2-Methylbenzimidazole-copper nanozyme with high laccase activity for colorimetric differentiation and detection of aminophenol isomers.

Laccase is well-known for its eco-friendly applications in environmental remediation and biotechnology, but its high cost and low stability have limited its practical use. Therefore, there is an urgent need to develop efficient laccase mimetics. In this study, a novel laccase-mimicking nanozyme (MBI-Cu) was successfully synthesized using 2-methylbenzimidazole (MBI) coordinated with Cu2+ by mimicking the copper active site and electron transfer pathway of natural laccase. MBI-Cu nanozyme exhibited excellent catalytic activity and higher stability than laccase, and was utilized to oxidize a series of phenolic compounds. Environmental pollutant aminophenol isomers were found to display different color in solution when catalytically oxidized by MBI-Cu, which provided a simple and feasible method to identify them by the naked eye. Based on the distinct absorption spectra of the oxidized aminophenol isomers, a colorimetric method for quantitatively detecting o-AP, m-AP, and p-AP was established, with detection limits of 0.06 µM, 0.27 µM, and 0.18 µM, respectively. Furthermore, by integrating MBI-Cu-based cotton pad colorimetric strips with smartphone and utilizing color recognition software to identify and analyze the RGB values of the images, a portable colorimetric sensing platform was designed for rapid detection of aminophenol isomers without the need for any analytical instrument. This work provides an effective reference for the design of laccase nanozymes and holds significant potential for applications in the field of environmental pollutant monitoring.

A Self-Catalytic NO/O2 Gas-Releasing Nanozyme for Radiotherapy Sensitization through Vascular Normalization and Hypoxia Relief.

Radiotherapy (RT), essential for treating various cancers, faces challenges from tumor hypoxia, which induces radioresistance. A tumor-targeted "prosthetic-Arginine" coassembled nanozyme system, engineered to catalytically generate nitric oxide (NO) and oxygen (O2) in the tumor microenvironment (TME), overcoming hypoxia and enhancing radiosensitivity is presented. This system integrates the prosthetic heme of nitric oxide synthase (NOS) and catalase (CAT) with NO-donating Fmoc-protected Arginine and Ru3+ ions, creating HRRu nanozymes that merge NOS and CAT functionalities. Surface modification with human heavy chain ferritin (HFn) improves the targeting ability of nanozymes (HRRu-HFn) to tumor tissues. In the TME, strategic arginine incorporation within the nanozyme allows autonomous O2 and NO release, triggered by endogenous hydrogen peroxide, elevating NO and O2 levels to normalize vasculature and improve blood perfusion, thus mitigating hypoxia. Employing the intrinsic O2-transporting ability of heme, HRRu-HFn nanozymes also deliver O2 directly to the tumor site. Utilizing esophageal squamous cell carcinoma as a tumor model, the studies reveal that the synergistic functions of NO and O2 production, alongside targeted delivery, enable the HRRu-HFn nanozymes to combat tumor hypoxia and potentiate radiotherapy. This HRRu-HFn nanozyme based approach holds the potential to reduce the radiation dose required and minimize side effects associated with conventional radiotherapy.

ß-CD@AgNPs with peroxisase-like activity for colorimetric determination of chiral tryptophan.

Different enantiomer forms of amino acids play different roles in multifarious fields, and improper use will cause irreversible effects. Therefore, the identification of chiral amino acids is a vital issue in the field of pharmaceutical analysis. Herein, a chiral sensing system of ß-cyclodextrin coated silver nanoparticle (ß-CD@AgNPs) with peroxidase-like activity was designed for the fast and efficient colorimetric identification of tryptophan (Trp) enantiomers based on the difference in binding capacity between D/L-Trp and ß-CD. The results showed the satisfactory linearity for detecting D/L-Trp over the concentration range from 0.2 to 4 mM with a LOD of 0.16 and 0.18 mM, respectively. Moreover, the absorbance increased linearly with the rise of D-Trp concentration percentage in the Trp enantiomer mixture. The proposed method avoided the use of natural enzymes and improved the stability due to the protective effect of cyclodextrin, which provided a new idea for selective colorimetric recognition and detection of D/L-Trp based on cyclodextrin.

Ultra-small CuOx/GDYO nanozyme with boosting peroxidase-like activity via electrochemical strategy: Toward applicable colorimetric detection of organophosphate pesticides.

In this paper, an ultra-small-sized CuOx/GDYO nanozyme in situ grown on ITO glass was rationally synthesized from mixed precursors of graphdiyne oxide (GDYO) and copper based infinite coordination polymer (Cu-ICP, consisting of Cu ions and two organic ligands 3,5-di-tert-butylcatechol and 1,4-bis(imidazole-1-ylmethyl)benzene) via mild and simple electrochemical strategy. On one hand, the preferential electro-reduction of Cu-ICP enabled the formation of ultra-small CuOx with Cu(I) as the main component and avoided the loss of oxygen-containing functional groups and defects on the surface of GDYO; on the other hand, GDYO can also serve as electroless reductive species to facilitate the electrochemical deposition of CuOx and turn itself to a higher oxidation state with more exposed functional groups and defects. This one-stone-two-birds electrochemical strategy empowered CuOx/GDYO nanozyme with superior peroxidase-mimicking activity and robust anchoring stability on ITO glass, thus enabled further exploration of the portable device with availability for point-of-use applications. Based on the organophosphorus pesticides (OPs) blocked acetylcholinesterase (AChE) activity, the competitive redox reaction was regulated to initiate the chromogenic reaction of 3,3',5,5'-tetramethylbenzidine (TMB) catalyzed by CuOx/GDYO peroxidase-like nanozyme, which laid out a foundation for the detection of OPs (with chlorpyrifos as an example). With a detection of limit low to 0.57 nM, the OPs residues during agricultural production can be directly monitored by the portable device we developed.

Photo-Activated Oxidative Stress Amplifier: A Strategy for Targeting Glutathione Metabolism and Enhancing ROS-Mediated Therapy in Triple-Negative Breast Cancer Treatment.

Amplifying oxidative stress within tumor cells can effectively inhibit the growth and metastasis of triple-negative breast cancer (TNBC). Therefore, the development of innovative nanomedicines that can effectively disrupt the redox balance represents a promising yet challenging therapeutic strategy for TNBC. In this study, an oxidative stress amplifier, denoted as PBCH, comprising PdAg mesoporous nanozyme and a CaP mineralized layer, loaded with GSH inhibitor L-buthionine sulfoximine (BSO), and further surface-modified with hyaluronic acid that can target CD44, is introduced. In the acidic tumor microenvironment, Ca2+ is initially released, thereby leading to mitochondrial dysfunction and eventually triggering apoptosis. Additionally, BSO suppresses the synthesis of intracellular reduced GSH and further amplifies the level of oxidative stress in cancer cells. Furthermore, PdAg nanozyme can be activated by near-infrared light to induce photothermal and photodynamic effects, causing a burst of ROS and simultaneously promoting cell apoptosis via provoking immunogenic cell death. The high-performance therapeutic effects of PBCH, based on the synergistic effect of aforementioned multiple oxidative damage and photothermal ablation, are validated in TNBC cells and animal models, declaring its potential as a safe and effective anti-tumor agent. The proposed approach offers new perspectives for precise and efficient treatment of TNBC.

Development of a Zn-Based Single-Atom Nanozyme for Efficient Hydrolysis of Glycosidic Bonds.

Hydrolytic enzymes are essential components in second-generation biofuel technology and food fermentation processes. Nanozymes show promise for large-scale industrial applications as replacements for natural enzymes due to their distinct advantages. However, there remains a research gap concerning glycosidase nanozymes. In this study, a Zn-based single-atom nanozyme (ZnN4-900) is developed for efficient glycosidic bond hydrolysis in an aqueous solution. The planar structure of the class-porphyrin N4 material approximatively mimicked the catalytic centers of natural enzymes, facilitating oxidase-like (OXD-like) activity and promoting glycosidic bond cleavage. Theoretical calculations show that the Zn site can act as Lewis acids, attacking the C─O bond in glycosidic bonds. Additionally, ZnN4-900 has the ability to degrade starch and produce reducing sugars that increased yeast cell biomass by 32.86% and ethanol production by 14.56%. This catalyst held promising potential for enhancing processes in ethanol brewing and starch degradation industries.

Oriented cellulose hydrogel: Directed tissue regeneration for reducing corneal leukoplakia and managing fungal corneal ulcers.

Fungal corneal ulcer is one of the leading causes of corneal blindness in developing countries. Corneal scars such as leukoplakia are formed due to inflammation, oxidative stress and non-directed repair, which seriously affect the patients' subsequent visual and life quality. In this study, drawing inspiration from the oriented structure of collagen fibers within the corneal stroma, we first proposed the directional arrangement of CuTA-CMHT hydrogel system at micro and macro scales based on the 3D printing extrusion method combined with secondary patterning. It played an antifungal role and induced oriented repair in therapy of fungal corneal ulcer. The results showed that it effectively inhibited Candida albicans, Aspergillus Niger, Fusarium sapropelum, which mainly affects TNF, NF-kappa B, and HIF-1 signaling pathways, achieving effective antifungal functions. More importantly, the fibroblasts interacted with extracellular matrix (ECM) of corneal stroma through formation of focal adhesions, promoted the proliferation and directional migration of cells in vitro, induced the directional alignment of collagen fibers and corneal stromal orthogonally oriented repair in vivo. This process is mainly associated with MYLK, MYL9, and ITGA3 molecules. Furthermore, the downregulation the growth factors TGF-ß and PDGF-ß inhibits myofibroblast development and reduces scar-type ECM production, thereby reducing corneal leukoplakia. It also activates the PI3K-AKT signaling pathway, promoting corneal healing. In conclusion, the oriented CuTA-CMHT hydrogel system mimics the orthogonal arrangement of collagen fibers, inhibits inflammation, eliminates reactive oxygen species, and reduces corneal leukoplakia, which is of great significance in the treatment of fungal corneal ulcer and is expected to write a new chapter in corneal tissue engineering.

Emerging nanozyme therapy incorporated into dental materials for diverse oral pathologies.

OBJECTIVE: Nanozyme materials combine the advantages of natural enzymes and artificial catalysis, and have been widely applied in new technologies for dental materials and oral disease treatment. Based on the role of reactive oxygen species (ROS) and oxidative stress pathways in the occurrence and therapy of oral diseases, a comprehensive review was conducted on the methods and mechanisms of nanozymes and their dental materials in treating different oral diseases. METHODS: This review is based on literature surveys from PubMed and Web of Science databases, as well as reviews of relevant researches and publications on nanozymes in the therapy of oral diseases and oral tumors in international peer-reviewed journals. RESULTS: Given the unique function of nanozymes in the generation and elimination of ROS, they play an important role in the occurrence, development, and treatment of different oral diseases. The application of nanozymes in dental materials and oral disease treatment was introduced, including the latest advances in their use for dental caries, pulpitis, jaw osteomyelitis, periodontitis, oral mucosal diseases, temporomandibular joint disorders, and oral tumors. Future approaches were also summarized and proposed based on the characteristics of these diseases. SIGNIFICANCE: This review will guide biomedical researchers and oral clinicians to understand the mechanisms and applications of nanozymes in the therapy of oral diseases, promoting further development in the field of dental materials within the oral medication. It is anticipated that more suitable therapeutic agents or dental materials encapsulating nanozymes, specifically designed for the oral environment and simpler for clinical utilization, will emerge in the forthcoming future.

Cholesterol Depletion-Enhanced Ferroptosis and Immunotherapy via Engineered Nanozyme.

Ferroptosis, an iron- and reactive oxygen species (ROS)-dependent cell death, holds significant promise for tumor therapy due to its ability to induce lipid peroxidation (LPO) and trigger antitumor immune responses. However, elevated cholesterol levels in cancer cells impede ferroptosis and compromise immune function. Here, a novel nanozyme, Fe-MOF/CP, composed of iron metal-organic framework (Fe-MOF) nanoparticles loaded with cholesterol oxidase and PEGylation for integrated ferroptosis and immunotherapy is introduced. Fe-MOF/CP depletes cholesterol and generates hydrogen peroxide, enhancing ROS levels and inducing LPO, thereby promoting ferroptosis. This process disrupts lipid raft integrity and downregulates glutathione peroxidase 4 and ferroptosis suppressor protein 1, further facilitating ferroptosis. Concurrently, Fe-MOF/CP augments immunogenic cell death, reduces programmed death-ligand 1 expression, and revitalizes exhausted CD8+ T cells. In vivo studies demonstrate significant therapeutic efficacy in abscopal, metastasis, and recurrent tumor models, highlighting the robust antitumor immune responses elicited by Fe-MOF/CP. This study underscores the potential of Fe-MOF/CP as a multifunctional therapeutic agent that combines ferroptosis and immunotherapy, offering a promising strategy for effective and durable cancer treatment.

Engineering the nanozyme hydrogel beads by polyvinyl alcohol/chitosan encapsulation with recyclable and sustainable catalytic activity for visual analysis of hydrogen peroxide.

BACKGROUND: Hydrogen peroxide (H2O2) plays a vital role in human health and have been regarded as a crucial analyte in metabolic processes, redox transformations, foods research and medical fields. Especially, the long-time and excessive digestion of H2O2 may even cause severe diseases. Although conventional instrumental methods and nanozymes-based colorimetric methods have been developed to accomplish the quantitative analysis of H2O2, the drawbacks of instrument dependence, cost-effectiveness, short lifespan, non-portable and unsustainable detection efficacies will limit their applications in different detection scenarios. RESULTS: Herein, to address these challenges, we have proposed a novel strategy for nanozyme (RuO2) hydrogel preparation by the solid support from cross-linked polyvinyl alcohol (PVA) and chitosan (CS) to both inherit the dominant peroxidase-like (POD) activity and protect the RuO2 from losing efficacies. Taking advantages from the hydrogel, the encapsulated RuO2 were further prepared as the regularly spherical beads (PCRO) to exhibit the sustainable, recyclable, and robust catalysis. Moreover, the intrinsic color interferences which originated from RuO2 can be avoided by the encapsulation strategy to promote the detection accuracy. Meanwhile, the high mechanical strength of PCRO shows the high stability, reproducibility, and cyclic catalysis to achieve the recyclable detection performance and long lifetime storage (40 days), which enables the sensitively detection of H2O2 with the detection limit as lower to 15 µM and the wide detection linear range from 0.025 to 1.0 mM. SIGNIFICANCE: On the basis of the unique properties, PCRO has been further adopted to construct a smartphone detection platform to realize the instrument-free and visual analysis of H2O2 in multi-types of milk and real water samples through capturing, processing, and analyzing the RGB values from the colorimetric photographs. Therefore, PCRO with the advanced detection efficacies holds the great potential in achieving the portable and on-site analysis of targets-of-interest.

In-Situ Grown Nanocrystal TiO2 on 2D Ti3C2 Nanosheets with Anti-Tumor Activity from Photo-Sonodynamic Treatment and Immunology.

Introduction: Traditional cancer treatment strategies often have severe toxic side effects and poor therapeutic efficacy. To address the long-standing problems related to overcoming the complexity of tumors, we develop a novel nanozyme based on the in situ oxidation of 2D Ti3C2 structure to perform simultaneous phototherapy and sonodynamic therapy on tumors. Ti3C2 nanozymes exhibit multi-enzyme activity, including intrinsic peroxidase (POD) activities, which can react with H2O2 in the tumor microenvironment. This new material can construct Ti3C2/TiO2 heterostructures in vivo. Methods: Photothermal (PTT), sonodynamic (SDT) effects, and photoacoustic (PA) image-guided synergy therapy can be achieved. Finally, anticancer immune responses occur with this nanozyme. In vivo experiments revealed that the Ti3C2/TiO2 heterostructure inhibited tumor growth. Results: Complementarily, our results showed that the Ti3C2/TiO2 heterostructure enhanced the immunogenic activity of tumors by recruiting cytotoxic T cells, thereby enhancing the tumor ablation effect. Mechanistic studies consistently indicated that Reactive Oxygen Species (ROS) regulates apoptosis of HCC cells by modulating NRF2/OSGIN1 signaling both in vitro and in vivo. As a result, Ti3C2 nanozyme effectively inhibited tumor through its synergistic ability to modulate ROS and enhance immune infiltration of cytotoxic T cells in the tumor microenvironment. Discussion: These findings open up new avenues for enhancing 2D Ti3C2 nanosheets and suggest a new way to develop more effective sonosensitizers for the treatment of cancer.

Synthesis of histidine, serine and folic acid-functionalized and boron and iron-doped graphene quantum dot with excellent optical behavior and peroxidase-like activity for colorimetric and fluorescence detection of H2O2 in food.

Low fluorescence under visible light excitation and catalytic activity limit many applications of graphene quantum dots in optical detection, biosensing, catalysis and biomedical. The paper reports design and synthesis of histidine, serine and folic acid-functionalized and boron and iron-doped graphene quantum dot (Fe/B-GQD-HSF). The Fe/B-GQD-HSF shows excellent fluorescence behavior and peroxidase-like activity. Excitation of 330 nm ultraviolet light produces the strongest blue fluorescence and excitation of 480 nm visible light produces the strongest yellow fluorescence. The specific activity reaches 92.67 U g-1, which is higher than that of other graphene quantum dots. The Fe/B-GQD-HSF can catalyze oxidation of 3,3',5,5'-tetramethylbenzidine with H2O2 to form blue compound. Based on this, it was used for colorimetric and fluorescence detection of H2O2. The absorbance at 652 nm linearly increases with the increase of H2O2 concentration between 0.5 and 100 µM with detection limit of 0.43 µM. The fluorescence signal linearly decreases with the increase of H2O2 concentration between 0.05 and 100 µM with detection limit of 0.035 µM. The analytical method has been satisfactorily applied in detection of H2O2 in food. The study also paves one way for design and synthesis of functional graphene quantum dots with ideal fluorescence behavior and catalytic activity.

Immobilizing DNase in ternary AuAgCu hydrogels to accelerate biofilm disruption for synergistically enhanced therapy of MRSA infections.

Bacterial biofilm-related infections have become a significant global concern in public health and economy. Extracellular DNA (eDNA) is regarded as one of the key elements of extracellular polymeric substances (EPS) in bacterial biofilm, providing robust support to maintain the stability of bacterial biofilms for fighting against environmental stresses (such as antibiotics, reactive oxygen species (ROS), and hyperthermia). In this study, ternary AuAgCu hydrogels nanozyme with porous network structures were utilized for the immobilization of DNase (AuAgCu@DNase hydrogels) to realize enhanced biofilm decomposition and antibacterial therapy of MRSA. The prepared AuAgCu@DNase hydrogels can efficiently hydrolyze eDNA in biofilms so that the generated ROS and hyperthermia by laser irradiation can permeate into the interior of the biofilm to achieve deep sterilization. The typical interface interactions between AuAgCu hydrogels and DNase and the excellent photothermal-boost peroxidase-like performances of AuAgCu hydrogels take responsibility for the enhanced antibacterial activity. In the MRSA-infected wounds model, the in vivo antibacterial results revealed that the AuAgCu@DNase hydrogels possess excellent drug-resistant bacteria-killing performance with superb biocompatibility. Meanwhile, the pathological analysis of collagen deposition and fibroblast proliferation of wounds demonstrate highly satisfactory wound healing. This work offers an innovative path for developing nanozyme-enzyme antibacterial composites against drug-resistant bacteria and their biofilms.

Mitochondria-targeting nanozyme for catalytical therapy and radiotherapy with activation of cGAS-STING.

BACKGROUND: Overcoming radio-resistance and enhance radio-sensitivity to obtain desired therapeutic outcome plays an important role in treating cancer. METHODS: Here we constructed a versatile enzyme-like nano-radiosensitizer MDP. MDP is composed of MnCO decorated and Ru-based nanozyme with triphenylphosphine (TPP) group coordinated on the surface. RESULTS: Due to the mitochondria-targeting ability of TPP and enhanced permeability and retention effect (EPR) effect of MDP, MDP accumulated in the mitochondria of tumor cells. Therefore, quantities of reactive oxygen species were produced via multiple enzyme-like properties including peroxidase (POD) and catalase (CAT) in a tumor microenvironment mimicking status. In additional, more energy of radiation ionizing was deposed in tumor site via Compton effect and secondary electron scattering by Ru element. Impressively, it was disclosed that the nanozyme can act as a cGAS-STING agonist to provoke immune response of the system, which hereby further elevated this combined therapy. CONCLUSIONS: Collectively, we fabricated a novel nanozyme with POD and CAT mimicking properties for the combination therapy of catalytical therapy, radiotherapy as well as immune therapy to eliminate cancer.

Hypoxia Reversion and STING Pathway Activation through Large Mesoporous Nanozyme for Near-Infrared-II Light Amplified Tumor Polymetallic-Immunotherapy.

cGAS/STING pathway, which is highly related to tumor hypoxia, is considered as a potential target for remodeling the immunosuppressive microenvironment of solid tumors. Metal ions, such as Mn2+, activate the cGAS/STING pathway, but their efficacy in cancer therapy is limited by insufficient effect on immunogenic tumor cell death of a single ion. Here, we evaluate the association between tumor hypoxia and cGAS/STING inhibition and report a polymetallic-immunotherapy strategy based on large mesoporous trimetal-based nanozyme (AuPdRh) coordinated with Mn2+ (Mn2+@AuPdRh) to activate cGAS/STING signaling for robust adaptive antitumor immunity. Specifically, the inherent CAT-like activity of this polymetallic Mn2+@AuPdRh nanozyme decomposes the endogenous H2O2 into O2 to relieve tumor hypoxia induced suppression of cGAS/STING signaling. Moreover, the Mn2+@AuPdRh nanozyme displays a potent near-infrared-II photothermal effect and strong POD-mimic activity; and the generated hyperthermia and •OH radicals synergistically trigger immunogenic cell death in tumors, releasing abundant dsDNA, while the delivered Mn2+ augments the sensitivity of cGAS to dsDNA and activates the cGAS-STING pathway, thereby triggering downstream immunostimulatory signals to kill primary and distant metastatic tumors. Our study demonstrates the potential of metal-based nanozyme for STING-mediated tumor polymetallic-immunotherapy and may inspire the development of more effective strategies for cancer immunotherapy.

Nanozymes and their biomolecular conjugates as next-generation antibacterial agents: A comprehensive review.

Antimicrobial resistance (AMR), the ability of bacterial species to develop resistance against exposed antibiotics, has gained immense global attention in the past few years. Bacterial infections are serious health concerns affecting millions of people annually worldwide. Therefore, developing novel antibacterial agents that are highly effective and avoid resistance development is imperative. Among various strategies, recent developments in nanozyme technology have shown promising results as antibacterials in several antibiotic-sensitive and resistant bacterial species. Nanozymes offer several advantages over corresponding natural enzymes, such as inexpensive, stable, multifunctional, tunable catalytic properties. Although the use of nanozymes as antibacterial agents has provided promising results, the specific biomolecule-conjugated nanozymes have shown further improvement in catalytic performance and associated antibacterial efficacy. The exclusive design of functional nanozymes with theranostic potential is found to simultaneously inhibit the growth and image of AMR bacterial species. This review comprehensively summarizes the history of nanozymes, their classification, biomolecules conjugated nanozyme, and their mechanism of enzyme-mimetic activity and associated antibacterial activity in antibiotic-sensitive and resistant species. The future needs to effectively engineer the existing or new nanozymes to curb AMR have also been discussed.

Alkaline phosphatase-activated prodrug system based on a bifunctional CuO NP tandem nanoenzyme for on-demand bacterial inactivation and wound disinfection.

Nanozymes are promising antimicrobials, as they produce reactive oxygen species (ROS). However, the intrinsic lack of selectivity of ROS in distinguishing normal flora from pathogenic bacteria deprives nanozymes of the necessary selectivities of ideal antimicrobials. Herein, we exploit the physiological conditions of bacteria (high alkaline phosphatase (ALP) expression) using a novel CuO nanoparticle (NP) nanoenzyme system to initiate an ALP-activated ROS prodrug system for use in the on-demand precision killing of bacteria. The prodrug strategy involves using 2-phospho-L-ascorbic acid trisodium salt (AAP) that catalyzes the ALP in pathogenic bacteria to generate ascorbic acid (AA), which is converted by the CuO NPs, with intrinsic ascorbate oxidase- and peroxidase-like activities, to produce ROS. Notably, the prodrug system selectively kills Escherichia coli (pathogenic bacteria), with minimal influence on Staphylococcus hominis (non-pathogenic bacteria) due to their different levels of ALP expression. Compared to the CuO NPs/AA system, which generally depletes ROS during storage, CuO NPs/AAP exhibits a significantly higher stability without affecting its antibacterial activity. Furthermore, a rat model is used to indicate the applicability of the CuO NPs/AAP fibrin gel in wound disinfection in vivo with negligible side effects. This study reveals the therapeutic precision of this bifunctional tandem nanozyme platform against pathogenic bacteria in ALP-activated conditions.

Oral enzyme-responsive nanoprobes for targeted theranostics of inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a progressive and debilitating inflammatory disease of the gastrointestinal tract (GIT). Despite recent advances, precise treatment and noninvasive monitoring remain challenging. METHODS: Herein, we developed orally-administered, colitis-targeting and hyaluronic acid (HA)-modified, core-shell curcumin (Cur)- and cerium oxide (CeO2)-loaded nanoprobes (Cur@PC-HA/CeO2 NPs) for computed tomography (CT) imaging-guided treatment and monitoring of IBD in living mice. RESULTS: Following oral administration, high-molecular-weight HA maintains integrity with little absorption in the upper GIT, and then actively accumulates at local colitis sites owing to its colitis-targeting ability, leading to specific CT enhancement lasting for 24 h. The retained NPs are further degraded by hyaluronidase in the colon to release Cur and CeO2, thereby exerting anti-inflammatory and antioxidant effects. Combined with the ability of NPs to regulate intestinal flora, the oral NPs result in substantial relief in symptoms. Following multiple treatments, the gradually decreasing range of the colon with high CT attenuation correlates with the change in the clinical biomarkers, indicating the feasibility of treatment response and remission. CONCLUSION: This study provides a proof-of-concept for the design of a novel theranostic integration strategy for concomitant IBD treatment and the real-time monitoring of treatment responses.

Phosphatase-mimicking Zr@PDA nanozyme with excellent dispersion stability for the detection of fructose 1,6-diphosphate.

Zr4+-doped polydopamine (Zr@PDA) nanozyme with phosphatase-like activity was synthesized by a one-pot hydrothermal method for the first time. Compared with previous representative phosphatase-mimicking nanozymes (i.e., CeO2 NPs, ZrO2 NPs and UiO-66), Zr@PDA not only exhibited higher dispersion stability in water, but also higher catalytical efficiency. Kcat/Km of Zr@PDA is 35 and 12 times that of UiO-66 and ZrO2 NPs, respectively, which would endow the Zr@PDA-based analytical methods with high sensitivity. As a demonstration, a novel colorimetric method based on Zr@PDA nanozyme was developed for sensitive detection of the drug fructose 1,6-diphosphate. The linear range is 1-15 µM with a detection limit as low as 0.38 µM.

Facile synthesis of copper carbonate analog with peroxidase-like activity for colorimetric detection of isoniazid.

In this article, copper carbonate analog with good peroxidase-like activity was successfully synthesized for the first time via a simple co-precipitation of CuSO4▪5H2O and Na2CO3. The obtained copper carbonate analog exhibited excellent intrinsic peroxidase-like activity towards a classical peroxidase substrate of 3, 3', 5, 5' -tetramethylbenzidine (TMB) in the presence of hydrogen peroxide (H2O2) under an acidic environment. The study of the catalytic mechanism confirmed that the hydroxyl radical produced from the decomposition of H2O2 is the main reactive oxygen species responsible for the catalytic oxidation of TMB to oxTMB. Moreover, results from kinetic parameter analysis indicated that H2O2 was more easily and/or likely to attach to the copper carbonate analog than TMB. Subsequently, the effects of experimental conditions (buffer pH, temperature, and incubation time) on the catalytic activity of the copper carbonate analog were also optimized. Finally, a copper carbonate analog-based colorimetric sensor was developed to determine isoniazid. Under the optimal conditions, the linear range for isoniazid was as broad as 0-178.6 µM, and the detection limit was as low as 8.47 µM. The spiked recoveries of isoniazid in normal human serum has been observed in the range of 94.8%-105.5 %. This strategy focuses on the development of a green, cost-efficient peroxidase mimic with high activity, good biocompatibility, and a simple synthesis process.