RESUMEN
Co-immobilization of cells and enzymes is often essential for the cascade biocatalytic processes of industrial-scale feasibility but remains a vast challenge. Herein, we create a facile co-immobilization platform integrating enzymes and cells in covalent organic frameworks (COFs) to realize the highly efficient cascade of inulinase and E. coli for bioconversion of natural products. Enzymes can be uniformly immobilized in the COF armor, which coats on the cell surface to produce cascade biocatalysts with high efficiency, stability and recyclability. Furthermore, this one-pot in situ synthesis process facilitates a gram-scale fabrication of enzyme-cell biocatalysts, which can generate a continuous-flow device conversing inulin to D-allulose, achieving space-time yield of 161.28 g L-1 d-1 and high stability (remaining >90% initial catalytic efficiency after 7 days of continuous reaction). The created platform is applied for various cells (e.g., E. coli, Yeast) and enzymes, demonstrating excellent universality. This study paves a pathway to break the bottleneck of extra- and intracellular catalysis, creates a high-performance and customizable platform for enzyme-cell cascade biomanufacturing, and expands the scope of biocatalysis process intensification.
Asunto(s)
Biocatálisis , Células Inmovilizadas , Enzimas Inmovilizadas , Escherichia coli , Glicósido Hidrolasas , Escherichia coli/metabolismo , Enzimas Inmovilizadas/metabolismo , Enzimas Inmovilizadas/química , Glicósido Hidrolasas/metabolismo , Glicósido Hidrolasas/química , Células Inmovilizadas/metabolismo , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/metabolismo , Saccharomyces cerevisiae/metabolismoRESUMEN
Continuously monitoring neurotransmitter dynamics can offer profound insights into neural mechanisms and the etiology of neurological diseases. Here, we present a miniaturized implantable fluorescence probe integrated with metal-organic frameworks (MOFs) for deep brain dopamine sensing. The probe is assembled from physically thinned light-emitting diodes (LEDs) and phototransistors, along with functional surface coatings, resulting in a total thickness of 120 µm. A fluorescent MOF that specifically binds dopamine is introduced, enabling a highly sensitive dopamine measurement with a detection limit of 79.9 nM. A compact wireless circuit weighing only 0.85 g is also developed and interfaced with the probe, which was later applied to continuously monitor real-time dopamine levels during deep brain stimulation in rats, providing critical information on neurotransmitter dynamics. Cytotoxicity tests and immunofluorescence analysis further suggest a favorable biocompatibility of the probe for implantable applications. This work presents fundamental principles and techniques for integrating fluorescent MOFs and flexible electronics for brain-computer interfaces and may provide more customized platforms for applications in neuroscience, disease tracing, and smart diagnostics.
Asunto(s)
Dopamina , Estructuras Metalorgánicas , Ratas , Animales , Dopamina/análisis , Estructuras Metalorgánicas/metabolismo , Colorantes Fluorescentes/metabolismo , Fluorescencia , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Neurotransmisores/metabolismoRESUMEN
The development of semi-artificial photosynthetic systems, which integrate metal-organic frameworks (MOFs) with industrial microbial cell factories for light-driven synthesis of fuels and valuable chemicals, represents a highly promising avenue for both research advancements and practical applications. In this study, an MOF (PCN-222) utilizing racemic-(4-carboxyphenyl) porphyrin and zirconium chloride (ZrCl4) as primary constituents is synthesized. Employing a self-assembly process, a hybrid system is constructed, integrating engineered Escherichia coli (E. coli) to investigate light-driven hydrogen and lysine production. These results demonstrate that the light-irradiated biohybrid system efficiently produce H2 with a quantum efficiency of 0.75% under full spectrum illumination, the elevated intracellular reducing power NADPH is also observed. By optimizing the conditions, the biohybrid system achieves a maximum lysine production of 18.25 mg L-1, surpassing that of pure bacteria by 332%. Further investigations into interfacial electron transfer mechanisms reveals that PCN-222 efficiently captures light and facilitates the transfer of photo-generated electrons into E. coli cells. It is proposed that the interfacial energy transfer process is mediated by riboflavin, with facilitation by secreted small organic acids acting as hole scavengers for PCN-222. This study establishes a crucial foundation for future research into the light-driven biomanufacturing using E. coli-based hybrid systems.
Asunto(s)
Escherichia coli , Luz , Estructuras Metalorgánicas , Escherichia coli/metabolismo , Escherichia coli/genética , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/metabolismo , Fotosíntesis , Lisina/metabolismo , Lisina/química , Hidrógeno/metabolismoRESUMEN
Chiral alcohols are not only important building blocks of various bioactive natural compounds and pharmaceuticals, but can serve as synthetic precursors for other valuable organic chemicals, thus the synthesis of these products is of great importance. Bio-catalysis represents one effective way to obtain these molecules, however, the weak stability and high cost of enzymes often hinder its broad application. In this work, we designed a biological nanoreactor by embedding alcohol dehydrogenase (ADH) and glucose dehydrogenase (GDH) in metal-organic-framework ZIF-8. The biocatalyst ADH&GDH@ZIF-8 could be applied to the asymmetric reduction of a series of ketones to give chiral alcohols in high yields (up to 99 %) and with excellent enantioselectivities (>99 %). In addition, the heterogeneous biocatalyst could be recycled and reused at least four times with slight activity decline. Moreover, E.â coli containing ADH and GDH was immobilized by ZIF-8 to form biocatalyst E.â coli@ZIF-8, which also exhibits good catalytic behaviours. Finally, the chiral alcohols are further converted to marketed drugs (R)-Fendiline, (S)-Rivastigmine and NPS R-568 respectively.
Asunto(s)
Alcohol Deshidrogenasa , Biocatálisis , Enzimas Inmovilizadas , Escherichia coli , Glucosa 1-Deshidrogenasa , Cetonas , Estructuras Metalorgánicas , Alcohol Deshidrogenasa/metabolismo , Alcohol Deshidrogenasa/química , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/metabolismo , Cetonas/química , Cetonas/metabolismo , Enzimas Inmovilizadas/metabolismo , Enzimas Inmovilizadas/química , Escherichia coli/enzimología , Escherichia coli/metabolismo , Glucosa 1-Deshidrogenasa/metabolismo , Glucosa 1-Deshidrogenasa/química , Oxidación-Reducción , EstereoisomerismoRESUMEN
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.
Asunto(s)
Accidente Cerebrovascular Isquémico , Estructuras Metalorgánicas , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Estructuras Metalorgánicas/metabolismo , Estructuras Metalorgánicas/farmacología , Enfermedades Neuroinflamatorias , Especies Reactivas de Oxígeno/metabolismo , Barrera Hematoencefálica , Gliburida/metabolismo , Gliburida/farmacología , Gliburida/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/metabolismoRESUMEN
Exosomes, a growing focus for liquid biopsies, contain diverse molecular cargos. In particular, exosome metabolites with valuable information have exhibited great potential for improving the efficiency of liquid biopsies for addressing complex medical conditions. In this work, we design the directional growth of Ti-metal-organic frameworks on polar-functionalized magnetic particles. This design facilitates the rapid synergistic capture of exosomes with the assistance of an external magnetic field and additionally synergistically enhances the ionization of their metabolites during mass spectrometry detection. Benefiting from this dual synergistic effect, we identified three high-performance exosome metabolites through the differential comparison of a large number of serum samples from individuals with Alzheimer's disease (AD) and normal cognition. Notably, the accuracy of AD identification ranges from 93.18 to 100% using a single exosome metabolite and reaches a flawless 100% with three metabolites. These findings emphasize the transformative potential of this work to enhance the precision and reliability of AD diagnosis, ushering in a new era of improved diagnostic accuracy.
Asunto(s)
Enfermedad de Alzheimer , Exosomas , Estructuras Metalorgánicas , Humanos , Enfermedad de Alzheimer/patología , Estructuras Metalorgánicas/metabolismo , Exosomas/química , Reproducibilidad de los Resultados , Titanio/análisisRESUMEN
Although mitochondria are crucial for recovery after spinal cord injury (SCI), therapeutic strategies to modulate mitochondrial metabolic energy to coordinate the immune response and nerve regeneration are lacking. Here, a ligand-screened cerium-based metal-organic framework (MOF) with better ROS scavenging and drug-loading abilities is encapsulated with polydopamine after loading creatine to obtain microcapsules (Cr/Ce@PDA nanoparticles), which reverse the energy deficits in both macrophages and neuronal cells by combining ROS scavenging and energy supplementation. It reprogrames inflammatory macrophages to the proregenerative phenotype via the succinate/HIF-1α/IL-1ß signaling axis. It also promotes the regeneration and differentiation of neural cells by activating the mTOR pathway and paracrine function of macrophages. In vivo experiments further confirm the effect of the microcapsules in regulating early ROS-inflammation positive-feedback chain reactions and continuously promoting nerve regeneration. This study provides a new strategy for correcting mitochondrial energy deficiency in the immune response and nerve regeneration following SCI.
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Estructuras Metalorgánicas , Traumatismos de la Médula Espinal , Humanos , Estructuras Metalorgánicas/metabolismo , Ligandos , Cápsulas/metabolismo , Cápsulas/farmacología , Cápsulas/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Regeneración Nerviosa/fisiología , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/metabolismo , Mitocondrias/metabolismoRESUMEN
A composite nanoagent capable of phototriggered tumor microenvironment (TME) regulation is developed based on copper (II) metal-organic frameworks (MOFs) with encapsulation of blebbistatin (Bb) and surface modification of fibroblast activation protein-αtargeted peptide (Tp). Tp enables active targeting of the nanoagents to cancer-associated fibroblast (CAF) while near-infrared light triggers Cu2+ -to-Cu+ photoreduction in MOFs, which brings about the collapse of MOFs and the release of Bb and Cu+ . Bb mediates photogeneration of hydroxyl radicals (â¢OH) and therefore inhibits extracellular matrix production by inducing CAF apoptosis, which facilitates the penetration of nanoagent to deep tumor tissue. The dual-channel generation of â¢OH based on Bb and the Cu+ species, via distinct mechanisms, synergistically reinforces oxidative stress in TME capable of inducing immunogenic cell death, which activates the antitumor immune response and therefore reverses the immunosuppressive TME. The synergistic antitumor phototherapy efficacy of such a type of nanoagent based on the abovementioned TME remodeling is unequivocally verified in a cell-derived tumor xenograft model.
Asunto(s)
Fibroblastos Asociados al Cáncer , Estructuras Metalorgánicas , Neoplasias , Humanos , Estructuras Metalorgánicas/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Microambiente Tumoral , Cobre/metabolismo , Neoplasias/metabolismo , Línea Celular TumoralRESUMEN
BACKGROUND/AIM: Hypertrophic scars (HS) are an abnormal cutaneous condition of wound healing characterized by excessive fibrosis and disrupted collagen deposition. This study assessed the potential of a silicone patch embedded with chemically stable zirconium-based metal-organic frameworks (MOF)-808 structures to mitigate HS formation using a rabbit ear model. MATERIALS AND METHODS: A silicone patch was strategically engineered by incorporating Zr-MOF-808, a composite structure comprising metal ions and organic ligands. Structural integrity of the Zr-MOF-808 silicone patch was validated using scanning electron microscopy and X-ray diffraction analysis. The animals were divided into three groups: a control, no treatment group (Group 1), a silicone patch treatment group (Group 2), and a group treated with a 0.2% loaded Zr-MOF-808 silicone patch (Group 3). HS suppression effects were quantified using scar elevation index (SEI), dorsal skin thickness measurements, and myofibroblast protein expression. RESULTS: Histopathological examination of post-treatment HS samples revealed substantial reductions in SEI (34.6%) and epidermal thickness (49.5%) in Group 3. Scar hyperplasia was significantly diminished by 53.5% (p<0.05), while collagen density declined by 15.7% in Group 3 compared to Group 1. Western blot analysis of protein markers, including TGF-ß1, collagen-1, and α-SMA, exhibited diminished levels by 8.8%, 12%, and 21.3%, respectively, in Group 3, and substantially higher levels by 21.9%, 27%, and 39.9%, respectively, in Group 2. On the 35th day post-wound generation, Zr-MOF-808-treated models exhibited smoother, less conspicuous, and flatter scars. CONCLUSION: Zr-MOF-808-loaded silicone patch reduced HS formation in rabbit ear models by inducing the proliferation and remodeling of the wound healing process.
Asunto(s)
Cicatriz Hipertrófica , Estructuras Metalorgánicas , Animales , Conejos , Cicatriz Hipertrófica/metabolismo , Cicatriz Hipertrófica/patología , Estructuras Metalorgánicas/metabolismo , Estructuras Metalorgánicas/farmacología , Fibroblastos , Colágeno Tipo I/metabolismo , Colágeno Tipo I/farmacología , Colágeno/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/farmacologíaRESUMEN
Photocatalytic technology showed significant potential for addressing the issue of cyanobacterial blooms resulting from eutrophication in bodies of water. However, the traditional powder materials were easy to agglomerate and settle, which led to the decrease of photocatalytic activity. The emergence of floating photocatalyst was important for the practical application of controlling harmful algal blooms. This study was based on the efficient powder photocatalyst bismuth oxide composite copper-metal organic framework (Bi2O3 @Cu-MOF), which was successfully loaded onto melamine sponge (MS) by sodium alginate immobilization to prepare a floating photocatalyst MS/Bi2O3 @Cu-MOF for the inactivation of Microcystis aeruginosa (M. aeruginosa) under visible light. When the capacity was 0.4 g (CA0.4), MS/Bi2O3 @Cu-MOF showed good photocatalytic activity, and the inactivation rate of M. aeruginosa reached 74.462% after 120 h. MS/Bi2O3 @Cu-MOF-CA0.4 showed a large specific surface area of 30.490 m2/g and an average pore size of 22.862 nm, belonging to mesoporous materials. After 120 h of treatment, the content of soluble protein in the MS/Bi2O3 @Cu-MOF-CA0.4 treatment group decreased to 0.365 mg/L, the content of chlorophyll a (chla) was 0.023 mg/L, the content of malondialdehyde (MDA) increased to 3.168 nmol/mgprot, and the contents of various antioxidant enzymes experienced drastic changes, first increasing and then decreasing. The photocatalytic process generated·OH and·O2-, which played key role in inactivating the algae cells. Additionally, the release of Cu2+ and adsorption of the material also contributed to the process.
Asunto(s)
Estructuras Metalorgánicas , Microcystis , Triazinas , Cobre/metabolismo , Microcystis/metabolismo , Estructuras Metalorgánicas/metabolismo , Clorofila A , Seda/metabolismo , Polvos/metabolismo , Bismuto , Floraciones de Algas NocivasRESUMEN
The rapid development of antimicrobial resistance (AMR) among infectious pathogens has become a major threat and challenge in healthcare systems globally. A strategy distinct from minimizing the overuse of antimicrobials involves the development of novel antimicrobials with a mode of action that prevents the development of AMR microbial strains. Reactive oxygen species (ROS) are formed as a natural byproduct of the cellular aerobic metabolism. However, it becomes pathological when ROS is produced at excessive levels. Exploiting this phenomenon, research on redox-active bactericides has been demonstrated to be beneficial. Materials that release ROS via photodynamic, thermodynamic, and photocatalytic interventions have been developed as nanomedicines and are used in various applications. However, these materials require external stimuli for ROS release to be effective as biocides. In this paper, we report novel zinc-based metal organic framework (Zn@MOF) particles that promote the spontaneous release of active ROS species. The synthesized Zn@MOF spontaneously releases superoxide anions and hydrogen peroxide, exhibiting a potent antimicrobial efficacy against various microbes. Zn@MOF-incorporated plastic films and coatings show excellent, long-lasting antimicrobial potency even under continuous microbial challenge and an aging process. These disinfecting surfaces maintain their antimicrobial properties even after 500× surface wipes. Zn@MOF is also biocompatible and safe on the skin, illustrating its broad potential applications in medical technology and consumer care applications.
Asunto(s)
Antiinfecciosos , Estructuras Metalorgánicas , Especies Reactivas de Oxígeno/metabolismo , Antibacterianos/farmacología , Estructuras Metalorgánicas/farmacología , Estructuras Metalorgánicas/metabolismo , Zinc , Oxidación-ReducciónRESUMEN
Enzymatic catalysis with high efficiency allows them a great prospect in metabolite monitoring in living cells. However, complex tumor microenvironments, such as acidity, H2 O2 , and hypoxia, are bound to disturb catalytic reactions for misleading results. Here, we report a spatially compartmentalized artificial organelle to correct intratumoral glucose analysis, where the zeolitic imidazolate framework-8 immobilized glucose oxidase-horseradish peroxidase cascade core and catalase-directed shell act as signal transduction and guarding rooms respectively. The acid-digested core and stable shell provide appropriate spaces to boost biocatalytic efficiency with good tolerability. Notably, the endogenous H2 O2 is in situ decomposed to O2 by catalase, which not only overcomes the interference in signal output but also alleviates the hypoxic states to maximize glucose oxidation. The marked protective effect and biocompatibility render artificial organelles to correct the signal transduction for dynamic monitoring glucose in vitro and in vivo, achieving our goal of accurate intratumoral metabolite analysis.
Asunto(s)
Células Artificiales , Estructuras Metalorgánicas , Estructuras Metalorgánicas/metabolismo , Glucosa/análisis , Catalasa/metabolismo , Oxidación-Reducción , Glucosa Oxidasa/metabolismoRESUMEN
In this study, PD-L1 and CYP51 were selected as key dual-target enzymes, which play an important role in the process of fungal proliferation and immune suppression. A series of novel bifonazole dual-target compounds were designed through the method of fragment combination. Their chemical structure was synthesized, characterized, and evaluated. Among them, the compounds (10c-1, 14a-2, 17c-2) exhibited excellent antifungal and antidrug-resistant fungal activity in vitro. In particular, the preferred compound 14a-2 with high-efficiency dual-target inhibitor ability could block the fungal proliferation and activate the organism's immune efficacy. Moreover, the corresponding covalent organic framework carrier was also successfully constructed to improve its bioavailability. This significantly accelerated the body's recovery process from fungal infection in vivo. In summary, this study expanded the scientific frontier of antifungal drugs and provided a feasible candidate pathway for clinical treatment of fungal infections.
Asunto(s)
Antifúngicos , Estructuras Metalorgánicas , Antifúngicos/química , Estructuras Metalorgánicas/metabolismo , Candida albicans , Pruebas de Sensibilidad MicrobianaRESUMEN
The lethality and chemotherapy resistance of pancreatic cancer necessitates the urgent development of innovative strategies to improve patient outcomes. To address this issue, we designed a novel drug delivery system named GDMCN2,which uses iron-based metal organic framework (Fe-MOF) nanocages encased in a covalent organic framework (COF) and modified with the pancreatic cancer-specific antibody, NRP2. After being targeted into tumor cells, GDMCN2 gradually release the sonosensitizer sinoporphyrin sodium (DVDMS) and chemotherapeutic gemcitabine (GEM) and simultaneously generated reactive oxygen species (ROS) under ultrasound (US) irradiation. This system can overcome gemcitabine resistance in pancreatic cancer and reduce its toxicity to non-targeted cells and tissues. In a mechanistic cascade, the release of ROS activates the mitochondrial transition pore (MPTP), leading to the release of Ca2+ and induction of endoplasmic reticulum (ER) stress. Therefore, microtubule-associated protein 1A/1B-light chain 3 (LC3) is activated, promoting lysosomal autophagy. This process also induces autophagy-dependent ferroptosis, aided by the upregulation of Nuclear Receptor Coactivator 4 (NCOA4). This mechanism increases the sensitivity of pancreatic cancer cells to chemotherapeutic drugs and increases mitochondrial and DNA damage. The findings demonstrate the potential of GDMCN2 nanocages as a new avenue for the development of cancer therapeutics.
Asunto(s)
Ferroptosis , Estructuras Metalorgánicas , Neoplasias Pancreáticas , Humanos , Estructuras Metalorgánicas/metabolismo , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo , Apoptosis , Anticuerpos Monoclonales/uso terapéutico , Autofagia , Gemcitabina , Neoplasias Pancreáticas/tratamiento farmacológico , Retículo Endoplásmico/metabolismo , Neoplasias PancreáticasRESUMEN
The effect of photodynamic therapy (PDT) is severely limited by tumor hypoxia and the short half-life of reactive oxygen species (ROS). Herein, we constructed a near-infrared (NIR) light-regulated PDT nanoplatform (TPP-UCNPs@MOF-Pt) consisting of an upconversion nanoparticle (UCNP) core and porphyrin-based metal-organic framework (MOF) shell with platinum nanoparticles (PtNPs) and a mitochondria-targeting triphenylphosphine (TPP) group on the surface. TPP-UCNPs@MOF-Pt could effectively relieve the tumor hypoxia by converting intracellular H2O2 to oxygen (O2) and elevated the ROS level to enhance PDT efficacy under NIR light irradiation. In addition, the mitochondria-targeting TPP-UCNPs@MOF-Pt was localized on the mitochondria, leading to severe depolarization of the mitochondrial membrane and activation of the apoptotic pathway, further amplifying the therapeutic efficacy. In vitro and in vivo experiments demonstrated that the greatly enhanced photodynamic therapeutic efficacy of TPP-UCNPs@MOF-Pt was achieved by combining relief of tumor hypoxia with mitochondrial targeting and NIR activation. This study provides a promising strategy for construction of an MOF-based multifunctional nanoplatform to address the current limitations of PDT treatment for hypoxic tumors.
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Nanopartículas del Metal , Estructuras Metalorgánicas , Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Estructuras Metalorgánicas/farmacología , Estructuras Metalorgánicas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Peróxido de Hidrógeno/metabolismo , Platino (Metal) , Nanopartículas/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Oxígeno/metabolismo , Mitocondrias/metabolismo , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/metabolismo , Línea Celular TumoralRESUMEN
Metal-organic frameworks (MOFs) are used as ideal support materials thanks to their unique properties and have become the focus of interest in enzyme immobilization studies, especially in recent years. In order to increase the catalytic activity and stability of Candida rugosa lipase (CRL), a new fluorescence-based MOF (UiO-66-Nap) derived from UiO-66 was synthesized. The structures of the materials were confirmed by spectroscopic techniques such as FTIR, 1H NMR, SEM, and PXRD. CRL was immobilized on UiO-66-NH2 and UiO-66-Nap by adsorption technique and immobilization and stability parameters of UiO-66-Nap@CRL were examined. Immobilized lipases UiO-66-Nap@CRL exhibited higher catalytic activity (204 U/g) than UiO-66-NH2 @CRL (168 U/g), which indicates that the immobilized lipase (UiO-66-Nap@CRL) carries sulfonate groups, this is due to strong ionic interactions between the surfactant's polar groups and certain charged locations on the protein surface. The Free CRL lost its catalytic activity completely at 60 °C after 100 min, while UiO-66-NH2 @CRL and UiO-66-Nap@CRL retained 45 % and 56 % of their catalytic activity at the end of 120 min, respectively. After 5 cycles, the activity of UiO-66-Nap@CRL remained 50 %, while the activity of UiO-66-NH2 @CRL was about 40 %. This difference is due to the surfactant groups (Nap) in UiO-66-Nap@CRL. These results show that the newly synthesized fluorescence-based MOF derivative (UiO-66-Nap) can be an ideal support material for enzyme immobilization and can be used successfully to protect and increase the activities of enzymes.
Asunto(s)
Estructuras Metalorgánicas , Biocatálisis , Estructuras Metalorgánicas/metabolismo , Tensoactivos , Candida , Enzimas Inmovilizadas/química , Lipasa/químicaRESUMEN
Electroactive bacteria (EAB) and metal oxides are capable of synergistically removing chloramphenicol (CAP). However, the effects of redox-active metal-organic frameworks (MOFs) on CAP degradation with EAB are not yet known. This study investigated the synergism of iron-based MOFs (Fe-MIL-101) and Shewanella oneidensis MR-1 on CAP degradation. 0.5 g/L Fe-MIL-101 with more possible active sites led to a three-fold higher CAP removal rate in the synergistic system with MR-1 (initial bacterial concentration of 0.2 at OD600), and showed a superior catalytic effect than exogenously added Fe(III)/Fe(II) or magnetite. Mass spectrometry revealed that CAP was transformed into smaller molecular weight and less toxic metabolites in cultures. Transcriptomic analysis showed that Fe-MIL-101 enhanced the expression of genes related to nitro and chlorinated contaminants degradation. Additionally, genes encoding hydrogenases and c-type cytochromes associated with extracellular electron transfer were significantly upregulated, which may contribute to the simultaneous bioreduction of CAP both intracellularly and extracellularly. These results indicated that Fe-MIL-101 can be used as a catalyst to synergize with EAB to effectively facilitate CAP degradation, which might shed new light on the application in the in situ bioremediation of antibiotic-contaminated environments.
Asunto(s)
Estructuras Metalorgánicas , Shewanella , Compuestos Férricos/metabolismo , Estructuras Metalorgánicas/metabolismo , Cloranfenicol/farmacología , Cloranfenicol/metabolismo , Shewanella/genética , Shewanella/metabolismo , Oxidación-ReducciónRESUMEN
Antisense oligonucleotides (ASOs) are promising tools for gene silencing and have been exploited as therapeutics for human disease. However, delivery of therapeutic ASOs to diseased tissues or cells and subsequent escape from the endosomes and release of ASO in the cytosol remain a challenge. Here, we reported a neutrophil-membrane-coated zeolitic imidazolate framework-8 (ZIF-8) nanodelivery platform (AM@ZIF@NM) for the targeted transportation of ASOs against microRNA-155 (anti-miRNA-155) to the endothelial cells in atherosclerotic lesions. Neutrophil membrane could improve plaque endothelial cells targeting through the interaction between neutrophil membrane protein CD18 and endothelial cell membrane protein intercellular adhesion molecule-1 (ICAM-1). The ZIF-8 "core" provided high loading capacity and efficient endolysosomal escaping ability. Delivery of anti-miR-155 effectively downregulated miR-155 expression and also saved the expression of its target gene BCL6. Moreover, RELA expression and the expression of its downstream target genes CCL2 and ICAM-1 were correspondingly reduced. Consequently, this anti-miR-155 nanotherapy can inhibit the inflammation of atherosclerotic lesions and alleviate atherosclerosis. Our study shows that the designed biomimetic nanodelivery system has great application prospects in the treatment of other chronic diseases.
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Aterosclerosis , Estructuras Metalorgánicas , MicroARNs , Nanopartículas , Humanos , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Estructuras Metalorgánicas/metabolismo , Células Endoteliales/metabolismo , Antagomirs , Neutrófilos/metabolismo , Aterosclerosis/metabolismo , Silenciador del Gen , MicroARNs/genéticaRESUMEN
Metal-organic framework (MOF) nanoparticles have recently emerged as a promising vehicle for drug delivery with high porosity and feasibility. However, employing a MOF-based drug delivery system remains a challenge due to the difficulty in controlling interfaces of particles in a biological environment. In this paper, protein corona-blocked Zr6 -based MOF (PCN-224) nanoparticles are presented for targeted cancer therapy with high efficiency. The unmodified PCN-224 surface is precoated with glutathione transferase (GST)-fused targetable affibody (GST-Afb) proteins via simple mixing conjugations instead of chemical modifications that can induce the impairment of proteins. GST-Afb proteins are shown to stably protect the surface of PCN-224 particles in a specific orientation with GST adsorbed onto the porous surface and the GST-linked Afb posed outward, minimizing the unwanted interfacial interactions of particles with external biological proteins. The Afb-directed cell-specific targeting ability of particles and consequent induction of cell death is demonstrated both in vitro and in vivo by using two kinds of Afb, which targets the surface membrane receptor, human epidermal growth factor receptor 2 (HER2) or epidermal growth factor receptor (EGFR). This study provides insight into the way of regulating the protein-adhesive surface of MOF nanoparticles and designing a more effective MOF-hosted targeted delivery system.
Asunto(s)
Estructuras Metalorgánicas , Nanopartículas , Neoplasias , Humanos , Estructuras Metalorgánicas/metabolismo , Sistemas de Liberación de Medicamentos , Neoplasias/tratamiento farmacológico , Proteínas de la MembranaRESUMEN
Disulfiram (DSF), a drug for alcohol withdrawal, has attracted extensive scientific attention due to its potential to treat cancer. The metabolite of DSF, diethyl dithiocarbamate (DDTC), forms a Cu-DDTC complex in vivo with copper ions, which has been shown to be a proteasome inhibitor with high antitumor activity. However, the in vivo stability of Cu-DDTC complexes remains a challenge. In this study, the nanomedicine Cu-BTC@DDTC with high antitumor activity was prepared by using the nanoscale metal-organic framework (MOF) Cu-BTC as a carrier and loading diethyldithiocarbamate (DDTC) through coordination interaction. The results showed that Cu-BTC@DDTC had high drug loading and adequate stability, and exhibited DDTC-Cu(I) chemical valence characteristics and polycrystalline structure features. In vitro cytocompatibility investigation and animal xenograft tumor model evaluation demonstrated the anti-cancer potential of Cu-BTC@DDTC, especially the combination of Cu-BTC@DDTC with low-dose cisplatin showed significant antitumor effect and biosafety. This study provides a feasible protocol for developing antitumor drugs based on the drug repurposing strategy.