RESUMEN
Chemodynamic therapy (CDT) is an emerging therapeutic modality triggered by endogenous substances in the tumor microenvironment (TME) to generate reactive oxygen species. However, the mild acid pH, low H2O2 concentration, and overexpressed glutathione can suppress the CDT efficiency. Herein, ultrasound (US)-triggered Cu2+-based single-atom nanoenzymes (FA-NH2-UiO-66-Cu, FNUC) are constructed with the performance of target and glutathione depletion. In the TME, the single-atom Cu sites of FNUC consume glutathione and the FNUC:Cu+ generates â¢OH via peroxidase-like activity. The US-activated FNUC exhibits a fast â¢OH generation rate, a low Michaelis constant, and a large â¢OH concentration, indicating the cavitation effect of US promotes the â¢OH generation. Meanwhile, the tumor target of FNUC is confirmed by NIR-II fluorescence imaging, in which it is modified with IR-1061. Combined with the antitumor performance of FNUC in vitro and in vivo, the novel Cu-based SAzymes can achieve efficient and precise cancer treatment.
Asunto(s)
Cobre , Estructuras Metalorgánicas , Microambiente Tumoral , Cobre/química , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Humanos , Animales , Microambiente Tumoral/efectos de los fármacos , Ratones , Catálisis , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Línea Celular Tumoral , Glutatión/química , Ondas Ultrasónicas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Bioorthogonal chemistry represents a powerful tool in chemical biology, which shows great potential in epigenetic modulation. As a proof of concept, the epigenetic modulation model of mitochondrial DNA (mtDNA) is selected because mtDNA establishes a relative hypermethylation stage under oxidative stress, which impairs the mitochondrion-based therapeutic effect during cancer therapy. Herein, we design a new biocompatible hydrogen-bonded organic framework (HOF) for a HOF-based mitochondrion-targeting bioorthogonal platform TPP@P@PHOF-2. PHOF-2 can activate a prodrug (pro-procainamide) in situ, which can specifically inhibit DNA methyltransferase 1 (DNMT1) activity and remodel the epigenetic modification of mtDNA, making it more susceptible to ROS damage. In addition, PHOF-2 can also catalyze artemisinin to produce large amounts of ROS, effectively damaging mtDNA and achieving better chemodynamic therapy demonstrated by both in vitro and in vivo studies. This work provides new insights into developing advanced bioorthogonal therapy and expands the applications of HOF and bioorthogonal catalysis.
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ADN Mitocondrial , Epigénesis Genética , Mitocondrias , Especies Reactivas de Oxígeno , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Humanos , ADN Mitocondrial/genética , Epigénesis Genética/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Enlace de Hidrógeno , Animales , Ratones , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , ADN (Citosina-5-)-Metiltransferasa 1/antagonistas & inhibidores , ADN (Citosina-5-)-Metiltransferasa 1/genética , Profármacos/farmacología , Profármacos/química , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacologíaRESUMEN
Engineering a highly tumor microenvironment-responsive nanoplatform toward effective chemotherapy has always been a challenge in targeted cancer treatment. Metal-organic frameworks are a promising delivery system to reformulate previously approved drugs for enhanced chemotherapy, such as disulfiram (DSF). Herein, a tumor microenvironment-activated metal-organic framework-based nanoplatform DSF@MOF-199@FA has been fabricated to realize amplified oxidative stress-induced enhanced chemotherapy. Our results unveil that the copper ions and DSF released by DSF@MOF-199@FA in an acidic environment can be converted into toxic bis(N, N-diethyl dithiocarbamate) copper and then induce cell apoptosis. Simultaneously, we determined that the apoptosis outcome is further promoted by amplified oxidative stress through effective generation of reactive oxygen species and GSH elimination. In conclusion, this work provides a promising platform for effective anticancer treatment.
Asunto(s)
Estructuras Metalorgánicas , Línea Celular Tumoral , Cobre/farmacología , Disulfiram/farmacología , Estructuras Metalorgánicas/farmacología , Estrés Oxidativo , Microambiente Tumoral , Ratones Endogámicos BALB C , Femenino , Animales , RatonesRESUMEN
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
Cellular communication mediated by messenger molecules plays an important role in the progression of cancer. Herein, pH-sensitive zeolitic imidazolate framework-8 (ZIF-8) loaded with PtCl2(OH)2(NH3)2 [i.e., Pt(IV)] bimetallic nanoplatforms were developed for prostate cancer therapy by interfering inositol-1, 4, 5-trisphosphate (IP3)-mediated cellular communication. As an important messenger in cells, the function of IP3 was found to be efficiently interfered with by the Pt(IV)-binding inositol unit. This finding effect of Pt(IV) is totally different from its traditional function as a prodrug of cis-platinum for chemotherapy. The decreased IP3 signal further downregulated the cytoplasmic Ca2+ concentration and downstream signal transduction to inhibit proliferation and invasion of tumor cells. Meanwhile, Zn2+ released from ZIF-8 under an acidic tumor microenvironment decreased adenosine triphosphate biosynthesis, which could further limit the cellular communication. Such a proposed strategy of interfering cellular communication has demonstrated its feasibility in this study, which may provide new perspectives for cancer therapy.
Asunto(s)
Antineoplásicos , Neoplasias de la Próstata , Humanos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Masculino , Antineoplásicos/farmacología , Antineoplásicos/química , Comunicación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Inositol 1,4,5-Trifosfato/metabolismo , Inositol 1,4,5-Trifosfato/química , Concentración de Iones de Hidrógeno , Imidazoles/química , Imidazoles/farmacología , Zinc/química , Zinc/farmacologíaRESUMEN
Drug-resistant bacterial infections cause significant harm to public life, health, and property. Biofilm is characterized by overexpression of glutathione (GSH), hypoxia, and slight acidity, which is one of the main factors for the formation of bacterial resistance. Traditional antibiotic therapy gradually loses its efficacy against multi-drug-resistant (MDR) bacteria. Therefore, synergistic therapy, which regulates the biofilm microenvironment, is a promising strategy. A multifunctional nanoplatform, SnFe2O4-PBA/Ce6@ZIF-8 (SBC@ZIF-8), in which tin ferrite (SnFe2O4, denoted as SFO) as the core, loaded with 3-aminobenzeneboronic acid (PBA) and dihydroporphyrin e6 (Ce6), and finally coated with zeolite imidazole salt skeleton 8 (ZIF-8). The platform has a synergistic photothermal therapy (PTT)/photodynamic therapy (PDT) effect, which can effectively remove overexpressed GSH by glutathione peroxidase-like activity, reduce the antioxidant capacity of biofilm, and enhance PDT. The platform had excellent photothermal performance (photothermal conversion efficiency was 55.7 %) and photothermal stability. The inhibition rate of two MDR bacteria was more than 96 %, and the biofilm clearance rate was more than 90 % (150 µg/mL). In the animal model of MDR S. aureus infected wound, after 100 µL SBC@ZIF-8+NIR (150 µg/mL) treatment, the wound area of mice was reduced by 95 % and nearly healed. The serum biochemical indexes and H&E staining results were within the normal range, indicating that the platform could promote wound healing and had good biosafety. In this study, we designed and synthesized multifunctional nanoplatforms with good anti-drug-resistant bacteria effect and elucidated the molecular mechanism of its anti-drug-resistant bacteria. It lays a foundation for clinical application in treating wound infection and promoting wound healing.
Asunto(s)
Antibacterianos , Estructuras Metalorgánicas , Fotoquimioterapia , Antibacterianos/farmacología , Antibacterianos/química , Fotoquimioterapia/métodos , Animales , Ratones , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Biopelículas/efectos de los fármacos , Terapia Fototérmica , Staphylococcus aureus/efectos de los fármacos , Nanopartículas/química , Pruebas de Sensibilidad Microbiana , Compuestos Férricos/química , Compuestos Férricos/farmacología , Compuestos de Estaño/química , Compuestos de Estaño/farmacología , Zeolitas/química , Zeolitas/farmacologíaRESUMEN
Chronic diabetic wounds remain a worldwide challenge for both the clinic and research. Given the vicious circle of oxidative stress and inflammatory response as well as the impaired angiogenesis of the diabetic wound tissues, the wound healing process is disturbed and poorly responds to the current treatments. In this work, a nickel-based metal-organic framework (MOF, Ni-HHTP) with excellent antioxidant activity and proangiogenic function is developed to accelerate the healing process of chronic diabetic wounds. The Ni-HHTP can mimic the enzymatic catalytic activities of antioxidant enzymes to eliminate multi-types of reactive species through electron transfer reactions, which protects cells from oxidative stress-related damage. Moreover, this Ni-based MOF can promote cell migration and angiogenesis by activating transforming growth factor-ß1 (TGF-ß1) in vitro and reprogram macrophages to the anti-inflammatory phenotype. Importantly, Ni-HHTP effectively promotes the healing process of diabetic wounds by suppressing the inflammatory response and enhancing angiogenesis in vivo. This study reports a versatile and promising MOF-based nanozyme for diabetic wound healing, which may be extended in combination with other wound dressings to enhance the management of diabetic or non-healing wounds.
Asunto(s)
Diabetes Mellitus Experimental , Estructuras Metalorgánicas , Animales , Especies Reactivas de Oxígeno , Estructuras Metalorgánicas/farmacología , Níquel , Angiogénesis , Cicatrización de Heridas/fisiología , Antioxidantes , HidrogelesRESUMEN
In recent years, there has been growing interest in developing innovative materials and therapeutic strategies to enhance wound healing outcomes, especially for chronic wounds and antimicrobial resistance. Metal-organic frameworks (MOFs) represent a promising class of materials for next-generation wound healing and dressings. Their high surface area, pore structures, stimuli-responsiveness, antibacterial properties, biocompatibility, and potential for combination therapies make them suitable for complex wound care challenges. MOF-based composites promote cell proliferation, angiogenesis, and matrix synthesis, acting as carriers for bioactive molecules and promoting tissue regeneration. They also have stimuli-responsivity, enabling photothermal therapies for skin cancer and infections. Herein, a critical analysis of the current state of research on MOFs and MOF-based composites for wound healing and dressings is provided, offering valuable insights into the potential applications, challenges, and future directions in this field. This literature review has targeted the multifunctionality nature of MOFs in wound-disease therapy and healing from different aspects and discussed the most recent advancements made in the field. In this context, the potential reader will find how the MOFs contributed to this field to yield more effective, functional, and innovative dressings and how they lead to the next generation of biomaterials for skin therapy and regeneration.
Asunto(s)
Vendajes , Estructuras Metalorgánicas , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Humanos , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacologíaRESUMEN
Chemodynamic therapy (CDT) has emerged as a promising approach for treating infected diabetic wounds, while reliable imaging technology for simultaneous monitoring of ROS and therapeutic processes is still a formidable challenge. Herein, smart covalent organic framework (COF) nanoreactors (COF NRs) are constructed by hyaluronic acid (HA) packaged glucose oxidase (GOx) covalently linked Fe-COF for diabetic wound healing. Upon the breakdown of the HA protective layer, GOx consumes glucose to produce gluconic acid and hydrogen peroxide (H2O2), resulting in decreased local pH and H2O2 supplementation. Density functional theory (DFT) calculations show that Fe-COF has high catalytic activity towards H2O2, leading to in situ generation of hydroxyl radicals (·OH) for sterilization, and the localized downregulation of glucose effectively improved the microenvironment of diabetic wounds. Meanwhile, based on the near-infrared photothermal imaging of oxidized 3,3',5,5'-tetramethylbenzidine (oxTMB), the authors showed that TMB can be applied for the point-of-care testing of ·OH and glucose, and assessing the sterilization progress in vivo. More significantly, the facile photothermal signaling strategy can be extended to monitor various ROS-mediated therapeutic systems, enabling accurate prediction of treatment outcomes.
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Especies Reactivas de Oxígeno , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Animales , Glucosa Oxidasa/metabolismo , Glucosa Oxidasa/química , Peróxido de Hidrógeno/química , Esterilización/métodos , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Ratones , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , GlucosaRESUMEN
Nanocatalytic-based wound therapeutics present a promising strategy for generating reactive oxygen species (ROS) to antipathogen to promote wound healing. However, the full clinical potential of these nanocatalysts is limited by their low reactivity, limited targeting ability, and poor biodegradability in the wound microenvironment. Herein, a bio-organic nanozyme is developed by encapsulating a FeZn-based bimetallic organic framework (MOF) (MIL-88B-Fe/Zn) in platelet membranes (PM@MIL-88B-Fe/Zn) for antimicrobial activity during wound healing. The introduction of Zn in MIL-88B-Fe/Zn modulates the electronic structure of Fe thus accelerating the catalytic kinetics of its peroxidase-like activity to catalytically generate powerful ROS. The platelet membrane coating of MOF innovatively enhanced the interaction between nanoparticles and the biological environment, further developing bacterial-targeted therapy with excellent antibacterial activity against both gram-positive and gram-negative bacteria. Furthermore, this nanozyme markedly suppressed the levels of inflammatory cytokines and promoted angiogenesis in vivo to effectively treat skin surface wounds and accelerate wound healing. PM@MIL-88B-Fe/Zn exhibited superior biodegradability, favourable metabolism and non-toxic accumulation, eliminating concerns regarding side effects from long-term exposure. The high catalytic reactivity, excellent targeting features, and biodegradability of these nanoenzymes developed in this study provide useful insights into the design and synthesis of nanocatalysts/nanozymes for practical biomedical applications.
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Antibacterianos , Estructuras Metalorgánicas , Cicatrización de Heridas , Antibacterianos/farmacología , Antibacterianos/química , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Animales , Cicatrización de Heridas/efectos de los fármacos , Plaquetas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ratones , HumanosRESUMEN
To address the issue of bacterial growth on fresh-cut fruits, this paper reports the synthesis of nanosized γ-cyclodextrin metal-organic frameworks (CD-MOFs) using an ultrasound-assisted method and their application as carriers of limonene for antibacterial active packaging. The effects of the processing parameters on the morphology and crystallinity of the CD-MOFs are investigated, and the results prove that the addition of methanol is the key to producing nanosized CD-MOFs. The limonene loading content of the nanosized CD-MOFs can reach approximately 170 mg g-1. The sustained-release behaviors of limonene in the CD-MOFs are evaluated. Molecular docking simulations reveal the distribution and binding sites of limonene in the CD-MOFs. CD-MOFs are deposited on the surfaces of polycaprolactone (PCL) nanofibers via an immersion method, and limonene-loaded CD-MOF@PCL nanofibers are prepared. The morphology, crystallinity, thermal stability, mechanical properties, and antibacterial activity of the nanofibers are also studied. The nanofiber film effectively inhibits bacterial growth and prolongs the shelf life of fresh-cut apples. This study provides a novel strategy for developing antibacterial active packaging materials based on CD-MOFs and PCL nanofibers.
Asunto(s)
Frutas , Limoneno , Estructuras Metalorgánicas , Nanofibras , Poliésteres , gamma-Ciclodextrinas , Limoneno/química , Limoneno/farmacología , Nanofibras/química , Poliésteres/química , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , gamma-Ciclodextrinas/química , Frutas/química , Terpenos/química , Terpenos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Simulación del Acoplamiento MolecularRESUMEN
Nanocatalytic therapy, an emerging approach in cancer treatment, utilizes nanomaterials to initiate enzyme-mimetic catalytic reactions within tumors, inducing tumor-suppressive effects. However, the targeted and selective catalysis within tumor cells is challenging yet critical for minimizing the adverse effects. The distinctive reliance of tumor cells on glycolysis generates abundant lactate, influencing the tumor's pH, which can be manipulated to selectively activate nanozymatic catalysis. Herein, small interfering ribonucleic acid (siRNA) targeting lactate transporter-mediated efflux is encapsulated within the iron-based metal-organic framework (FeMOF) and specifically delivered to tumor cells through cell membrane coating. This approach traps lactate within the cell, swiftly acidifying the tumor cytoplasm and creating an environment for boosting the catalysis of the FeMOF nanozyme. The nanozyme generates hydroxyl radical (·OH) in the reversed acidic environment, using endogenous hydrogen peroxide (H2O2) produced by mitochondria as a substrate. The induced cytoplasmic acidification disrupts calcium homeostasis, leading to mitochondrial calcium overload, resulting in mitochondrial dysfunction and subsequent tumor cell death. Additionally, the tumor microenvironment is also remodeled, inhibiting migration and invasion, thus preventing metastasis. This groundbreaking strategy combines metabolic regulation with nanozyme catalysis in a toxic drug-free approach for tumor treatment, holding promise for future clinical applications.
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Neoplasias , Humanos , Neoplasias/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/terapia , Catálisis , Línea Celular Tumoral , Microambiente Tumoral , ARN Interferente Pequeño/metabolismo , Animales , Mitocondrias/metabolismo , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Peróxido de Hidrógeno/metabolismo , Concentración de Iones de Hidrógeno , Radical Hidroxilo/metabolismo , Nanoestructuras/químicaRESUMEN
Pyroptosis, a new mode of regulatory cell death, holds a promising prospect in tumor therapy. The occurrence of pyroptosis can trigger the release of damage-associated molecular patterns (DAMPs) and activate the antitumor immune response. Moreover, enhancing intracellular reactive oxygen species (ROS) generation can effectively induce pyroptosis. Herein, an integrated nanoplatform (hCZAG) based on zeolitic imidazolate framework-8 (ZIF-8) with Cu2+ and Zn2+ as active nodes and glucose oxidase (GOx) loading is constructed to evoke pyroptosis. GOx can effectively elevate intracellular hydrogen peroxide (H2O2) levels to regulate the unfavorable tumor microenvironment (TME). Cu2+ can be reduced to Cu+ by endogenous overexpressed GSH and both Cu2+ and Cu+ can exert Fenton-like activity to promote ROS generation and amplify oxidative stress. In addition, the accumulation of Cu2+ leads to the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT), thus resulting in cuproptosis. Notably, the outburst of ROS induced by hCZAG activates Caspase-1 proteins, leads to the cleavage of gasdermin D (GSDMD), and induces pyroptosis. Pyroptosis further elicits an adaptive immune response, leading to immunogenic cell death (ICD). This study provides effective strategies for triggering pyroptosis-mediated immunotherapy and achieving improved therapeutic effects.
Asunto(s)
Glucosa Oxidasa , Piroptosis , Especies Reactivas de Oxígeno , Microambiente Tumoral , Piroptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Microambiente Tumoral/efectos de los fármacos , Animales , Glucosa Oxidasa/metabolismo , Glucosa Oxidasa/química , Humanos , Ratones , Cobre/química , Peróxido de Hidrógeno/química , Línea Celular Tumoral , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Nanopartículas/química , Inmunidad/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , ImidazolesRESUMEN
The clinical application of oncology therapy is hampered by high glutathione concentrations, hypoxia, and inefficient activation of cell death mechanisms in cancer cells. In this study, Fe and Mo bimetallic sulfide nanomaterial (FeS2@MoS2) based on metal-organic framework structure is rationally prepared with peroxidase (POD)-, catalase (CAT)-, superoxide dismutase (SOD)-like activities and glutathione depletion ability, which can confer versatility for treating tumors and mending wounds. In the lesion area, FeS2@MoS2 with SOD-like activity can facilitate the transformation of superoxide anions (O2 -) to hydrogen peroxide (H2O2), and then the resulting H2O2 serves as a substrate for the Fenton reaction with FMS to produce highly toxic hydroxyl radicals (âOH). Simultaneously, FeS2@MoS2 has an ability to deplete glutathione (GSH) and catalyze the decomposition of nicotinamide adenine dinucleotide phosphate (NADPH) to curb the regeneration of GSH from the source. Thus it can realize effective tumor elimination through synergistic apoptosis-ferroptosis strategy. Based on the alteration of the H2O2 system, free radical production, glutathione depletion and the alleviation of hypoxia in the tumor microenvironment, FeS2@MoS2 NPS can not only significantly inhibit tumors in vivo and in vitro, but also inhibit multidrug-resistant bacteria and hasten wound healing. It may open the door to the development of cascade nanoplatforms for effective tumor treatment and overcoming wound infection.
Asunto(s)
Antineoplásicos , Estructuras Metalorgánicas , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Animales , Antiinfecciosos/farmacología , Antiinfecciosos/química , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/química , Línea Celular Tumoral , Ratones , Glutatión/metabolismo , Hierro/química , Hierro/metabolismo , Apoptosis/efectos de los fármacos , Molibdeno/química , Molibdeno/farmacología , Nanoestructuras/química , Ferroptosis/efectos de los fármacosRESUMEN
The prevalence of drug-resistant bacteria presents a significant challenge to the antibiotic treatment of Helicobacter pylori (H. pylori), while traditional antimicrobial agents often suffer from shortcomings such as poor gastric retention, inadequate alleviation of inflammation, and significant adverse effects on the gut microbiota. Here, a selenized chitosan (CS-Se) modified bismuth-based metal-organic framework (Bi-MOF@CS-Se) nanodrug is reported that can target mucin through the charge interaction of the outer CS-Se layer to achieve mucosal adhesion and gastric retention. Additionally, the Bi-MOF@CS-Se can respond to gastric acid and pepsin degradation, and the exposed Bi-MOF exhibits excellent antibacterial properties against standard H. pylori as well as clinical antibiotic-resistant strains. Remarkably, the Bi-MOF@CS-Se effectively alleviates inflammation and excessive oxidative stress by regulating the expression of inflammatory factors and the production of reactive oxygen species (ROS), thereby exerting therapeutic effects against H. pylori infection. Importantly, this Bi-MOF@CS-Se nanodrug does not affect the homeostasis of gut microbiota, providing a promising strategy for efficient and safe treatment of H. pylori infection.
Asunto(s)
Microbioma Gastrointestinal , Helicobacter pylori , Inflamación , Estructuras Metalorgánicas , Helicobacter pylori/efectos de los fármacos , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Animales , Inflamación/tratamiento farmacológico , Infecciones por Helicobacter/tratamiento farmacológico , Quitosano/química , Antibacterianos/farmacología , Antibacterianos/química , Especies Reactivas de Oxígeno/metabolismo , RatonesRESUMEN
Reactive oxygen species (ROS) have emerged as a promising treatment option for antibacterial and biofilm eradication. However, their therapeutic efficacy is significantly hampered by the unique microenvironments of diabetic wounds. In this study, we designed and synthesized porphyrin-based Fe covalent organic frameworks (Fe-COF) through a Schiff base condensation reaction. Subsequently, Fe-COF were encapsulated with hyaluronic acid (HA) through electrostatic adsorption, resulting in a novel formulation named HA-Fe-COF for diabetic wound healing. HA-Fe-COF were engineered to respond to hyaluronidase in the infected wound, leading to the controlled release of Fe-COF. Those released Fe-COF served a dual role as photosensitizers, generating singlet oxygen and localized heating when exposed to dual light sources. Additionally, they acted as peroxidase-like nanozymes, facilitating the production of ROS through enzymatic reactions. This innovative approach enabled a synergistic therapeutic effect combining photodynamic, photothermal, and chemodynamic modalities. Furthermore, the sustained release of HA from HA-Fe-COF promoted angiogenesis, collagen deposition, and re-epithelialization during the diabetic wound healing process. This "all-in-one" strategy offers a novel approach for the development of antimicrobial and biofilm eradication strategies that minimize damage to healthy tissues in vivo.
Asunto(s)
Ácido Hialurónico , Estructuras Metalorgánicas , Porfirinas , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Porfirinas/química , Porfirinas/farmacología , Ratones , Especies Reactivas de Oxígeno/metabolismo , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/administración & dosificación , Fármacos Fotosensibilizantes/síntesis química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Piel/efectos de los fármacos , Humanos , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Hierro/química , Fotoquimioterapia/métodos , HialuronoglucosaminidasaRESUMEN
The abuse of antibiotics leads to an increasing emergence of drug-resistant bacteria, which not only causes a waste of medical resources but also seriously endangers people's health and life safety. Therefore, it is highly desirable to develop an efficient antibacterial strategy to reduce the reliance on traditional antibiotics. Antibacterial photodynamic therapy (aPDT) is regarded as an intriguing antimicrobial method that is less likely to generate drug resistance, but its efficiency still needs to be further improved. Herein, a robust titanium-based metal-organic framework ACM-1 was adopted to support Ag nanoparticles (NPs) to obtain Ag NPs@ACM-1 for boosting antibacterial efficiency via synergistic chemical-photodynamic therapy. Apart from the intrinsic antibacterial nature, Ag NPs largely boost ROS production and thus improve aPDT efficacy. As a consequence, Ag NPs@ACM-1 shows excellent antibacterial activity under visible light illumination, and its minimum bactericidal concentrations (MBCs) against E. coli, S. aureus, and MRSA are as low as 39.1, 39.1, and 62.5 µg mL-1, respectively. Moreover, to expand the practicability of Ag NPs@ACM-1, two (a dense and a loose) Ag NPs@ACM-1 films were readily fabricated by simply dispersing Ag NPs@ACM-1 into heated aqueous solutions of edible agar and sequentially cooling through heating or freeze-drying, respectively. Notably, these two films are mechanically flexible and exhibit excellent antibacterial activities, and their antimicrobial performances can be well retained in their recyclable and remade films. As agar is nontoxic, degradable, inexpensive, and ecosustainable, the dense and loose Ag NPs@ACM-1 films are potent to serve as recyclable and degradable antibacterial plastics and antibacterial dressings, respectively.
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Antiinfecciosos , Nanopartículas del Metal , Estructuras Metalorgánicas , Fotoquimioterapia , Humanos , Plata/farmacología , Titanio/farmacología , Estructuras Metalorgánicas/farmacología , Staphylococcus aureus , Escherichia coli , Agar , Antibacterianos/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
A biocompatible metal-organic framework (MOF), named HSTC-4, constructed using the flexible 4,4'-oxybis(benzoic acid) (OBA), was developed to enable efficient loading and controlled release of vitamin C (VC) through a combination of strategies involving ligand length, structure design, and metal selection. The kinetic product HSTC-4 demonstrates a propensity for transforming into the thermodynamically stable HSTC-5 under external stimuli, such as photoillumination and vacuum heating, as witnessed by single-crystal to single-crystal transformation. Density functional theory (DFT) calculations reveal that the VC guest molecules exhibit stronger binding affinity with HSTC-5 due to its narrower pores compared to HSTC-4, resulting in a slower release of VC from VC@HSTC-5. Furthermore, precise control over VC release can be achieved by introducing surface modifications involving SiO2 onto the structure of VC@HSCT-5, while simultaneously adjusting environmental factors such as pH and temperature conditions. Preliminary cell culture experiments and cytotoxicity assays highlight the biocompatibility of HSTC-5, suggesting that it is a promising platform for sustained drug delivery and diverse biomedical applications.
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Ácido Ascórbico , Estructuras Metalorgánicas , Termodinámica , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Ácido Ascórbico/química , Cinética , Humanos , Teoría Funcional de la Densidad , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/química , Estructura Molecular , Liberación de FármacosRESUMEN
The widespread use and contamination of natural sources by new-generation drugs and pesticides have enhanced concern about environmental pollution. Understanding the above importance, we developed a superhydrophobic metal-organic framework (MOF) (SHMOF': [Zr6O4(OH)4(BDC-NH-CO-R)2.4(BDC-NH2)0.6(CF3COO)6]·2.5H2O·4DMF) for ecological remediation via adsorption-based separation of hydrophobic drugs (flurbiprofen) and pesticides (fluazinam). The newly developed SHMOF' has a high adsorption capacity toward flurbiprofen and fluazinam, i.e., 435 and 575 mg/g, respectively. The adsorption equilibrium time of the MOF is very short (15 and 10 min for flurbiprofen and fluazinam, respectively). The outstanding superhydrophobic nature of the MOF was employed to separate flurbiprofen and fluazinam from highly alkaline and acidic media and environmental water samples. The SHMOF' has excellent selectivity toward the adsorption-based separation of flurbiprofen and fluazinam in the coexistence of common analytes. Again, we developed a polypropylene (PP) fabric-based composite of SHMOF' (SHMOF'@PP) to separate the hydrophobic targeted analytes by using a zero-energy-consuming filtration-based separation method, which made this separation process cost-efficient and user-friendly. Moreover, Ag nanoparticles were doped to the superhydrophobic composite. The Ag-doped reusable SHMOF'@PP@Ag composite exhibited excellent bacterial antiadhesion and antibacterial properties toward Staphylococcus aureus bacteria.
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Antibacterianos , Interacciones Hidrofóbicas e Hidrofílicas , Estructuras Metalorgánicas , Plaguicidas , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Plaguicidas/aislamiento & purificación , Plaguicidas/química , Plaguicidas/farmacología , Adsorción , Staphylococcus aureus/efectos de los fármacos , Contaminantes Químicos del Agua/aislamiento & purificación , Contaminantes Químicos del Agua/química , Pruebas de Sensibilidad Microbiana , Propiedades de Superficie , Flurbiprofeno/química , Flurbiprofeno/farmacología , Flurbiprofeno/aislamiento & purificación , Estructura MolecularRESUMEN
Pathogenic bacteria have consistently posed a formidable challenge to human health, creating the critical need for effective antibacterial solutions. In response, enzyme-metal-organic framework (MOF) composites have emerged as a promising class of antibacterial agents. This study focuses on the development of an enzyme-MOF composite based on HZIF-8, incorporating the advantages of simple synthesis, ZIF-8 antibacterial properties, lysozyme hydrolysis, and high biological safety. Through a one-pot method, core-shell nanoparticles (HZIF-8) were synthesized. This structure enables efficient immobilization of lysozyme and lactoferrin within the HZIF-8, resulting in the formation of the lysozyme-lactoferrin@HZIF-8 (LYZ-LF@HZIF-8) composite. Upon exposure to light irradiation, HZIF-8 itself possessed antibacterial properties. Lysozyme initiated the degradation of bacterial peptidoglycan and lactoferrin synergistically enhanced the antibacterial effect of lysozyme. All of the above ultimately contributed to comprehensive antibacterial activity. Antibacterial assessments demonstrated the efficacy of the LYZ-LF@HZIF-8 composite, effectively eradicating Staphylococcus aureus at a cell density of 1.5 × 106 CFU/mL with a low dosage of 200 µg/mL and completely inactivating Escherichia coli at 400 µg/mL with the same cell density. The enzyme-MOF composite exhibited significant and durable antibacterial efficacy, with no apparent cytotoxicity in vitro, thereby unveiling expansive prospects for applications in the medical and food industries.