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Developing ultrasensitive lateral flow immunoassays (LFIAs) has garnered significant attention in the field of point-of-care testing. In this study, a trimetallic dendritic nanozyme (Pd@Pt-Ru) was synthesized through Ru deposition on a Pd@Pt core and utilized to enhancing the sensitivity of LFIAs. Pd@Pt-Ru exhibited a Km value of 5.23 mM for detecting H2O2, which indicates an H2O2 affinity comparable with that of horseradish peroxidase. The Ru surface layer reduces the activation energy barrier, which increases the maximum reaction rate. As a proof of concept, the proposed Pd@Pt-Ru nanozyme was incorporated into LFIAs (A-Pd@Pt-Ru-LFIAs) for detecting human chorionic gonadotropin (hCG). Compared with conventional gold nanoparticle (AuNP)-LFIAs, A-Pd@Pt-Ru-LFIAs demonstrated 250-fold increased sensitivity, thereby enabling a visible detection limit as low as 0.1 IU/L. True positive and negative rates both reached 100%, which renders the proposed Pd@Pt-Ru nanozyme suitable for detecting hCG in clinical samples.
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Gonadotropina Coriônica , Peróxido de Hidrogênio , Limite de Detecção , Nanopartículas Metálicas , Paládio , Platina , Rutênio , Paládio/química , Platina/química , Imunoensaio/métodos , Humanos , Rutênio/química , Gonadotropina Coriônica/análise , Nanopartículas Metálicas/química , Peróxido de Hidrogênio/análise , Peróxido de Hidrogênio/química , Ouro/química , Dendrímeros/química , Técnicas Biossensoriais/métodos , Peroxidase/química , CatáliseRESUMO
Spinel oxides have emerged as a promising candidate in the realm of nanozymes with variable oxidation states, while their limited active sites and low conductivity hinder further application. In this work, we synthesize a series of metal-doped NiCo2O4 nanospheres decorated with Pd, which are deployed as highly efficient nanozymes for the detection of cancer biomarkers. Through meticulous modulation of the molar ratio between NiCo2O4 and Pd, we orchestrated precise control over the oxygen vacancies and electronic structure within the nanozymes, a key factor in amplifying the catalytic prowess. Leveraging the superior H2O2 reduction catalytic properties of Fe-NiCo2O4@Pd, we have successfully implemented its application in the electrochemical detection of biomarkers, achieving unparalleled analytical performance, much higher than that of Pd/C and other reported nanozymes. This research paves the way for innovative electron modification strategies in the design of high-performance nanozymes, presenting a formidable tool for clinical diagnostic analyses.
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Cobalto , Peróxido de Hidrogênio , Óxidos , Paládio , Catálise , Paládio/química , Cobalto/química , Óxidos/química , Peróxido de Hidrogênio/química , Oxirredução , Níquel/química , Humanos , Técnicas EletroquímicasRESUMO
Rectifying the aberrant microenvironment of a disease through maintenance of redox homeostasis has emerged as a promising perspective with significant therapeutic potential for Alzheimer's disease (AD). Herein, we design and construct a novel nanozyme-boosted MOF-CRISPR platform (CMOPKP), which can maintain redox homeostasis and rescue the impaired microenvironment of AD. By modifying the targeted peptides KLVFFAED, CMOPKP can traverse the blood-brain barrier and deliver the CRISPR activation system for precise activation of the Nrf2 signaling pathway and downstream redox proteins in regions characterized by oxidative stress, thereby reinstating neuronal antioxidant capacity and preserving redox homeostasis. Furthermore, cerium dioxide possessing catalase enzyme-like activity can synergistically alleviate oxidative stress. Further in vivo studies demonstrate that CMOPKP can effectively alleviate cognitive impairment in 3xTg-AD mouse models. Therefore, our design presents an effective way for regulating redox homeostasis in AD, which shows promise as a therapeutic strategy for mitigating oxidative stress in AD.
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Doença de Alzheimer , Estresse Oxidativo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/genética , Animais , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Estruturas Metalorgânicas/química , Modelos Animais de Doenças , Sistemas CRISPR-Cas/genética , Cério/química , Cério/uso terapêutico , Cério/farmacologia , Barreira Hematoencefálica/metabolismo , Oxirredução , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêuticoRESUMO
Phyllosilicates-based nanomaterials, particularly iron-rich vermiculite (VMT), have wide applications in biomedicine. However, the lack of effective methods to activate the functional layer covered by the external inert layer limits their future applications. Herein, we report a mineral phase reconfiguration strategy to prepare novel nanozymes by a molten salt method. The peroxidase-like activity of the VMT reconfiguration nanozyme is 10 times that of VMT, due to the electronic structure change of iron in VMT. Density-functional theory calculations confirmed that the upward shifted d-band center of the VMT reconfiguration nanozyme promoted the adsorption of H2O2 on the active iron sites and significantly elongated the O-O bond lengths. The reconfiguration nanozyme exhibited nearly 100% antibacterial activity toward Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), much higher than that of VMT (E. coli 10%, S. aureus 21%). This work provides new insights for the rational design of efficient bioactive phyllosilicates-based nanozyme.
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Escherichia coli , Staphylococcus aureus , Peróxido de Hidrogênio , Silicatos de Alumínio/farmacologia , Ferro , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
The lateral flow immunoassay (LFIA) is a sought-after point-of-care testing platform, yet the insufficient sensitivity of the LFIA limits its application in the detection of tumor biomarkers. Here, a colorimetric signal amplification method, bimetallic nanozyme-mediated in situ-catalyzed reporter deposition (BN-ISCRD), was designed for ultrasensitive cancer diagnosis. The bimetallic nanozyme used, palladium@iridium core-shell nanoparticles (Pd@Ir NPs), had ultrahigh enzyme-like activity, which was further explained by the electron transfer of Pd@Ir NPs and the change in the Gibbs free energy during catalysis through density functional theory calculations. With gastric cancer biomarkers pepsinogen I and pepsinogen II as model targets, this assay could achieve a cutoff value of 10 pg/mL, which was 200-fold lower than that without signal enhancement. The assay was applied to correctly identify 8 positive and 28 negative clinical samples. Overall, this BN-ISCRD-based LFIA showed great merits and potential in the application of ultrasensitive disease diagnosis.
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Nanopartículas Metálicas , Nanopartículas , Neoplasias , Humanos , Imunoensaio/métodos , Biomarcadores Tumorais , Catálise , Neoplasias/diagnóstico , Limite de Detecção , OuroRESUMO
Single-atom nanozymes (SANs) are considered to be ideal substitutes for natural enzymes due to their high atom utilization. This work reported a strategy to manipulate the second coordination shell of the Ce atom and reshape the carbon carrier to improve the oxidase-like activity of SANs. Internally, S atoms were symmetrically embedded into the second coordination layer to form a Ce-N4S2-C structure, which reduced the energy barrier for O2 reduction, promoted the electron transfer from the Ce atom to O atoms, and enhanced the interaction between the d orbital of the Ce atom and p orbital of O atoms. Externally, in situ polymerization of mussel-inspired polydopamine on the precursor helps capture metal sources and protects the 3D structure of the carrier during pyrolysis. On the other hand, polyethylene glycol (PEG) modulated the interface of the material to enhance water dispersion and mass transfer efficiency. As a proof of concept, the constructed PEG@P@Ce-N/S-C was applied to the multimodal assay of butyrylcholinesterase activity.
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Cério , Cério/química , Polietilenoglicóis/química , Oxirredutases/química , Oxirredutases/metabolismo , Butirilcolinesterase/química , Butirilcolinesterase/metabolismo , Polímeros/química , Indóis/química , Oxigênio/química , OxirreduçãoRESUMO
Metal nanoclusters feature a hierarchical structure, facilitating their ability to mimic enzyme-catalyzed reactions. However, the lack of true catalytic centers, compounded by tightly bound surface ligands hindering electron transfers to substrates, underscores the need for universal rational design methodologies to emulate the structure and mechanisms of natural enzymes. Motivated by the electron transfer in active centers with specific chemical structures, by integrating the peroxidase cofactor Fe-TCPP onto the surface of glutathione-stabilized gold nanoclusters (AuSG), we engineered AuSG-Fe-TCPP clusterzymes with a remarkable 39.6-fold enhancement in peroxidase-like activity compared to AuSG. Fe-TCPP not only mimics the active center structure, enhancing affinity to H2O2, but also facilitates the electron transfer process, enabling efficient H2O2 activation. By exemplifying the establishment of a detecting platform for trace H2O2 produced by ultrasonic cleaners, we substantiate that the bioinspired surface-ligand-engineered electron transfer can improve sensing performance with a wider linear range and lower detection limit.
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Ouro , Peróxido de Hidrogênio , Nanopartículas Metálicas , Ouro/química , Peróxido de Hidrogênio/química , Transporte de Elétrons , Ligantes , Catálise , Nanopartículas Metálicas/química , Técnicas Biossensoriais/métodos , Glutationa/químicaRESUMO
Uricase-catalyzed uric acid (UA) degradation has been applied for hyperuricemia therapy, but this medication is limited by H2O2 accumulation, which can cause oxidative stress of cells, resulting in many other health issues. Herein, we report a robust cubic hollow nanocage (HNC) system based on polyvinylpyrrolidone-coated PdPt3 and PdIr3 to serve as highly efficient self-cascade uricase/peroxidase mimics to achieve the desired dual catalysis for both UA degradation and H2O2 elimination. These HNCs have hollow cubic shape with average wall thickness of 1.5 nm, providing desired synergy to enhance catalyst's activity and stability. Density functional theory calculations suggest the PdIr3 HNC surface tend to promote OH*/O* desorption for better peroxidase-like catalysis, while the PdPt3 HNC surface accelerates the UA oxidation by facilitating O2-to-H2O2 conversion. The dual catalysis power demonstrated by these HNCs in cell studies suggests their great potential as a new type of nanozyme for treating hyperuricemia.
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Hiperuricemia , Peroxidase , Humanos , Peroxidase/uso terapêutico , Urato Oxidase/uso terapêutico , Povidona/uso terapêutico , Hiperuricemia/tratamento farmacológico , Peróxido de Hidrogênio , Ácido Úrico/metabolismo , Oxirredutases , CorantesRESUMO
Fabrication of nanozyme with catecholase-like catalytic activity faces the great challenge of merging outstanding activity with low cost as well as simple, rapid, and low-energy-consumed production, restricting its industrial applications. Herein, an inexpensive yet robust nanozyme (i.e., DT-Cu) via simple one-step coordination between diaminotriazole (DT) and CuSO4 within 1 h in water at room temperature is constructed. The asymmetric dicopper site with CuN3O configuration for each copper as well as CuâO bond length of ≈1.83 Å and Cu···Cu distance of ≈3.5 Å in DT-Cu resemble those in catechol oxidase (CO), which ensure its prominent intrinsic activity, outperforming most CO-mimicking nanozymes and artificial homogeneous catalysts. The use of inexpensive DT/CuSO4 in this one-pot strategy endows DT-Cu with only ≈20% cost of natural CO per activity unit. During catalysis, O2 experienced a 4e-dominated reduction process accompanied by the formation of 1O2 and H2O2 intermediates and the product of H2O. Benefiting from the low cost as well as the distinctive structure and superior intrinsic activity, DT-Cu presents potential applications ranging from biocatalysis to analytical detection of biomolecules such as epinephrine and beyond.
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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 , Estruturas Metalorgânicas , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/química , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Animais , Cicatrização/efeitos dos fármacos , Plaquetas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Camundongos , HumanosRESUMO
Intrinsic or acquired radioresistance remained an important challenge in the successful management of cancer. Herein, a novel "smart" multifunctional copper-based nanocomposite (RCL@Pd@CuZ) to improve radiotherapy (RT) sensitivity is designed and developed. In this nanoplatform, DSPE-PEG-RGD modified on the liposome surface enhanced tumor targeting and permeability; capsaicin inserted into the phospholipid bilayer improved the hypoxic conditions in the tumor microenvironment (TME) by inhibiting mitochondrial respiration; a Cu MOF porous cube encapsulated in liposome generated highly active hydroxyl radicals (OH·), consumed GSH and promoted cuproptosis by releasing Cu2+; the ultrasmall palladium (Pd) nanozyme within the cubes exhibited peroxidase activity, catalyzing toxic OH· generation and releasing oxygen from hydrogen peroxide; and lastly, Pd, as an element with a relatively high atomic number (Z) enhanced the photoelectric and Compton effects of X-rays. Therefore, RCL@Pd@CuZ enhance RT sensitivity by ameliorating hypoxia, promoting cuproptosis, depleting GSH, amplifying oxidative stress, and enhancing X-ray absorption , consequently potently magnifying immunogenic cell death (ICD). In a mouse model , RCL@Pd@CuZ combined with RT yielded >90% inhibition compared with that obtained by RT alone in addition to a greater quantity of DC maturation and CD8+ T cell infiltration. This nanoplatform offered a promising remedial modality to facilitate cuproptosis-related cancer radioimmunotherapy.
Assuntos
Cobre , Radioimunoterapia , Animais , Radioimunoterapia/métodos , Cobre/química , Camundongos , Respiração Celular/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Humanos , Linhagem Celular Tumoral , Paládio/química , Paládio/farmacologia , Lipossomos/química , Nanocompostos/química , Nanocompostos/uso terapêuticoRESUMO
Boosting the biomimetic catalytic activity of nanozyme is important for its potential application. One common strategy to achieve this goal mainly focused on manipulating the electronic state of metal site through the first coordination shell to modulate the adsorption/desorption strength of related reactant, intermediate and/or product, but remained challenging. Taking Cu-based catecholase-mimicking nanozyme for example, this work herein reports a different strategy involving amino-induced modulation of electronic state through the second shell to raise the electron density of Cu site, which further triggers the repulsion effect between neighboring geminal Cu centers to increase the CuâCu distance. The resulting nanozyme with electron-rich Cu site (DT-Cu) presents a lower work function and an upshifted d-band center in comparison with its counterpart (i.e., relatively electron-deficient TA-Cu), which promotes the electron transfer and enhances the adsorption strengths of Cu site for O2, catechol and H2O2 intermediate. The longer CuâCu distance of DT-Cu accelerated the OâO bond dissociation of H2O2 intermediate. This expedites the oxygen reduction process during catecholase-like catalysis, which together with the enhanced O2/H2O2/catechol adsorption corporately boosts the catecholase-like activity of DT-Cu.
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Chronic wounds of significant severity and acute injuries are highly vulnerable to fungal infections, drastically impeding the expected wound healing trajectory. The clinical use of antifungal therapeutic drug is hampered by poor solubility, high toxicity and adverse reactions, thereby necessitating the urgent development of novel antifungal therapy strategy. Herein, this study proposes a new strategy to enhance the bioactivity of small-molecule antifungal drugs based on multifunctional metal nanozyme engineering, using amphotericin B (AmB) as an example. AmB-decorated gold nanoparticles (AmB@AuNPs) are synthesized by a facile one-pot reaction strategy, and the AmB@AuNPs exhibit superior peroxidase (POD)-like enzyme activity, with maximal reaction rates (Vmax) 3.4 times higher than that of AuNPs for the catalytic reaction of H2O2. Importantly, the enzyme-like activity of AuNPs significantly enhanced the antifungal properties of AmB, and the minimum inhibitory concentrations of AmB@AuNPs against Candida albicans (C. albicans) and Saccharomyces cerevisiae (S. cerevisiae) W303 are reduced by 1.6-fold and 50-fold, respectively, as compared with AmB alone. Concurrent in vivo studies conducted on fungal-infected wounds in mice underscored the fundamentally superior antifungal ability and biosafety of AmB@AuNPs. The proposed strategy of engineering antifungal drugs with nanozymes has great potential for enhanced therapy of fungal infections and related diseases.
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Anfotericina B , Antifúngicos , Candida albicans , Ouro , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Ouro/química , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/uso terapêutico , Anfotericina B/farmacologia , Anfotericina B/química , Anfotericina B/uso terapêutico , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Candida albicans/efeitos dos fármacos , Animais , Saccharomyces cerevisiae/efeitos dos fármacos , CamundongosRESUMO
Keratitis, an inflammation of the cornea caused by bacterial or fungal infections, is one of the leading causes of severe visual disability and blindness. Keratitis treatment requires both the prevention of infection and the reduction of inflammation. However, owing to their limited therapeutic functions, in addition to the ocular barrier, existing conventional medications are characterized by poor efficacy and low bioavailability, requiring high dosages or frequent topical treatment, which represents a burden on patients and increases the risk of side effects. In this study, manganese oxide nanocluster-decorated graphdiyne nanosheets (MnOx/GDY) are developed as multienzyme-like nanozymes for the treatment of infectious keratitis and loaded into hyaluronic acid and polymethyl methacrylate-based ocular microneedles (MGMN). MGMN not only exhibits antimicrobial and anti-inflammatory effects owing to its multienzyme-like activities, including oxidase, peroxidase, catalase, and superoxide dismutase mimics but also crosses the ocular barrier and shows increased bioavailability via the microneedle system. Moreover, MGMN is demonstrated to eliminate pathogens, prevent biofilm formation, reduce inflammation, alleviate ocular hypoxia, and promote the repair of corneal epithelial damage in in vitro, ex vivo, and in vivo experiments, thus providing a better therapeutic effect than commercial ophthalmic voriconazole, with no obvious microbial resistance or cytotoxicity.
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Ceratite , Agulhas , Ceratite/tratamento farmacológico , Animais , Camundongos , Enzimas/metabolismo , Biofilmes/efeitos dos fármacos , Humanos , Óxidos , Compostos de ManganêsRESUMO
Nanozymes, as substitutes for natural enzymes, are constructed as cascade catalysis systems for biomedical applications due to their inherent catalytic properties, high stability, tunable physicochemical properties, and environmental responsiveness. Herein, a multifunctional nanozyme is reported to initiate cascade enzymatic reactions specific in acidic environments for resistant Helicobacter pylori (H. pylori) targeting eradication. The cobalt-coated Prussian blue analog based FPB-Co-Ch NPs displays oxidase-, superoxide dismutase-, peroxidase-, and catalase- mimicking activities that trigger ⢠O 2 - ${\mathrm{O}}_2^ - {\bm{\ }}$ and H2O2 to supply O2, thereby killing H. pylori in the stomach. To this end, chitosan is modified on the surface to exert bacterial targeted adhesion and improve the biocompatibility of the composite. In the intestinal environment, the cascade enzymatic activities are significantly inhibited, ensuring the biosafety of the treatment. In vitro, sensitive and resistant strains of H. pylori are cultured and the antibacterial activity is evaluated. In vivo, murine infection models are developed and its success is confirmed by gastric mucosal reculturing, Gram staining, H&E staining, and Giemsa staining. Additionally, the antibacterial capacity, anti-inflammation, repair effects, and biosafety of FPB-Co-Ch NPs are comprehensively investigated. This strategy renders a drug-free approach that specifically targets and kills H. pylori, restoring the damaged gastric mucosa while relieving inflammation.
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Integrating the plasmonic chirality with excellent catalytic activities in plasmonic hybrid nanostructures provides a promising strategy to realize the chiral nanocatalysis toward many chemical reactions. However, the controllable synthesis of catalytically active chiral plasmonic nanoparticles with tailored geometries and compositions remains a significant challenge. Here it is demonstrated that chiral Au-Pd alloy nanorods with tunable optical chirality and catalytically active surfaces can be achieved by a seed-mediated coreduction growth method. Through manipulating the chiral inducers, Au nanorods selectively transform into two different intrinsically chiral Au-Pd alloy nanorods with distinct geometric chirality and tunable optical chirality. By further adjusting several key synthetic parameters, the optical chirality, composition, and geometry of the chiral Au-Pd nanorods are fine-tailored. More importantly, the chiral Au-Pd alloy nanorods exhibit appealing chiral catalytic activities as well as polarization-dependent plasmon-enhanced nanozyme catalytic activity, which has great potential for chiral nanocatalysis and plasmon-induced chiral photochemistry.
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Nanozymes have shown promise for antibacterial applications, but their effectiveness is often hindered by low catalytic performances in physiological conditions and uncontrolled production of hydroxyl radicals (·OH). To address these limitations, a comprehensive approach is presented through the development of an adenosine triphosphate (ATP)-activated cascade reactor (GGPcs). The GGPcs reactor synergistically combines the distinct properties of zeolitic imidazolate framework-8 (ZIF-8) and chitosan-integrated hydrogel microsphere. The ZIF-8 allows for the encapsulation of G-quadruplex/hemin DNAzyme to achieve ATP-responsive ·OH generation at neutral pH, while the hydrogel microsphere creates a confinement environment that facilitates glucose oxidation and provides a sufficient supply of H2O2. Importantly, the integrated chitosan in the hydrogel microsphere shields ZIF-8 from undesired disruption caused by gluconic acid, ensuring the responsive specificity of ZIF-8 toward ATP. By activating GGPcs with ATP secreted by bacteria, its effectiveness as an antibacterial agent is demonstrated for the on-demand treatment of bacterial infection with minimal side effects. This comprehensive approach has the potential to facilitate the design of advanced nanozyme systems and broaden their biological applications.
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Trifosfato de Adenosina , Antibacterianos , Radical Hidroxila , Radical Hidroxila/metabolismo , Trifosfato de Adenosina/metabolismo , Antibacterianos/farmacologia , Antibacterianos/química , Quitosana/química , Quitosana/farmacologia , Microesferas , Peróxido de Hidrogênio/química , Zeolitas/química , Zeolitas/farmacologiaRESUMO
Engineering of catalytically active inorganic nanomaterials holds promising prospects for biomedicine. Catalytically active metal oxides show applications in enhancing wound healing but have also been employed to induce cell death in photodynamic or radiation therapy. Upon introduction into a biological system, nanomaterials are exposed to complex fluids, causing interaction and adsorption of ions and proteins. While protein corona formation on nanomaterials is acknowledged, its modulation of nanomaterial catalytic efficacy is less understood. In this study, proteomic analyses and nano-analytic methodologies quantify and characterize adsorbed proteins, correlating this protein layer with metal oxide catalytic activity in vitro and in vivo. The protein corona comprises up to 280 different proteins, constituting up to 38% by weight. Enhanced complement factors and other opsonins on nanocatalyst surfaces lead to their uptake into macrophages when applied topically, localizing >99% of the nanomaterials in tissue-resident macrophages. Initially, the formation of the protein corona significantly reduces the nanocatalysts' activity, but this activity can be partially recovered in endosomal conditions due to the proteolytic degradation of the corona. Overall, the research reveals the complex relationship between physisorbed proteins and the catalytic characteristics of specific metal oxide nanoparticles, providing design parameters for optimizing nanocatalysts in complex biological environments.
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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.
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Diabetes Mellitus Experimental , Estruturas Metalorgânicas , Animais , Espécies Reativas de Oxigênio , Estruturas Metalorgânicas/farmacologia , Níquel , Angiogênese , Cicatrização/fisiologia , Antioxidantes , HidrogéisRESUMO
Natural and artificial enzyme oxygen-generating systems for photodynamic therapy (PDT) are developed for tumor treatment, yet they have fallen short of the desired efficacy. Moreover, both the enzymes and photosensitizers usually need carriers for efficient delivery to tumor sites. Here, a self-cascade-enhanced multimodal tumor therapy is developed by ingeniously integrating self-cascade-enhanced PDT with Zn2+-overloading therapy. Manganese-porphyrin (TCPP-Mn) is chosen both as the photosensitizer and catalase (CAT) mimic, which can be encapsulated within glucose oxidase (GOx). Acid-responsive zeolitic imidazolate framework-8 (ZIF-8) is applied as the carrier for TCPP-Mn@GOx (T@G), attaining TCPP-Mn@GOx@ZIF-8 (T@G@Z). T@G@Z demonstrates robust anti-tumor ability as follows: upon the structural degradation of ZIF-8, GOx can mediate the oxidation of glucose and generate hydrogen peroxide (H2O2); TCPP-Mn can catalyze H2O2 into O2 for self-cascade-enhanced PDT; meanwhile, the released Zn2+ can enhance oxidative stress and induce mitochondrial dysfunction by destroying mitochondrial membrane potential; furthermore, immunotherapy can be activated to resist primary tumor and tumor metastasis. The self-cascade-enhanced T@G@Z exhibited its potential application for further tumor management.