RESUMEN
Metal-organic frameworks (MOFs) have great potential for combating pathogenic bacterial infections and are expected to become an alternative to antibiotics. However, organic linkers obstruct and saturate the inorganic nodes of MOF structures, making it challenging to utilize the applied potential of metal centers. Here, we combined controlled ligand decarboxylation with noble metal nanoparticles to rationally remodel MIL-53, resulting in a hybrid nanozyme (AgAu@QMIL-53, AAQM) with excellent multiple enzyme-like activities that both eradicate bacteria and promote diabetic wound healing. Specifically, benefitting from oxidase (OXD)-like and peroxidase (POD)-like activities, AAQM converts oxygen (O2) and hydrogen peroxide (H2O2) into superoxide anion radicals (O2-) and hydroxyl radicals (OH) to eradicate bacteria. In in vitro antibacterial experiments, AAQM exhibited favorable killing efficacy against Pseudomonas aeruginosa (P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA) (>99 %). Notably, due to its superoxide (SOD)-like activity and outstanding reactive nitrogen species (RNS) elimination capacity, AAQM can produce adequate O2 and alleviate oxidative stress in diabetic wounds. Benefiting from the rational modification of MIL-53, the synthesized hybrid nanozyme can effectively kill bacteria while alleviating oxidative stress and ultimately promote infected diabetic wound healing. Overall, this biomimetic enzyme-catalyzed strategy will bring enlightenment to the design of self-antibacterial agents for efficient disinfection and wound healing simultaneously.
Asunto(s)
Diabetes Mellitus , Staphylococcus aureus Resistente a Meticilina , Humanos , Desinfección , Peróxido de Hidrógeno , Antibacterianos/farmacologíaRESUMEN
Programmed death ligand 1 (PD-L1) is highly expressed in cancer cells and participates in the immune escape process of tumor cells. However, as one of the most promising biomarkers for cancer immunotherapy monitoring, the key problem ahead of practical usage is how to effectively improve the detection sensitivity of PD-L1. Herein, an electrochemical aptasensor for the evaluation of tumor immunotherapy is developed based on the immune checkpoint protein PD-L1. The fundamental principle of this method involves the utilization of DNA nanotetrahedron (NTH)-based capture probes and aptamer-modified magnetic metal-organic framework nanocomposites as signaling probes. A synergistic enhancement is observed in the electrocatalytic effect between Fe3O4 and UiO-66 porous shells in Fe3O4@UiO-66 nanocomposites. Therefore, the integration of aptamer-modified Fe3O4@UiO-66@Au with NTH-assisted target immobilization as an electrochemical sensing platform can significantly enhance sensitivity and specificity for target detection. This method enables the detection of targets at concentrations as low as 7.76 pg mL-1 over a wide linear range (0.01 to 1000 ng mL-1). The authors have successfully employed this sensor for in situ characterization of PD-L1 on the cell surface and for monitoring changes in PD-L1 expression during drug therapy, providing a cost-effective yet robust alternative to highly expensive and expertise-dependent flow cytometry.
Asunto(s)
Aptámeros de Nucleótidos , Técnicas Biosensibles , Estructuras Metalorgánicas , Ácidos Ftálicos , Estructuras Metalorgánicas/química , Antígeno B7-H1 , Proteínas de Punto de Control Inmunitario , Límite de Detección , Técnicas Biosensibles/métodos , Aptámeros de Nucleótidos/química , Fenómenos MagnéticosRESUMEN
Removal of invasive bacteria is critical for proper wound healing. This task is challenging because these bacteria can trigger intense oxidative stress and gradually develop antibiotic resistance. Here, the use of a multienzyme-integrated nanocatalytic platform is reported for efficient bacterial clearance and mitigation of inflammatory responses, constructed by physically adsorbing natural superoxide dismutase (SOD), in situ reduction of gold nanoparticles (Au NPs), and incorporation of a DNAzyme on 2D NiCoCu metal-organic frameworks (DNAzyme/SOD/Au@NiCoCu MOFs, termed DSAM), which can adapt to infected wounds. O2 and H2 O2 replenishment is achieved and alleviated the hypoxic microenvironment using the antioxidant properties of SOD. The H2 O2 produced during the reaction is decomposed by peroxidase (POD)-like activity enhanced by Au NPs and DNAzyme, releasing highly toxic hydroxyl radicals (â¢OH) to kill the bacteria. In addition, it possesses glutathione peroxidase (GPx)-like activity, which depletes GSH and prevents â¢OH loss. Systematic antimicrobial tests are performed against bacteria using this multienzyme-integrated nanoplatform. A dual-mode strategy involving natural enzyme-enhanced antioxidant capacity and artificial enzyme-enhanced â¢OH release to develop an efficient and novel enzyme-integrated therapeutic platform is integrated.
RESUMEN
Metal-organic frameworks (MOFs) with peroxidase (POD)-like activity have great potential for combating drug-resistant bacterial infections. However, the use of POD-like activities is severely limited by low oxygen levels and high levels of glutathione (GSH) within the microenvironment of bacterial infection. Herein, G-quadruplex/hemin DNAzyme-aptamer probes and tannic acid-chelated Au nanoparticle (Au-TA)-decorated Cu-based MOF nanosheets (termed GATC) with triple-enzyme activities were developed for visual detection and efficient antibacterial therapy. First, the monometallic MOFs (Cu-ZIF) showed the best catalytic and loading capacity performance compared with the bimetallic MOFs (CoCu-ZIF and ZnCu-ZIF). Then, Cu-MOFs, Au-TA, and DNAzyme improve the POD-like activity to generate more hydroxyl radicals (â¢OH) to kill bacteria. GATC can bind to bacteria through aptamer recognition, increasing the bacterial surface contact area for efficient antibacterial activity. GATC can decompose H2O2 into O2 to alleviate hypoxia and improve the microenvironment due to its catalase (CAT)-like activity. In addition, GATC exhibited GSH peroxidase-like activity, which can avoid the loss of â¢OH and result in bacterial death more easily. Compared with previous studies, GATC exhibited extraordinary bactericidal ability at an extremely low dosage of 3 µg/mL against methicillin-resistant Staphylococcus aureus (MRSA). Notably, the GATC-catalyzed chromogenic reaction could accurately monitor the MRSA infection treatment process. Overall, this work could establish a therapeutic platform for the monitoring and management of bacteria-infected wounds.
RESUMEN
Fighting against bacterial infection and accelerating wound healing remain important and challenging in infected wound care. Metal-organic frameworks (MOFs) have received much attention for their optimized and enhanced catalytic performance in different dimensions of these challenges. The size and morphology of nanomaterials are important in their physiochemical properties and thereby their biological functions. Enzyme-mimicking catalysts, based on MOFs of different dimensions, display varying degrees of peroxidase (POD)-like activity toward hydrogen peroxide (H2O2) decomposition into toxic hydroxyl radicals (â¢OH) for bacterial inhibition and accelerating wound healing. In this study, we investigated the two most studied representatives of copper-based MOFs (Cu-MOFs), three-dimensional (3D) HKUST-1 and two-dimensional (2D) Cu-TCPP, for antibacterial therapy. HKUST-1, with a uniform and octahedral 3D structure, showed higher POD-like activity, resulting in H2O2 decomposition for â¢OH generation rather than Cu-TCPP. Because of the efficient generation of toxic â¢OH, both Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus could be eliminated under a lower concentration of H2O2. Animal experiments indicated that the as-prepared HKUST-1 effectively accelerated wound healing with good biocompatibility. These results reveal the multivariate dimensions of Cu-MOFs with high POD-like activity, providing good potential for further stimulation of specific bacterial binding therapies in the future.
Asunto(s)
Estructuras Metalorgánicas , Staphylococcus aureus Resistente a Meticilina , Animales , Cobre/química , Peróxido de Hidrógeno/química , Antibacterianos/farmacologíaRESUMEN
Bacterial-infected wounds are a serious threat to public health. Bacterial invasion can easily delay the wound healing process and even cause more serious damage. Therefore, effective new methods or drugs are needed to treat wounds. Nanozyme is an artificial enzyme that mimics the activity of a natural enzyme, and a substitute for natural enzymes by mimicking the coordination environment of the catalytic site. Due to the numerous excellent properties of nanozymes, the generation of drug-resistant bacteria can be avoided while treating bacterial infection wounds by catalyzing the sterilization mechanism of generating reactive oxygen species (ROS). Notably, there are still some defects in the nanozyme antibacterial agents, and the design direction is to realize the multifunctionalization and intelligence of a single system. In this review, we first discuss the pathophysiology of bacteria infected wound healing, the formation of bacterial infection wounds, and the strategies for treating bacterially infected wounds. In addition, the antibacterial advantages and mechanism of nanozymes for bacteria-infected wounds are also described. Importantly, a series of nanomaterials based on nanozyme synthesis for the treatment of infected wounds are emphasized. Finally, the challenges and prospects of nanozymes for treating bacterial infection wounds are proposed for future research in this field.