Multifunctional RGD coated a single-atom iron nanozyme:A highly selective approach to inducing ferroptosis and enhancing immunotherapy for pancreatic cancer

Nanozyme is a new promising approach to cancer therapy for its ability to induce ferroptosis by activating H_(2)O_(2)via a traditional radical pathway and enhance cancer immunotherapy.However,short half-life period of hydroxyl radical(·OH)results in unsatisfied effectiveness.Herein,we synthesized a single-atom iron nanozyme(Fe-SAzyme),which can activate H_(2)O_(2)via a non-radical pathway to generate Fe-based reactive oxygen species(ROS)(O=FeO_(3)=O)for promoting the ferroptosis of pancreatic cancer cells.This Fe-SAzyme could be specifically phagocytosed by pancreatic cancer cells,increasing ROS levels and inhibiting glutathione(GSH)synthesis,which activates ferroptosis.Tumor magnetic resonance imaging(MRI)showed decreased T2 signal after intravenous injection of RGD@Fe-AC(AC=activated carbon).Moreover,RGD@Fe-AC promoted dendritic cell(DC)maturation,overcame Treg-mediated immunosuppression,activated T cells to trigger adaptive immune responses,and enhanced the efficacy ofα-PD-L1 immunotherapy.Our research demonstrated that RGD@Fe-AC provided a straightforward,easily implemented,and selective approach for pancreatic cancer treatment and immunotherapy.

Coordinatively unsaturated cobalt single-atom nanozymes for visual pesticides detection by smartphone-based platform

By adjusting the coordination environment of single-atom catalysts,the enzyme-like activity can be finely tuned for highly sensitive biosensing.Herein,we demonstrated that coordinatively unsaturated cobalt-nitrogen sites doped within porous carbon(SA-CoN_(3))could serve as highly efficient oxidase mimic.Compared with the typical planar four-coordination structure(SA-CoN_(4)),the as-obtained single-atom Co nanozymes anchored by three nitrogen atoms are found to display much higher oxidase-like catalytic efficiency.Combined theoretical and experimental analysis revealed that the coordinatively unsaturated Co sites could facilitate adsorption and activation of O_(2) molecule and thus improve their oxidase-like activity.Based on the enhanced oxidase-like activity of SA-CoN_(3),a paper/smartphone sensor for organophosphorus pesticides(OPs)was successfully constructed and used to quantify glyphosate in environmental and food samples with a low detection limit of 0.66μM.This work not only highlights the important role of coordination unsaturation of SA nanozymes for promoting oxidase-like activity,but also provides an easy and cost-effective way to conduct effective quantification of OPs in the field.

On the mechanism of H2 activation over single-atom catalyst: An understanding of Pt1/WOx in the hydrogenolysis reaction

Owing to the atomic dispersion of active sites via electronic interaction with supports,single-atom catalysts(SACs)grant maximum utilization of metals with unique activity and/or selectivity in various catalytic processes.However,the stability of single atoms under oxygen-poor conditions,and the mechanism of hydrogen activation on SACs remain elusive.Here,through a combination of theoretical calculation and experiments,the stabilization of metal single atoms on tungsten oxide and its catalytic properties in H2 activation are investigated.Our calculation results indicate that the oxygen defects on the WO3(001)surface play a vital role in the stabilization of single metal atoms through electron transfer from the oxygen vacancies to the metal atoms.In comparison with Pd and Au,Pt single atoms possess greatly enhanced stability on the WOx(001)surface and carry negative charge,facilitating the dissociation of H-2 to metal-H species(Hδ-)via homolytic cleavage of H2 similar to that occurring in metal ensembles.More importantly,the facile diffusion of Pt-H to the WOx support results in the formation of Bronsted acid sites(Hδ+),imparting bifunctionality to Pt1/WOx.The dynamic formation of Br?nsted acid sites in hydrogen atmosphere proved to be the key to chemoselective hydrogenolysis of glycerol into 1,3-propanediol,which was experimentally demonstrated on the Pt1/WOx catalyst.

Single-atom nanozymes with axial ligand-induced self-adaptive conformation in alkaline medium boost chemiluminescence

Mimicking the structure of natural enzymes for designing advanced alternatives provides great opportunities to address the bottleneck of enzyme-involved chemiluminescence(CL). Herein, according to theoretical calculations, we found that an endogenous axial ligand of M-N-C single-atom nanozymes(SAzymes), originating from OH-spontaneously bonding to the metal center in an alkaline medium, can self-adaptively change its strength to facilitate intermediate steps. Furthermore, the lowest energy barrier of the rate-determining step and the strongest affinity and fastest electron transfer with luminol anion endow CoN-C with the highest peroxidase-like activity. Guided by the theoretical calculations, a series of M-N-C SAzymes(M=Fe, Co,Ni) were synthesized to boost CL, where Co-N-C SAzymes with superior catalytic activity and high selective generation of O_(2)·- were validated. As a proof-of-concept, Co-N-C SAzymes were employed for sensitive detection of acetylcholinesterase and organophosphorus pesticide.

Rapid and sensitive detection of Epstein-Barr virus antibodies in nasopharyngeal carcinoma by chemiluminescence strips based on iron-porphyrin single atom nanozyme

The correlation between Epstein-Barr virus(EBV)infection and nasopharyngeal carcinoma(NPC)risk has been extensively researched.The continual monitoring of EBV-IgAs provides a promising approach of NPC screening in its early stage.In this study,we successfully synthesized a single-atom nanozyme(SANzyme)through the application of iron-porphyrin based metal organic framework(MOF-FeP).The MOF-FeP possesses precisely-defined electronic and geometric structures that accurately mimic highly-evolved catalytic site of natural peroxidase.The peroxidase-like activity of MOF-FeP enables it to catalyze the chemiluminescence of luminol substrate.By integrating MOF-FeP into a traditional strip,we created a rapid and highly-sensitive evaluation tool for detecting EBV-IgAs.Importantly,the MOF-FeP strip enables the simultaneous detection of three EBV-IgAs,greatly improving the accuracy of EBV-associated NPC screening.The sensitivities of the MOF-FeP strip(75.56%–93.30%)surpass those of current enzyme-linked immunosorbent assay(ELISA)methods(64.44%–82.22%).This test takes only 16 min to perform as opposed to the customary 1–2 h required for standard ELISA.Additionally,the MOF-FeP strip is suitable for whole blood samples,thereby significantly simplifying the sample preparation and detection process.In conclusion,the MOF-FeP strip combines the simplicity of traditional strip with the high catalytic activity of SANzyme.Our innovative MOF-FeP strip offers a new point-of-care strategy for EBV-IgAs detection,which is expected to markedly facilitate early screening for EBV-associated diseases.

内源性类氧化酶Pt@MXene复合材料(PMCs)纳米酶用于杀菌与伤口愈合

为了开发具有高抗菌活性和生物相容性且对公众健康和安全有较高要求的杀菌材料,成功合成了一种新型纳米酶复合材料,即具有类氧化酶活性的Pt@MXene复合材料(PMCs),并开展了应用PMCs以高效抑制革兰氏阳性金黄色葡萄球菌(Staphylococcus aureus)和革兰氏阴性大肠杆菌(Escherichia coli)的研究。抗菌机理研究表明,PMCs既具有类氧化酶及相应电子传递能力,又具有较大的比表面积,且有显著的抑制细菌生长的效果。此外,动物实验表明,该材料表现出优异的伤口愈合能力,并具有良好的生物相容性。研究提出了一种新型纳米酶抗菌复合材料的制备方法,探索了纳米酶灭菌的作用机理,并展示了该材料在抑菌和伤口愈合治疗中良好的应用潜力。

Single-atom nanozymes:From bench to bedside

Single-atom nanozymes(SANs)are the new emerging catalytic nanomaterials with enzyme-mimetic activities,which have many extraordinary merits,such as low-cost preparation,maximum atom utilization,ideal catalytic activity,and optimized selectivity.With these advantages,SANs have received extensive research attention in the fields of chemistry,energy conversion,and environmental purification.Recently,a growing number of studies have shown the great promise of SANs in biological applications.In this article,we present the most recent developments of SANs in anti-infective treatment,cancer diagnosis and therapy,biosensing,and antioxidative therapy.This text is expected to better guide the readers to understand the current state and future clinical possibilities of SANs in medical applications.

单原子铂纳米酶的简便构建及其类过氧化物酶活性

采用浸渍吸附法,以多孔碳纳米笼(CNC)作为载体,简便构建了单原子铂/CNC(SA-Pt/CNC)纳米酶。通过透射电子显微镜(TEM)、高分辨透射电子显微镜(HRTEM)和X射线光电子能谱(XPS)深入解析了SA-Pt/CNC的微观结构。酶活性测试表明,SAPt/CNC表现出优异的类过氧化物酶活性,能高效催化过氧化氢氧化各种底物分子。

Dual-active-site Fe/Cu single-atom nanozymes with multifunctional specific peroxidase-like properties for S^(2-)detection and dye degradation

Designing single-atom nanozymes with densely exposed metal atom active sites and enhancing catalytic activity to detect pollutants remain a serious challenge.Herein,we reported a single-atom nanozyme with layered stacked Fe/Cu dual active sites(Fe/Cu-NC SAzyme)synthesized via hydrothermal and hightemperature pyrolysis using folic acid as a template.Compared with Fe-NC and Cu-NC SAzyme,Fe/Cu-NC SAzyme has higher peroxidase-like activity,which indicates that the doping of synthesized Fe/Cu bimetals can improve the catalytic activity and that the atomic loading of Fe and Cu in Fe/Cu-NC is 5.5 wt%and 2.27 wt%,respectively.When S^(2-)is added to the Fe/Cu-NC catalytic system,a high-sensitivity and high-selectivity S^(2-)colorimetric sensing platform can be established,with a wide linear range(0.09-6μmol/L)and a low detection limit(30 nmol/L),which can be used to detect S^(2-)in environmental water samples.What’s more,the Fe/Cu-NC SAzyme can activate peroxymonosulfate(PMS)to degrade 99.9%of rhodamine B(Rh B)within 10 min with a degradation kinetics of 0.5943 min^(-1).This work details attractive applications in Fe/Cu-NC SAzyme colorimetric sensing and dye degradation.

Single-atom nanozymes towards central nervous system diseases

Nanozymes have a similar catalytic mechanism to natural enzymes,with excellent performance,facile synthesis,and better stability.Single-atom nanozymes are developed based on single-atom catalysts due to their advantages in coordination structure and electronic configuration,making them highly enzymatic-like biomimetic catalysts.Central nervous system(CNS)diseases have become one of the biggest killers of human health because they are difficult to diagnose and treat,expensive,and result in serious illness.Single-atom nanozymes have been widely used for biomedical applications,especially in oxidative-stressinduced diseases and most CNS diseases which are closely related to oxidative stress.Therefore,single-atom nanozymes show promising application prospects for the treatment of CNS diseases.In addition,due to the outstanding material properties and sensitivity of single-atom nanozymes,they also exhibit great advantages in detecting various CNS disease markers for diagnosis.

Recent progress in single-atom nanozymes research

Single-atom nanozyme(SAzyme)is the hot topic of the current nanozyme research.Its intrinsic properties,such as high activity,stability,and low cost,present great substitutes to natural enzymes.Moreover,its fundamental characteristics,i.e.,maximized atom utilizations and well-defined geometric and electronic structures,lead to higher catalytic activities and specificity than traditional nanozymes.SAzymes have been applied in many biomedical areas,such as anti-tumor therapy,biosensing,antibiosis,and anti-oxidation therapy.Here,we will discuss a series of representative examples of SAzymes categorized by their biomedical applications in this review.In the end,we will address the future opportunities and challenges SAzymes facing in their designs and applications.

Carbon-supported CoS_(4)-C single-atom nanozyme for dramatic improvement in CO_(2)electroreduction to HCOOH:A DFT study combined with hybrid solvation model

Single-atom nanozymes(SANs)have attracted extensive attention due to their characteristics of both single-atom catalysts(SACs)and enzymes.Using spin-polarized density functional theory(DFT)calculations combined with the hybrid solvation model,this work designed a series of carbon-supported Group VIII transition metals TMS_(4)-C SANs,similar to the TMS_(4)active center of formate dehydrogenase(FADH),aiming to develop highly efficient SANs for CO_(2)electroreduction.DFT calculations show that compared with TMN4-C,TMS_(4)-C have FADH-like feature,which can selectively reduce CO_(2)to formic acid.Particularly,CoS4-C is the most promising SAN for CO_(2)reduction,with a low limiting potential of-0.07 V,which exceeds most reported catalysts.Two descriptors of TMX4-C(X=N,S)based on intrinsic and electronic structure properties were proposed to shed light on the origin activity of candidates.The findings presented here will provide new insights into the design of novel enzyme-like catalysts for electrochemical CO_(2)reduction.

Atomically dispersed hierarchically ordered porous Fe-N-C single-atom nanozymes for dyes degradation

The development of novel nanozymes for environmental contamination remediation is a worthwhile research direction.However,most of the reported nanozymes cannot degrade efficiently due to the limitation of the internal active sites not being able to come into direct contact with contaminants.Therefore,we reported Fe-N-C single-atom nanozymes(SAzymes)with atomically dispersed FeN4 active sites anchored on a three-dimensional hierarchically ordered microporous-mesoporous-macroporous nitrogen doped carbon matrix(3DOM Fe-N-C)for the degradation of a targeted environmental pollutant(rhodamine B(RhB)).The three-dimensional(3D)hierarchically ordered porous structure may accelerate mass transfer and improve the accessibility of active sites.This structure and high metal atom utilization endow Fe-N-C SAzyme with enhanced tri-enzyme-mimic activities,comprising oxidase-mimic,peroxidase-mimic,and catalase-mimic activities.Based on its excellent peroxidase-mimic activity,3DOM Fe-N-C can degrade RhB by hydroxyl radicals(·OH)generated in the presence of hydrogen peroxide.This study provides a new idea for designing porous Fe-N-C SAzymes for environmental contamination remediation.

Revealing the Intrinsic Peroxidase-Like Catalytic Mechanism of Heterogeneous Single-Atom Co-MoS2

The single-atom nanozyme is a new concept and has tremendous prospects to become a next-generation nanozyme.However,few studies have been carried out to elucidate the intrinsic mechanisms for both the single atoms and the supports in single-atom nanozymes.Herein,the heterogeneous single-atom Co-MoS2(SA Co-MoS2)is demonstrated to have excellent potential as a high-performance peroxidase mimic.Because of the well-defined structure of SA Co-MoS2,its peroxidase-like mechanism is extensively interpreted through experimental and theoretical studies.Due to the different adsorption energies of substrates on different parts of SA Co-MoS2 in the peroxidase-like reaction,SA Co favors electron transfer mechanisms,while MoS2 relies on Fenton-like reactions.The different catalytic pathways provide an intrinsic understanding of the remarkable performance of SA Co-MoS2.The present study not only develops a new kind of single-atom catalyst(SAC)as an elegant platform for understanding the enzyme-like activities of heterogeneous nanomaterials but also facilitates the novel application of SACs in biocatalysis.

Design of high performance nanozymes: a single-atom strategy

Nanozymes, nanomaterials with enzyme-like characteristics,are emerging as novel artificial enzymes (Gao et al., 2007;Manea et al., 2004;Yan, 2018). They are superior to natural enzymes in many ways, such as higher stability, lower cost in preparation, and better robustness toward harsh environments (Wei and Wang, 2013).

Copper single-atom catalysts with photothermal performance and enhanced nanozyme activity for bacteria-infected wound therapy

Nanozymes have become a new generation of antibiotics with exciting broad-spectrum antibacterial properties and negligible biological toxicity.However,their inherent low catalytic activity limits their antibacterial properties.Herein,Cu single-atom sites/N doped porous carbon(Cu SASs/NPC)is successfully constructed for photothermal-catalytic antibacterial treatment by a pyrolysis-etching-adsorption-pyrolysis(PEAP)strategy.Cu SASs/NPC have stronger peroxidase-like catalytic activity,glutathione(GSH)-depleting function,and photothermal property compared with non-Cu-doped NPC,indicating that Cu doping significantly improves the catalytic performance of nanozymes.Cu SASs/NPC can effectively induce peroxidase-like activity in the presence of H2O2,thereby generating a large amount of hydroxyl radicals(•OH),which have a certain killing effect on bacteria and make bacteria more susceptible to temperature.The introduction of near-infrared(NIR)light can generate hyperthermia to fight bacteria,and enhance the peroxidase-like catalytic activity,thereby generating additional•OH to destroy bacteria.Interestingly,Cu SASs/NPC can act as GSH peroxidase(GSH-Px)-like nanozymes,which can deplete GSH in bacteria,thereby significantly improving the sterilization effect.PTT-catalytic synergistic antibacterial strategy produces almost 100%antibacterial efficiency against Escherichia coli(E.coli)and methicillin-resistant Staphylococcus aureus(MRSA).In vivo experiments show a better PTT-catalytic synergistic therapeutic performance on MRSA-infected mouse wounds.Overall,our work highlights the wide antibacterial and anti-infective bio-applications of Cu single-atom-containing catalysts.

Advances in Single-Atom Nanozymes Research

Nanozymes with intrinsic enzyme-like properties have attracted significant interest owing to their capability to address the limitations of traditional enzymes such as fragility,high cost and dificult mass production.However,the currently reported nanozymes are generally less active than natural enzymes.In recent years,with the rapid development of nanoscience and nanotechnology,single-atom nanozymes(SAzymes)with well-defined electronic and geometric structures have shown a promise to serve as direct surrogates of traditional enzymes by mimicking the highly evolved catalytic center of natural enzymes.In this review,we will introduce the enzymatic characteristics and recent advances of SAzymes,and summarize their significant applications from in vitro detection to in vivo monitoring and therapy.

Biomimetic copper single-atom nanozyme system for self-enhanced nanocatalytic tumor therapy

Single-atom nanozymes(SAZs)with peroxidase(POD)-like activity have good nanocatalytic tumor therapy(NCT)capabilities.However,insufficient hydrogen peroxide(H2O2)and hydrogen ions in the cells limit their therapeutic effects.Herein,to overcome these limitations,a biomimetic single-atom nanozyme system was developed for self-enhanced NCT.We used a previously described approach to produce platelet membrane vesicles.Using a high-temperature carbonization approach,copper SAZs with excellent POD-like activity were successfully synthesized.Finally,through physical extrusion,a proton pump inhibitor(PPI;pantoprazole sodium)and the SAZs were combined with platelet membrane vesicles to create PPS.Both in vivo and in vitro,PPS displayed good tumor-targeting and accumulation abilities.PPIs were able to simultaneously regulate the hydrogen ion,glutathione(GSH),and H2O2 content in tumor cells,significantly improve the catalytic ability of SAZs,and achieve self-enhanced NCT.Our in vivo studies showed that PPS had a tumor suppression rate of>90%.PPS also limited the synthesis of GSH in cells at the source;thus,glutamine metabolism therapy and NCT were integrated into an innovative method,which provides a novel strategy for multimodal tumor therapy.

Nanozymes: created by learning from nature

Nanozymes,a type of nanomaterials with enzyme-like activity,have shown great potential to replace natural enzymes in many fields such as biochemical detection,environmental management and disease treatment.However,the catalytic efficiency and substrate specificity of nanozymes still need improvement.To further optimize the enzymatic properties of nanozymes,recent studies have introduced the structural characteristics of natural enzymes into the rational design of nanozymes,either by employing small molecules to mimic the cofactors of natural enzymes to boost nanozymes’catalytic potential,or by simulating the active center of natural enzymes to construct the nanostructure of nanozymes.This review introduces the commonly used bio-inspired strategies to create nanozymes,aiming at clarifying the current progress and bottlenecks.Advances and challenges focusing on the research of bio-inspired nanozymes are outlined to provide ideas for the de novo design of ideal nanozymes.

Formation of active oxygen species on single-atom Pt catalyst and promoted catalytic oxidation of toluene

Catalytic oxidation of toluene over noble metal catalysts is a representative reaction for elimination of volatile organic compounds(VOCs).However,to fully understand the activation of molecular oxygen and the role of active oxygen species generated in this reaction is still a challenging target.Herein,MgO nanosheets and single-atom Pt loaded MgO(Pt SA/MgO)nanosheets were synthesized and used as catalysts in toluene oxidation.The activation process of molecular oxygen and oxidation performance on the two catalysts were contrastively investigated.The Pt SA/MgO exhibited significantly enhanced catalytic activity compared to MgO.The oxygen vacancies can be easily generated on the Pt SA/MgO surface,which facilitate the activation of molecular oxygen and the formation of active oxygen species.Based on the experimental data and theoretical calculations,an active oxygen species promoted oxidation mechanism for toluene was proposed.In the presence of H2O,the molecular oxygen is more favorable to be dissociated to generate•OH on the oxygen vacancies of the Pt SA/MgO surface,which is the dominant active oxygen species.We anticipate that this work may shed light on further investigation of t10.1007/s12274-020-2765-1he oxidation mechanism of toluene and other VOCs over noble metal catalysts.