Multifunctional Nanozyme Research Articles

Engineering Strain-Defects to Enhance Enzymatic Therapy and Induce Ferroptosis.

The effect of mimetic enzyme catalysis is often limited by insufficient activity and a single therapy is not sufficient to meet the application requirements. In this study, a multifunctional nanozyme, MMSR-pS-PEG, is designed and fabricated by modifying poly (ethylene glycol) grafted phosphorylated serine (pS-PEG) on mesoporous hollow MnMoOx spheres, followed by loading sorafenib (SRF) into the pores. Strain engineering-induced oxygen defects endow the nanozyme with enhanced dual-enzymatic activity to mimic catalase and oxidase-like activities, which catalyze the conversion of endogenous H2O2 into oxygen and subsequently into superoxide ions in the acidic tumor microenvironment. Moreover, as an n-type semiconductor, MnMoOx generates reactive oxygen species by separating electrons and holes upon ultrasonic irradiation and simultaneously deplete glutathione by holes, thereby further augmenting its catalytic effect. As a ferroptosis inducer, SRF restrains the system xc - and indirectly inhibits glutathione synthesis, synergistically interacting with the nanozyme to stimulate ferroptosis by promoting lipid peroxidation and accumulation and the downregulation of glutathione peroxidase 4. These results provide valuable insights into the design of enzymatic therapy with high performance and highlight a promising approach for the synergism of ferroptosis and enzymatic tumor therapy.

Integrating recognition peptide into a nanozyme to mimic uricase binding pocket as a multifunctional nanoplatform for highly selective uric acid recognition, sensing and degrading

Nanozyme based colorimetric sensor for physiological biomarkers detection is becoming an increasingly influential technology in diagnosis, but the selective discrimination of biomarkers using single nanozyme without natural enzyme is greatly challenging. Here, a colorimetric detection platform for biomarker is successfully constructed by integrating recognition peptide (RGPT) into a nanozyme to mimic the binding pocket in natural enzyme. Firstly, RGPT-ultrafine palladium nanoparticles (PdNPs)@reduced graphene oxide (rGO) composite was facilely prepared using an arginine-rich RGPT. RGPT-PdNP@rGO composite displays outstanding laccase-like activity with Km being 0.075 mM at significantly low dosage used, which is one magnitude lower than that of natural enzyme. RGPT-PdNP@rGO nanozyme based one-step sensor can selectively detect uric acid (UA) with a comprehensive linear range from 0.2 to 110 μM and a limit of detection of 120 nM. Moreover, RGPT-PdNP@rGO composite displays an outstanding activity for UA oxidation with Km being 0.024 mM, revealing the nanozyme exhibits a similar affinity towards UA as natural uricase due to the cooperation of the three components. Compared with our previous work, these extremely improved UA recognition, sensing and degrading performances not only support the role of RGPT in enhancing with the recognition ability of the composite nanozyme for targeted UA, but also reveal the recognition role of RGPT is associated closely with inorganic components in the composite. This work provides more definitive and comprehensive information about multifunctional nanozymes for precise biomarker recognition by introducing recognition peptide, which is highly significant for applications beyond mimic-enzyme catalyst, including theranostic, sensing, and energy fields.

Mo-doped carbon-dots nanozyme with peroxide-like activity for sensitive and selective smartphone-assisted colorimetric S2− ion detection and antibacterial application

Sulfur ion (S2−) plays a significant and considerable role in many living organisms and ecosystems, while its abnormal content can pose a serious hazard to human health and ecological environment. Hence, it is extremely meaningful to construct a highly sensitive and selective analytical platform for S2− detection in complex microenvironment, particularly in biological systems. In this study, phosphomolybdic acid and L-Arg were utilized to prepare a new molybdenum doped carbon-dots nanozyme (Mo-CDs) with great peroxidase-like activity by one-step hydrothermal approach. In the presence of H2O2, Mo-CDs converted 3, 3′, 5, 5′-tetramethyl benzidine (TMB) into blue oxTMB, but S2− strongly reduced the blue solution to colorless and then brown, which established significant selectivity toward S2−. Mo-CDs illustrated a wide linear range (2.5 μM-900 μM) and low detection limit (LOD = 76 nM) by ultraviolet and smartphone-assisted visualized colorimetric analysis. Especially, the smartphone-assisted analysis platform successfully realized quick, portable, sensitive and visible identification of S2− with high recovery (95.7–106.7 %) and excellent specificity in water samples. More importantly, Mo-CDs was developed to antibacterial applications based on good peroxidase-like activity. This research not only constructed a new and efficient carbon-dots nanozyme and a low-cost, portable, visual analysis platform for real-time detection of S2−, but also proposed a novel design strategy and methodology for exploiting multifunctional nanozyme detection tool with great practical application.

Atomically Fe(Ⅲ) anchored metal-organic frameworks-based fluorescent nanozyme for smartphone-adopted chemiluminescence-fluorescence dual-mode analysis of Uric acid

BackgroundChemiluminescence (CL) analysis is a promising analytical method with advantages including easy operation, high sensitivity and simple instrument. However, the single CL mode usually suffered from poor stability and reproducibility as a result of the flash-type nature of luminescent molecules, leading to false positive or negative results in practical applications. Dual-mode detection is an advanced sensing methodology that identifies analytes through independent output signals. This approach has the ability to circumvent the inherent constraints of individual sensing modes while integrating their respective strengths, thereby yielding a synergistic enhancement in the detection system. ResultsHerein, a chemiluminescence-fluorescence (FL) dual-mode analysis and imaging system is designed by constructing an atomically Fe(Ⅲ) anchored PCN-224 peroxidase-mimicking nanozyme (PCN-224/Fe(Ⅲ)) and achieve an ultrasensitive detection of Uric Acid (UA). The multifunctional PCN-224/Fe(Ⅲ) serves as a high-efficiency co-reaction promoter in the generation of reactive oxygen species (ROS) in both the CL and FL system, while also demonstrating exceptional capabilities as fluorescent nanoprobes. Ultimately, a smartphone-adopted CL imaging device was developed to achieve a visual CL detection through the design of portable paper-based chips. Besides, with the assistance of the TMB-mediated fluorescence energy resonance transfer, the fluorescent PCN-224/Fe(Ⅲ) nanoprobes exhibited good fluorescence detection performance for UA. The limit of detection was achieved as low as 2.45 × 10−10 M and 1.99 × 10−9 M in the CL and FL mode, respectively. SignificanceThis study engineered an atomically Fe(Ⅲ)- MOF-based multifunctional nanozyme and developed an innovative approach for creating CL-FL dual-mode analysis and imaging detection for UA. The proposed CL-FL dual-mode detection system not only provided a portable and sensitive method for UA detection but also offered valuable insights into the mechanism of the co-reaction promoter enhanced CL and FL analysis.

MnO2 nanozyme boosts synergistic photodynamic/photothermal therapy of bacterial biofilm infections

As a near-infrared (NIR) adsorbing dye approved by the FDA, indocyanine green (ICG) can serve as an attractive therapeutic agent to combat biofilm infections through synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) due to its deep-tissue penetration ability. However, ICG usually suffers from photo/thermal instability. Herein, to tackle the issues, bovine serum albumin (BSA) stabilized nanozyme MnO2 (BSA/MnO2) was synthesized by reducing manganese permanganate (KMnO4) with BSA, which was further loaded with ICG and coated with the positively charged hydroxypropyltrimethyl ammonium chloride chitosan (HACC) as the bacterial targeting moiety through noncovalent interactions. The constructed ICG@BSA/MnO2@HACC (IBMH) displays good photodynamic/thermal effects and bacterial targetability, enabling a synergistic PDT/PTT therapy against biofilm-associated infections. Compared with free ICG, IBMH exhibits enhanced photo/thermal stability owing to the O2-generating and photothermal capacities of MnO2, which significantly promotes biofilm phototherapy. Meanwhile, IBMH can effectively achieve anti-inflammatory effect due to the reactive oxygen species (ROS) scavenging capacity of nanozyme MnO2, thereby greatly accelerating wound healing after synergistic PDT/PTT. Both in vitro and in vivo assays solidly demonstrate its satisfactory anti-biofilm and anti-inflammatory effects. Therefore, our research proposes a promising and convenient strategy for developing multifunctional nanozyme for synergistic PDT/PTT of biofilm infection.

An Unusual Application of Multifunctional Nanozyme Derived from COF: Augmenting Chemoimmunotherapy while Attenuating Cardiotoxicity

AbstractEnhancing therapeutic efficacy while reducing the adverse effects of drugs is crucial in cancer treatments. In this study, nitrogen‐doped carbon nanospheres are synthesized with variable enzymatic activities through the pyrolysis of a covalent organic framework (COF). These nanospheres show increased peroxidase (POD) and oxidase (OXD) activities in the tumor microenvironment, generating reactive oxygen species (ROS) that help eliminate tumor cells. Under normal conditions, they display catalase (CAT) and superoxide dismutase (SOD) activities, promoting antioxidative protection. Their porous structure and π–π/hydrophobic interactions allow for the loading of the chemotherapeutic agent doxorubicin (DOX). The nanospheres are then enveloped by tumor cell membranes, stabilizing the drug load and enabling targeted drug delivery with pH‐sensitive release. This targeted system induces ferroptosis in tumor cells and activates a strong anti‐tumor immune response, leading to enhanced immunotherapy for breast cancer and reduced tumor metastasis to the lungs. Importantly, the varied enzymatic activities of the nanomedicine system help mitigate the cardiotoxicity of DOX chemotherapy, improving cancer treatment while minimizing side effects. This approach introduces a nano‐enzyme drug system with distinctive activities and innovative preparation, setting a new standard for efficient, low‐toxicity cancer therapy.

Rational design of Au-Bi bimetallic nanozyme for NIR-II laser mediated multifunctional combined tumor therapy

To maximize the therapeutic effects and minimize the adverse effects of synergistic tumor therapies, a multifunctional nanozyme Au-Bi/ZIF-8@DOX@HA (ABZ@DOX@HA) was designed and synthesized through the Au and Bi bimetallic doping of ZIF-8, loading of the DOX, and modifying with hyaluronic acid (HA). The ABZ@DOX@HA nanoparticles (NPs) could simulate the enzymatic activities of glucose oxidase (GOx) and peroxidase (POD). Upon irradiated by near-infrared region (NIR-II) laser, the strong synergism of the photothermal abilities of the loaded Au and Bi nanodots accelerated the collapse of the ABZ structure at the tumor site considerably and released Au, Bi nanodots and DOX. The results in vitro and in vivo proved that ABZ@DOX@HA nanozyme could effectively exert the combined tumor therapy of starvation treatment, photothermal therapy (PTT), chemodynamic therapy (CDT) and chemotherapy. The current research provides a new strategy to address the inherent challenges of easy clearance and short blood circulation of small-sized NPs during the treatment of tumors with nanomedicine, as well as the aggregation and oxidation of inorganic nanodots.

A thermo-sensitive hydrogel with prominent hemostatic effect prevents tumor recurrence via anti-anoikis-resistance

Tumor cells can survive when detached from the extracellular matrix (ECM) or lose cell–cell connections, a phenomenon known as anoikis-resistance (AR). AR is closely associated with tumor cell metastasis and recurrence, enabling tumor cells to disseminate, migrate, and invade after detachment. To address this issue, a novel intervention method combining intraoperative hemostasis with multifunctional nanozyme driven-enhanced chemodynamic therapy (ECDT) has been proposed, which holds the potential to weaken the AR capability of tumor cells and suppress tumor recurrence. Here, a nanocomposite containing a dendritic mesoporous nanoframework with Cu2+ was developed using an anion-assisted approach after surface PEG grafting and glucose oxidase (GOx) anchoring (DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG was further encapsulated in a thermal-sensitive hydrogel (H@DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG utilizes its high peroxidase (POD) activity to elevate intracellular ROS levels, thereby weakening the AR capability of bladder cancer cells. Additionally, through its excellent catalase (CAT) activity, DMSN-Cu@GOx/PEG converts the high level of hydrogen peroxide (H2O2) catalyzed by intracellular GOx into oxygen (O2), effectively alleviating tumor hypoxia, downregulating hypoxia-inducible factor-1α (HIF-1α) expression, inhibiting epithelial-mesenchymal transition (EMT) processes, and ultimately suppressing the migration and invasion of bladder cancer cells. Interestingly, in vivo results showed that the thermosensitive hydrogel H@DMSN-Cu@GOx/PEG could rapidly gel at body temperature, forming a gel film on wounds to eliminate residual tumor tissue after tumor resection surgery. Importantly, H@DMSN-Cu@GOx/PEG exhibited excellent hemostatic capabilities, effectively enhancing tissue coagulation during post-tumor resection surgery and mitigating the risk of cancer cell dissemination and recurrence due to surgical bleeding. Such hydrogels undoubtedly possess strong surgical application. Our developed novel nanosystem and hydrogel can inhibit the AR capability of tumor cells and prevent recurrence post-surgery. This study represents the first report of using dendritic mesoporous silica-based nanoreactors for inhibiting the AR capability of bladder cancer cells and suppressing tumor recurrence post-surgery, providing a new avenue for developing strategies to impede tumor recurrence after surgery.Graphical

“Four - in - one” platform based on multifunctional nanozyme for ultra - accurate detection and on - demand disinfection of Listeria monocytogenes

The inability to integrate detection and disinfection hindered building a unified pathogen monitoring platform, risking secondary contamination. Herein, a novel “four - in - one” platform for monitoring foodborne Listeria monocytogenes (L. monocytogenes) was presented. The magnetic daptomycin - functionalized Fe3O4 (Dap/Fe3O4) could selectively bind to L. monocytogenes, enhancing detection accuracy. The separated bacteria were captured by aptamers - functionalized Fe - doped - silica nanoparticles (Apt/Fe@SiNPs) for tri - mode detection. Besides fluorescence, the Apt/Fe@SiNPs converted 3,3′,5,5′ - tetramethylbenzidine (TMB) to oxidized TMB (oxTMB) via peroxidase activity, allowing colorimetric and subsequent photothermal detection upon irradiation, as low as 2.06 CFU/mL. Magnetic - induced aggregation of Apt/Fe@SiNPs generated toxic hydroxyl radicals around L. monocytogenes, achieving ∼99.6% disinfection. Furthermore, the biofilm of L. monocytogenes was effectively inhibited by the action of hydroxyl radicals. The platform might offer a promising prospect to control L. monocytogenes in food industries.

Multifunctional cerium oxide nanozymes with high ocular surface retention for dry eye disease treatment achieved by restoring redox balance

Dry eye disease (DED) is a kind of multifactorial ocular surface disease that displays ocular discomfort, visual disturbance, and tear film instability. Oxidative stress is a fundamental pathogenesis in DED. An imbalance between the reactive oxygen species (ROS) level and protective enzyme action will lead to oxidative stress, cell dysfunction, tear hyperosmolarity, and inflammation. Herein, a multifunctional cerium oxide nanozyme with high ocular surface retention property was designed to neutralize over-accumulated ROS and restore redox balance. Cerium oxide nanozymes were fabricated via branched polyethylenimine-graft-poly (ethylene glycol) nucleation and dispersion, followed by phenylboronic acid (PBA) functionalization (defined as Ce@PB). Due to the dynamic chemical bonding formation between the PBA segment and the cis-diol groups in the mucin layer of the tear film, Ce@PB nanozymes possess good adhesive capability to the ocular surface, thus extending the drug's retention time. On the other hand, Ce@PB nanozymes could mimic the cascade processes of superoxide dismutase and catalase to maintain intracellular redox balance. In vitro and in vivo studies suggest that such multifunctional nanozymes possess good biocompatibility and hemocompatibility. More importantly, Ce@PB nanozymes treatment in the animal model could repair corneal epithelial defect, increase the number of goblet cells and promote tear secretion, thus achieving an effective treatment for DED. Statement of significance•PBA-functionalized bPEI-g-PEG-based cerium oxide (Ce@PB) nanozymes were designed and fabricated.•The Ce@PB nanozymes have superoxide dismutase (SOD) and catalase (CAT) enzyme-like activity scavenging excessive intracellular reactive oxygen species (ROS).•The Ce@PB nanozymes demonstrate extended retention on the ocular surface and can effectively treat dry eye disease.

Bimetallic phosphidethe nanoparticles as photo-enhanced nanozymes for synergistic cancer immunotherapy

<p class="MsoNormal" style="margin-top: 12pt; text-align: justify;"><span lang="EN-US" style="font-family: 'times new roman', times, serif; font-size: 14pt;">Nanozyme with biomimetic enzyme activity has the advantages of good catalytic performance, high stability, and is not easily affected by temperature. However, the application of tumor microenvironment (TME) in the tumor is limited due to its low catalytic activity. Herein, a multifunctional nanozyme based on CuCoP with multivalent metal ions (Cu+/Cu2+ and Co2+/ Co3+) provides an innovative strategy for constructing acid-responsive cancer therapy. CuCoP has excellent photothermal properties (photothermal conversion efficiency of 66.9%) as well as glutathione (GSH) peroxidase activity and high photo-enhanced peroxidase-like (POD) enzyme activity in weak acid TME. CuCoP can consume the overexpressed GSH, thus alleviating the antioxidant capacity of the tumor, and reduces Cu2+/ Co3+ to Cu+/ Co 2+. Subsequently, the generated Cu+/Co2+ will react with endogenous H2O2 to generate cytotoxic hydroxyl radical (•OH), which have high catalytic efficiency in weakly acidic TME. Crucially, the synergistic effect of PTT and the cascade reaction of bimetallic atoms with GSH and H2O2 can effectively reduce antioxidant capacity, inhibit tumors and trigger effective immune cell death (ICD) process, which caused a strong immune response and inhibit tumor recurrence and metastasis. As a novel bimetallic sulfide nanoenzyme triggered by TME, CuCoP has great research value in cancer therapy.</span></p>

Mn-based Prussian blue analogues: Multifunctional nanozymes for hydrogen peroxide detection and photothermal therapy of tumors

Nanozymes have the advantages of simple synthesis, high stability, low cost and easy recycling, and can be applied in many fields including molecular detection, disease diagnosis and cancer therapy. However, most of the current nanozymes suffer from the defects of low catalytic activity and single function, which limits their sensing sensitivity and multifunctional applications. The development of highly active and multifunctional nanozymes is an important way to realize multidisciplinary applications. In this work, Mn-based Prussian blue analogues (Mn-PBA) and their derived double-shelled nanoboxes (DSNBs) are synthesized by co-precipitation method. The nanobox structure of DSNBs formed by etching Mn-PBA with tannic acid endows Mn-PBA DSNBs with better peroxidase-like activity than Mn-PBA. A colorimetric method for the rapid and sensitive determination of H2O2 is developed using Mn-PBA DSNBs-1.5 as a sensor with a detection limit as low as 0.62 μM. Moreover, Mn-PBA DSNBs-2 has excellent photothermal conversion ability, which can be applied to the photothermal therapy of tumors to inhibit the proliferation of tumor cells without damaging other tissues and organs. This study provides a new idea for the rational design of nanozymes and the expansion of their multi-functional applications in various fields.

Cascaded Nanozyme Based pH-Responsive Oxygenation for Targeted Eradication of Resistant Helicobacter Pylori.

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 • 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.

Polymeric Nanozyme with SOD Activity Capable of Inhibiting Self- and Metal-Induced α-Synuclein Aggregation.

Despite decades of research, Parkinson's disease is still an idiopathic pathology for which no cure has yet been found. This is partly explained by the multifactorial character of most neurodegenerative syndromes, whose generation involves multiple pathogenic factors. In Parkinson's disease, two of the most important ones are the aggregation of α-synuclein and oxidative stress. In this work, we address both issues by synthesizing a multifunctional nanozyme based on grafting a pyridinophane ligand that can strongly coordinate CuII, onto biodegradable PEGylated polyester nanoparticles. The resulting nanozyme exhibits remarkable superoxide dismutase activity together with the ability to inhibit the self-induced aggregation of α-synuclein into amyloid-type fibrils. Furthermore, the combination of the chelator and the polymer produces a cooperative effect whereby the resulting nanozyme can also halve CuII-induced α-synuclein aggregation.

Electron Reservoir MoO3–x‐Driven Cu+ Doped Nanozyme with Enhanced Antibacterial Activity via Disrupting Redox Homeostasis

Comprehensive SummaryRedox nanozymes offer an appealing reactive oxygen species (ROS)‐based antibacterial strategy via disrupting intracellular homeostasis, however, they still face many obstacles such as low enzymic activity and irreversible loss of catalytic active center. Meanwhile, the antioxidant glutathione (GSH) overexpressed in infected sites would limit the therapy efficiency. Herein, we develop a multifunctional nanozyme based on copper(I) (Cu+) ion doped MoO3–x (Cu+‐MoO3–x) by a simple yet efficient oxygen vacancy‐reduced strategy without any pretreatment or additional agents. The resultant Cu+‐MoO3–x hybrid possesses enhanced peroxidase‐like (POD‐like) activity, rapid GSH‐depleting function and biodegradable ability. It can achieve highly efficient elimination of Pseudomonas aeruginosa (P. aeruginosa) via disrupting cellular redox balance. More intriguingly, GSH‐depleting redox reaction between Cu+‐MoO3–x and GSH could translate Mo6+ into Mo5+, thereby leading to partial recovery of POD‐like activity of Cu+‐MoO3–x hybrid for continuous ∙OH generation. In vitro and in vivo experiments demonstrated that Cu+‐MoO3–x hybrid had stronger antibacterial property compared to MoO3–x by rapid GSH consumption and plentiful ∙OH generation without providing extra H2O2, as well as neglective toxicity to healthy organs. In view of its remarkable enzymic activity and good biosafety, the developed Cu+‐MoO3–x redox nanozyme can be used as a promising antimicrobial for P. aeruginosa infection.

Luminescent gold nanoclusters loaded on iron metal–organic framework with enhanced peroxidase-like activity for the colorimetric/fluorescent determination of H2O2

In this work, a composite nanozyme, termed AuNCs/Fe-MIL, was obtained by combining glutathione-stabilized gold nanoclusters (AuNCs) on the surface of the Fe metal–organic framework (Fe-MIL-88B-NH2). The AuNCs/Fe-MIL nanocomposite retains the red emission of AuNCs, exhibiting unique dual-emission fluorescence with remarkable stability. This nanozyme exhibits improved peroxidase-like activity as a result of the heightened rate of electron transfer. As a result, the decomposition of H2O2 is accelerated, leading to the generation of more •OH radicals that oxidize 3,3′,5,5′-tetramethylbenzidine (TMB) into blue ox-TMB. The generated ox-TMB can quench the fluorescence of AuNCs/Fe-MIL in the red-light region. By leveraging the dual function of the catalytic product ox-TMB, a fusion of colorimetric and fluorescence signals enabled H2O2 detection within 10 min. The sensing platform demonstrated wide linear ranges of 5–1000 μM with a detection limit of 2.78 μM in colorimetry mode and 5–500 μM with a detection limit of 0.78 μM in fluorescence mode. This method was successfully utilized for accurate in situ monitoring of H2O2 release from different types of living cells. Additionally, a dual-mode portable sensing platform based on AuNCs/Fe-MIL/TMB hydrogel was constructed for convenient H2O2 detection. Through a smartphone application, precise quantitation of H2O2 added to milk samples was achieved. This work provides a rational design of multifunctional nanozymes for reliable biomimetic catalysis.

MOF derivatization of multifunctional nanozyme: Peroxidase-like catalytic activity combined with magnetic solid phase extraction for colorimetric detection of Hg2+

Nanozyme-based colorimetric sensing has drawn immense attention due to the rapid development of nanozyme in recent years. However, the selectivity of nanozyme-based colorimetric sensing greatly limits its subsequent practical application. It is well known that sample pretreatment can not only improve selectivity by eliminating the sample matrix interference, but also improve sensitivity by enriching trace targets. Based on the easy facile surface modification properties of nanozyme, we rationally designed nanozyme combined with sample pretreatment for colorimetric biosensing, through separation and enrichment, thereby improving the selectivity and sensitivity of the nanozyme colorimetric biosensing. As a proof of concept, the detection of Hg2+ by nanozyme-based colorimetric sensing was used as an example. Magnetic peroxidase-like nanozyme Fe3S4 was designed and synthesized. The selectivity is improved by the specific adsorption of S-Hg bond and the interference elimination after magnetic separation. In addition, the sensitivity is improved by magnetic solid-phase extraction enrichment. Our established colorimetric sensing based on Fe3S4 nanozyme integrated sample pretreatment with an enrichment factor of 100 and the limit of detection (LOD) is 26 nM. In addition, this strategy was successfully applied to detect Hg2+ in environmental water samples. Overall, the strategy showed good selectivity and sensitivity, providing a new practical method for the application of nanozyme-based biosensing in sample pretreatment.

Rational design of nanozyme with integrated sample pretreatment for colorimetric biosensing

Nanozymes have been widely used in the field of biosensing owing to their high stability, low cost, adjustable catalytic activity, and convenient modification. However, achieving high selectivity and sensitivity simultaneously in nanozyme-based colorimetric sensing remains a major challenge. Nanozymes are nanomaterials with enzyme-simulating activity that are often used as solid-phase adsorbents for sample pretreatment. Our design strategy integrated sample pretreatment function into the nanozyme through separation and enrichment, thereby improving the selectivity and sensitivity of nanozyme-based colorimetric biosensing. As a proof-of-concept, glucose was used as the model analyte in this study. A phenylboric acid-modified magnetic nanozyme (Cu/Fe3O4@BA) was rationally designed and synthesized. Selectivity was enhanced by boronate-affinity specific adsorption and the elimination of interference after magnetic separation. In addition, magnetic solid-phase extraction enrichment was used to improve the sensitivity. A recovery rate of more than 80% was reached when the enrichment factor was 50. The synthesized magnetic Cu/Fe3O4@BA was recyclable at least five times. The proposed method exhibited excellent selectivity and sensitivity, simple operation, and recyclability, providing a novel and practical strategy for designing multifunctional nanozymes for biosensing.

Iron-carbon dots embedded in molybdenum single-atom nanoflowers as multifunctional nanozyme for dual-mode detection of hydrogen peroxide and uric acid

Single-atom catalysts (SACs) have attracted extensive attention in the field of catalysis due to their excellent catalytic ability and enhanced atomic utilization, but the multi-mode single-atom nanozymes for biosensors remain a challenging issue. In this work, iron-doped carbon dots (Fe CDs) were loaded onto the edges and pores of Mo SACs with nanoflower morphology; accordingly, a composite material Fe CDs/Mo SACs was prepared successfully, which improves the catalytic performance and develops a fluorescence mode without changing the original morphology. The steady-state kinetic data indicates that the material prepared have better affinity for substrates and faster reaction rates under optimized conditions. The specific kinetic parameters Km and Vmax were calculated as 0.39 mM and 7.502×10−7 M·s−1 respectively. The excellent peroxidase-like activity of Fe CDs/Mo SACs allows H2O2 to decompose into •OH, which in turn oxidizes colorless o-phenylenediamine (OPD) to yellow 2,3-diaminophenazine (DAP). At the same time, the fluorescence signal of Fe CDs/Mo SACs quenches obviously by DAP at 460 nm through internal filtration effect (IFE), while the characteristic fluorescence response of DAP gradually increases at 590 nm. Based on this sensing mechanism, a sensitive and accurate dual-mode (colorimetric and ratiometric fluorescent) sensor was constructed to detect H2O2 and uric acid, and the rate of recovery and linearity were acceptable for the detection of UA in human serum and urine samples. This method provides a new strategy for rapid and sensitive detection of UA, and also broadens the development of SACs in the field of biosensors.

Space-confined nanozyme with cascade reaction based on PCN-224 for synergistic bacterial infection treatment and NIR fluorescence imaging of wound bacterial infections

The rapid development of bacterial infections has become a significant global health challenge. The overuse or prolonged use of antibiotics is considered a major contributor to the development of bacterial resistance. Therefore, there is an urgent need to develop a new therapeutic approach to combat infectious diseases caused by bacteria. In this study, we demonstrate the effectiveness of a novel strategy for synergistic antibacterial therapy and fluorescence imaging of wound bacterial infections through the nano-confined construction of LL-37-HA-Au-Pt@PCN-224 nanozymes. The nanozyme is composed of Au NPs and Pt NPs confined to PCN-224 through in situ reduction, with its outer layer modified with HA and LL-37. The nanozyme catalyzes the conversion of low-concentration H2O2 into O2 and •OH, with the generated O2 further catalyzed into 1O2 by PCN-224. In vivo imaging experiments demonstrate that LL-37-HA-Au-Pt@PCN-224 labeled with near-infrared fluorescent dye MPA can effectively realize fluorescence imaging of wound bacterial infections and real-time monitoring of the wound healing process. In vitro and in vivo antibacterial experiments reveal that LL-37-HA-Au-Pt@PCN-224 enhances the healing efficiency of bacteria-infected wounds due to its synergistic antibacterial effect. The multifunctional nanozyme offers various synergistic antibacterial therapies, including antimicrobial peptides, peroxide nanozymes, hydrogen peroxide nanozymes, and photodynamic therapy. Moreover, it provides real-time wound imaging and monitoring of the wound healing process, while maintaining high biocompatibility. Overall, this study presents a promising perspective on the potential use of nanozymes as antibacterial agents against wound bacterial infections in the future.