Surfactant-Impregnated MOF-Coated Fabric for Antimicrobial Applications.

Since the onset of the SARS-CoV-2 pandemic, the world has witnessed over 617 million confirmed cases and more than 6.54 million confirmed deaths, but the actual totals are likely much higher. The virus has mutated at a significantly faster rate than initially projected, and positive cases continue to surge with the emergence of ever more transmissible variants. According to the CDC, and at the time of this manuscript submission, more than 77% of all current US cases are a result of the B.5 (omicron). The continued emergence of highly transmissible variants makes clear the need for more effective methods of mitigating disease spread. Herein, we have developed an antimicrobial fabric capable of destroying a myriad of microbes including betacoronaviruses. We have demonstrated the capability of this highly porous and nontoxic metal organic framework (MOF), γ-CD-MOF-1, to serve as a host for varied-length benzalkonium chlorides (BACs; active ingredient in Lysol). Molecular docking simulations predicted a binding affinity of up to -4.12 kcal·mol-1, which is comparable to that of other reported guest molecules for this MOF. Similar Raman spectra and powder X-ray diffraction patterns between the unloaded and loaded MOFs, accompanied by a decrease in the Brunauer-Emmett-Teller surface area from 616.20 and 155.55 m2 g-1 respectively, corroborate the suggested potential for pore occupation with BAC. The MOF was grown on polypropylene fabric, exposed to a BAC-loading bath, washed to remove excess BAC from the external surface, and evaluated for its microbicidal activity against various bacterial and viral classes. Significant antimicrobial character was observed against Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, bacteriophage, and betacoronavirus. This study shows that a common mask material (polypropylene) can be coated with BAC-loaded γ-CD-MOF-1 while maintaining the guest molecule's antimicrobial effects.

A computational study of metal-organic frameworks (MOFs) as potential nanostructures to combat SARS-CoV-2.

The COVID-19 causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a critical surface protein called spike protein (S protein), which is the target of many vaccines and drugs developments. Among non-structural proteins of SARS-CoV-2, main protease (M^pro) has drawn much attention to itself for designing antiviral drugs since it is very crucial for the virus replication in host cells. In the first part of the present study, the application of metal-organic frameworks (MOFs), one of the developing nanomaterials in the deformation and consequently inhibition of S protein binding to the receptor, angiotensin-converting enzyme 2 (ACE 2), is investigated. In this line, various S protein inhibitors were designed virtually, including ZIF, UIO, and IRMOF that their interactions with S protein and were investigated using molecular dynamics (MD) simulation. The results revealed that ZIF is the best candidate among the investigated MOFs with the least amount of energy interference with S protein. In the second part, the interaction of three-dimensional (3D) MOFs (such as ZIF, IRMOF, and HKUST) with SARS-CoV-2 M^pro was investigated. HKUST had the most potent interaction with M^pro and showed more promise in deforming this protein's secondary structure among all materials tested. Furthermore, we investigated the interaction of HKUST-OH with M^pro to determine the effect of functionalization. The findings of this study could be used in future studies to introduce bioconjugates of MOFs and biological molecules (e.g., antibody or nanobody) or to use MOFs as carriers for antiviral drug delivery.

Photocatalytic Biocidal Coatings Featuring Zr6Ti4-Based Metal-Organic Frameworks.

The world is currently suffering socially, economically, and politically from the recent pandemic outbreak due to the coronavirus disease 2019 (COVID-19), and those in hospitals, schools, and elderly nursing homes face enhanced threats. Healthcare textiles, such as masks and medical staff gowns, are susceptible to contamination of various pathogenic microorganisms, including bacteria and viruses. Metal-organic frameworks (MOFs) can potentially address these challenges due to their tunable reactivity and ability to be incorporated as porous coatings on textile materials. Here, we report how incorporating titanium into the zirconium-pyrene-based MOF NU-1000, denoted as NU-1012, generates a highly reactive biocidal photocatalyst. This MOF features a rare ligand migration phenomenon, and both the Ti/Zr center and the pyrene linker act synergistically as dual active centers and widen the absorption band for this material, which results in enhanced reactive oxygen species generation upon visible light irradiation. Additionally, we found that the ligand migration process is generally applicable to other csq topology Zr-MOFs. Importantly, NU-1012 can be easily incorporated onto cotton textile cloths as a coating, and the resulting composite material demonstrates fast and potent biocidal activity against Gram-negative bacteria (Escherichia coli), Gram-positive bacteria (Staphylococcus epidermidis), and T7 bacteriophage virus with up to a 7-log(99.99999%) reduction within 1 h under simulated daylight.

Metal-organic frameworks as a therapeutic strategy for lung diseases.

Lung diseases remain a global burden today. Lower respiratory tract infections alone cause more than 3 million deaths worldwide each year and are on the rise every year. In particular, with coronavirus disease raging worldwide since 2019, we urgently require a treatment for lung disease. Metal organic frameworks (MOFs) have a broad application prospect in the biomedical field due to their remarkable properties. The unique properties of MOFs allow them to be applied as delivery materials for different drugs; diversified structural design endows MOFs with diverse functions; and they can be designed as various MOF-drug synergistic systems. This review concentrates on the synthesis design and applications of MOF based drugs against lung diseases, and discusses the possibility of preparing MOF-based inhalable formulations. Finally, we discuss the chances and challenges of using MOFs for targeting lung diseases in clinical practice.

Anti-Influenza Virus Study of Composite Material with MIL-101(Fe)-Adsorbed Favipiravir.

Nanomaterial technology has attracted much attention because of its antibacterial and drug delivery properties, among other applications. Metal-organic frameworks (MOFs) have advantages, such as their pore structure, large specific surface area, open metal sites, and chemical stability, over other nanomaterials, enabling better drug encapsulation and adsorption. In two examples, we used the common pathogenic bacterium Staphylococcus aureus and highly infectious influenza A virus. A novel complex MIL-101(Fe)-T705 was formed by synthesizing MOF material MIL-101(Fe) with the drug favipiravir (T-705), and a hot solvent synthesis method was applied to investigate the in vitro antibacterial and antiviral activities. The results showed that MIL-101(Fe)-T705 combined the advantages of nanomaterials and drugs and could inhibit the growth of Staphylococcus aureus at a concentration of 0.0032 g/mL. Regarding the inhibition of influenza A virus, MIL-101(Fe)-T705 showed good biosafety at 12, 24, 48, and 72 h in addition to a good antiviral effect at concentrations of 0.1, 0.2, 0.4, 0.8, 1.6, and 3 µg/mL, which were higher than MIL-101(Fe) and T-705.

Microencapsulated Isoniazid-Loaded Metal-Organic Frameworks for Pulmonary Administration of Antituberculosis Drugs.

Tuberculosis (TB) is an infectious disease that causes a great number of deaths in the world (1.5 million people per year). This disease is currently treated by administering high doses of various oral anti-TB drugs for prolonged periods (up to 2 years). While this regimen is normally effective when taken as prescribed, many people with TB experience difficulties in complying with their medication schedule. Furthermore, the oral administration of standard anti-TB drugs causes severe side effects and widespread resistances. Recently, we proposed an original platform for pulmonary TB treatment consisting of mannitol microspheres (Ma MS) containing iron (III) trimesate metal-organic framework (MOF) MIL-100 nanoparticles (NPs). In the present work, we loaded this system with the first-line anti-TB drug isoniazid (INH) and evaluated both the viability and safety of the drug vehicle components, as well as the cell internalization of the formulation in alveolar A549 cells. Results show that INH-loaded MOF (INH@MIL-100) NPs were efficiently microencapsulated in Ma MS, which displayed suitable aerodynamic characteristics for pulmonary administration and non-toxicity. MIL-100 and INH@MIL-100 NPs were efficiently internalized by A549 cells, mainly localized in the cytoplasm. In conclusion, the proposed micro-nanosystem is a good candidate for the pulmonary administration of anti-TB drugs.

Immobilized Regenerable Active Chlorine within a Zirconium-Based MOF Textile Composite to Eliminate Biological and Chemical Threats.

The most recent global health crisis caused by the SARS-CoV-2 outbreak and the alarming use of chemical warfare agents highlight the necessity to produce efficient protective clothing and masks against biohazard and chemical threats. However, the development of a multifunctional protective textile is still behind to supply adequate protection for the public. To tackle this challenge, we designed multifunctional and regenerable N-chlorine based biocidal and detoxifying textiles using a robust zirconium metal-organic framework (MOF), UiO-66-NH2, as a chlorine carrier which can be easily coated on textile fibers. A chlorine bleaching converted the amine groups located on the MOF linker to active N-chlorine structures. The fibrous composite exhibited rapid biocidal activity against both Gram-negative bacteria (E. coli) and Gram-positive bacteria (S. aureus) with up to a 7 log reduction within 5 min for each strain as well as a 5 log reduction of SARS-CoV-2 within 15 min. Moreover, the active chlorine loaded MOF/fiber composite selectively and rapidly degraded sulfur mustard and its chemical simulant 2-chloroethyl ethyl sulfide (CEES) with half-lives less than 3 minutes. The versatile MOF-based fibrous composite designed here has the potential to serve as protective cloth against both biological and chemical threats.

Bioinspired Spiky Peroxidase-Mimics for Localized Bacterial Capture and Synergistic Catalytic Sterilization.

Besides the pandemic caused by the coronavirus outbreak, many other pathogenic microbes also pose a devastating threat to human health, for instance, pathogenic bacteria. Due to the lack of broad-spectrum antibiotics, it is urgent to develop nonantibiotic strategies to fight bacteria. Herein, inspired by the localized "capture and killing" action of bacteriophages, a virus-like peroxidase-mimic (V-POD-M) is synthesized for efficient bacterial capture (mesoporous spiky structures) and synergistic catalytic sterilization (metal-organic-framework-derived catalytic core). Experimental and theoretical calculations show that the active compound, MoO3 , can serve as a peroxo-complex-intermediate to reduce the free energy for catalyzing H2 O2 , which mainly benefits the generation of •OH radicals. The unique virus-like spikes endow the V-POD-M with fast bacterial capture and killing abilities (nearly 100% at 16 µg mL-1 ). Furthermore, the in vivo experiments show that V-POD-M possesses similar disinfection treatment and wound skin recovery efficiencies to vancomycin. It is suggested that this inexpensive, durable, and highly reactive oxygen species (ROS) catalytic active V-POD-M provides a promising broad-spectrum therapy for nonantibiotic disinfection.

Cracking the Chloroquine Conundrum: The Application of Defective UiO-66 Metal-Organic Framework Materials to Prevent the Onset of Heart Defects-In Vivo and In Vitro.

In this study, we present a modulated synthesis nanocrystalline defective UiO-66 metal-organic framework as a potential chloroquine diphosphate (CQ) delivery system. Increasing the concentration of hydrochloric acid during the modulated synthesis resulted in a considerable increase of pore volume, which enhanced the CQ loading in CQ@UiO-66 composites. Drug release tests for CQ@UiO-66 composites have confirmed prolonged CQ release in comparison with pure CQ. In vivo tests on a Danio reiro model organism have revealed that CQ released from CQ@UiO-66 25% showed lower toxicity and fewer cardiotoxic effects manifested by cardiac malformations and arrhythmia in comparison to analogous doses of CQ. Cytotoxicity tests proved that the CQ loaded on the defective UiO-66 cargo resulted in increased viability of cardiac cells (H9C2) as compared to incubation with pure CQ. The experimental results presented here may be a step forward in the context of reducing the cardiotoxicity CQ.