Oxide Nanozyme Research Articles

Pseudo-water-soluble Fe2O3 as Nanozyme catalyzed chemiluminescent reaction for detection of brilliant blue in gelatin and beverages

Converting solid iron oxide nanoparticles into a “pseudo-water-soluble” form before applying them to chemiluminescent reactions leads to enhance the chemiluminescence intensity. Using 8-hydroxyquinoline as a colloidal agent, a new, fast, and simple method of synthesizing pseudo-water-soluble Fe2O3 nanoparticles was developed. SEM, VSM, SAED, HRTEM, XRD, FTIR, and EDS techniques were used to characterize the synthesized Fe2O3 nanoparticles. Fe2O3 nanoparticles synthesized in this study have superior peroxidase-like activity (POD-like) and are stable under a wide range of pH and temperature. The chemiluminescence reaction of luminol-H2O2 is intensified and accelerated by a colloidal solution of Fe-nanoparticles/8-hydroxyquinoline. Reverse-flow injection analysis was employed to determine brilliant blue. A chemiluminescent sensing method based on iron oxide nanozymes was utilized for sensitive detection of the brilliant blue synthetic dye, achieving a limit of detection of 0.06 mg/L and a dynamic linear range of 0.1 to 50 mg/L. The recovery and relative standard deviations of real samples were found to be 97.83–99.93% and 0.09–3.07%, respectively. An analysis of a sample, from injection to obtaining the maximum peak, could be performed in less than one minute.

Cerium Oxide Nanozymes Improve Skeletal Muscle Function in Gestational Diabetic Offspring by Attenuating Mitochondrial Oxidative Stress.

Gestational diabetes mellitus (GDM) is a significant complication during pregnancy that results in abnormalities in the function of multiple systems in the offspring, which include skeletal muscle dysfunction and reduced systemic metabolic capacity. One of the primary causes behind this intergenerational effect is the presence of mitochondrial dysfunction and oxidative stress in the skeletal muscle of the offspring due to exposure to a high-glucose environment in utero. Cerium oxide (CeO2) nanozymes are antioxidant agents with polymerase activity that have been widely used in the treatment of inflammatory and aging diseases. In this study, we synthesized ultrasmall particle size CeO2 nanozymes and applied them in GDM mouse offspring. The CeO2 nanozymes demonstrated an ability to increase insulin sensitivity and enhance skeletal muscle motility in GDM offspring by improving mitochondrial activity, increasing mitochondrial ATP synthesis function, and restoring abnormal mitochondrial morphology. Furthermore, at the cellular level, CeO2 nanozymes could ameliorate metabolic dysregulation and decrease cell differentiation in adult muscle cells induced by hyperglycemic stimuli. This was achieved through the elimination of endogenous reactive oxygen species (ROS) and an improvement in mitochondrial oxidative respiration function. In conclusion, CeO2 nanozymes play a crucial role in preserving muscle function and maintaining the metabolic stability of organisms. Consequently, they serve to reverse the negative effects of GDM on skeletal muscle physiology in the offspring.

Self-sacrificing-induced defect enhances the oxidase-like activity of MnOOH for total antioxidant capacity evaluation

Nanozymes is a kind of nanomaterials with enzyme catalytic properties. Compared with natural enzymes, nanozymes merge the advantages of both nanomaterials and natural enzymes, which is highly important in applications such as biosensing, clinical diagnosis, and food inspection. In this study, we prepared β-MnOOH hexagonal nanoflakes with a high oxygen vacancy ratio by utilizing SeO2 as a sacrificial agent. The defect-rich MnOOH hexagonal nanoflakes demonstrated excellent oxidase-like activity, catalyzing the oxidation substrate in the presence of O2, thereby rapidly triggering a color reaction. Consequently, a colorimetric sensing platform was constructed to assess the total antioxidant capacity in commercial beverages. The strategy of introducing defects in situ holds great significance for the synthesis of a series of high-performance metal oxide nanozymes, driving the development of faster and more efficient biosensing and analysis methods.

A dual-signal output electrochemical aptasensor for glypican-3 ultrasensitive detection based on reduced graphene oxide-cuprous oxide nanozyme catalytic amplification strategy

Glypican-3 (GPC3) is an essential reference target for hepatocellular carcinoma detection, follow-up and prediction. Herein, a dual-signal electrochemical aptasensor based on reduced graphene oxide-cuprous oxide (RGO-Cu2O) nanozyme was developed for GPC3 detection. The RGO-Cu2O nanoenzyme displayed excellent electron transport effect, large specific surface area and outstanding peroxidase-like ability. The differential pulse voltammetry (DPV) signal of Cu2O oxidation fraction and the chronoamperometry (i-t) signal of H2O2 decomposition catalyzed by RGO-Cu2O nanozyme were used as dual-signal detection. Under optimal conditions, the log-linear response ranges were 0.1 to 500.0 ng/mL with the limit of detection 0.064 ng/mL for DPV technique, and 0.1–50.0 ng/mL for i-t technique (detection limit of 0.0177 ng/mL). The electrochemical aptasensor has remarkably analytical performance with wide response range, low detection limit, excellent repeatability and specificity, good recovery in human serum samples. The two output signals of one sample achieve self-calibration of the results, effectively avoiding the occurrence of possible leakage and misdiagnosis of a single detection signal, suggesting that it will be a promising method in the early biomarker detection.

A Multifunctional Nanozyme Integrating Antioxidant, Antimicrobial and Pro-Vascularity for Skin Wound Management.

Skin wounds are a prevalent issue that can have severe health consequences if not treated correctly. Nanozymes offer a promising therapeutic approach for the treatment of skin wounds, owing to their advantages in regulating redox homeostasis to reduce oxidative damage and kill bacteria. These properties make them an effective treatment option for skin wounds. However, most of current nanozymes lack the capability to simultaneously address inflammation, oxidative stress, and bacterial infection during the wound healing process. There is still great potential for nanozymes to increase their therapeutic functional diversity and efficacy. Herein, copper-doped hollow mesopores cerium oxide (Cu-HMCe) nanozymes with multifunctional of antioxidant, antimicrobial and pro-vascularity is successfully prepared. Cu-HMCe can be efficiently prepared through a simple and rapid solution method and displays sound physiological stability. The biocompatibility, pro-angiogenic, antimicrobial, and antioxidant properties of Cu-HMCe were assessed. Moreover, a full-thickness skin defect infection model was utilized to investigate the wound healing capacity, as well as anti-inflammatory and pro-angiogenic properties of nanozymes in vivo. Both in vitro and in vivo experiments have substantiated Cu-HMCe's remarkable biocompatibility. Moreover, Cu-HMCe possesses potent antioxidant enzyme-like catalytic activity, effectively clearing DPPH radicals (with a scavenging rate of 80%), hydroxyl radicals, and reactive oxygen species. Additionally, Cu-HMCe exhibits excellent antimicrobial and pro-angiogenic properties, with over 70% inhibition of both E. coli and S. aureus. These properties collectively promote wound healing, and the wound treated with Cu-HMCe achieved a closure rate of over 90% on the 14th day. The results indicate that multifunctional Cu-HMCe with antioxidant, antimicrobial, and pro-angiogenic properties was successfully prepared and exhibited remarkable efficacy in promoting wound healing. This nanozymes providing a promising strategy for skin repair.

Biosafe cerium oxide nanozymes protect human pluripotent stem cells and cardiomyocytes from oxidative stress

BackgroundCardiovascular diseases (CVDs) have the highest mortality worldwide. Human pluripotent stem cells (hPSCs) and their cardiomyocyte derivatives (hPSC-CMs) offer a valuable resource for disease modeling, pharmacological screening, and regenerative therapy. While most CVDs are linked to significant over-production of reactive oxygen species (ROS), the effects of current antioxidants targeting excessive ROS are limited. Nanotechnology is a powerful tool to develop antioxidants with improved selectivity, solubility, and bioavailability to prevent or treat various diseases related to oxidative stress. Cerium oxide nanozymes (CeONZs) can effectively scavenge excessive ROS by mimicking the activity of endogenous antioxidant enzymes. This study aimed to assess the nanotoxicity of CeONZs and their potential antioxidant benefits in stressed human embryonic stem cells (hESCs) and their derived cardiomyocytes (hESC-CMs).ResultsCeONZs demonstrated reliable nanosafety and biocompatibility in hESCs and hESC-CMs within a broad range of concentrations. CeONZs exhibited protective effects on the cell viability of hESCs and hESC-CMs by alleviating excessive ROS-induced oxidative stress. Moreover, CeONZs protected hESC-CMs from doxorubicin (DOX)-induced cardiotoxicity and partially ameliorated the insults from DOX in neonatal rat cardiomyocytes (NRCMs). Furthermore, during hESCs culture, CeONZs were found to reduce ROS, decrease apoptosis, and enhance cell survival without affecting their self-renewal and differentiation potential.ConclusionsCeONZs displayed good safety and biocompatibility, as well as enhanced the cell viability of hESCs and hESC-CMs by shielding them from oxidative damage. These promising results suggest that CeONZs may be crucial, as a safe nanoantioxidant, to potentially improve the therapeutic efficacy of CVDs and be incorporated into regenerative medicine.Graphical

MOFs@POMs-derived bimetallic oxide Fe2(MoO4)3 nanoparticles for sensitive colorimetric detection of salicylic acid in aspirin.

Acolorimetric sensing method for salicylic acid (SA) was developed by designing and fabricating bimetallic oxide nanozymes. Firstly, by calcinating MIL-100(Fe)@PMo12 (MOFs@POMs) at different temperature, Fe2(MoO4)3-Ts (T = 400℃, 500℃, 600℃, 700℃) nanoparticles (NPs) were successfully prepared. Secondly, by evaluating the peroxidase-like activities, Fe2(MoO4)3-600 NPs shows the best peroxidase-like activity attributed to the Fenton-like effect and the synergistic coupling interaction between Mo and Fe. Finally, based on the specific complexation between SA and Fe3+, a sensitive colorimetric sensor for SA was established, which exhibits superior selectivity and interference with a detection limit of 0.11μM anda linear range of 10 to 100μM, the lowest LOD for SA to date, to the best of our knowledge.

Enhanced ·OH-Scavenging Activity of Cu-CeOx Nanozyme via Resurrecting Macrophage Nrf2 Transcriptional Activity Facilitates Diabetic Wound Healing.

Diabetic wounds are a prevalent and devastating complication of diabetes, which may impede their healing and regeneration. In diabetic wounds, excess reactive oxygen species (ROS) activate the nuclear factor kappa-B pathway, leading to transcriptional silencing of nuclear factor erythroid 2-related factor 2 (Nrf2), resulting in a vicious cycle of oxidative stress and inflammation. Conventional nanozymes have limitations in preventing the continuous production of ROS, including the most oxidizing reactive hydroxyl radical (·OH), although they can remove pre-existing ROS. Herein, a novel antioxidant nanoplatform addresses this challenge by incorporating JSH-23 into the mesoporous of cupric-doped cerium oxide nanozymes. Additionally, for rapid wound adaptability and durable tissue adhesion, a nanozyme hydrogel spray consisting of oxidized sodium alginate and methacrylate gelatin is constructed, named OG@CCJs. This platform resurrects Nrf2 transcriptional activity of macrophages in vitro, curbing the production of ROS at its source, particularly ·OH, while enabling the nanozymes to scavenge previously generated ROS. OG@CCJs significantly alleviate oxidative stress in diabetic wounds in vivo, promoting wound healing. Overall, the proposed nanozyme-hydrogel spray with enhanced ·OH-scavenging activity uses a "two-track" antioxidant strategy to rebuild the antioxidant defense barrier of macrophages. This pioneering approach highlights the tremendous potential of OG@CCJs for facilitating diabetic wound healing.

Advanced Biological Applications of Cerium Oxide Nanozymes in Disease Related to Oxidative Damage.

Due to their excellent catalytic activities, cerium oxide nanoparticles have promise as biological nanoenzymes. A redox reaction occurs between Ce3+ ions and Ce4+ ions during which they undergo conversion by acquiring or losing electrons as well as forming oxygen vacancies (or defects) in the lattice structure, which can act as antioxidant enzymes and simulate various enzyme activities. A number of cerium oxide nanoparticles have been engineered with multienzyme activities, including catalase, superoxide oxidase, peroxidase, and oxidase mimetic properties. Cerium oxide nanoparticles have nitric oxide radical clearing and radical scavenging properties and have been widely used in a number of fields of biology, including biomedicine, disease diagnosis, and treatment. This review provides a comprehensive introduction to the catalytic mechanisms and multiple enzyme activities of cerium oxide nanoparticles, along with their potential applications in the treatment of diseases of the brain, bones, nerves, and blood vessels.

Single substrate-functionalized molybdenum oxide nanozyme for specific colorimetric monitoring of xanthine oxidase activity.

Xanthine-functionalized molybdenum oxide nanodots (X-MoO3-x NDs) with peroxidase (POD)-like activity were developed for selective, sensitive, and facile colorimetric quantification of xanthine oxidase (XO). Xanthine functionalization can not only be favorable for the successful nanozyme preparation, but also for the specific recognition of XO as well as the simultaneous generation of hydrogen peroxide, which was subsequently transformed into hydroxyl radical to oxidize the chromogenic reagent based on the POD-like catalysis. Under the optimized conditions, the colorimetric biosensing platform was established for XO assay without addition of further substrates, showing good linearity relationship between absorbance difference (ΔA) and XO concentrations in the range 0.05-0.5 U/mL (R2 = 0.998) with alimit of detection (LOD) of 0.019 U/mL. The quantification of XO occursin 25 min, which is superior to the previously reported and commercial XO assays. Theproposed method has been successfully used in theassay of human serum samples, showing its highpotential in the field of clinical monitoring.

A portable colorimetric sensing platform for rapid and sensitive quantification of dichlorvos pesticide based on Fe-Mn bimetallic oxide nanozyme-participated highly efficient chromogenic catalysis

BackgroundDichlorvos (DDVP), as a highly effective insecticide, is widely used in agricultural production. However, DDVP residue in foodstuffs adversely affects human health. Conventional instrumental analysis can provide highly sensitive and accurate detection of DDVP, while the need of bulky and expensive equipment limits their application in resource-poor areas and on-site detection. Therefore, the development of easily portable sensing platforms for convenient, rapid and sensitive quantification of DDVP is very essential for ensuring food safety. ResultA portable colorimetric sensing platform for rapid and sensitive quantification of DDVP is developed based on nanozyme-participated highly efficient chromogenic catalysis. The Fe-Mn bimetallic oxide (FeMnOx) nanozyme possesses excellently oxidase-like activity and can efficiently catalyze oxidation of 3, 3′, 5, 5′-tetramethylbenzidine (TMB) into a blue oxide with a very low Michaelis constant (Km) of 0.0522 mM. The nanozyme-catalyzed chromogenic reaction can be mediated by DDVP via inhibiting the acetylcholinesterase (AChE) activity. Thus, trace DDVP concentration-dependent color evolution is achieved and DDVP can be sensitively detected by spectrophotometry. Furthermore, a smartphone-integrated 3D-printed miniature lightbox is fabricated as the colorimetric signal acquisition and processing device. Based on the FeMnOx nanozyme and smartphone-integrated lightbox system, the portable colorimetric sensing platform of DDVP is obtained and it has a wide linear range from 1 to 3000 ng mL−1 with a low limit of detection (LOD) of 0.267 ng mL−1 for DDVP quantification. SignificanceThis represents a new portable colorimetric sensing platform that can perform detection of DDVP in foodstuffs with simplicity, sensitivity, and low cost. The work not only offers an alternative to rapid and sensitive detection of DDVP, but also provides a new insight for the development of advanced sensors by the combination of nanozyme, 3D-printing and information technologies.

Facile synthesis of nanoparticles-stacked Co3O4 nanoflakes with catalase-like activity for accelerating wound healing.

Delayed wound healing caused by excessive reactive oxygen species (ROS) remains a considerable challenge. In recent years, metal oxide nanozymes have gained significant attention in biomedical research. However, a comprehensive investigation of Co3O4-based nanozymes for enhancing wound healing and tissue regeneration is lacking. This study focuses on developing a facile synthesis method to produce high-stability and cost-effective Co3O4 nanoflakes (NFs) with promising catalase (CAT)-like activity to regulate the oxidative microenvironment and accelerate wound healing. The closely arranged Co3O4 nanoparticles (NPs) within the NFs structure result in a significantly larger surface area, thereby amplifying the enzymatic activity compared to commercially available Co3O4 NPs. Under physiological conditions, it was observed that Co3O4 NFs efficiently break down hydrogen peroxide (H2O2) without generating harmful radicals (·OH). Moreover, they exhibit excellent compatibility with various cells involved in wound healing, promoting fibroblast growth and protecting cells from oxidative stress. In a rat model, Co3O4 NFs facilitate both the hemostatic and proliferative phases of wound healing, consequently accelerating the process. Overall, the promising results of Co3O4 NFs highlight their potential in promoting wound healing and tissue regeneration.

A phosphatase-like nanomaterial promotes autophagy and reprograms macrophages for cancer immunotherapy.

Macrophages are plastic and play a key role in the maintenance of tissue homeostasis. In cancer progression, macrophages also take part in all processes, from initiation to progression, to final tumor metastasis. Although energy deprivation and autophagy are widely used for cancer therapy, most of these strategies do not target macrophages, resulting in undesired effects and unsatisfactory outcomes for cancer immunotherapy. Herein, we developed a lanthanum nickel oxide (LNO) nanozyme with phosphatase-like activity for ATP hydrolysis. Meanwhile, the autophagy of macrophages induced by LNO promotes the polarization of macrophages from M2-like macrophages (M2) to M1-like macrophages (M1) and reduces tumor-associated macrophages in tumor-bearing mice, exhibiting the capability of killing tumor-associated macrophages and antitumor effects in vivo. Furthermore, pre-coating the surface of LNO with a myeloid cell membrane significantly enhanced antitumor immunity. Our findings demonstrate that phosphatase-like nanozyme LNO can specifically induce macrophage autophagy, which improves therapeutic efficacy and offers valuable strategies for cancer immunotherapy.

Manganese-based nanozyme enabled efficient mitigation of Huanglongbing-induced oxidative damage in Citrus

Manganese oxide nanozymes (MONPs) facilitate the alleviation of Huanglongbing (HLB) symptoms in Citrus by mitigating oxidative stress.

A gold cluster fused manganese dioxide nanocube loaded with dihydroartemisinin for effective cancer treatment via amplified oxidative stress.

Chemodynamic therapy, leveraging metabolic processes for reactive oxygen species (ROS) generation, shows promise in cancer eradication. However, its efficacy is hampered by hypoxic conditions, substrate scarcity, and abundant ROS scavengers. In this study, we have devised a cubic manganese oxide nanozyme (BSA-AuNC-MnO2@DHA) to tackle these obstacles. This nanozyme integrates MnO2 with bovine serum albumin (BSA)-coated gold nanoclusters (AuNC), forming BSA-AuNC-MnO2, and further incorporates dihydroartemisinin (DHA) to confer both bioimaging and anticancer capabilities. The BSA-AuNC-MnO2 nanoparticles exhibit a uniform cubic morphology, with an average hydrated particle diameter of 76.4 ± 7.1 nm and a zeta potential of -32.6 mV, indicative of their excellent dispersion and stability. The encapsulation efficiency of DHA within the BSA-AuNC-MnO2@DHA system achieved a remarkable value of 72.45%, attesting to its substantial drug-loading capacity. MnO2 serves a dual function within the nanozyme: it augments oxidative stress while concurrently inhibiting antioxidant defenses. It depletes the antioxidant glutathione (GSH) to release Mn2+, which in turn catalyzes ROS production from intracellular substrates and DHA. The remarkable anticancer efficacy of this tailored approach is evidenced by the potent inhibition of tumor growth observed after a single-dose administration, which underscores the amplification of oxidative stress. Additionally, BSA-AuNC-MnO2@DHA exhibits negligible toxicity to major organs, highlighting its exceptional biocompatibility and safety profile.

Facile green synthesis of wasted hop-based zinc oxide nanozymes as peroxidase-like catalysts for colorimetric analysis.

Hops are a common ingredient in beer production, and a considerable quantity of hops is usually discarded as a waste material once the brewing process is completed. Transforming this waste material into valuable nanomaterials offers a sustainable approach that has the potential to significantly mitigate environmental impact. Herein, a facile and green protocol for the production of zinc oxide nanozymes (ZnO NZs) using wasted hop extract (WHE) as a natural precursor was demonstrated. The process involved a hydrothermal synthesis method followed by a calcination step to form the final ZnO NZs. The results revealed that lupulon, the main β-acid in hops, particularly the phenolic hydroxy group, is primarily responsible for the biosynthesis of ZnO NZs. The WHE-ZnO NZs exhibited exceptional peroxidase-like (POD-like) activity and served as effective catalysts for the oxidation of 3,3,5,5-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide (H2O2). Analysis of the catalytic mechanism revealed that the POD-like activity of these WHE-ZnO NZs originated from their ability to expedite the transfer of electrons between TMB and H2O2, resulting in the enzymatic kinetics following the standard Michaelis-Menten mechanism. Furthermore, we developed a straightforward and user-friendly colorimetric technique for detecting both H2O2 and glucose. By utilizing the WHE-ZnO NZs as POD-like catalysts, we achieved a linear detection range of 1-1000 μM and a limit of detection of 0.24 μM (S/N = 3) for H2O2 detection and a linear range of 0-100 mM and a detection limit of 16.73 μM (S/N = 3) for glucose detection. These results highlighted the potential applications of our waste-to-resource approach for nanozyme synthesis in the field of analytical chemistry.

Magnetic iron oxide-based nanozymes: from synthesis to application.

Iron oxide nanozymes (IONzymes) are a class of magnetic nanoparticles that mimic the enzymatic activity of natural enzymes. These particles have received significant attention in recent years due to their unique properties, such as high stability, tunable magnetic responsiveness, and ability to act as biocatalysts for various chemical reactions. In this review, we aim to provide an overview of the production methods of magnetic nanozymes, including chemical, physical, and biological synthesis. The structure and design of magnetic nanozymes are also discussed in detail, as well as their applications in various fields such as biomedicine and environmental science. The results of various studies and the latest advances in the field of magnetic nanozymes are also discussed. This review provides valuable insights into the current state of magnetic nanozymes and highlights their potential for further development and application in various fields.

Iron oxide nanozymes enhanced by ascorbic acid for macrophage-based cancer therapy.

In recent years, using pharmacological ascorbic acid has emerged as a promising therapeutic approach in cancer treatment, owing to its capacity to induce extracellular hydrogen peroxide (H2O2) production in solid tumors. The H2O2 is then converted into cytotoxic hydroxyl free radicals (HO˙) by redox-active Fe2+ inside cells. However, the high dosage of ascorbic acid required for efficacy is hampered by adverse effects such as kidney stone formation. In a recent study, we demonstrated the efficient catalytic conversion of H2O2 to HO˙ by wüstite (Fe1-xO) nanoparticles (WNPs) through a heterogenous Fenton reaction. Here, we explore whether WNPs can enhance the therapeutic potential of ascorbic acid, thus mitigating its dose-related limitations. Our findings reveal distinct pH dependencies for WNPs and ascorbic acid in the Fenton reaction and H2O2 generation, respectively. Importantly, WNPs exhibit the capability to either impede or enhance the cytotoxic effect of ascorbic acid, depending on the spatial segregation of the two reagents by cellular compartments. Furthermore, our study demonstrates that treatment with ascorbic acid promotes the polarization of WNP-loaded macrophages toward a pro-inflammatory M1 phenotype, significantly suppressing the growth of 4T1 breast cancer cells. This study highlights the importance of orchestrating the interplay between ascorbic acid and nanozymes in cancer therapy and presents a novel macrophage-based cell therapy approach.

Surface Chemistry of Biologically Active Reducible Oxide Nanozymes.

Reducible metal oxide nanozymes (rNZs) are a subject of intense recent interest due to their catalytic nature, ease of synthesis, and complex surface character. Such materials contain surface sites which facilitate enzyme-mimetic reactions via substrate coordination and redox cycling. Further, these surface reactive sites are shown to be highly sensitive to stresses within the nanomaterial lattice, the physicochemical environment, and to processing conditions occurring as part of their syntheses. When administered in vivo, a complex protein corona binds to the surface, redefining its biological identity and subsequent interactions within the biological system. Catalytic activities of rNZs each deliver a differing impact on protein corona formation, its composition, and in turn, their recognition, and internalization by host cells. Improving the understanding of the precise principles that dominate rNZ surface-biomolecule adsorption raises the question of whether designer rNZs can be engineered to prevent corona formation, or indeed to produce "custom" protein coronas applied either in vitro, and preadministration, or formed immediately upon their exposure to body fluids. Here, fundamental surface chemistry processes and their implications in rNZ material performance are considered. In particular, material structures which inform component adsorption from the application environment, including substrates for enzyme-mimetic reactions are discussed.

Peroxide-Simulating and GSH-Depleting Nanozyme for Enhanced Chemodynamic/Photodynamic Therapy via Induction of Multisource ROS.

Reactive oxygen species (ROS) generation, using photodynamic therapy (PDT) and chemodynamic therapy (CDT), is a promising strategy for cancer treatment. However, the production of ROS in tumor cells is often limited by hypoxia, insufficient substrates, and high level of ROS scavengers in a tumor microenvironment, which seriously affects the efficacy of ROS-related tumor therapies. Herein, we report a lipid-supported manganese oxide nanozyme, MLP@DHA&Ce6, by decorating a MnO2 nano-shell on the liposome loaded with dihydroartemisinin (DHA) and photosensitizer Ce6 for generating multisource ROS to enhance cancer therapy. MLP@DHA&Ce6 can be accumulated in tumors and can release active components, Mn2+ ions, and O2. The conjugate generates ROS via nanozyme-catalyzed CDT using DHA as a substrate, PDT through Ce6, and the Fenton reaction catalyzed by Mn2+ ions. The production of O2 from MnO2 enhanced Ce6-mediated PDT under near-infrared light irradiation. Meanwhile, MLP@DHA&Ce6 showed prominent glutathione depletion, which allowed ROS to retain high activity in tumor cells. In addition, the release of Mn2+ ions and DHA in tumor cells induced ferroptosis. This multisource ROS generation and ferroptosis effect of MLP@DHA&Ce6 led to enhanced therapeutic effects in vivo.