Coupling metal organic frameworks nanozyme with carbon nanotubes on the gradient porous hollow fiber membrane for nonenzymatic electrochemical H2O2 detection.

In this paper, we present a gradient porous hollow fiber structure integrated the signal transduction within a microspace, serving as a platform for cellular metabolism monitoring. We developed a nonenzymatic electrochemical electrode by coupling carbon nanotubes (CNT) and metal organic frameworks (MOF) nanozyme on three-dimensional (3D) gradient porous hollow fiber membrane (GPF) for in-situ detection of cell released hydrogen peroxide (H2O2). The GPF was used as a substrate for cell culture as well as the supporting matrix of the working electrode. The ultrasonically coupled CNT@MOF composite was immobilized on the outer surface of the GPF by means of pressure filtration. Notably, the MOF, acting as a peroxidase mimic, exhibits superior stability compared to traditional horseradish peroxidase. The incorporation of CNT not only provided sufficient specific surface area to improve the uniform distribution of MOF nanozyme, but also formed 3D conductive network. This network efficiently facilitates the electrons transfer during the catalytic process of the MOF, addressing the inherent poor conductivity of MOFs. The GPF-CNT@MOF nonenzymatic bioelectrode demonstrated excellent electrocatalytic performance including rapid response, satisfactory sensing selectivity, and attractive stability, which enabled the development of a robust in-situ cellular metabolic monitoring platform.

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.

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.

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.

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.

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.