A Macrophage Membrane-Coated Cu-WO3-x-Hydro820 Nanoreactor for Treatment and Photoacoustic/Fluorescence Dual-Mode Imaging of Inflamed Liver Tissue.

A disease-targeting nanoplatform that integrates imaging with therapeutic activity would facilitate early diagnosis, treatment, and therapeutic monitoring. To this end, a macrophage membrane-coated Cu-WO3-x-Hydro820 (CWHM) nanoreactor was prepared. This reactor was shown to target inflammatory tissues. The reactive oxygen species (ROS) such as H2O2 and ·OH in inflammatory tissues can react with Hydro820 in the reactor to form the NIR fluorophore IR820. This process allowed photoacoustic/fluorescence dual-mode imaging of H2O2 and ·OH, and it is expected to permit visual diagnosis of inflammatory diseases. The Cu-WO3-x nanoparticles within the nanoreactor shown catalase and superoxide enzyme mimetic activity, allowing the nanoreactor to catalyze the decomposition of H2O2 and ·O2- in inflammatory cells of hepatic tissues in a mouse model of liver injury, thus alleviating the oxidative stress of damaged liver tissue. This nanoreactor illustrates a new strategy for the diagnosis and treatment of hepatitis and inflammatory liver injury.

Rational design of cuprofullerene bipyridine nanozyme with high peroxidase-like activity for colorimetric sensing of bleomycin.

The high catalytic activity of Cu-based nanozymes mainly depends on the efficient Fenton-like reaction of Cu+/ H2O2, but Cu+ cannot exist stably. Trying to find a material that can stably support Cu+ while promoting the electron cycle of Cu2+/Cu+ still faces serious challenges. C60 is expected to be an ideal candidate to solve this problem due to its unique structure and rich physicochemical properties. Here, we designed and synthesized a C60-doped Cu+-based nanozyme (termed as C60-Cu-Bpy) by loading high catalytic active site Cu+ onto C60 and coordinating with 2,2'-bipyridine (Bpy). The single crystal diffraction analysis and a series of auxiliary characterization technologies were used to demonstrate the successful preparation of C60-Cu-Bpy. Significantly, the C60-Cu-Bpy exhibited superior peroxidase-like activity during the catalytic oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). Then, the catalytic mechanism of C60-Cu-Bpy as peroxidase was elucidated in detail, mainly benefiting from the dual function of C60. On the one hand, C60 acted as a carrier to directly support Cu+, which has the ability to efficiently decompose H2O2 to produce reactive oxygen species. The other was that C60 acted as an electron buffer, contributing to promoting the Cu2+/Cu+ cycle to facilitate the reaction. Furthermore, a colorimetric sensor for the quantitative analysis of bleomycin was established based on the principle of bleomycin specific inhibition of C60-Cu-Bpy peroxidase-like activity, with satisfactory results in practical samples. This study provides a new strategy for the direct synthesis of Cu+-based nanozymes with high catalytic performance.

A gas-pressure-assisted ratiometric atomic flame assay for the point-of-care testing of tumor-cell-derived exosomes.

The multicolor-based point-of-care testing (POCT) of tumor cell-derived exosomes is of vital importance for understanding tumor growth and metastasis. Multicolor-based ratiometric signals most often rely on molecular optics, such as fluorescence resonance energy transfer (FRET)-dependent molecular fluorescence and localized surface plasmon resonance (LSPR)-related molecular colorimetry. However, finding acceptable FRET donor-acceptor fluorophore pairs and the kinetically slow color responses during size-related molecular colorimetry have greatly impeded POCT applications. Herein, an atomic flame was used to develop a visual sensing platform for the POCT of tumor-cell-derived exosomes. In comparison with common molecular optics, the atomic flame possessed the advantages of providing both a variety of ratiometric flame signals and fast response sensitivity. The integration of a gas-pressure-assisted flame reaction and dual-aptamer recognition guaranteed the sensitive and selective analysis of exosomes with a low limit of detection (LOD) of 7.6 × 102 particles per mL. Such a novel optical signal will inspire the development of more user-friendly POCT approaches.

A self-correcting fluorescent assay of tyrosinase based on Fe-MIL-88B-NH2 nanozyme.

A self-correcting fluorescent assay of tyrosinase (TYR) was developed by utilization of Fe-MIL-88B-NH2 as a peroxidase-like nanozyme and a capture probe. Fe-MIL-88B-NH2 nanozyme was selected as an electron donor, and the oxidization product (dopamine-o-quinone) acts as an energy acceptor. First, TYR catalyzes the oxidation of tyramine hydrochloride to dopamine and then to dopamine-o-quinone. Second, Fe-MIL-88B-NH2 with intrinsic peroxidase-like activity decomposes H2O2 to produce ·OH radicals, which further accelerate the oxidation of dopamine to dopamine-o-quinone. Excessive H2O2 and ·OH radicals reduce the interferences from ascorbic acid at the same time providing a self-correcting ability. Dopamine-o-quinone reacts with -NH2 groups on the ligand of Fe-MIL-88B-NH2 through Michael reaction which results in fluorescence quenching. Under 365-nm excitation, the fluorescence emission intensity at 452 nm gradually decreased with increasing TYR concentration varying from 0 to 10 U mL-1. The linear range is from 1 to 5 U mL-1 and the detection limit is 0.05679 U mL-1. This self-correcting fluorescent assay of tyrosinase exhibits good sensitivity and selectivity which is also successfully applied for tyrosinase inhibitor detection. Schematic representation of fluorescent assay for tyrosinase determination based on Fe-MIL-88B-NH2 nanozyme. A self-correcting fluorescent assay for tyrosinase was developed based on the Fe-MIL-88B-NH2 nanozyme.

A competitive immunoassay for electrochemical impedimetric determination of chlorpyrifos using a nanogold-modified glassy carbon electrode based on enzymatic biocatalytic precipitation.

A direct competitive impedimetric immunoassay for chlorpyrifos (CPF) was developed that is based on the specific affinity of immunoassay and the enzymatic biocatalytic precipitation amplification strategy. The CPF antibody (anti-CPF) was anchored onto an electro-deposited nanogold modified glassy carbon electrode surface by adsorption of the Au-NH2 bond and Au-SH bond. This improved the electrode reactivity and the loading amount of anti-CPF. Abundant horseradish peroxidase (HRP) and bovine serum albumin-CPF (BSA-CPF) were anchored onto spherical gold nanoparticles (AuNPs, 16 ± 2 nm) to form HRP-AuNP-BSA-CPF (analyte competitor). CPF determination was achieved when the competitive immunoassay occurred between CPF and analyte competitor with anti-CPF. In the presence of H2O2 and 4-chloro-1-naphthol, an enzyme-mediated biocatalytic precipitation process was triggered and produced an insoluble 4-chloro-1(4H)-naphthalenone. This insoluble substance increased the Faradaic impedance of the base electrode. The impedimetric signal was determined at the formal potential of 220 mV and alternating voltage of 10 mV. This signal decreased with increasing concentration of CPF over a linear range of 1.0 × 10-3 ng mL-1~10 ng mL-1 with a detection limit of 0.070 pg mL-1. The immunoassay has been tested for determination of chlorpyrifos in complex matrices such as artificially spiked vegetables with recoveries in the range 85 to 110%. The relative standard deviations were less than 7.5%. Graphical abstractSchematic representation of electrochemical impedimetric immunoassay for chlorpyrifos determination before enzymatic biocatalytic precipitation (BCP, red line) process and after BCP process (blue line).

Boric-Acid-Functionalized Covalent Organic Framework for Specific Enrichment and Direct Detection of cis-Diol-Containing Compounds by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry.

Design and synthesis of a novel matrix that serves as highly selective adsorption material are significant for the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis of small molecules in complicated biosamples. In this work, we presented a facile one-pot strategy for the synthesis of boric-acid-functionalized covalent organic frameworks (B-COFs) by using 2,4,6-trihydroxy-1,3,5-benzenetrialdehyde, benzidine, and 4-aminophenyl-boronic acid as ligands. Compared with bare COFs, the B-COFs have similar crystallinity, specific surface, and well-developed pore structure. The surface area and average pore size of B-COFs were 238.0 m2/g and 1.2 nm, respectively. The resulting material was used as an adsorbent for selective enrichment of cis-diol-containing compounds based on an affinity reaction between phenylboronic acid and cis-diol. Using luteolin, riboflavin, and pyrocatechol as model analytes, the enrichment ability of B-COFs as a matrix was examined by MALDI-TOF MS assay, and its high selectivity against target analytes was obtained in the presence of 100 times more anti-nonspecific compounds than that even in the complicated biosample. The limits of detection for luteolin, riboflavin, and pyrocatechol were as low as fg/mL with B-COF enrichment. The B-COFs were further employed and validated for specific enrichment and direct detection of target analytes with complex samples such as human serum, milk, and Capsicum samples. Large surface area, numerous boric-acid active sites, and super stability make B-COFs with high enrichment capacity, high selectivity and sensitivity, satisfying reproducibility, and excellent applicability in MALDI-TOF MS assays.

Magnetic Cu/Fe3O4@FeOOH with intrinsic HRP-like activity at nearly neutral pH for one-step biosensing.

The convenience of colorimetric sensors is useful for practical applications. In this work, we constructed a novel colorimetric sensor with magnetic separation ability that can be operated in nearly neutral conditions and achieve one-step detection of metabolites. Magnetic Cu doped Fe3O4@FeOOH magnetic nanocomposite (Cu/Fe3O4@FeOOH) with an oxygen vacancy was prepared by a one-step self-assembly hydrothermal method, and fully characterized by different methods. The oxygen vacancy generated by the incorporation of Cu2+ cations into the Fe3O4@FeOOH structure was confirmed to be a vital reactive site for enhancing the catalytic activity, which opens up a new way of designing highly efficient enzyme mimics. Benefiting from its inherent horseradish-peroxidase-like activity, a simple and selective enzyme-based colorimetric sensor was developed for one-step detection of H2O2 and cholesterol, and 3,3',5,5'-tetramethylbenzidine was catalyzed by H2O2 to generate a colored product of oxidized 3,3',5,5'-tetramethylbenzidine for signaling. H2O2 and cholesterol can be linearly detected in the same range from 0.01 to 0.4 mmol L-1 with detection limits of 0.0075 mmol L-1 and 0.0082 mmol L-1, respectively. The proposed colorimetric sensor has satisfactory reusability, accuracy, and practicability in human serum samples, indicating its potential application for the detection of different metabolites in the fields of life science and analytical science. Graphical abstract.

A bifunctional metal organic framework of type Fe(III)-BTC for cascade (enzymatic and enzyme-mimicking) colorimetric determination of glucose.

A metal organic framework (MOF) of type Fe(III)-BTC (where BTC is 1,3,5-benzenetricarboxylic acid) was utilized to construct an integrated system for cascade colorimetric determination of glucose. The MOF performs a dual function in acting (a) as a peroxidase (POx) mimic, and (b) as a solid support for immobilization of glucose oxidase (GOx). The MOF was prepared by a one-pot method. Glucose is consumed while H2O2 is produced during the enzymatic oxidation by GOx. In the presence of H2O2, the POx mimic catalytically oxidizes 3,3',5,5'-tetramethylbenzidine (TMB) to form a blue-green product. The absorbance of oxidized TMB (measured at 652 nm) increases linearly in the 5.0-100 µM glucose concentration range, and the detection limit is 2.4 µM. The GOx@Fe-BTC MOF was successfully applied to the determination of glucose in serum. Graphical abstract Schematic presentation of a bifunctional metal organic framework of type Fe-BTC for cascade (enzymatic and enzyme-mimicking) colorimetric determination of glucose. The Fe-BTC performs a dual function in acting as both a peroxidase mimic and support for immobilizing glucose oxidase. Using the integrated enzyme, a colorimetric method was successfully applied to one-step detection of glucose in human serum.

Facile one-pot preparation of a novel imidazolium-based monolith by thiol-ene click chemistry for capillary liquid chromatography.

In this work, a novel imidazolium-based monolith was fabricated through a simple route. With 1-vinyl-3-octadecylimidazolium bromide and ethylene dimethacrylate as monomers, pentaerythritol tetra-(3-mercaptopropionate) as crosslinker, AIBN as thermal initiator, the monolith was facilely fabricated by one-pot thiol-ene click chemistry. The influences of both the content of monomer/crosslinker and porogenic systems on the morphology, and permeability of the monolith were studied. The optimal reaction conditions were used to prepare a homogeneous and permeable monolith. The optimal preparation of monolithic column was characterized by scanning electron microscopy, Fourier transform infrared spectrometry, X-ray photoelectron spectroscopy, and thermogravimetric analysis. High efficiency and quick separation of alkylbenzenes, styrene and ethylbenzene, polycyclic aromatic hydrocarbon, phenols, anilines, and aromatic acids were achieved. The minimum plate height of this monolith were determined as 11.42 µm for thiourea and 13.26 µm for benzene. All results indicated that thiol-ene click chemistry provides a quick way for the fabrication of imidazolium-based monolith.

Bioinspired Synthesis of Cu2+ -Modified Covalent Triazine Framework: A New Highly Efficient and Promising Peroxidase Mimic.

Artificial enzymes is an emerging field of research owing to the remarkable advantages of enzyme mimics over their natural counterpart, including tunable catalytic efficiencies, lower cost, ease of preparation, and excellent tolerance to variations of the reaction system. Herein, we report an efficient peroxidase mimic based on a copper-modified covalent triazine framework (CCTF). Owing to its unique specific surface area, atomically dispersed active Cu sites, efficient electron transfer, and enhanced photo-assisted enzyme-like activity, the CCTF showed enhanced peroxidase-like enzyme activity. Therefore, copper modification represents an effective route to tailor the peroxidase-like activity of the covalent triazine frameworks. Furthermore, the mechanism of the enhanced peroxidase-like activity and stability of the CCTF were investigated. As a proof of concept, the CCTF was used for the colorimetric detection of H2 O2 and decomposition of organic pollutants. This work provides a new strategy for the design of enzyme mimics with a broad range of potential applications.

One-pot preparation of an organic polymer monolith by thiol-ene click chemistry for capillary electrochromatography.

A novel organic monolith was successfully fabricated by a one-pot thiol-ene click reaction of triallyl isocyanurate with pentaerythritol tetrakis-(2-mercaptoacetate) and mercaptopropionic acid in the presence of porogens. We investigated the effects of the ratio of monomer and cross-linking agent, the type and ratio of porogen, and click reaction temperature on the permeability and morphology of the prepared poly triallyl isocyanurate-co-pentaerythritol tetrakis (2-mercaptoacetate) monoliths. The monolith was also characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. The results indicated that the monoliths had continuous porous framework, good permeability, and high mechanical stability. A series of analytes with different properties such as alkylbenzenes, polycyclic aromatic hydrocarbons, anilines, and phenols were used to evaluate the electrochromatographic performance of the prepared monoliths in pressurized capillary electrochromatography. The prepared polymer monolith showed typical reversed-phase electrochromatographic behavior for hydrophobic substances. Moreover, the prepared monolith showed a mix of reversed-phase and cation exchange interaction modes for basic aniline compounds. The minimum plate height of the monolith was 8.76 µm (132 100 plates/m) for propylbenzene. These results demonstrated that one-pot thiol-ene click chemistry can provide a simple and reliable method for the preparation of organic monoliths.

Ionic-liquid-modified magnetic nanoparticles as a solid-phase extraction adsorbent coupled with high-performance liquid chromatography for the determination of linear alkylbenzene sulfonates in water samples.

Novel ionic-liquid-functionalized Fe3 O4 magnetic nanoparticles were synthesized by the thiol-ene click reaction. The prepared functionalized Fe3 O4 nanoparticles possessed multiple interactions, such as electrostatic, hydrophobic, and π-π interactions. The functionalized Fe3 O4 nanoparticles were characterized by using Fourier transform infrared spectroscopy, X-ray diffraction, vibrating sample magnetometry, and transmission electron microscopy. Four kinds of linear alkylbenzene sulfonates, namely, sodium decylbenzenesulfonate, sodium undecylbenzene sulfonate, sodium dodecylbenzenesulfonate, and sodium tridecylbenzenesulfonate, were selected as model compounds to evaluate the applicability of adsorbents for extraction and subjected to high-performance liquid chromatography analysis. In addition, the effects of various parameters, such as sorbent amount, pH value, ionic strength, sample volume, extraction time, and elution conditions on extraction efficiency were studied in detail. Under the optimum conditions, good linearities were attained, with correlation coefficients between 0.9912 and 0.9968. The proposed method exhibited limits of detection ranging from 0.061 to 0.099 µg/L for all the target analytes. The spiked recoveries of the target analytes in real water samples ranged from 86.3 to 107.5%, with relative standard deviations lower than 7.96%. The enrichment factors of the analytes ranged from 364 to 391, indicating that the obtained functionalized Fe3 O4 nanoparticles can effectively extract trace target analytes from environmental water samples.

In situ synthesis of metal-organic frameworks in a porous polymer monolith as the stationary phase for capillary liquid chromatography.

In this study, HKUST-1 was synthesized in situ on the porous polymer monolith as the stationary phase for capillary liquid chromatography (cLC). The unique carboxyl functionalized poly(methacrylic acid-co-ethylene dimethacrylate) (poly(MAA-co-EDMA)) monolith was used as a support to directly grow HKUST-1 by a controlled layer-by-layer self-assembly strategy. X-ray diffraction, scanning electron microscopy, energy dispersive X-ray spectrometry, and Fourier transform infrared spectroscopy of the resulting HKUST-1-poly(MAA-co-EDMA) monoliths indicated that HKUST-1 was successfully grafted onto the pore surface of the poly(MAA-co-EDMA) monolith. The column performance of HKUST-1-poly(MAA-co-EDMA) monoliths for the separation of various small molecules, such as benzenediols, xylenes, ethylbenzenes, and styrenes, was evaluated. The chromatographic performance was found to improve with increasing HKUST-1 density, and the column efficiencies and resolutions of HKUST-1-poly(MAA-co-EDMA) monoliths were 18 320-19 890 plates m(-1) and 1.62-6.42, respectively, for benzenediols. The HKUST-1-poly(MAA-co-EDMA) monolith displayed enhanced resolution for the separation of positional isomers when compared to the traditional C18 and HKUST-1 incorporated polymer monoliths. Hydrophobic, π-π, and hydrogen bonding interactions within the HKUST-1-poly(MAA-co-EDMA) monolith were observed in the separation of small molecules. The results showed that the HKUST-1-poly(MAA-co-EDMA) monoliths are promising stationary phases for cLC.

Preparation of polyhedral oligomeric silsesquioxane based hybrid monoliths by thiol-ene click chemistry for capillary liquid chromatography.

A facile organic-silica hybrid monolith was prepared by a thiol-ene click reaction of polyhedral oligomeric silsesquioxane methacryl substituted (POSS-MA) with 1,4-bis(mercaptoacetoxy) butane (BMAB) using toluene and dodecanol as a porogenic system. The effects of the ratio of POSS-MA-BMAB and porogenic solvents and click reaction temperature on the morphology, permeability and column performance of the resulting POSS-BMAB hybrid monoliths were studied in detail. A uniform monolithic network with a high porosity was obtained. The POSS-BMAB hybrid monolith exhibited good permeability and high thermal and mechanical stability. A series of test compounds, including alkylbenzenes, polycyclic aromatic hydrocarbon, phenols and, anilines were used to evaluate the retention behaviors of the POSS-BMAB hybrid monolith in capillary liquid chromatography. The prepared POSS-BMAB hybrid monolith exhibited typical reversed-phase chromatographic behavior toward neutral solutes. The minimum plate height of this hybrid monolith was determined as 12.6 and 13.7 µm for thiourea and benzene, respectively. These results demonstrate that thiol-ene click chemistry can provide a facile and robust approach for the preparation of a POSS-based hybrid monolith.

Rational design of nanozyme with integrated sample pretreatment for colorimetric biosensing.

Nanozymes have been widely used in the field of biosensing owing to their high stability, low cost, adjustable catalytic activity, and convenient modification. However, achieving high selectivity and sensitivity simultaneously in nanozyme-based colorimetric sensing remains a major challenge. Nanozymes are nanomaterials with enzyme-simulating activity that are often used as solid-phase adsorbents for sample pretreatment. Our design strategy integrated sample pretreatment function into the nanozyme through separation and enrichment, thereby improving the selectivity and sensitivity of nanozyme-based colorimetric biosensing. As a proof-of-concept, glucose was used as the model analyte in this study. A phenylboric acid-modified magnetic nanozyme (Cu/Fe3O4@BA) was rationally designed and synthesized. Selectivity was enhanced by boronate-affinity specific adsorption and the elimination of interference after magnetic separation. In addition, magnetic solid-phase extraction enrichment was used to improve the sensitivity. A recovery rate of more than 80% was reached when the enrichment factor was 50. The synthesized magnetic Cu/Fe3O4@BA was recyclable at least five times. The proposed method exhibited excellent selectivity and sensitivity, simple operation, and recyclability, providing a novel and practical strategy for designing multifunctional nanozymes for biosensing.

MOF derivatization of multifunctional nanozyme: Peroxidase-like catalytic activity combined with magnetic solid phase extraction for colorimetric detection of Hg2.

Nanozyme-based colorimetric sensing has drawn immense attention due to the rapid development of nanozyme in recent years. However, the selectivity of nanozyme-based colorimetric sensing greatly limits its subsequent practical application. It is well known that sample pretreatment can not only improve selectivity by eliminating the sample matrix interference, but also improve sensitivity by enriching trace targets. Based on the easy facile surface modification properties of nanozyme, we rationally designed nanozyme combined with sample pretreatment for colorimetric biosensing, through separation and enrichment, thereby improving the selectivity and sensitivity of the nanozyme colorimetric biosensing. As a proof of concept, the detection of Hg2+ by nanozyme-based colorimetric sensing was used as an example. Magnetic peroxidase-like nanozyme Fe3S4 was designed and synthesized. The selectivity is improved by the specific adsorption of S-Hg bond and the interference elimination after magnetic separation. In addition, the sensitivity is improved by magnetic solid-phase extraction enrichment. Our established colorimetric sensing based on Fe3S4 nanozyme integrated sample pretreatment with an enrichment factor of 100 and the limit of detection (LOD) is 26 nM. In addition, this strategy was successfully applied to detect Hg2+ in environmental water samples. Overall, the strategy showed good selectivity and sensitivity, providing a new practical method for the application of nanozyme-based biosensing in sample pretreatment.

Analyte-induced laccase-mimicking activity inhibition and conductivity enhancement of electroactive nanozymes for ratiometric electrochemical detection of thiram.

Most nanozyme-based electrochemical sensing strategies depend on the catalytic formation of electroactive substances, while the electrochemical properties of nanozymes have rarely been explored. In this study, magnetic nanoparticles encapsulated metal-organic framework served as precursors to prepare bioinspired nanozymes with both laccase-mimicking activity and electroactivity. Owing to the strong affinity between thiram (THR) and Cu(II) active sites in the nanozymes, the binding of THR inhibited nanozyme catalytic activity toward catechol (CT) oxidation and enhanced nanozyme conductivity. A lower oxidation current (ICT) of CT was accompanied by a higher oxidation signal (ICu) of Cu(II), allowing a ratiometric electrochemical response of the electroactive nanozymes toward the incoming THR. The signal ratio (ICu/ICT) displayed a good linear relationship over a THR concentration range of 10.0 nM-3.0 µM with a limit of detection of 0.15 nM, and the entire THR detection process was rapidly accomplished within 5 min. The high sensitivity and selectivity of the developed electrochemical strategy guaranteed the reliable detection of THR in fruit, vegetable, and river water samples. This study provides new insights into the development of nanozymes for electrochemical analysis.

Doping Engineering To Modulate Surface Plasmon Resonance and Enzyme-like Activities for Enhancing Photoacoustic Imaging-Guided Targeted Cancer Therapy in the Second Near-Infrared Window.

Biological imaging-guided targeted tumor therapy has been a soughtafter goal in the field of cancer diagnosis and treatment. To this end, we proposed a strategy to modulate surface plasmon resonance and endow WO3-x nanoparticles (NPs) with enzyme-like catalytic properties by doping Fe2+ in the structure of the NPs. Doping of the Fe2+ introduced oxygen vacancies into the structure of the NPs, inducing a red shift of the maximum absorption wavelength into the near-infrared II (NIR-II) region and enhancing the photoacoustic (PA) and photothermal properties of the NPs for more effective imaging-guided cancer therapy. Under NIR-II laser irradiation, the Fe-WO3-x NPs produced very strong NIR-II PA and photothermal effects, which significantly enhanced the PA imaging and photothermal treatment effects. On the other hand, Fe2+ in Fe-WO3-x could undergo Fenton reactions with H2O2 in the tumor tissue to generate ·OH for chemodynamic therapy. In addition, Fe-WO3-x can also catalyze the above reactions to produce more reactive oxygen species (ROS) and induce the oxidation of NADH to interfere with intracellular adenosine triphosphate (ATP) synthesis, thereby further improving the efficiency of cancer therapy. Specific imaging of tumor tissue and targeted synergistic therapy was achieved after ligation of a MUC1 aptamer to the surface of the Fe-WO3-x NPs by the complexing of -COOH in MUC1 with tungsten ions on the surface of the NPs. These results demonstrated that Fe-WO3-x NPs could be a promising diagnosis and therapeutic agent for cancer. Such a study opens up new avenues into the rational design of nanodiagnosis and treatment agents for NIR-II PA imaging and cancer therapy.

Preparation of a dual-enzyme co-immobilized capillary microreactor and simultaneous screening of multiple enzyme inhibitors by capillary electrophoresis.

A CE method based on a dual-enzyme co-immobilized capillary microreactor was developed for the simultaneous screening of multiple enzyme inhibitors. The capillary microreactor was prepared by co-immobilizing adenosine deaminase and xanthine oxidase on the inner wall at the inlet end of the separation capillary. The enzymes were first immobilized on gold nanoparticles, and the functionalized gold nanoparticles were then assembled on the inner wall at the inlet end of the separation capillary treated with polyethyleneimine. With the developed CE method, the substrates and products were baseline separated within 3 min. The activity of the immobilized enzyme can be directly detected by measuring the peak height of the products. A statistical parameter Z' factor was recommended for evaluation of the accuracy of a drug screening system. In the present study, it was calculated to be larger than 0.5, implying a good accuracy. Finally, screening a small compound library containing two known enzyme inhibitors and 20 natural extracts by the proposed method was demonstrated. The known inhibitors were identified, and some natural extracts were found to be positive for two-enzyme inhibition by the present method.

A Ce-MOF@polydopamine composite nanozyme as an efficient scavenger for reactive oxygen species and iron in thalassemia disease therapy.

Patients with ß-thalassemia are prone to complications such as cardiovascular diseases and secretory gland injury due to iron overload (IO) and reactive oxygen species (ROS) production caused by blood transfusions. Simultaneously scavenging ROS and eliminating IO using nanomedicine remains challenging. Herein, we designed a dual-functional Ce-based metal-organic framework@polydopamine (Ce-MOF@PDA) composite that integrates oxidative stress reduction and IO elimination and evaluated its protective effect on IO injury in thalassemia. Using Ce-MOF with multiple active sites as the core, dopamine, which can coordinate iron ions, was modified on the surface of Ce-MOF and spontaneously polymerized to obtain PDA with iron elimination ability. Dopamine modification also adjusted the Ce3+/Ce4+ ratio to further enhance the catalytic activity for scavenging ROS. Ce-MOF@PDA exhibited multiple nanozyme activities, such as superoxide dismutase- and catalase-like activities, and decreased iron-mediated oxidative stress levels in vitro. Furthermore, the serum ferritin levels and iron concentrations in the liver of IO mice were reduced following treatment with Ce-MOF@PDA, and the fecal clearance ability was comparable to that of deferoxamine. These results indicate that Ce-MOF@PDA can eliminate IO while scavenging ROS and reduce tissue damage caused by oxidative stress. Therefore, the Ce-MOF@PDA nanozyme is a promising therapeutic nanomedicine for treating thalassemia IO.