UiO-66/AgNPs Coating for Dental Implants in Preventing Bacterial Infections.

Titanium (Ti)-based biomaterials lack inherent antimicrobial activities, and the dental plaque formed on the implant surface is one of the main risk factors for implant infections. Construction of an antibacterial surface can effectively prevent implant infections and enhance implant success. Silver nanoparticles (AgNPs) exhibit broad antibacterial activity and a low tendency to induce drug resistance, but AgNPs easily self-aggregate in the aqueous environment, which significantly impairs their antibacterial activity. In this study, UiO-66/AgNP (U/A) nanocomposite was prepared, where zirconium metal-organic frameworks (UiO-66) were employed as the confinement matrix to control the particle size and prevent aggregation of AgNPs. The bactericidal activity of U/A against methicillin-resistant Staphylococcus aureus and Escherichia coli increased nearly 75.51 and 484.50 times compared with individually synthesized Ag. The antibacterial mechanism can be attributed to the enhanced membrane rupture caused by the ultrafine AgNPs on UiO-66, leading to protein leakage and generation of intracellular reactive oxygen species. Then, U/A was loaded onto Ti substrates (Ti-U/A) by using self-assembly deposition methods to construct an antibacterial surface coating. Ti-U/A exhibited excellent antibacterial activities and desired biocompatibility both in vitro and in vivo. The U/A nanocomposite coating technique is thus expected to be used as a promising surface modification strategy for Ti-based dental implants for preventing dental implant infections.

Homologous-magnetic dual-targeted metal-organic framework to improve the Anti-hepatocellular carcinoma efficacy of PD-1 inhibitor.

The insufficient abundance and weak activity of tumour-infiltrating lymphocytes (TILs) are two important reasons for the poor efficacy of PD-1 inhibitors in hepatocellular carcinoma (HCC) treatment. The combined administration of tanshinone IIA (TSA) and astragaloside IV (As) can up-regulate the abundance and activity of TILs by normalising tumour blood vessels and reducing the levels of immunosuppressive factors respectively. For enhancing the efficacy of PD-1 antibody, a magnetic metal-organic framework (MOF) with a homologous tumour cell membrane (Hm) coating (Hm@TSA/As-MOF) is established to co-deliver TSA&As into the HCC microenvironment. Hm@TSA/As-MOF is a spherical nanoparticle and has a high total drug-loading capacity of 16.13 wt%. The Hm coating and magnetic responsiveness of Hm@TSA/As-MOF provide a homologous-magnetic dual-targeting, which enable Hm@TSA/As-MOF to counteract the interference posed by ascites tumour cells and enhance the precision of targeting solid tumours. Hm coating also enable Hm@TSA/As-MOF to evade immune clearance by macrophages. The release of TSA&As from Hm@TSA/As-MOF can be accelerated by HCC microenvironment, thereby up-regulating the abundance and activity of TILs to synergistic PD-1 antibody against HCC. This study presents a nanoplatform to improve the efficacy of PD-1 inhibitors in HCC, providing a novel approach for anti-tumour immunotherapy in clinical practice.

Competitive coordination assembly of light-degradable gold nanocluster-intercalated metal organic frameworks for photoresponsive drug release.

On-demand controlled drug release holds great promise for cancer therapy. Light-degradable nanocarriers have gained increasing attention for designing controllable drug delivery systems owing to their spatiotemporally controllable properties. Herein, a highly luminescent and light-degradable nanocarrier is constructed by intercalating glutathione-capped gold nanoclusters (AuNCs) into zeolitic imidazolate framework-8 (ZIF-8) via competitive coordination assembly, named AuNC@ZIF-8, for light-triggered drug release. Glutathione-capped AuNCs and 2-methylimidazole (MIm) competitively coordinated with Zn2+ to form AuNC@ZIF-8 using a one step process in an aqueous solution. Specifically, the obtained AuNC@ZIF-8 has a high quantum yield of 52.96% and displays a distinctive property of photolysis. Competitive coordination interactions within AuNC@ZIF-8 were evidenced by X-ray diffraction and X-ray photoelectron spectroscopy, in which Zn2+ strongly coordinated with the N of MIm and weakly coordinated with the carboxyl/amino groups in the glutathione of AuNCs. Under light irradiation, the Au-S bond in AuNCs breaks, enhancing the coordination ability between carboxyl/amino groups and Zn2+. This collapses the crystal structure of AuNC@ZIF-8 and causes subsequent fluorescence quenching. Additionally, AuNC@ZIF-8 is successfully employed as a luminescent nanocarrier of anticancer drugs to form drug-AuNC@ZIF-8, in which three typical anticancer drugs are selected due to different coordination interactions. The obtained smart drug-AuNC@ZIF-8 can be effectively internalized into HeLa cells and degraded in response to blue light, with negligible dark cytotoxicity and high light cytotoxicity. This study highlights the crucial role of competitive coordination interactions in synthesizing functional materials with fluorescence efficiency and photolytic properties.

Chitosan synergizes with bismuth-based metal-organic frameworks to construct double S-type heterojunctions for enhancing photocatalytic antimicrobial activity.

In recent years, photocatalytic technology has been introduced to develop a new kind antimicrobial agents fighting antibiotic abusing and related drug resistance. The efforts have focused on non-precious metal photocatalysts along with green additives. In the present work, a novel bis-S heterojunctions based on the coupling of polysaccharide (CS) and bismuth-based MOF (CAU-17) s synthesized through a two-step method involving amidation reaction under mild conditions. The as prepared photocatalyst literally extended the light response to the near-infrared region. Owing to its double S-type heterostructure, the lifetime of the photocarriers is significantly prolonged and the redox capacity are enhanced. As a result, the as prepared photocatalyst indicated inhibition up to 99.9 % under 20 min of light exposure against Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria as well as drug-resistant bacteria (MRSA). The outstanding photocatalytic performance is attributed to the effective charge separation and migration due to the unique double S heterostructure. Such a double S heterostructure was confirmed through transient photocurrent response, electrochemical impedance spectroscopy tests and electron spin resonance measurements. The present work provides a basis for the simple synthesis of high-performance heterojunction photocatalytic inhibitors, which extends the application of CAU-17 in environmental disinfection and wastewater purification.

Coordination Self-Assembled AuTPyP-Cu Metal-Organic Framework Nanosheets with pH/Ultrasound Dual-Responsiveness for Synergistically Triggering Cuproptosis-Augmented Chemotherapy.

Reactive oxygen species (ROS) mediated tumor cell death is a powerful anticancer strategy. Cuproptosis is a copper-dependent and ROS-mediated prospective tumor therapy strategy. However, the complex tumor microenvironment (TME), low tumor specificity, poor therapy efficiency, and lack of imaging capability impair the therapy output of current cuproptosis drugs. Herein, we designed a dual-responsive two-dimensional metal-organic framework (2D MOF) nanotheranostic via a coordination self-assembly strategy using Au(III) tetra-(4-pyridyl) porphine (AuTPyP) as the ligand and copper ions (Cu2+) as nodes. The dual-stimulus combined with the protonation of the pyridyl group in AuTPyP and deep-penetration ultrasound (US) together triggered the controlled release in an acidic TME. The ultrathin structure (3.0 nm) of nanotheranostics promoted the release process. The released Cu2+ was reduced to Cu+ by depleting the overexpressed glutathione (GSH) in the tumor, which not only activated the Ferredoxin 1 (FDX1)-mediated cuproptosis but also catalyzed the overexpressed hydrogen peroxide (H2O2) in the tumor into reactive oxygen species via Fenton-like reaction. Simultaneously, the released AuTPyP could specifically bind with thioredoxin reductase and activate the redox imbalance of tumor cells. These together selectively induced significant mitochondrial vacuoles and prominent tumor cell death but did not damage the normal cells. The fluorescence and magnetic resonance imaging (MRI) results verified this nanotheranostic could target the HeLa tumor to greatly promote the self-enhanced effect of chemotherapy/cuproptosis and tumor inhibition efficiency. The work helped to elucidate the controlled assembly of multiresponsive nanotheranostics and the high-specificity ROS regulation for application in anticancer therapy.

Covalent organic framework based cytoprotective therapy after ischemic stroke.

Cytoprotection has emerged as an effective therapeutic strategy for mitigating brain injury following acute ischemic stroke (AIS). The sulfonylurea receptor 1-transient receptor potential M4 (SUR1-TRPM4) channel plays a pivotal role in brain edema and neuroinflammation. However, the practical use of the inhibitor glyburide (GLB) is hindered by its low bioavailability. Additionally, the elevated reactive oxygen species (ROS) after AIS exacerbate SUR1-TRPM4 activation, contributing to irreversible brain damage. To overcome these challenges, GLB and superoxide dismutase (SOD) were embedded in a covalent organic framework (COF) with a porous structure and great stability. The resulting S/G@COF demonstrated significant improvements in survival and neurological functions. This was achieved by eliminating ROS, preventing neuronal loss and apoptosis, suppressing neuroinflammation, modulating microglia activation, and ameliorating blood-brain barrier (BBB) disruption. Mechanistic investigations revealed that S/G@COF concurrently activated the Wnt/ß-catenin signaling pathway while suppressing the upregulation of SUR1-TRPM4. This study underscores the potential of employing multi-target therapy and drug modification in cytoprotective strategies for ischemic stroke.

A review of recent advancement in covalent organic framework (COFs) synthesis and characterization with a focus on their applications in antibacterial activity.

The primary objective of this review is to present a comprehensive examination of the synthesis, characterization, and antibacterial applications of covalent organic frameworks (COFs). COFs represent a distinct category of porous materials characterized by a blend of advantageous features, including customizable pore dimensions, substantial surface area, and adaptable chemical properties. These attributes position COFs as promising contenders for various applications, notably in the realm of antibacterial activity. COFs exhibit considerable potential in the domain of antibacterial applications, owing to their amenability to functionalization with antibacterial agents. The scientific community is actively exploring COFs that have been imbued with metal ions, such as copper or silver, given their observed robust antibacterial properties. These investigations strongly suggest that COFs could be harnessed effectively as potent antibacterial agents across a diverse array of applications. Finally, COFs hold immense promise as a novel class of materials for antibacterial applications, shedding light on the synthesis, characterization, and functionalization of COFs tailored for specific purposes. The potential of COFs as effective antibacterial agents beckons further exploration and underscores their potential to revolutionize antibacterial strategies in various domains.

Crown-ether threaded covalent organic polyrotaxane framework (COPF) towards synergistic crown/Zn2+/photothermal/photodynamic antibacterial and infected wound healing therapy.

Controllable preparation of materials with new structure has always been the top priority of polymer materials science research. Here, the supramolecular binding strategy is adopted to develop covalent organic frameworks (COFs) with novel structures and functions. Based on this, a two-dimensional crown-ether ring threaded covalent organic framework (COF), denoted as Crown-COPF with intrinsic photothermal (PTT) and photodynamic (PDT) therapeutic capacity, was facilely developed using crown-ether threaded rotaxane and porphyrin as building blocks. Crown-COPF with discrete mechanically interlocked blocks in the open pore could be used as a molecular machine, in which crown-ether served as the wheel sliding along the axle under the laser stimulation. As a result, Crown-COPF combining with the bactericidal power of crown ether displayed a significant photothermal and photodynamic antibacterial activity towards both the Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus), far exceeding the traditional Crown-free COF. Noteworthily, the bactericidal performance could be further enhanced via impregnation of Zn2+ ions (Crown-COPF-Zn) flexible coordinated with the multiple coordination sites (crown-ether, bipyridine, and porphyrin), which not only endow the positive charge with the skeleton, enhancing its ability to bind to the bacterial membrane, but also introduce the bactericidal ability of zinc ions. Notably, in vivo experiments on mice with back infections indicates Crown-COPF-Zn with self-adaptive multinuclear zinc center, could effectively promote the repairing of wounds. This study paves a new avenue for the effectively preparation of porous polymers with brand new structure, which provides opportunities for COF and mechanically interlocked polymers (MIPs) research and applications.

Silk Fibroin-Coated Nano-MOFs Enhance the Thermal Stability and Immunogenicity of HBsAg.

Vaccines are widely regarded as one of the most effective weapons in the fight against infectious diseases. Currently, vaccines must be stored and transported at low temperatures as high temperatures can lead to a loss of vaccine conformation and reduced therapeutic efficacy. Metal-organic frameworks (MOFs), such as zeolitic imidazole framework-8 (ZIF-8), are a new class of hybrid materials with large specific surface areas, high loading rates, and good biocompatibility and are successful systems for vaccine delivery and protection. Silk fibroin (SF) has a good biocompatibility and thermal stability. In this study, the hepatitis B surface antigen (HBsAg) was successfully encapsulated in ZIF-8 to form HBsAg@ZIF-8 (HZ) using a one-step shake and one-pot shake method. Subsequently, the SF coating modifies HZ through hydrophobic interactions to form HBsAg/SF@ZIF-8 (HSZ), which enhanced the thermal stability and immunogenicity of HBsAg. Compared to free HBsAg, HZ and HSZ improved the thermostability of HBsAg, promoted the antigen uptake and lysosomal escape, stimulated dendritic cell maturation and cytokine secretion, formed an antigen reservoir to promote antibody production, and activated CD4+ T and CD8+ T cells to enhance memory T-cell production. Importantly, HSZ induced a strong immune response even after 14 days of storage at 25 °C. Furthermore, the nanoparticles prepared by the one-step shake method exhibited superior properties compared to those prepared by the one-pot shake method. This study highlights the importance of SF-coated ZIF-8, which holds promise for investigating thermostable vaccines and breaking the vaccine cold chain.

Postsynthetic Modification of Thermo-Treated Metal-Organic Framework for Combined Photothermal/Photodynamic Antibacterial Therapy.

Metal-organic frameworks (MOFs) are emerging porous materials that can serve as carriers of photosensitizers and photothermal agents. Meanwhile, a large number of active sites in MOFs endow them with the characteristics of modification by postsynthetic modification. Herein, a dual-modal PDT/PTT therapeutic agent HMIL-121-acriflavine-tetrakis (4-amoniophenyl) porphyrin (HMIL-ACF-Por), prepared by the postsynthetic modification of the MOF (HMIL-121), was reported for antibacterial applications. The prepared HMIL-ACF-Por enables the generation of abundant reactive oxygen species, including the superoxide anion radical (O2-) and singlet oxygen (1O2), and thermal energy under 808 nm NIR laser irradiation. HMIL-ACF-Por showed good antibacterial ability against Escherichia coli and Staphylococcus aureus in vitro. Meanwhile, HMIL-ACF-Por can effectively inhibit the inflammatory response caused by bacterial infection and accelerate S. aureus-infected wound healing under laser irradiation owing to the synergistic effect of photodynamic therapy (PDT) and photothermal therapy (PTT). These results demonstrate that HMIL-ACF-Por is a promising PDT/PTT therapeutic agent. This work also contributes to offering an effective solution for treating bacterial infections and promotes the application of MOF-based materials in biomedicine.

Research progress on antibacterial applications of metal-organic frameworks and their biomacromolecule composites.

With the extensive use of antibiotics, resulting in increasingly serious problems of bacterial resistance, antimicrobial therapy has become a global concern. Metal-organic frameworks (MOFs) are low-density porous coordination materials composed of metal ions and organic ligands, which can form composite materials with biomacromolecules such as proteins and polysaccharides. In recent years, MOFs and their derivatives have been widely used in the antibacterial field as efficient antibacterial agents. This review offers a detailed summary of the antibacterial applications of MOFs and their composites, and the different synthesis methods and antibacterial mechanisms of MOFs and MOF-based composites are briefly introduced. Finally, the challenges and prospects of MOFs-based antibacterial materials in the rapidly developing medical field were briefly discussed. We hope this review will provide new strategies for the medical application of MOFs-based antibacterial materials.

MOF@COF Nanocapsules Enhance Soft Tissue Sarcoma Treatment: Synergistic Effects of Photodynamic Therapy and PARP Inhibition on Tumor Growth Suppression and Immune Response Activation.

Soft tissue sarcomas (STS) are highly malignant tumors with limited treatment options owing to their heterogeneity and resistance to conventional therapies. Photodynamic therapy (PDT) and poly-ADP-ribose polymerase (PARP) inhibitors (PARPi) have shown potential for STS treatment, with PDT being effective for sarcomas located on the extremities and body surface and PARPi targeting defects in homologous recombination repair. To address the limitations of PDT and harness the potential of PARPi, herein, a novel therapeutic approach for STS treatment combining nanocapsules bearing integrated metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), i.e., MOF@COF, with PDT and PARPi is proposed. Nanocapsules are designed, referred to as ZTN@COF@poloxamer, which contain a Zr-based MOF and tetrakis (4-carbethoxyphenyl) porphyrin as a photosensitizer, are coated with a COF to improve the sensitizing properties, and are loaded with niraparib to inhibit DNA repair. Experiments demonstrate that this new nanocapsules treatment significantly inhibits STS growth, promotes tumor cell apoptosis, exhibits high antitumor activity with minimal side effects, activates the immune response of the tumor, and inhibits lung metastasis in vivo. Therefore, MOF@COF nanocapsules combined with PARPi offer a promising approach for STS treatment, with the potential to enhance the efficacy of PDT and prevent tumor recurrence.

Symmetrical Localized Built-in Electric Field by Induced Polarization Effect in Ionic Covalent Organic Frameworks for Selective Imaging and Killing Bacteria.

Photocatalytic materials are some of the most promising substitutes for antibiotics. However, the antibacterial efficiency is still inhibited by the rapid recombination of the photogenerated carriers. Herein, we design a cationic covalent organic framework (COF), which has a symmetrical localized built-in electric field due to the induced polarization effect caused by the electron-transfer reaction between the Zn-porphyrin unit and the guanidinium unit. Density functional theory calculations indicate that there is a symmetrical electrophilic/nucleophilic region in the COF structure, which results from increased electron density around the Zn-porphyrin unit. The formed local electric field can further inhibit the recombination of photogenerated carriers by driving rapid electron transfer from Zn-porphyrin to guanidinium under light irradiation, which greatly increases the yield of reactive oxygen species. This COF wrapped by DSPE-PEG2000 can selectively target the lipoteichoic acid of Gram-positive bacteria by electrostatic interaction, which can be used for selective discrimination and imaging of bacteria. Furthermore, this nanoparticle can rapidly kill Gram-positive bacteria including 99.75% of Staphylococcus aureus and 99.77% of Enterococcus faecalis at an abnormally low concentration (2.00 ppm) under light irradiation for 20 min. This work will provide insight into designing photoresponsive COFs through engineering charge behavior.

Fabrication of a Nanoscale Magnesium/Copper Metal-Organic Framework on Zn-Based Guided Bone Generation Membranes for Enhancing Osteogenesis, Angiogenesis, and Bacteriostasis Properties.

Recently, zinc (Zn) and its alloys have demonstrated great potential as guided bone regeneration (GBR) membranes to treat the problems of insufficient alveolar bone volume and long-term osseointegration instability during dental implantology. However, bone regeneration is a complex process consisting of osteogenesis, angiogenesis, and antibacterial function. For now, the in vivo osteogenic performance and antibacterial activity of pure Zn are inadequate, and thus fabricating a platform to endow Zn membranes with multifunctions may be essential to address these issues. In this study, various bimetallic magnesium/copper metal-organic framework (Mg/Cu-MOF) coatings were fabricated and immobilized on pure Zn. The results indicated that the degradation rate and water stability of Mg/Cu-MOF coatings could be regulated by controlling the feeding ratio of Cu2+. As the coating and Zn substrate degraded, an alkaline microenvironment enriched with Zn2+, Mg2+, and Cu2+ was generated. It significantly improved calcium phosphate deposition, differentiation of osteoblasts, and vascularization of endothelial cells in the extracts. Among them, Mg/Cu1 showed the best comprehensive performance. The superior antibacterial activity of Mg/Cu1 was demonstrated in vitro and in vivo, which indicated significantly enhanced bacteriostatic activity against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli as compared to that of the bare sample. Bimetallic Mg/Cu-MOF coating could properly coordinate the multifunction on a Zn membrane and could be a promising platform for promoting its bone regeneration, which could pave the way for Zn-based materials to be used as barrier membranes in oral clinical trials.

A Lactate-Depleting metal organic framework-based nanocatalyst reinforces intratumoral T cell response to boost anti-PD1 immunotherapy.

Infiltration and activation of intratumoral T lymphocytes are critical for immune checkpoint blockade (ICB) therapy. Unfortunately, the low tumor immunogenicity and immunosuppressive tumor microenvironment (TME) induced by tumor metabolic reprogramming cooperatively hinder the ICB efficacy. Herein, we engineered a lactate-depleting MOF-based catalytic nanoplatform (LOX@ZIF-8@MPN), encapsulating lactate oxidase (LOX) within zeolitic imidazolate framework-8 (ZIF-8) coupled with a coating of metal polyphenol network (MPN) to reinforce T cell response based on a "two birds with one stone" strategy. LOX could catalyze the degradation of the immunosuppressive lactate to promote vascular normalization, facilitating T cell infiltration. On the other hand, hydrogen peroxide (H2O2) produced during lactate depletion can be transformed into anti-tumor hydroxyl radical (•OH) by the autocatalytic MPN-based Fenton nanosystem to trigger immunogenic cell death (ICD), which largely improved the tumor immunogenicity. The combination of ICD and vascular normalization presents a better synergistic immunopotentiation with anti-PD1, inducing robust anti-tumor immunity in primary tumors and recurrent malignancies. Collectively, our results demonstrate that the concurrent depletion of lactate to reverse the immunosuppressive TME and utilization of the by-product from lactate degradation via cascade catalysis promotes T cell response and thus improves the effectiveness of ICB therapy.

Sustainable Gold Nanoparticle (Au-NP) Growth within Interspaces of Porphyrinic Zirconium-Based Metal-Organic Frameworks: Green Synthesis of PCN-224/Au-NPs and Its Anticancer Effect on Colorectal Cancer Cells Assay.

In this work, a simple green synthesis method of the novel metal-organic framework (MOF) nanocomposite PCN-224/Au-NPs (Au-NPs = gold nanoparticles) is described. In this regard, initially, PCN-224 was synthesized. Afterward, in a single-step, one-pot procedure, under visible-light irradiation, Au-NPs were fabricated on PCN-224. The cytotoxicity effect of the synthesized PCN-224/Au-NPs nanocomposite was investigated in human colon cancer cells. Determination of the apoptosis induction was done by the Annexin- V/propidium iodide flow cytometry method. Besides, to ascertain the biocompatibility of the synthesized sample, the cytotoxicity of PCN-224/Au-NPs was evaluated on the human embryonic kidney (HEK)-293 cell line. The substantial anticancer activity with the biocompatibility of the structure, the green facile synthesis, and the MOF surface of the synthesized nanocomposite make it special for utilization in therapeutic applications.

Development of Novel Chimeric Endolysin Conjugated with Chitosan-Zn-Metal-Organic Framework Nanocomposites with Antibacterial Activity.

Bacterial diseases have been considered the most crucial issue and are threatening human health all around the world. Also, resistance to antimicrobial drugs has become a big hurdle against efficient therapy. As a result, recombinant chimeric endolysin was produced in E. coli host to use as a potential antibacterial agent against bacteria resistance and replacement to conventional antibiotics in this study. Then, chitosan (C)-coated nanoscale metal-organic frameworks (CS-NMOFs) nanocomposite was synthesized as a novel nano delivery system to further improve the antibacterial activity of endolysin. After characterization of nanocomposite with analytical devices such as FT-IR, DLS, and TEM and determining the nanometric size of samples (30 nm to 90 nm), endolysin was covalently (endolysin-CS-NMOFs (C)) and non-covalently (endolysin-CS-NMOFs (NC)) conjugated to nanocomposite. Thereafter, the lytic ability, synergistic interaction, and biofilm reduction manner of endolysin-containing CS-NMOF nanocomposites were evaluated on E. coli, S. aureus, and P. aeruginosa strains. The results depicted an excellent lytic ability of nanocomposites after 24 h and 48 h of treatment, especially endolysin-CS-NMOFs (NC) on E. coli and P. aeruginosa strains. The synergistic interaction between nanocomposite and vancomycin did not attain for P. aeruginosa strain whereas the reverse was true for E. coli and S. aureus strains at 8 ng/mL concentration. Next, nanocomposites demonstrated potential biofilm reduction activities in various strains, especially in S. aureus and P. aeruginosa. Ultimately, our outputs demonstrate an efficient performance of the synthesized nanocomposite as an appropriate substitution for conventional antibiotics against bacteria.

pH-responsive double-enzyme active metal-organic framework for promoting the healing of infected wounds.

The abuse of antibiotics accelerates the spread and evolution of drug-resistant bacteria, which seriously threatens human health. Hydroxyl radicals (•OH) are generated by peroxidase in the presence of H2O2, which is strongly oxidizing and can effectively kill bacteria. However, high production costs and poor stability limit the clinical use of natural enzymes. "Nanozyme" is a general term for nanomaterials with catalytic activity similar to that of biological enzymes. Compared to biological enzymes, nanozymes have the advantages of low cost, facile preparation, and easy storage, making them a good choice for the development of antibacterial agents. Here, a nickel-based metal-organic framework (Ni-MOF) with dual enzymatic activity that switches depending on the pH environment was studied. In a slightly acidic environment, Ni-MOF can react with hydrogen peroxide to produce hydroxyl radicals that kill bacteria; in a neutral environment, Ni-MOF instead removes excessive reactive oxygen species (ROS) and promotes the transformation of macrophages into M2 macrophages. Compared to most nanozymes, Ni-MOF has unique electrical conductivity and better biosafety. The results of animal experiments show that Ni-MOF can not only treat infected wounds but also promote the healing of acute wounds and exhibits great clinical application potential.

Copper-gallate metal-organic framework encapsulated multifunctional konjac glucomannan microneedles patches for promoting wound healing.

An ideal chronic wound dressing needs to have some properties, such as antibacterial, antioxidant, regulating macrophage polarization and promoting angiogenesis. This work presents a microneedle patch fabricated from oxidized konjac glucomannan (OKGM-MNs), in which Copper-gallate metal-organic framework (CuGA-MOF) is encapsulated for wound healing (denoted as CuGA-MOF@OKGM-MNs). CuGA-MOF is composed of Cu2+ and gallic acid (GA), which are released through microneedles in the deep layer of the dermis. The released Cu2+ is able to act as an antibacterial agent and promote angiogenesis, while GA as a reactive oxygen species scavenger displays antioxidant activity. More attractively, the material OKGM used to prepare the microneedle patch is not only a drug carrier but also plays a role in promoting macrophage polarization M2 phenotype. In vitro experiments showed that CuGA-MOF@OKGM-MNs had good antibacterial and antioxidant properties. The therapeutic effect on wound healing has been confirmed in full-thickness skin wounds of diabetes mice models, which showed that the wound could be completely healed within 21 days under the treatment of CuGA-MOF@OKGM-MNs, and the healing effect was better than other groups. These indicated that the proposed CuGA-MOF@OKGM-MNs could be applicable in the treatment of clinical wound healing.

Spatial targeting of fibrosis-promoting macrophages with nanoscale metal-organic frameworks for idiopathic pulmonary fibrosis therapy.

Targeted delivery of therapeutic drugs to fibrosis-promoting macrophages (FPMs) holds promise as a challenging yet effective approach for the treatment of idiopathic pulmonary fibrosis (IPF). Here, nanocarriers composed of Mn-curcumin metal-organic frameworks (MOFs) were utilized to deliver the immune inhibitor BLZ-945 to the lungs, with the goal of depleting fibrosis-promoting macrophages (FPMs) from fibrotic lung tissues. FPM targeting was achieved by functionalizing the nanocarrier surface with an M2-like FPM binding peptide (M2pep). As a result, significant therapeutic benefits were observed through the successful depletion of approximately 80 % of the M2-like macrophages (FPMs) in a bleomycin-induced fibrosis mouse model treated with the designed M2-like FPM-targeting nanoparticle (referred to as M2NP-BLZ@Mn-Cur). Importantly, the released Mn2+ and curcumin after the degradation of M2NP-BLZ@Mn-Cur accumulated in the fibrotic lung tissue, which can alleviate inflammation and oxidative stress reactions, thereby further improving IPF therapy. This study presents a novel strategy with promising prospects for molecular-targeted fibrosis therapy. STATEMENT OF SIGNIFICANCE: Metal-organic frameworks (MOFs)- based nanocarriers equipped with both fibrosis-promoting macrophage (FPM)-specific targeting ability and therapeutic drugs are appealing for pulmonary fibrosis treatment. Here, we prepared M2pep (an M2-like FPM binding peptide)-modified and BLZ945 (a small molecule inhibitor of CSF1/CSF-1R axis)-loaded Mn-curcumin MOF nanoparticles (M2NP-BLZ@Mn-Cur) for pulmonary fibrosis therapy. The functionalized M2NP-BLZ@Mn-Cur nanoparticles can be preferentially taken up by FPMs, resulting in their depletion from fibrotic lung tissues. In addition, Mn2+and curcumin released from the nanocarriers have anti-inflammation and immune regulation effects, which further enhance the antifibrotic effect of the nanoparticles.