Oxide Nanozyme Research Articles

Redox Homeostasis Strategy for Inflammatory Macrophage Reprogramming in Rheumatoid Arthritis Based on Ceria Oxide Nanozyme-Complexed Biopolymeric Micelles.

The synovial tissues under rheumatoid arthritis conditions are usually infiltrated by inflammatory cells, particularly M1 macrophages with aberrant redox homeostasis, which causes rapid deterioration of articular structure and function. Herein, we created an ROS-responsive micelle (HA@RH-CeOX) through the in situ host-guest complexation between ceria oxide nanozymes and hyaluronic acid biopolymers, which precisely delivered nanozyme and clinically approved rheumatoid arthritis drug Rhein (RH) to proinflammatory M1 macrophage populations in inflamed synovial tissues. The abundant cellular ROS could cleave the thioketal linker to trigger the release of RH and Ce. Specifically, the Ce3+/Ce4+ redox pair could present SOD-like enzymatic activity to rapidly decompose ROS and alleviate the oxidative stress in M1 macrophages, while RH could inhibit the TLR4 signaling in M1 macrophages, both of which could act in a concerted manner to induce their repolarization into anti-inflammatory M2 phenotype to ameliorate local inflammation and promote cartilage repair. Notably, rats bearing rheumatoid arthritis showed a drastic increase in the M1-to-M2 macrophage ratio from 1:0.48 to 1:1.91 in the inflamed tissue and significantly reduced inflammatory cytokine levels including TNF-α and IL-6 following the intra-articular injection of HA@RH-CeOX, accompanied by efficient cartilage regeneration and restored articular function. Overall, this study revealed an approach to in situ modulate the redox homeostasis in inflammatory macrophages and reprogram their polarization states through micelle-complexed biomimetic enzymes, which offers alternative opportunities for the treatment of rheumatoid arthritis.

Oxygen vacancies rich Co-Mo metal oxide microspheres as efficient oxidase mimetic for colorimetric detection of sulfite

Modulation of surface oxygen vacancies (Ov) by defect engineering is an attractive strategy for designing high performance transition metal oxide nanozymes. In this work, we reported the fabrication of the CoMoO4 oxidase-like nanozyme, i.e. CoMo-300r, by first pyrolyzing the CoMo layered double hydroxide precursor in an air atmosphere at 300 °C and subsequent NaBH4 reduction strategy. Various characterization outcomes confirm the mesoporous structures of both CoMo-300r and no NaBH4 treated CoMo-300, while the specific surface area of CoMo-300 is significantly increased from 103.54 m2·g−1 to 165.24 m2·g−1 after NaBH4 reduction. Also, NaBH4 reduction treatment leads to the formation of Ov rich CoMoO4 and reduced metal ion species on the surface, promoting the redox reaction kinetics. The CoMo-300r prepared at a molar ratio of Co to Mo of 1:2, pyrolysis temperature of 300 °C and 10 mM NaBH4 exhibited the best oxidase-like activity. The oxidase-like activity of CoMo-300r is 2.6-fold times that of no NaBH4 treated optimal CoMo-300. The CoMo-300r can effectively promote TMB oxidation to produce blue color and has the Michaelis-Menten constant of 0.0428 mM, which was lower than most cobalt-based oxide nanozymes and indicated a higher affinity for TMB. In terms of inhibition of SO32− on the CoMo-300r/TMB system, a sensitive SO32− colorimetric sensing platform was established. The linear range and limit of detection for sulfite determination were 0.2–40 μM and 0.09 μM, respectively. The relative standard deviation for the determination of 10 μM sulfite was 1.41% (n = 11). The method was successfully applied to the detection of sulfite in white wine. This work provides a new strategy to fabricate high activity oxidase mimetic for food analysis.

Cerium oxide nanozymes confer a cytoprotective and bio-friendly surface micro-environment to methacrylate based oro-facial prostheses

Poly-(methyl methacrylate) (PMMA) is the preferred biomaterial for orofacial prostheses used for the rehabilitation of naso-palatal defects. However, conventional PMMA has limitations determined by the complexity of the local microbiota and the friability of oral mucosa adjacent to these defects. Our purpose was to develop a new type of PMMA, i-PMMA, with good biocompatibility and better biological effects such as higher resistance to microbial adhesion of multiple species and enhanced antioxidant effect. The addition of cerium oxide nanoparticles to PMMA using a mesoporous nano-silica carrier and polybetaine conditioning, resulted in an increased release of cerium ions and enzyme mimetic activity, without tangible loss of mechanical properties. Ex vivo experiments confirmed these observations. In stressed human gingival fibroblasts, i-PMMA reduced the levels of reactive oxygen species and increased the expression of homeostasis-related proteins (PPARg, ATG5, LCI/III). Furthermore, i-PMMA increased the levels of expression of superoxide dismutase and mitogen-activated protein kinases (ERK and Akt), and cellular migration. Lastly, we demonstrated the biosafety of i-PMMA using two in vivo models: skin sensitization assay and oral mucosa irritation test, respectively. Therefore, i-PMMA offers a cytoprotective interface that prevents microbial adhesion and attenuates oxidative stress, thus supporting physiological recovery of the oral mucosa.

Direct and Specific Detection of Glyphosate Using a Phosphatase-like Nanozyme-Mediated Chemiluminescence Strategy.

Most organophosphorus pesticide (OP) sensors reported in the literature rely on the inhibition effect of OPs on the activity of acetylcholinesterase (AChE), which suffer from the drawbacks of lack of selective recognition of OPs, high cost, and poor stability. Herein, we proposed a novel chemiluminescence (CL) strategy for the direct detection of glyphosate (an organophosphorus herbicide) with high sensitivity and specificity, which is based on the porous hydroxy zirconium oxide nanozyme (ZrOX-OH) obtained via a facile alkali solution treatment of UIO-66. ZrOX-OH displayed excellent phosphatase-like activity, which could catalyze the dephosphorylation of 3-(2'-spiroadamantyl)-4-methoxy-4-(3'-phosphoryloxyphenyl)-1,2-dioxetane (AMPPD) to generate strong CL. The experimental results showed that the phosphatase-like activity of ZrOX-OH is closely related to the content of hydroxyl groups on their surface. Interestingly, ZrOX-OH with phosphatase-like properties exhibited a unique response to glyphosate because of the consumption of the surface hydroxyl group by the unique carboxyl group of glyphosates and was thus employed to develop a CL sensor for direct and selective detection of glyphosate without using bio-enzymes. The recovery for glyphosate detection of cabbage juice ranged from 96.8 to 103.0%. We believe that the as-proposed CL sensor based on ZrOX-OH with phosphatase-like properties supplies a simpler and more highly selective approach for OP assay and provides a new method for the development of CL sensors for the direct analysis of OPs in real samples.

Rapid colorimetric detection of H2O2 in living cells and its upstream series of molecules based on oxidase-like activity of CoMnO3 nanofibers

Most studies on nanozymes in recent years have focused on enhancing their catalytic activity and synthesizing directly, although this task is still complicated. Bimetallic oxides are particularly desirable due to their mixed valence and structural properties. In this study, bimetallic oxide nanofibers (CoMnO3 NFs) were prepared using a quick and effective hydrothermal synthesis technique, and exhibited outstanding oxidase-like activity. The catalytic activity of CoMnO3 NFs displayed an inhibitory response on exposure to H2O2, which was applied in detecting H2O2 and its upstream molecules (glucose and uric acid). Based on this, a straightforward, affordable, and accurate colorimetric approach was developed by combining with 3,3′,5,5′-tetramethylbenzidine. Employing the oxidase activity rather than the traditional peroxidase activity to detect H2O2 drastically reduces the detection time. This method was also successfully used for in situ quantitative monitoring of intracellular H2O2, as well as detecting uric acid and glucose levels in human serum. Moreover, a smartphone-assisted colorimetric sensing system built on self-developed software was developed, enabling the on-site detection of H2O2 without laboratory instruments. This study established theoretical support for the valid design of bimetallic oxide nanozyme activity and might guide the development of detection systems for accurately analyzing biomarkers in foods and biochemical products.

Transition metal-doped germanium oxide nanozyme with enhanced enzyme-like activity for rapid detection of pesticide residues in water samples

Designing highly active nanozymes for bioanalysis and environmental sensing remains a challenge. In this study, transition metal, palladium (Pd) and iron (Fe), doped germanium oxide (GeO2) nanozyme was designed and optimized. Compared with the pristine GeO2 nanozyme, the transition metal doped GeO2 nanozyme have lower Michaelis-Menten constants and higher catalytic activity, indicating that the Pd and Fe doped GeO2 nanozyme not only enhance their affinity for the substrate but also improve its catalytic activity. In addition, a colorimetric sensor based on the GeO2@Pd–H2O2-TMB system was constructed for the visual detection of simazine in water samples due to the good affinity between TMB and simazine. This sensor has good selectivity and sensitivity with a detection limit of 6.21 μM because of the highest catalytic performance of GeO2@Pd nanozyme. This study broadens the application of nanozymes in environmental field and other nanozymes can also be enhanced in activity by simple transition metal doping.

Orally administration of cerium oxide nanozyme for computed tomography imaging and anti-inflammatory/anti-fibrotic therapy of inflammatory bowel disease

BackgroundInflammatory bowel disease (IBD) is a chronic nonspecific disease with unknown etiology. Currently, the anti-inflammatory therapeutic approaches have achieved a certain extent of effects in terms of inflammation alleviation. Still, the final pathological outcome of intestinal fibrosis has not been effectively improved yet.ResultsIn this study, dextran-coated cerium oxide (D-CeO2) nanozyme with superoxide dismutase (SOD) and catalase (CAT) activities was synthesized by chemical precipitation. Our results showed that D-CeO2 could efficiently scavenge reactive oxide species (ROS) as well as downregulate the pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and iNOS) to protect cells from H2O2-induced oxidative damage. Moreover, D-CeO2 could suppress the expression of fibrosis-related gene levels, such as α-SMA, and Collagen 1/3, demonstrating the anti-fibrotic effect. In both TBNS- and DSS-induced colitis models, oral administration of D-CeO2 in chitosan/alginate hydrogel alleviated intestinal inflammation, reduced colonic damage by scavenging ROS, and decreased inflammatory factor levels. Notably, our findings also suggested that D-CeO2 reduced fibrosis-related cytokine levels, predicting a contribution to alleviating colonic fibrosis. Meanwhile, D-CeO2 could also be employed as a CT contrast agent for noninvasive gastrointestinal tract (GIT) imaging.ConclusionWe introduced cerium oxide nanozyme as a novel therapeutic approach with computed tomography (CT)-guided anti-inflammatory and anti-fibrotic therapy for the management of IBD. Collectively, without appreciable systemic toxicity, D-CeO2 held the promise of integrated applications for diagnosis and therapy, pioneering the exploration of nanozymes with ROS scavenging capacity in the anti-fibrotic treatment of IBD.

Multifunctional Hybrid Nanozymes for Magnetic Enrichment and Bioelectrocatalytic Sensing of Circulating Tumor RNA during Minimal Residual Disease Monitoring

Iron oxide nanozymes are a form of nanomaterial with both superparamagnetic and enzyme-mimicking properties. Ongoing research efforts have been made to create multifunctional iron oxide hybrid nanozymes with auxiliary properties through biomolecular modifications. Such iron oxide hybrid nanozymes can be useful for rapid and cost-effective analysis of circulating tumor nucleic acids (ctNAs) in patient liquid biopsies during minimal residual disease (MRD) monitoring of cancer recurrence. Herein, the use of streptavidin-modified iron oxide hybrid nanozymes is reported for magnetic enrichment and bioelectrocatalytic sensing of three prostate cancer (PCa) ctRNA biomarkers with high detection specificity and sensitivity (10 copies) over an ultrabroad dynamic range (five orders of magnitude). Furthermore, the feasibility of ctRNA analysis for pre- and post-cancer treatment MRD monitoring is demonstrated using PCa urinary liquid biopsy samples.

Ratiometric colorimetric detection of nitrite using CoMnO3 nanofibers as an oxidase-like enzyme to induce diazotization reaction.

Nitrite is a typical food additive and preservative used in the food industry, which has attracted considerable attention due to its severe adverse effects on human health. Herein, a sensitive and highly selective ratiometric colorimetric sensing platform for the detection of nitrite was created based on a polymetallic oxide nanozyme, CoMnO3 nanofibers (CMO) catalysis integrated with the particular diazotization reaction. The nanozyme has superior oxidase-like activity (Km was 0.105 mM and Vmax was 63.7 × 10-8 M S-1) and could catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to oxidized TMB (oxTMB), as CMO could achieve the conversion of oxygen in the solution to superoxide anion (O2˙-). In addition, it is interesting to note that oxTMB can be diazotized in the presence of nitrite under acidic conditions, causing a shift in the ratio of nitrite concentration to the absorbance peaks at 450 and 652 nm (A450/A652). The ratio of A450/A652 exhibited a positive linear relationship with the concentration of nitrite within the concentration range of 0.2-200 μM, with a detection limit of 0.094 μM. Simultaneously, this method was also successful in quantifying the nitrite produced by brined and pickled foods and the dynamic tracking of the nitrite levels in various types of dishes. The analysis method not only offers dual-signal ratio sensing with high sensitivity but also holds the benefit of outstanding selectivity for the use of the particular reaction, which has a wide range of application prospects in food safety management.

Nanozyme-based guanidinium peptides mediate surface reactive oxygen species for multidrug resistant bacterial infection management.

Nanozymes are effective novel antibacterial agents. However, they still have some shortcomings such as low catalytic efficiency, poor specificity, and non-negligible toxic side effects. Here, we synthesized iridium oxide nanozymes (IrOx NPs) by a one-pot hydrothermal method and used guanidinium peptide-betaine (SNLP/BS-12) to modify the surface of IrOx NPs (SBI NPs) to obtain a high-efficiency and low-toxicity antibacterial agent. In vitro experiments showed that SBI NPs with SNLP/BS12 could enhance IrOx NPs to target bacteria, mediate bacterial surface catalysis and reduce the cytotoxicity of IrOx NPs to mammalian cells. Importantly, SBI NPs were able to effectively alleviate MRSA acute lung infection and effectively promote diabetic wound healing. Accordingly, iridium oxide nanozymes functionalized with guanidinium peptides are expected to be an effective antibiotic candidate in the postantibiotic era.

Conservation of the enzyme-like activity and biocompatibility of CeO2 nanozymes in simulated body fluids.

Cerium oxide nanozymes (CeO2NZs) are attracting vast attention due to their antioxidant and catalytic properties and mimic the activities of multiple endogenous enzymes. However, as is the case for nanomedicines in general, the success in showing their unique medical applications has not been matched by an understanding of their pharmacokinetics, which is delaying their implementation in clinical settings. Furthermore, the data of their modifications in body fluids and the impact on their activity are scarce. Herein, two types of widely used CeO2NZs, electrostatically stabilized and coated with a mesoporous silica shell, were exposed to simulated saliva and lung, gastric and intestinal fluids, and cell culture media. Their physicochemical modifications and bioactivity were tracked over time up to 15 days combining the data of different characterization techniques and biological assays. The results show that the biocompatibility and antioxidant activity are retained in all cases despite the different evolution behaviors in different fluids, including agglomeration. This work provides an experimental basis from a pharmacokinetic perspective that supports the therapeutic effectiveness of CeO2NZs observed in vivo for the treatment of many conditions related to chronic inflammation and cancer, and suggests that they can be safely administered through different portals of entry including intravenous injection, oral ingestion or inhalation.

Ce-doped indium oxide nanozymes with peroxidase-like activity induced by cerium–indium synergy for colourimetric detection of H2O2

InCex has a higher catalytic efficiency due to the presence of more oxygen vacancies and higher Ce3+ content, which can provide a wide range of binding sites for TMB, and also can accelerate the electron transfer rate.

Ir(IV) and Ir(III) in situ transition promotes ROS generation for eradicating multidrug-resistant bacterial infection.

Whether reactive oxygen species are a consequence or a cause of antibacterial activity is not fully known. A glutathione (GSH)-mediated oxidative defense mechanism is an important factor against bacterial infection. Reactive oxygen species (ROS) storm-mediated bacterial death by depleting GSH is also considered an effective strategy. Therefore, we designed and synthesized hybrid iridium ruthenium oxide nanozymes (IrRuOx NPs), where IrRuOx NPs alternately consume GSH through double redox electron pair auto-valent cycles, while an IrRuOx NP-mediated Fenton-like reaction occurs to realize an ROS storm, which in turn mediates lipid peroxidation to promote bacterial death. The results showed that IrRuOx NPs can effectively inhibit and kill Gram-positive and Gram-negative bacteria in vitro, and can be used as broad-spectrum antibiotics. Importantly, the wound and sepsis models of MRSA infection confirmed the efficient antibacterial activity of IrRuOx NPs in vivo. Accordingly, this study provides a new idea for metal oxide hybrid nanoenzymes and their biological functions.

Eg Occupancy as a Predictive Descriptor for Spinel Oxide Nanozymes

Functional nanomaterials offer an attractive strategy to mimic the catalysis of natural enzymes, which are collectively called nanozymes. Although the development of nanozymes shows a trend of diversification of materials with enzyme-like activity, most nanozymes have been discovered via trial-and-error methods, largely due to the lack of predictive descriptors. To fill this gap, this work identified eg occupancy as an effective descriptor for spinel oxides with peroxidase-like activity and successfully predicted that the eg value of spinel oxide nanozymes with the highest activity is close to 0.6. The LiCo2O4 with the highest activity, which is finally predicted, has achieved more than an order of magnitude improvement in activity. Density functional theory provides a rationale for the reaction path. This work contributes to the rational design of high performance nanozymes by using activity descriptors and provides a methodology to identify other descriptors for nanozymes.

Design of Monovalent Cerium-Based Metal Organic Frameworks as Bioinspired Superoxide Dismutase Mimics for Ionizing Radiation Protection.

Superoxide dismutase (SOD) is one of the major antioxidants in vivo and is expected to play critical roles on the defense against reactive oxygen species (ROS)-mediated damages, such as ionizing radiation damages. Herein, inspired by the function and structure of natural SODs and cerium oxide nanozymes, two monovalent cerium-based metal organic frameworks (Ce-MOFs), CeIIIBTC and CeIVBTC, were designed for superoxide radical (O2•-) elimination and ionizing radiation protection. These two Ce-MOFs selectively scavenge O2•- and are excellent SOD mimics. Like natural SODs and cerium oxide nanozymes, the SOD-like catalytic mechanism of Ce-MOFs involves a cycle between Ce(IV) and Ce(III). Furthermore, by constructing monovalent Ce-MOFs, we found that high-valent CeIVBTC are more effective SOD-like nanozymes compared to CeIIIBTC. With smaller size, better monodispersity, and more effective SOD-like activity, CeIVBTC nanozymes were further applied for ionizing radiation protection. Both in vitro and in vivo results demonstrated that CeIVBTC nanozymes could efficiently scavenge ROS, prevent cells from γ-ray radiation-induced cell viability decrease and DNA damages, and improve the survival rate of irradiated mice by recovering the bone marrow DNA damage and alleviating oxidative stress of tissues. The protective effect and good biocompatibility of CeIVBTC nanozymes will enable the development of Ce-MOFs-based radioprotectants and facilitate treatment of other ROS-related diseases.

Tumor Microenvironment-Activable Manganese-Boosted Catalytic Immunotherapy Combined with PD-1 Checkpoint Blockade.

Immune checkpoint blockade (ICB) therapy has attracted widespread attention in cancer treatment. Due to the low immunogenicity and immune suppression state in the tumor microenvironment (TME), the therapeutic effects are only moderate. Herein, a TME-activable manganese-boosted catalytic immunotherapy is designed for synergism with ICB therapy to kill tumors efficiently. The tumor cell membrane (CM)-wrapping multienzyme-mimic manganese oxide (MnOx) nanozyme termed CM@Mn showed intrinsic peroxidase and oxidase-like activities in an acidic TME. These activities can generate toxic hydroxyl (•OH) and superoxide radicals (•O2-) for tumor cell killing and evoking immunogenic cell death (ICD). Furthermore, the TME-responsive release of Mn2+ directly promotes dendritic cell maturation and macrophage M1 repolarization, resulting in the reversal of an immunosuppressive TME into an immune-activating environment. Additionally, tumor hypoxia relief caused by catalase-like activity also contributes to the process of TME reversal. Finally, a robust tumor-specific T cell-mediated antitumor response occurs with the support of the PD-1 checkpoint blockade. The proliferation of primary and metastatic tumors was inhibited, and a long-term immune memory effect was induced. The therapeutic strategy outlined here may serve as a promising candidate for tumor-integrated treatment.

Combining Cobalt Ferrite Nanozymes with a Natural Enzyme to Reshape the Tumor Microenvironment for Boosted Cascade Enzyme-Like Activities.

Nanozymes with the merits of effective enzyme-mimic activities, tunable catalytic properties, pH/temperature tolerance, and high stability have been consumingly researched for nanocatalytic therapy. Herein, the union nanozymes and a natural enzyme nanoplatform (DMSN@CoFe2O4/GOD-PCM) are elaborately designed by simply depositing an ultrasmall cobalt ferrite (CoFe2O4) bimetallic oxide nanozyme and natural glucose oxidase (GOD) that are loaded into the aperture (∼12 nm) of dendritic mesoporous silica (DMSN) for near-infrared-II-enhanced tumor therapy. Upon irradiation, the hyperthermia generated by CoFe2O4 nanozymes unlocks the "gate" of phase-change material (PCM) for releasing GOD, which reshapes the specific tumor microenvironment (TME) through the glucose metabolism pathway. The resulting strengthened acid condition and a considerable amount of H2O2 efficiently initiate the cascade catalysis reactions. Moreover, highly toxic hydroxyl radicals are generated with a Co/Fe dual-cycle system of ultrasmall CoFe2O4 nanozymes. The in situ glutathione consumption and hypoxia relief further amplify oxidative stress. In addition, chemotherapeutic effects due to the cytotoxicity of cobalt ions enhance the therapeutic performance. Collectively, this study provides a proof of concept for TME-reshaped natural and artificial nanozyme cascade catalysis for combined reactive oxygen species-based therapy and chemotherapy.

Plasmon-Enhanced Bimodal Nanosensors: An Enzyme-Free Signal Amplification Strategy for Ultrasensitive Detection of Pathogens.

Increasing foodborne illnesses have led to global health and economic burdens. E. coli O157:H7 is one of the most common disease-provoking pathogens and known to be lethal Shiga toxin-producing E. coli (STEC) strains. With a low infection dose in addition to person-to-person transmission, STEC infections are easily spread. As a result, specific and rapid testing methods to identify foodborne pathogens are urgently needed. Nanozymes have emerged as enzyme-mimetic nanoparticles, demonstrating intrinsic catalytic activity that could allow for rapid, specific, and accurate pathogen identification in the agrifood industry. In this study, we developed a sensitive nanoplatform based on the traditional ELISA assay with the synergistic properties of gold and iron oxide nanozymes, replacing the conventional enzyme horseradish peroxidase (HRP). We designed an easily interchangeable sandwich ELISA composed of a novel, multifunctional magneto-plasmonic nanosensor (MPnS) with target antibodies (MPnS-Ab). Our experiments demonstrate a 100-fold increase in catalytic activity in comparison to HRP with observable color changes within 15 min. Results further indicate that the MPnS-Ab is highly specific for E. coli O157:H7. Additionally, effective translatability of catalytic activity of the MPnS technology in the lateral flow assay (LFA) platform is also demonstrated for E. coli O157:H7 detection. As nanozymes display more stability, tunable activity, and multi-functionality than natural enzymes, our platform could provide customizable, low-cost assay that combines high specificity with rapid detection for a variety of pathogens in a point-of-care setup.

A novel approach for the prevention of ionizing radiation-induced bone loss using a designer multifunctional cerium oxide nanozyme.

The disability, mortality and costs due to ionizing radiation (IR)-induced osteoporotic bone fractures are substantial and no effective therapy exists. Ionizing radiation increases cellular oxidative damage, causing an imbalance in bone turnover that is primarily driven via heightened activity of the bone-resorbing osteoclast. We demonstrate that rats exposed to sublethal levels of IR develop fragile, osteoporotic bone. At reactive surface sites, cerium ions have the ability to easily undergo redox cycling: drastically adjusting their electronic configurations and versatile catalytic activities. These properties make cerium oxide nanomaterials fascinating. We show that an engineered artificial nanozyme composed of cerium oxide, and designed to possess a higher fraction of trivalent (Ce3+) surface sites, mitigates the IR-induced loss in bone area, bone architecture, and strength. These investigations also demonstrate that our nanozyme furnishes several mechanistic avenues of protection and selectively targets highly damaging reactive oxygen species, protecting the rats against IR-induced DNA damage, cellular senescence, and elevated osteoclastic activity in vitro and in vivo. Further, we reveal that our nanozyme is a previously unreported key regulator of osteoclast formation derived from macrophages while also directly targeting bone progenitor cells, favoring new bone formation despite its exposure to harmful levels of IR in vitro. These findings open a new approach for the specific prevention of IR-induced bone loss using synthesis-mediated designer multifunctional nanomaterials.

Multifunctional mesoporous silica-cerium oxide nanozymes facilitate miR129 delivery for high-quality healing of radiation-induced skin injury

Radiation-induced skin injury (RISI) is an important challenge for clinical treatments. The main causes of RISI include hypoxia in the wound microenvironment, reactive oxygen species (ROS) activation, and downregulation of DNA repair proteins. Here, a multiple radioresistance strategy was designed for microRNA therapy and attenuating hypoxia. A novel mesoporous silica (MS) firmly anchored and dispersed cerium (IV) oxide (CeO2) nanoparticles to form MS-CeO2 nanocomposites, which exhibit superior activity in inhibiting radiation-induced ROS and HIF-1α activation and ultimately promote RISI wound healing. The miR129 serum concentrations in patients can promote radioresistance by directly targeting RAD17 and regulating the Chk2 pathway. Subsequently, MS-CeO2 nanocomposites with miR129 were conjugated with iRGD-grafted polyoxyethylene glycol (short for nano-miR129), which increased the stability and antibacterial character, efficiently delivered miR129 to wound blood capillaries, and exhibited low toxicity. Notably, nano-miR129 promoted radioresistance and enhanced anti-ROS therapeutic efficacy in a subcutaneous RISI mouse model. Overall, this MS-CeO2 nanozyme and miR129-based multiresistance radiotherapy protection strategy provided a promising therapeutic approach for RISI.