Modular coupling MOF nanozyme with natural enzyme on hollow fiber membrane for rapid and reusable detection of H2O2 and glucose.

A novel strategy based on gradient porous hollow fiber membrane (GPF) is proposed for the modular assembly of enzyme-nanozyme cascade systems. The porous structure of GPF provided sufficient specific surface area, while the gradient structure effectively minimized the leaching of enzymes and nanozymes. To enhance stability, we prepared and immobilized metal-organic framework (MOF) nanozymes, resulting in the fabrication of GPF-MOF with excellent stability and reusability for colorimetric H2O2 detection. To improve specificity and expand the detection range, micro-crosslinked natural enzymes were modularly assembled, using glucose oxidase as the model enzyme. The assembled system, GPF-mGOx@MOF, achieved a low detection limit of 0.009 mM and a linear range of 0.2 to 11 mM. The sensor retained 87.2% and 80.7% of initial activity after being stored for 49 days and 9 recycles, respectively. Additionally, the reliability of the biosensor was validated through glucose determination of human blood and urine samples, yielding comparable results to a commercial glucose meter.

High-resolution liquid level sensor utilizing a microwave photonics interrogated multicore fiber interferometer.

We propose and experimentally demonstrate a high-resolution, high-sensitivity liquid level sensor based on a multicore fiber (MCF) Michelson interferometer (MI), where the sensing fiber is securely affixed to a cantilever beam, such that liquid level variations will change the beam's curvature, meanwhile leading to a substantial phase difference between the two interfering arms of the MI, and the sensor is interrogated using a microwave photonics filter (MPF) system, which can provide greatly enhanced measurement resolution compared to the traditional optical wavelength demodulation methods. The angular position of the MCF is precisely calibrated to ensure optimal sensitivity of the MI sensor. As a result, within a measurement range of up to ±14 cm, the proposed liquid level sensor achieves a sensitivity of 10.35 MHz/cm and an impressive resolution of 0.04835 cm. The proposed sensor has unique advantages of high sensitivity, superior resolution, long-term stability, etc.

C-176 loaded Ce DNase nanoparticles synergistically inhibit the cGAS-STING pathway for ischemic stroke treatment.

The neuroinflammatory responses following ischemic stroke cause irreversible nerve cell death. Cell free-double strand DNA (dsDNA) segments from ischemic tissue debris are engulfed by microglia and sensed by their cyclic GMP-AMP synthase (cGAS), which triggers robust activation of the innate immune stimulator of interferon genes (STING) pathway and initiate the chronic inflammatory cascade. The decomposition of immunogenic dsDNA and inhibition of the innate immune STING are synergistic immunologic targets for ameliorating neuroinflammation. To combine the anti-inflammatory strategies of STING inhibition and dsDNA elimination, we constructed a DNase-mimetic artificial enzyme loaded with C-176. Nanoparticles are self-assembled by amphiphilic copolymers (P[CL35-b-(OEGMA20.7-co-NTAMA14.3)]), C-176, and Ce4+ which is coordinated with nitrilotriacetic acid (NTA) group to form corresponding catalytic structures. Our work developed a new nano-drug that balances the cGAS-STING axis to enhance the therapeutic impact of stroke by combining the DNase-memetic Ce4+ enzyme and STING inhibitor synergistically. In conclusion, it is a novel approach to modulating central nervus system (CNS) inflammatory signaling pathways and improving stroke prognosis.

Stimuli-responsive nanozymes for biomedical applications.

With the rapid development of nanotechnology, nanozymes are regarded as excellent substitutes for natural enzymes due to their high activity, convenient preparation, low cost, robust stability and other unique properties of nanomaterials. In biomedical applications, the always-on activity of nanozymes is undesirable as it poses a potential threat to normal tissues. Stimuli-responsive nanozymes were designed to manipulate the activities of nanozymes. This review introduces two types of stimuli-responsive nanozymes. One is smart responsive nanozymes with stimuli-switchable activities, further divided into those with on/off switchable activity and one/another switchable activity. Another is nanozymes exhibiting responsive release from specific carriers. Additionally, the biomedical applications of stimuli-responsive nanozymes in cancer therapy, antibacterial therapy, biosensing and anti-inflammatory therapy are briefly reviewed. Finally, we address the challenges and prospects in this field.

Record-High Ultrasound-Sensitive NO Nanogenerators for Cascade Tumor Pyroptosis and Immunotherapy.

Pyroptosis is a pro-inflammatory cell death that is associated with innate immunity promotion against tumors. Excess nitric oxide (NO)-triggered nitric stress has potential to induce pyroptosis, but the precise delivery of NO is challenging. Ultrasound (US)-responsive NO production has dominant priority due to its deep penetration, low side effects, noninvasion, and local activation manner. In this work, US-sensitive NO donor N-methyl-N-nitrosoaniline (NMA) with thermodynamically favorable structure is selected and loaded into hyaluronic acid (HA)-modified hollow manganese dioxide nanoparticles (hMnO2 NPs) to fabricate hMnO2 @HA@NMA (MHN) nanogenerators (NGs). The obtained NGs have a record-high NO generation efficiency under US irradiation and can release Mn2+ after targeting the tumor sites. Later on, cascade tumor pyroptosis and cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING)-based immunotherapy is achieved and tumor growth is effectively inhibited.

Distributed twist sensing using frequency-scanning φ-OTDR in a spun fiber.

In this paper, a novel distributed twist sensor based on frequency-scanning phase-sensitive optical time-domain reflectometry (φ-OTDR) in a spun fiber is proposed and demonstrated. Owing to the unique helical structure of the stress rods in the spun fiber, fiber twist gives rise to the variation of the effective refractive index of the transmitting light, which can be quantitatively retrieved through frequency shift using frequency-scanning φ-OTDR. The feasibility of distributed twist sensing has been verified by both simulation and experiment. For proof of concept, distributed twist sensing over a 136 m spun fiber with a 1 m spatial resolution is demonstrated, and the measured frequency shift shows a quadratic fitting dependence on the twist angle. In addition, the responses of both clockwise and counterclockwise twist directions have also been explored and the experiment result indicates that the twist direction can be discriminated since the frequency shift directions are opposite in the correlation spectrum. The proposed twist sensor possesses some outstanding advantages, including high sensitivity, distributed twist measurement and twist direction recognition capability, etc., which is very promising for specific applications in industry, e.g., structural health monitoring, bionic robots, etc.

A nanomedicine based on stoichiometric coordination of camptothecin and organoplatinum (II) for synergistic antitumor therapy.

Precise combination therapy, involving multiple chemotherapeutics with pharmacologically synergistic antitumor effects, is a promising approach to address the challenge of monotherapy with insufficient activity towards their targets of interest. We employed Pt←pyridine coordination-driven assembly to construct a stoichiometric coordination complex of camptothecin and organoplatinum (II) (Pt-CPT). The Pt-CPT complex exhibited a remarkable synergistic effect toward several tumor cell lines, which is equal to the optimal synergistic effect of (PEt3)2Pt(OTf)2 (Pt) and CPT mixture at various ratios. An amphiphilic polymer with H2O2-responsiveness and glutathione (GSH)-depleting ability (PO) was used to encapsulate Pt-CPT complex to enable the nanomedicine (Pt-CPT@PO) with prolonged blood circulation and elevated tumor accumulation. The Pt-CPT@PO nanomedicine exhibited remarkable synergistic antitumor efficacy and antimetastatic effect on a mice orthotopic breast tumor model. This work demonstrated the potential of stoichiometric coordination-driven assembly of organic therapeutics with metal-based drugs in developing advanced nanomedicine with optimal synergistic antitumor activity. STATEMENT OF SIGNIFICANCE: In this study, for the first time, we employed Pt←pyridine coordination-driven assembly to construct a stoichiometric coordination complex of camptothecin and organoplatinum (II) (Pt-CPT), with an optimal synergistic effect at various ratios. Then it was encapsulated into an amphiphilic polymer with H2O2-responsiveness and glutathione (GSH)-depleting ability (PO) to enable the nanomedicine (Pt-CPT@PO) with prolonged blood circulation and elevated tumor accumulation. The Pt-CPT@PO nanomedicine exhibited remarkable synergistic antitumor efficacy and antimetastatic effect on a mice orthotopic breast tumor model.

Single-Atom Nanozymes: Fabrication, Characterization, Surface Modification and Applications of ROS Scavenging and Antibacterial.

Nanozymes are nanomaterials with intrinsic natural enzyme-like catalytic properties. They have received extensive attention and have the potential to be an alternative to natural enzymes. Increasing the atom utilization rate of active centers in nanozymes has gradually become a concern of scientists. As the limit of designing nanozymes at the atomic level, single-atom nanozymes (SAzymes) have become the research frontier of the biomedical field recently because of their high atom utilization, well-defined active centers, and good natural enzyme mimicry. In this review, we first introduce the preparation of SAzymes through pyrolysis and defect engineering with regulated activity, then the characterization and surface modification methods of SAzymes are introduced. The possible influences of surface modification on the activity of SAzymes are discussed. Furthermore, we summarize the applications of SAzymes in the biomedical fields, especially in those of reactive oxygen species (ROS) scavenging and antibacterial. Finally, the challenges and opportunities of SAzymes are summarized and prospected.

Reactive oxygen species-scavenging hollow MnO2 nanozymes as carriers to deliver budesonide for synergistic inflammatory bowel disease therapy.

Inflammatory bowel disease (IBD) is related to excessive reactive oxygen species (ROS) and high expression of proinflammatory cytokines. An enzymatically active drug carrier that can simultaneously scavenge excessive ROS and deliver anti-inflammatory drugs to inhibit the production of inflammatory cytokines may lead to improved therapeutic effects. Herein, nanoparticles (NPs) that can target activated macrophages, remove ROS and release anti-inflammatory drugs are fabricated by loading budesonide (Bud) into dextran sulfate sodium (DSS)-coated hollow mesoporous manganese dioxide (hMnO2) NPs. This strategy can treat IBD better through the synergistic effect of the ROS-scavenging hMnO2 carriers and anti-inflammatory drug by blocking the amplification effect of inflammation. In addition, compared with free Bud, the drug delivery system can reduce side effects of Bud and improve its treatment outcome at the same dosage. Therefore, this study provides a new method for the design of highly effective synergistic anti-inflammatory nanomedicines.

Hypoxia-alleviated nanoplatform to enhance chemosensitivity and sonodynamic effect in pancreatic cancer.

Pancreatic cancer is a severe disease that threatens human health. The hypoxic tumor microenvironment in pancreatic cancer leads to resistance to conventional therapies and helps to maintain tumor malignancy. First-line drugs present the disadvantage of systemic side effects, and a synergistic method with sonodynamic therapy (SDT) has been established as an emerging approach. In this study, we produced hypoxia-alleviating nanoplatforms (denoted as PZGI NPs) with zeolitic imidazolate frameworks-90 (ZIF-90) nanoparticles nucleating on platinum (Pt) nanoparticles and co-loaded with gemcitabine and IR780. This platform can catalyze peroxide to oxygen with loaded Pt nanoparticles to alleviate tumor hypoxia. Moreover, the loaded drugs could be quickly released in the lysosome microenvironment, which has a low pH value and high ATP level microenvironment in the mitochondria. This strategy could enhance the sensitivity of cancer cells to chemotherapy. Further, under ultrasound exposure, it could transfer the produced oxygen into a highly cytotoxic singlet oxygen for the augmented sonodynamic effect. Therefore, this multifunctional hypoxia-alleviating nanoplatform offers a promising strategy for chemo-sonodynamic therapy against pancreatic cancer.

Broad-Spectrum Reactive Oxygen Species Scavenging and Activated Macrophage-Targeting Microparticles Ameliorate Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a refractory chronic inflammatory disease. An excessively high level of reactive oxygen species (ROS) in the colon is one of the characteristics and pathogenic factors of IBD. Therefore, scavenging excessive ROS is a feasible method to treat IBD. Because ROS include many types of species, scavenging a single kind of ROS is not enough to reduce the ROS level and cure IBD effectively. Herein, broad-spectrum ROS scavenging and activated macrophage-targeting microparticles (MPs) are successfully fabricated by coprecipitation of catalase (CAT) and bovine serum albumin into a MnCO3 template followed by deposition of polydopamine (PDA), assembly of targeting molecules on the surface, and finally removal of MnCO3. The CAT content of MPs is about 34.1%. The obtained MPs can effectively scavenge the broad spectrum of ROS and retain 88% of the radical scavenging activity even after the treatment of simulated gastric fluid. The surface-modified dextran sulfate endows MPs with the targeting ability toward activated macrophages, achieving a better therapeutic effect. The MPs with components mostly derived from natural substances exhibit good biocompatibility and can show excellent ROS scavenging ability in cell experiments. In animal experiments, oral administration of a proper dosage of MPs can substantially mitigate colonic inflammation, as evidenced by disease activity index scores reduced by ∼40%, reduced body weight loss, and the production of typical proinflammatory cytokines in the inflammatory colon. This kind of MP can also be utilized for the treatment of other inflammatory diseases.

MOF-enzyme hybrid nanosystem decorated 3D hollow fiber membranes for in-situ blood separation and biosensing array.

Modified metal-organic frameworks (MOFs) doping with enzymes exhibit high enzyme stability and catalytic performance, which is a research hotspot in the field of enzyme-based sensing. Although the MOF-enzyme constitutes a 3D structure in the nanoscale, the macroscopic assembly configuration still stays in 1D or 2D structures, limiting sensing applications towards complex biological targets. Herein, the MOF-enzyme hybrid nanosystem was assembled into 3D porous conductive supports via a controllable physical embedding method, displaying high enzymatic loading, stability and cascade catalytic performance. The modified MOFs combing with enzymes served as a sensing reaction system, and the conductive hollow fiber membranes (HFMs) served as a functional platform. The multifunctional device integrates pumpless hydrodynamic transport, interconnected conductive polymer, and blood separation modules, showing fast capillary fluid flow, trace sampling (3 µL), high selectivity and accuracy. The linear sensing range was in 2-24 mM glucose, 0.05-6 mM lactic acid, and 0.1-10 mM cholesterol, respectively, with sensitivities of 24.2, 150, 73.6 nA mM-1. Furthermore, this strategy of modular assembly of biosensing array can easily implement multiplex metabolites detection simultaneously.

Erythrocyte Membrane-Camouflaged PCN-224 Nanocarriers Integrated with Platinum Nanoparticles and Glucose Oxidase for Enhanced Tumor Sonodynamic Therapy and Synergistic Starvation Therapy.

Sonodynamic therapy (SDT) is a promising method for tumor treatment, but self-quenching property, low loading efficiency of sonosensitizers, and hypoxia tumor microenvironment (TME) hinder the efficiency of SDT. Herein, an erythrocyte membrane (EM)-camouflaged metal-organic framework (MOF) of PCN-224 nanoparticles (NPs) integrated with platinum (Pt) NPs as well as glucose oxidase (GOx) has been developed to overcome these limits. Porphyrin-based PCN-224 NPs are synthesized as a sonosensitizer with a large amount of well-organized porphyrin molecules while simultaneously acting as the nanocarriers (NCs) for Pt NPs and GOx. When the NCs are internalized by tumor cells, Pt NPs on their surface are able to utilize endogenous hydrogen peroxide (H2O2) to produce oxygen for the relief of tumor hypoxia, thus enhancing the SDT effect. After EM cloaking, the longer circulation time can improve biocompatibility in vivo and enhance accumulation in tumor tissue. Loaded GOx is beneficial to local glucose consumption and can realize the tumor starvation therapy effect. Consequently, these multifunctional NCs show amplified synergistic therapeutic effects of tumor SDT and starvation therapy, which can efficiently inhibit the tumor growth.

Boosted peroxidase-like activity of metal-organic framework nanoparticles with single atom Fe(â ¢) sites at low substrate concentration.

Single atom nanomaterials possess catalytic activity like natural enzymes are termed as SAzymes which have gained great attention during last two years because of the maximal utilization of atoms and the benefit of understanding structure-property relationship. However, most of SAzymes are fabricated based on hydrophobic carbon, which disperse poorly in water and exhibit inferior affinity towards substrates, which may limit their biomedical applications. Here, we report a peroxidase-like SAzyme through the post-modification route based on hydrophilic defective metal-organic frameworks. Hydrochloric acid (HCl) is employed as ligand modulator to fabricate defective NH2-UiO-66 nanoparticles (HCl-NH2-UiO-66 NPs). Compared with the NPs fabricated through acetic acid modulation method (Ac-NH2-UiO-66 NPs), HCl-NH2-UiO-66 NPs have more missing linkers. Hence, more Fe(Ⅲ) ions can be successfully doped onto Zr6 clusters in HCl-NH2-UiO-66 NPs in a single atom state via formation of Fe-O-Zr bridge. The HCl-NH2-UiO-66 NPs doped with Fe(Ⅲ) ions (Fe-HCl-NH2-UiO-66 NPs) possess higher peroxidase-like activity than Fe-Ac-NH2-UiO-66 NPs due to the higher loading amount of Fe. Besides, both Fe-HCl-NH2-UiO-66 NPs and Fe-Ac-NH2-UiO-66 NPs exhibit lower Michaelis-Menten constants (Km) for hydrogen peroxide (H2O2) than most reported nanomaterials, indicating their higher affinity to H2O2. Due to their excellent catalytic activity to low concentration of substrates, Fe-HCl-NH2-UiO-66 NPs can detect H2O2 with a limit of detection (LOD) of 1.0 µM. Thus, our system can be used to detect the low cellular H2O2 concentration. With high peroxidase-like activity induced by plenty of single atom Fe(Ⅲ) sites, Fe-HCl-NH2-UiO-66 NPs can also find wide applications in other fields including nanomedicine, pollution degradation and catalysis.

Finely tuned Prussian blue-based nanoparticles and their application in disease treatment.

The Prussian blue (PB) based nanostructure is a mixed-valence coordination network with excellent biosafety, remarkable photothermal effect and multiple enzyme-mimicking behaviours. Compared with other nanomaterials, PB-based nanoparticles (NPs) exhibit several unparalleled advantages in biomedical applications. This review begins with the chemical composition and physicochemical properties of PB-based NPs. The tuning strategies of PB-based NPs and their biomedical properties are systemically demonstrated. Afterwards, the biomedical applications of PB-based NPs are comprehensively recounted, mainly focusing on treatment of tumors, bacterial infection and inflammatory diseases. Finally, the challenges and future prospects of PB-based NPs and their application in disease treatment are discussed.

Encapsulation of Methylene Blue in Zeolitic Imidazolate Framework-90 Nanoparticles to Protect Its Photodynamic Activity.

Methylene blue (MB) is widely used as a photosensitizer in photodynamic therapy applications. However, it is easily reduced by reductases in biological environments, which hampers its further applications. Here, we developed a one-pot method to synthesize MB-encapsulated and poly(vinylpyrrolidone) (PVP)-modified zeolitic imidazolate framework-90 (ZIF-90) nanoparticles (MB@ZIF-90/PVP NPs). The NPs show intact crystalline structure with improved colloidal dispersity and stability both in water and in the medium for cell culture. The size of the enzymes is much larger than the pore size of ZIF-9; thus, the access of reductive enzymes to encapsulated MB is prohibited, resulting in the protection of MB's photodynamic activity. Furthermore, cell experiments confirm that MB@ZIF-90/PVP NPs have lower dark cytotoxity than equivalent free MB but can efficiently induce photodynamic damage to tumor cells even in the presence of reductive enzymes upon light irradiation.

Construction of Self-activated Cascade Metal-Organic Framework/Enzyme Hybrid Nanoreactors as Antibacterial Agents.

Metal organic frameworks (MOFs) served as peroxidase-like artificial enzymes have been recently adopted for wide applications including therapy, pollution degradation, biosensing and so on. However, most of MOFs mimicking peroxidase cannot perform with the utmost efficiency under certain biological circumstances, such as bacterial infections. This is mainly because that the peroxidase-like MOFs exhibit highest activity at pH of 3-4, while bacterial infections cannot lower the environmental pH to the optimal value. This problem significantly restrains the therapy effect. Herein, self-activated cascade MOF/enzyme hybrid nanoreactors (MIL@GOx-MIL NRs) based on MIL (Materials of Institute Lavoisier) and GOx (Glucose oxidase) were successfully constructed through a two-step procedure. GOx was successfully loaded in the MIL shells and onto their surface as well. The GOx can catalyze the production of gluconic acid that reduces the pH value to around 4, at which the MIL@GOx-MIL NRs perform the highest cascade reaction activity. The continually produced hydrogen peroxide (H2O2) can be subsequently catalyzed by MIL NPs to generate highly toxic hydroxyl radicals (HO•) for antibacterial application. Thus, MIL@GOx-MIL NRs can significantly inhibit methicillin-resistant staphylococcus aureus (MRSA) growth and biofilm formation.

Construction of flexible enzymatic electrode based on gradient hollow fiber membrane and multi-wall carbon tubes meshes.

In this study, we developed a convenient way to construct a flexible enzymatic electrode with excellent stability and electrochemical performance for implanted glucose monitoring. The electrode was constructed through the co-immobilization of the glucose oxidase micro-particles (GOD MPs) and multi-wall carbon nanotubes (CNT) on the inner surface of a gradient-structured hollow fiber membrane (GHM), where CNT improved the electron transport efficiency and GHM controlled the transfer of substances and interferences. GOD MPs showed higher stability under various operation conditions than the free enzymes due to the MnCO3 template method, which enabled the biosensor to remain relative sensitivity at >86% over 9 days. The GOD MPs biosensor also showed high selectivity, reproducibility, and linear sensing range from 0 mM to 24 mM (R2 = 0.9993) with a current sensitivity of 25 nA/mM. The combination of porous-structured membrane and the flexible CNT meshes ensures the electrical connections and sensing accuracy of the biosensor under the deformation status. In-vivo experiments showed reliable current responses to variations in blood glucose concentrations that were consistent with tail blood test results. This co-immobilization of enzyme micro-particles in the 3D porous structure method developed a bio-composite platform technology towards the applications in flexible sensing and implantable medical devices.

Realization of linear-mapping between polarization Poincaré sphere and orbital Poincaré sphere based on stress birefringence in the few-mode fiber.

Based on the spatial profiles and polarization states evolution process of the first-order modes resulted from stress-induced birefringence in the few-mode fiber (FMF), we analyze the mapping relationship between the input polarization states represented on polarization PS and the output spatial profiles represented on the orbital PS of the FMF with respect to the magnitude and orientation of birefringence. When the input mode lobe orientation and the phase differences between the four eigenmodes of FMF induced by the stress birefringence satisfy a given condition, the mapping relationship between the input polarization PS and the output orbital PS is linear. Thus, the arbitrary points on the orbit PS can be generated at the output of stressed FMF by controlling the polarization state of the input modes. Then we experimentally verify that, an electrical single-mode polarization controller, a mode converter for converting fundamental mode to higher-order mode, a polarization controller mounting a coil of two-mode fiber and a polarizer can be employed to generate arbitrary first-order spatial modes on the orbital PS by controlling the input single-mode polarization states. The positions on the orbital PS of the generated first-order modes, which are obtained by calculating the three normalized Stokes parameters of output modes, agree well with the simulation ones. The correlation coefficients between the theoretical mode profiles and the experimental ones are higher than 80%. Since the spatial profile evolutions depend on the variations of the input polarization states, a potential advantage of this method is high-speed switching among desired first-order modes by using the commercial devices switching the state of polarization.

Kernel mapping for mitigating nonlinear impairments in optical short-reach communications.

Nonlinear impairments induced by the opto-electronic components are one of the fundamental performance-limiting factors in high-speed optical short-reach communications, significantly hindering capacity improvement. This paper proposes to employ a kernel mapping function to map the signals in a Hilbert space to its inner product in a reproducing kernel Hilbert space, which has been successfully demonstrated to mitigate nonlinear impairments in optical short-reach communication systems. The operation principle is derived. An intensity modulation/direct detection system with 1.5-µm vertical cavity surface emitting laser and 10-km 7-core fiber achieving 540.68-Gbps (net-rate 505.31-Gbps) has been carried out. The experimental results reveal that the kernel mapping based schemes are able to realize comparable transmission performance as the Volterra filtering scheme even with a high order.