to CuI through a single-electron transfer (SET) process, efficiently initiating the click reaction to form active antimicrobial agents under physiological conditions. Both in vitro and in vivo results demonstrated the effectiveness of MB@PMOF-catalyzed drug synthesis in inhibiting S. aureus, including their methicillin-resistant strains, thereby accelerating skin healing in severe bacterial infections. This study introduces a novel design paradigm for controlled, on-site drug synthesis, offering a promising alternative to realize precise treatment of bacterial infections without undesirable side effects.

pH Switchable Nanozyme Platform for Healing Skin Tumor Wound Infected with Drug-Resistant Bacteria.

Nanozymes capable of generating reactive oxygen species have recently emerged as promising treatments for wounds infected with drug-resistant bacteria, possessing a reduced possibility of inducing resistance. However, the therapeutic effect is limited by a shortage of endogenous oxy-substrates and undesirable off-target biotoxicity. Herein, a ferrocenyl coordination polymer (FeCP) nanozyme, featuring pH switchable peroxidase (POD)- and catalase (CAT)-like activity is incorporated with indocyanine green (ICG) and calcium peroxide (CaO2 ) to fabricate an H2 O2 /O2 self-supplying system (FeCP/ICG@CaO2 ) for precise treatment of bacterial infections. At the wound site, CaO2 reacts with water to generate H2 O2 and O2 . Acting as a POD mimic under an acidic bacterial microenvironment, FeCP catalyzes H2 O2 into hydroxyl radicals to prevent infection. However, FeCP switches to CAT-like activity in neutral tissue, decomposing H2 O2 into H2 O and O2 to prevent oxidative damage and facilitate wound healing. Additionally, FeCP/ICG@CaO2 shows photothermal therapy capability, as ICG can emit heat under near-infrared laser irradiation. This heat assists FeCP in fully exerting its enzyme-like activity. Thus, this system achieves an antibacterial efficiency of 99.8% in vitro for drug-resistant bacteria, and effectively overcomes the main limitations of nanozyme-based treatment assays, resulting in satisfactory therapeutic effects in repairing normal and special skin tumor wounds infected with drug-resistant bacteria.

Detection and discrimination of pathogenic bacteria with nanomaterials-based optical biosensors: A review.

Pathogenic bacteria can pose a great threat to food safety and human health. It is therefore imperative to develop a rapid, portable, and sensitive determination and discrimination method for pathogenic bacteria. Over the past few years, various nanomaterials (NMs) have been employed as desirable nanoprobes because they possess extraordinary properties that can be used for optical signal enabled detection and identification of bacteria. By means of modification, NMs can, depending on different mechanisms, sense targets directly or indirectly, which then provides an essential support for the detection and differentiation of pathogenic bacteria. In this review, recent application of NMs-based optical biosensors for food safety bacterial detection and discrimination is performed, mainly in but not limited to noble metal NMs, fluorescent NMs, and point-of-care testing (POCT). This review also focuses on future trends in bacterial detection and discrimination, and machine learning in performing intelligent rapid detection and multiple accurate identification of bacteria.

An ion-coordination hydrogel based sensor array for point-of-care identification and removal of multiple tetracyclines.

Misuse and overuse of tetracycline antibiotics (TCs) brings serious issues to ecological environment, food safety and human health. It is urgent to develop unique platform for high efficient identification and removal of TCs. In the present investigation, an effective and simple fluorescence sensor array was constructed based on the interaction between metal ions (Eu3+ and Al3+) and antibiotics. Benefiting from the different affinities between the ions and TCs, the sensor array can identify TCs from other antibiotics, which also can further differentiating four kinds of TCs (OTC, CTC, TC and DOX) from each other via linear discriminant analysis (LDA) technique. Meanwhile, the sensor array performed well in quantitative analysis of single TC antibiotic and differentiation of TCs mixtures. More interestingly, Eu3+ and Al3+-doped sodium alginate/polyvinyl alcohol hydrogel beads (SA/Eu/PVA and SA/Al/PVA) were further constructed, which can not only identify the TCs but simultaneously remove the antibiotics with high efficiency. The investigation provided an instructive way for rapid detection and environment protection.

Long-Lasting Chemiluminescence-Based POCT for Portable and Visual Pathogenic Detection and In Situ Inactivation.

Bacterial infections seriously threaten human health and also bring huge financial burden. It is critical to construct multifunctional platforms for effectively inactivating bacteria right after point-of-care testing (POCT). Chemiluminescence (CL) bioassays are considered as powerful candidates for POCT as they are free from using an excitation light source, while the flash-type emission limits their further application. Herein, a CL system with long, persistent, and intensive intensity was constructed based on the peroxidase-like property of 4-mercaptophenylboronic acid (MPBA)-functionalized CuSe nanoprobes (CuSeNPs@MPBA), which improved the detection accuracy and sensitivity. By further integrating a smartphone as an analyzer, quantitative POCT of bacteria was realized with high sensitivity. The limit of detection was as low as 1.25 and 1.01 cfu mL-1 for Staphylococcus aureus and Escherichia coli detection, respectively. Specifically, bacteria can be eliminated with high efficiency due to excellent photothermal property of CuSeNPs@MPBA. The developed multifunctional platform also has advantages of simple operation with low cost, suggesting its high potential for use in food safety, environment monitoring, and clinical applications.

Metabolism-Triggered Colorimetric Sensor Array for Fingerprinting and Antibiotic Susceptibility Testing of Bacteria.

The rapid identification and antibiotic susceptibility testing (AST) of bacteria would help us to accurately identify the infectious sources as well as guide the use of antibiotics, which are crucial for improving the survival rate and antimicrobial resistance. Herein, a colorimetric sensor array for bacteria fingerprinting was constructed with d-amino acid (d-AA)-modified gold nanoparticles (AuNPs) as probes (Au/d-AA). Bacteria can metabolize the d-AA, triggering the aggregation of AuNPs. Making use of different metabolic capabilities of bacteria toward different d-AA, eight kinds of bacteria including antibiotic-resistant bacteria and strains of the same bacterial species are successfully differentiated via learning the response patterns. Meanwhile, the sensor array also performs well in quantitative analysis of single bacterium and differentiation of bacteria mixtures. More interestingly, a rapid colorimetric AST approach has been developed based on the Au/d-AA nanoprobes by monitoring the d-AA metabolic activity of bacteria toward various antibiotic treatments. In this regard, the outlined work here would promote clinical practicability and facilitate antibiotic stewardship.

A multifunctional colorimetric sensor array for bacterial identification and real-time bacterial elimination to prevent bacterial contamination.

Effective identification and real-time inactivation of pathogenic microorganisms is of great importance for preventing their infection and spread in public health, especially considering the huge threat of coronavirus disease 2019 (COVID-19). Herein, a novel multifunctional colorimetric sensor array with 3,3',5,5'-tetramethylbenzidine (TMB) as a single probe has been constructed. TMB can be efficiently oxidized to generate oxidized TMB (oxTMB) by HAuCl4, which displays four characteristic absorption peaks. The presence of different bacteria could inhibit the oxidation reaction and cause diverse changes in the intensity of the four characteristic peaks. Based on linear discriminant analysis (LDA), not only are nine kinds of pathogenic bacteria successfully identified, but also drug-resistant strains are distinguished from sensitive ones. Interestingly, HAuCl4 can be employed as a germicidal agent to inactivate bacteria during the identification and avoid accessional bacterial contaminations. The developed strategy provides a new and simple avenue for bacterial identification and elimination to effectively protect the public from bacterial contamination.

A smartphone integrated ratiometric fluorescent sensor for point-of-care testing of fluoride ions.

In view of the high toxicity and widespread availability, it is of great importance to develop accurate, sensitive, and convenient assays for fluoride ion (F-) detection. Herein, a ratiometric fluorescent system is established for point-of-care testing (POCT) of F- with a smartphone as analyzer. The sensing system of calcein-QDs-Eu3+ contains two fluorescent probes of calcein (green emission) and ZnCdSe/ZnS QDs (red emission). The sensing system only presents red emission in that the calcein emission is quenched due to the combination between calcein and Eu3+. When F- is introduced, the fluorescence of calcein is recovered due to the stronger interaction between F- and Eu3+, which changes the emission from red to green. The ratiometric strategy offers an obvious fluorescence color change of the system, which eliminates interference and improves the detection accuracy. Specifically, the sensing system has excellent selectivity in that Eu3+ is more inclined to bind with F- rather than other anions. The developed assay was further used to prepare a test paper and hydrogel for POCT. To further improve the detection sensitivity and realize quantitative analysis, a smartphone installed with a color scan app is integrated as signal reader and analyzer, which is used for POCT of F- in real samples, showing great application potential in environmental protection and food safety evaluation.

Single Probe-Based Chemical-Tongue Sensor Array for Multiple Bacterial Identification and Photothermal Sterilization in Real Time.

Simple and efficient identification of multiple bacteria and sterilization in real time is of considerable significance for clinical diagnostics and quality control in food. Herein, a novel chemical-tongue sensor array with 3,3',5,5'-tetramethylbenzidine (TMB) as a single probe was developed for bacterial identification and photothermal elimination. The synthesized bimetallic palladium/platinum nanoparticles (Pd/PtNPs) present excellent catalytic capability that can catalyze TMB into oxidized TMB (oxTMB) with four feature absorption peaks. Bacteria have different ability on inhibiting the reaction between TMB and Pd/PtNPs. With the absorbance intensity of oxTMB at the four feature peaks as readout, nine kinds of bacteria including two drug-resistant bacteria can be successfully distinguished via linear discriminant analysis. Remarkably, oxTMB exhibits excellent photothermal properties and can effectively kill bacteria in real time under near-infrared laser irradiation. The strategy of selecting TMB as a single probe simplifies the experimental operation and reduces the time cost. Furthermore, the developed sensing system was used to promote the wound healing process of MRSA-infected mice in vivo. The investigation provides a promising simple and efficient strategy for bacterial identification and sterilization with a universal platform, which has great potential application in clinical diagnosis and therapy.

Bacteria-Triggered Multifunctional Hydrogel for Localized Chemodynamic and Low-Temperature Photothermal Sterilization.

Pathogenic infections seriously threaten public health and have been considered as one of the most critical challenges in clinical therapy. Construction of a safe and efficient photothermal antibacterial platform is a promising strategy for treatment of bacterial infections. Considering that high temperature does harm to the normal tissues and cells, herein, a bacteria-triggered multifunctional hydrogel is constructed for low-temperature photothermal sterilization with high efficiency by integrating localized chemodynamic therapy (L-CDT). The hydrogel is constructed by incorporating copper sulfide nanoparticles (CuSNPs ) with photothermal profile into the network of hyaluronic acid (HA) and Fe3+ -EDTA complexes, named as CHFH (CuSNPs -HA-Fe3+ -EDTA hydrogel). Bacteria can be accumulated on the surface of CHFH, which secretes hyaluronidase to decompose the HA and release Fe3+ . The Fe3+ is reduced into Fe2+ in microenvironment of bacteria to trigger Fenton reaction. The generated hydroxyl radicals result in sterilization based on L-CDT within short range. By integrating with photothermal property of CuSNPs , low-temperature photothermal therapy (LT-PTT) for sterilization is realized, which improves the antibacterial efficiency while minimizes damage to normal tissues. The CHFH is further used to prepare Band aid which effectively promotes the Staphylococcus aureus-infected wound healing process in vivo, confirming the great potential for clinical application.

Ratiometric fluorescence nanoplatform integrated with smartphone as readout device for sensing trace water.

In our investigation, a smartphone-integrated ratiometric fluorescent sensing system with lanthanide-based infinite coordination polymers (Ce-GMP-DPA@Tb-DPA) as signal probe has been successfully constructed for sensitive and portable detection of water in organic solvents. The Ce-GMP-DPA presents blue luminescence which is suppressed once the Tb-DPA is integrated to form the complex of Ce-GMP-DPA@Tb-DPA. Due to the energy transfer from Ce to Tb, the as-formed Ce-GMP-DPA@Tb-DPA exhibits green fluorescence of Tb-DPA. The presence of water can decompose the Tb-DPA, which blocks energy transfer from Ce to Tb, resulting in the decrease of green emission of Tb-DPA and the recovery of blue emission of Ce-GMP-DPA. Therefore, a ratiometric fluorescence assay is established for quantitative water detection within a wide linear range from 0.2 to 90.0% in ethanol. The limit of detection (LOD) reaches as low as 0.16% in ethanol, 0.62% in THF, and 0.0076% in acetonitrile, respectively. Furthermore, a smartphone installed with Color Picker APP as signal reader and analyzer is designed to integrate with the detection assay. With white spirit as real sample, water can be on-site detected with high accuracy (RSD < 2.81%). The developed platform presents great potential for portable water detection in practical application with merits of low cost, easy carry, and simple operation.

Universal Nanoplatform for Ultrasensitive Ratiometric Fluorescence Detection and Highly Efficient Photothermal Inactivation of Pathogenic Bacteria.

Pathogenic bacterial contamination in diverse environments seriously threatens human health. One of the most valuable approaches is to effectively combine sensitive detection with efficient sterilization to achieve source control of pathogens. Here, we constructed a nanoplatform of Bi2S3@MnO2@Van with targeting, photothermal, and oxidase properties for the detection and on-demand inactivation of bacteria. The Bi2S3@MnO2@Van nanorods (NRs) can be trapped on the surface of Gram-positive bacteria such as Staphylococcus aureus, forming a complex of Bi2S3@MnO2@Van/S. aureus. After being centrifuged, the suspension of Bi2S3@MnO2@Van NRs can catalyze the non-fluorescent Amplex Red (AR) into a fluorescent substrate and fluorescent Scopoletin (SC) into a non-fluorescent substrate. Thus, a ratiometric fluorescent sensor was constructed for the sensitive detection of bacteria with the fluorescent intensity ratio (SC/AR) as a readout, which improves anti-interference capability and can be used in real sample detection. The detection limit reaches as low as 6.0 CFU/mL. Meanwhile, the sediment contains Bi2S3@MnO2@Van/S. aureus where the bacteria can be effectively inactivated, thanks to the excellent photothermal property of Bi2S3@MnO2@Van NRs under near-infrared irradiation. The antibacterial efficiency reaches as high as 99.1%. The investigation provides an effective way for sensitive detection and highly efficient killing of pathogenic bacteria with a universal platform.

A smartphone-integrated ratiometric fluorescence sensing platform for visual and quantitative point-of-care testing of tetracycline.

A smartphone-integrated ratiometric fluorescent sensing system (DPA-Ce-GMP-Eu) for visual and point-of-care testing (POCT) of tetracycline with high sensitivity and accuracy was developed. The blue fluorescence of DPA-Ce-GMP was changed into red by doping with Eu3+ duo to the energy transfer from Ce3+ to Eu3+. Upon exposure to tetracycline, coordination between Eu3+ and tetracycline blocks energy transfer from Ce3+ to Eu3+, converting the fluorescent color from red to blue. The tetracycline detection can be realized within a wide concentration range from 0.01 µM to 45 µM. The limit of detection (LOD) reaches as low as 6.6 nM. To realize quantitative point-of-care detection in real samples, a portable device with smartphone as signal reader and analyzer is further designed to integrate with the DPA-Ce-GMP-Eu sensing platform. The Color Picker APP installed in the smartphone can convert the Red, Green and Blue (RGB) channels of the fluorescence images into digital values. With milk as real sample, tetracycline can be on-site detected with LOD of 10.8 nM. This developed platform presents a great promise for POCT in practical application with merits of low cost, easy carry, simple operation, and excellent selectivity and repeatability.

A ratiometric fluorescent nanoprobe consisting of ssDNA-templated silver nanoclusters for detection of histidine/cysteine, and the construction of combinatorial logic circuits.

A ratiometric fluorescent nanoprobe consisting of ssDNA-templated silver nanoclusters (DNA-AgNCs) as dual fluorophore has been constructed for highly sensitive and selective detection of cystein (Cys) and histidine (His). The DNA-AgNCs displays dual emission in that photoexcitation at 470 nm results in weak-green fluorescence peaking at 560 nm, while excitation at 550 nm gives strong red fluorescence with a peak at 595 nm. It is found that copper ions (Cu2+) enhance the green fluorescence but quenche the red fluorescence. A ratiometric nanoprobe for Cys (or His) is designed that is based on the competitive interaction of Cys (or His), Cu2+ and DNA-AgNCs. Cys can be distinguished from His by adding Ni2+ as the masking agent, andr His can be distinguished from Cys by adding N-ethylmaleimide (NEM) as the masking agent, respectively. The limits of detection are 5.1 and 4.5 nM for Cys and His, respectively. Furthermore, the ratiometric fluorescent nanoprobe is used for constructing combinatorial logic circuits in parallel, including OR//NOR and INHIBIT//IMPLICATION (INH//IMP). Graphical abstract Schematic representation of a ratiometric assay based on DNA-AgNCs with dual emission for detection of histidine/cysteine in serum sample. The sensing system are further used to construct combinatorial logic circuits.

Tumor-Microenvironment-Induced All-in-One Nanoplatform for Multimodal Imaging-Guided Chemical and Photothermal Therapy of Cancer.

Precisely locating tumor site based on tumor-microenvironment-induced (TMI) multimodal imaging is especially interesting for accurate and efficient cancer therapy. In the present investigation, a novel TMI all-in-one nanoplatform, CuSNC@DOX@MnO2-NS, has been successfully fabricated for chemical and photothermal (Chem-PTT) therapy guided by multimodal imaging on tumor site. Here, the CuS nanocages with mesoporous and hollow structure (CuSNC) acting as nanocarriers provide high capacity for loading the anticancer drug, doxorubicin (DOX). The outer layer of the MnO2 nanoshell (MnO2-NS) acts as "gatekeeper" to control the DOX release until the nanoplatform arrives at the tumor site, where abundant glutathione and H+ decompose MnO2-NS into paramagnetic Mn2+. The magnetic resonance imaging and fluorescent imaging were then triggered to locate the tumor, which was further improved by photothermal imaging on account of the intrinsic property of CuSNC. Guided by the multimode imaging, the combination of chemical therapy upon DOX and photothermal therapy upon CuSNC exhibits eminent efficiency on tumor ablation. The nanoplatform exhibits biocompatibility to avoid unwanted harm to normal tissues during trans-shipment in the body. The investigation thus develops a cost-effective TMI nanoplatform with facile preparations and easy integration of Chem-PTT treatment capabilities guided by multimodal imaging for potential application in precise therapy.