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Efficient nanozyme engineering for antibacterial therapy

Yonghai Feng Funing Chen Jessica M Rosenholm Lei Liu Hongbo Zhang

Yonghai Feng, Funing Chen, Jessica M Rosenholm, Lei Liu, Hongbo Zhang. Efficient nanozyme engineering for antibacterial therapy[J]. Materials Futures, 2022, 1(2): 023502. doi: 10.1088/2752-5724/ac7068
Citation: Yonghai Feng, Funing Chen, Jessica M Rosenholm, Lei Liu, Hongbo Zhang. Efficient nanozyme engineering for antibacterial therapy[J]. Materials Futures, 2022, 1(2): 023502. doi: 10.1088/2752-5724/ac7068
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Efficient nanozyme engineering for antibacterial therapy

doi: 10.1088/2752-5724/ac7068
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  • Scheme 1.  Illustration of proposed mechanism of nanozyme-based catalytic antibacterial therapy.

    Scheme 2.  Illustration of the types of antibacterial nanozymes resembling different natural enzymes and the enhancing strategies for improving the catalytic antibacterial activity of nanozymes.

    Figure  1.  Bioinspired synthesis of SAzymes with enzyme-like active centers. (A) Atomically isolated Fe-N4 sites on nitrogen-doped amorphous carbon (SAF NCs) mimicking the active center of HRP. (i) HRP structure with corresponding active center. (ii) Schematic illustration of SAF NCs model and its catalytic decomposition of H2O2 to ‧OH via the Fe-N4 single sites. (iii) TEM image of SAF NCs. (iv) HAADF-STEM image of SAF NCs. The bright dots as some marked by yellow circles are single iron atoms. Reprinted with permission from [63] John Wiley & Sons [© 2019 Wiley-VCH GmbH]. (B) Monodispersed ZIF-8 derived carbon nanospheres with a zinc-centered porphyrin-like structure (PMCS). (i) Cytochrome c structure with corresponding active center. (ii) PMCS model mimicking the active center of cytochrome c. (iii) TEM image of PMCS. (iv) HAADF-STEM image of Cu SASs/NPC. Reprinted with permission from [66] John Wiley & Sons [© 2019 Wiley-VCH GmbH]. (C) Hollow N-doped carbon sphere doped with a single-atom copper species (Cu-HNCS) mimicking the active center of laccase. (i) Laccase structure with corresponding active center. (ii) Model of Cu-HNCS mimicking the active center of laccase. (iii) TEM image of Cu-HNCS. (iv) HAADF-STEM image of Cu-HNCS. Reprinted with permission from [73] John Wiley & Sons [© 2020 WILEYVCH Verlag GmbH & Co. KGaA, Weinheim].

    Figure  2.  (A) (i) Catalytic mechanisms of decomposition of H2O2 into ‧OH over Fe-N4-C SAzymes; (ii) energy diagrams of Fe, Co, Zn-N-C SAzymes in proposed reaction process; (iii) EPR signals of ‧OH for different M-N-C SAzymes; (iv) time-dependent absorbance of 3,3-,5,5--Tetramethylbenzidine (TMB) catalyzed by Fe-C-N SAzymes with Fe-atom loading of 1.3 and 13.5 wt %, respectively. Reprinted with permission from [80]. © 2020, American Chemical Society. (B) (i) TEM image of R-CMs; (ii and iii) HRTEM image of RCMs; (iv) time-dependent absorbance changes at 652 nm of TMB for different MoS2; (v) TA signal for different MoS2 nanozymes under different conditions; (vi) proposed catalytic mechanism of decomposition of H2O2 into ‧OH over S-defect MoS2; (vii) energy diagrams of S-defect MoS2 in catalytic process. Reprinted with permission from [43]. John Wiley & Sons [© 2019 Wiley-VCH GmbH].

    Figure  3.  (A) Schematic illustration of ATP stimulation for enhancing the catalytic decomposition of H2O2 over Fe3O4 NPs for antibacterial application. Reprinted with permission from [38] © 2020 Elsevier. (B) Schematic illustration of glucose stimulation for enhancing the catalytic decomposition of H2O2 over APGH nanozymes. Reprinted with permission from [90] John Wiley and Sons [© 2021 WileyVCH GmbH]. (C) Schematic illustration of visible light stimulation for enhancing the catalytic decomposition of H2O2 over CuO NPs. Reprinted with permission from [39] © 2018, American Chemical Society. (D) Schematic illustration of NIR stimulation for enhancing the catalytic decomposition of H2O2 over N-GDQDs/AuAg NC. Reprinted with permission from [35] © 2022 American Chemical Society. (E) Schematic illustration of AMF stimulation for enhancing the catalytic decomposition of H2O2 over AIron NPs. Reprinted with permission from [92] © 2020 Elsevier B.V.

    Figure  4.  (A) Scanning electron microscope (SEM) (i) and TEM (ii) images of R-CMs, and SEM images of interaction between R-CMs and bacteria (iii and iv). Reprinted with permission from [43] John Wiley & Sons [© 2019 Wiley-VCH GmbH]. (B) SEM (i) and TEM (ii) images of MoS2/rGO VHS, and SEM images of interaction between MoS2/rGO VHS and bacteria (iii and iv). Reprinted with permission from [81] John Wiley & Sons [© 2020 Wiley-VCH GmbH]. (C) SEM (i) and TEM (ii) images of Fe3O4@MoS2-Ag, and SEM images of interaction between Fe3O4@MoS2-Ag and bacteria (iii and iv). Reprinted with permission from [82] © 2020 Elsevier B.V. (D) SEM (i) and TEM (ii) images of RCF, and SEM images of interaction between RCF and bacteria (iii and iv). Reprinted with permission from [102] © 2021, American Chemical Society.

    Figure  5.  Pseudopodia-like MOF@COF nanozyme for antibacterial therapy. (A) (i) TEM image of NMCTP-TTA and (ii-vi) corresponding element mappings of O, N, Fe, C, and Merge, respectively. (B) Morphologies of E. coli (i) and S. aureus (iv), and treated with NM-88 + H2O2 (ii and v) and NMCTP-TTA + H2O2 (iii and vi). (C) In vivo catalytic therapy of S. aureus wound-infection. (i) Schematic illustration of treatment strategy; (ii) photographs of wound-healing performance treated by different nanozyme catalysts; (iii) corresponding photographs of bacterial colonies isolated from different treated wound; (iv) H&E staining and immunohistochemical analysis of skin tissues. Reprinted with permission from [58] John Wiley and Sons [© 2020 WileyVCH GmbH].

    Table  1.   Classification of antibacterial nanozymes based on chemical design strategies for enhancing antibacterial efficiency.

    StrategiesEnhanced mechanismChemical approachesNanomaterialsCatalytic activityKm-H2O2 (mM)Vmax-H2O2 (10-8 M s-1)BacteriaResultsReferences
    Catalytic activity improvementEnzymic active centers mimickingPyrolysis and acid-etching of MOFs precursors to create metalloenzyme-like atomically dispersed MNx active centers.FeN4-SAF NCsPOD-like activity11.9522.3E. coli, S. aureusThe Fe-N4-SAF and Fe-N5 SA/CNF with active centers similar to HRP and cytochrome P450 shows much higher Vmax than Fe3O4 and CeO2 NPs, respectively. MOF@COF showed enhanced activity as compare to blank MOFs.[63]
    ZnN4-PMCSsPOD-like activity40.1612.15Pseudomonas aeruginosa[66]
    CuN4-SASs/NPCPOD-like activityE. coli, MRSA[64]
    FeN5 SA/CNFOXD-like activity0.148 (TMB)75.8 (TMB)E. coli, S. aureus[62]
    Control the growth of COFs to provide spatial microenvironment around active sites (MOFs).NMCTP-TTAPOD-like activity0.45857E. coli, S. aureus[58]
    Downsizing nanoparticlesUltrathin 2D MOFs confine the growth of ultrasmall Au clusters by in-situ reduction.UsAuNPs/MOFsPOD-like activity7.94E. coli, S. aureusThe UsAuNPs/MOFs, SA-Pt/g-C3N4-K, Fe-N-C SAzyme with small-sized metal clusters or single atom sites displayed enhanced catalytic activity compared to their large counterparts.[20]
    Pyrolysis of atomically dispersed Pt, Fe supported precursors.SA-Pt/g-C3N4-KPOD-like activity0.002175.0E. coli[27]
    Fe-N-C SAzymePOD-like activity4.8411.8E. coli, S. aureus[61]
    Engineering defectsBare Cu NWs, rGO, and Fe3O4 provided nucleation sites for the nucleation and growth of MoS2 nanosheets with defect-rich edges.R-CMsPOD-like activity0.032E. coli, S. aureusThe defect-rich edges for R-CMs, MoS2/rGO, Fe3O4@MoS2-Ag enhanced their H2O2 affinity as compared to MoS2.[43]
    MoS2/rGOPOD-like activity0.2625.6E. coli, S. aureus[81]
    Fe3O4@MoS2-AgPOD-like activity1.018.2E. coli[82]
    Composition regulationN-doped sponge-like carbon spheres (N-SCSs) were prepared through the pyrolysis of colloidal silica/polyaniline assemblies. Cu-doped phosphate-based glass (Cu-PBG) was prepared by hydrothermal method.N-SCSs Cu-PBG
    POD-like activity POD-like activity
    81.53
    23.3
    E. coli, S. aureusE. coli, S. aureus
    N, B, Cu doping endows carbon materials or PBG with multi-enzyme activities.[55] [83]
    CuCo2S4 can be controllably prepared by hydrothermal method, while Pd-Ir cubes can be synthesized by the wet chemical reduction method.CuCo2S4POD-like activity209.923.3E. coli, S. aureus MRSABimetallic nanozymes with dual active sites shows remarkably synergistic enhancement in catalytic activity.[84]
    Ir-Pd cubesPOD-like activity0.0345.1[85]
    Ultrathin 2D MOFs supported ultrasmall Au nanoparticles were prepared by in situ reduction.UsAuNPs/MOFsPOD-like activity7.94E. coli, S. aureus2D MOFs significantly improved the catalytic activity of UsAuNPs/MOFs as compared to Au NPs.[20]
    Different shaped Fe3O4 magnetite nanoparticles (MNPs) were synthesized by solvent-thermal method, while bamboo-like nitrogen-doped carbon nanotubes encapsulating cobalt nanoparticles (N-CNTs@Co) were prepared by pyrolysis of cobalt cyanide cobalt at high temperature.TO-shaped Fe3O4 MNPs Bamboo-like N-CNTs@Co
    POD-like activity OXD-like activity
    0.1 (TMB)
    130 (TMB)
    E. coli, S. aureus
    Different shapes of Fe3O4 MNPs and N-CNTs@Co displayed different catalytic activity[86] [87]
    External stimulipHThe addition of ATP or the microenvironment having glucose can be used as a trigger to induce the changes of pH and even H2O2 concentration, thus resulting in enhanced POD-like activities. A hyaluronic acid capsule functionalized with aptamer-Pt NPs and glucose oxidase (APGH) was constructed to break the limitations of pH and H2O2.
    ATP + Fe3O4 NPs APGH + glucose from bacteria
    POD-like activity POD-like activity


    E. coli, Bacillus subtilisS. aureus
    With ATP, the ‧OH generation for Fe3O4 is about 17 folds higher than that without ATP at neutral pH, resulting in enhanced antibacterial efficiency. When bacteria interacted with APGH, the released glucose oxidase could catalyze glucose into glucose acid and H2O2, providing raw-materials for Pt NPs to catalytic the ‧OH generation.
    [38] [90]
    Visible lightIntroduction of semiconductor to fabricate nanozymes can be used to enhance the catalytic activity of nanozymes under visible light illumination.CuO nanorods + lightPOD-like activity3.4 (in light) 14.8 (in dark)10.9 (in light) 0.6 (in dark)E. coliWith visible light irradiation, the nanozyme showed enhanced catalytic activity due to the improved affinity to H2O2.[39]
    MoS2/rGO + lightPOD-like activity0.26 (in dark)25.6 (in dark)E. coli, S. aureus[81]
    TiO2 NTs@MoS2 + lightPOD-like activity0.085 (in dark)120.5 (in dark)E. coli, S. aureus[45]
    NIRThe activity of nanozymes with absorption in NIR range can be enhanced by NIR irradiation.Au/CeO2 + NIRPOD-like activity0.006 (with NIR) 0.007 (in dark)133.4 (with NIR) 82.6 (in dark)E. coli, S. aureusThe catalytic activities of nanozymes with strong NIR absorption can be significantly enhanced by NIR generated photothermal effect. Moreover, with semiconductor hybrid, the plasmonic effect can also produce hot carrier to further enhance the catalytic activities.[91]
    N-GDQDs/AuAg NC + NIRPOD-like activity0.72 (with NIR) 1.24 (in dark)
    10.52 (with NIR) 4.75 (in dark)E. coli, S. aureus[35]
    Au NPTs + NIRPOD-like activityMRSA, E. coli[26]
    AuPt NDs + NIRPOD-like activityE. coli, S. aureus[32]
    NiS2 NPs + NIRPOD-like activityMRSA, E. coli[48]
    WS2 QDs + NIRPOD-like activityMu50, E. coli[126]
    MoO3-x NDs +NIRPOD-like activity0.26 (in dark)15.2 (in dark)MRSA, E. coli[127]
    R-CMs + NIRPOD-like activity0.032 (in dark)E. coli, S. aureus[43]
    Fe3O4@MoS2-Ag + NIRPOD-like activity1.0 (in dark)18.2 (in dark)E. coli[82]
    PEG-MoS2 NFs + NIRPOD-like activityE. coli, B. subtilis[106]
    Cu2MoS4 + NIRPOD/OXD-like activity25.46 (in dark)42.81 (in dark)E. coli, S. aureus, MRSA[111]
    CuN4-SASs/NPC + NIRPOD-like activity11.95 (in dark)22.3 (in dark)E. coli, S. aureus[63]
    CuN4-SASs/NPC + NIRPOD-like activityE. coli, MRSA[64]
    Mesoporous FeN4-C SAzymes + NIRPOD-like activity4.84 (in dark)11.8 (in dark)E. coli, S. aureus[61]
    RFC + NIRIIPOD-like activityE. coli, S. aureus, MRSA[102]
    N-SCSs + NIRPOD/OXD-like activity81.53 (in dark)23.27 (in dark)E. coli, S. aureus[55]
    PEG@zirconium-ferrocene MOF + NIRPOD-like activityE. coli[107]
    ZIF8-PEG@Zn/Pt-CN + NIRPOD-like activity0.067 (in dark)5.11 (in dark)E. coli, S. aureus[128]
    UiO-66-NH-CO-MoS2 + NIRPOD-like activity0.23 (in dark)15.7 (in dark)MRSA, AREC[129]
    AMFAmorphous iron nanoparticles (AIronNPs) were prepared by chemical precipitation with PVP, F-127, and ammonium iron (III) citrate as raw materialsAIronNPs + AMFPOD-like activity41.36 (with AMF) 117.23 (without AMF)1.19 (with AMF) 1.45 (without AMF)E. coli, S. aureusThe AMF can significantly improve the catalytic activity of AIronNPs due to the enhanced release of iron ions.[92]
    Bacterial affinity enhancementRough surface engineeringBare Cu NWs, rGO, and Fe3O4 provided nucleation sites for the nucleation and growth of MoS2 nanosheets with defect-rich edges, while RFC was synthesized by a three-step template-carbonization corrosion method.R-CMsPOD-like activity0.032E. coli, S. aureusNanozymes with strong bacterial capture ability due to the rough surfaces can localize the ROS-mediated damages around the bacteria, thus resulting in the enhanced catalytic therapeutic efficiency.[43]
    MoS2/rGOPOD-like activity0.2625.6E. coli, S. aureus[81]
    Fe3O4@MoS2-AgPOD-like activity1.018.2E. coli[82]
    RFCPOD-like activityE. coli, S. aureus, MRSA[102]
    Pseudopodia mimickingThe growth of COFs on MOFs form pseudopodia-like shapes, allowing the bacterial capture.NMCTP-TTAPOD-like activity0.45857E. coli, S. aureus[58]
    Multifunctional nanozyme-based platformsPTTNanozymes with NIR absorption can be used for CDT and PTT combined nanoplatforms.Listed in the part of NIR stimuliCDT + PTTE. coli, S. aureus, MRSA, Mu50, ARECNanozymes with strong NIR absorption can be a benign nanoplatform for combining CDT and PTT for synergistic enhanced antibacterial applications.As listed above
    Drug releaseUsing MOF-based nanozymes as nanocarriers to load metal ions or drugs due to the porosity and large surface area of MOFs.Pd-MOF@PAzo@SNPCDT + NOE. coli, S. aureus, BiofilmThe MOF-nanozyme based nanoplatforms can be used as a good synergistic germicidal system for chronic wound disinfection.[113]
    ZIF8/Au-GOx NPsCDT + Zn2+E. coli, S. aureus[114]
    NH2-MIL-88B(Fe)-AgCDT + Ag+E. coli, S. aureus[112]
    Fe3O4@MoS2-AgCDT + Ag+E. coli[82]
    Cascaded reactionsThe cascaded nanozymes are generally composed of POD-like nanozymes and GOx, which can be easily loaded on nanomaterials by the electrostatic interaction.APGHGlucose oxidation + POD catalysisS. aureusOwing to cascaded reactions, the nanozymes can act even at neutral conditions without H2O2 addition Since GOx catalyze the conversion of glucose into gluconic acid and H2O2.[90]
    Fe3O4-GOxGlucose oxidation + POD catalysisE. coli, MRSA[116]
    GOX-on-Fe-iCOFGlucose oxidation + POD catalysisE. coli, S. aureus[117]
    Fe2(MoO4)3@GOxGlucose oxidation + POD catalysisE. coli, MRSA[118]
    Pro-inflammatoryCuFe5O8 nanocubes can be synthesized by the solvent-thermal method.CuFe5O8 nanocubesCDT + Pro-inflammatoryE. coli, S. aureus, BiofilmCuFe5O8 nanocubes exhibit space-selective CDT and induce pro-inflammatory macrophage polarization for curing implant-related infection due to the different pH and H2O2 concentration inside and outside the biofilm.[119]
    HydrogelHydrogel can provide a versatile and porous framework of loading different kinds of nanomaterials for constructing a multifunctional platform for antibacterial therapy.MoS2-hydrogelPOD-like catalysis + bacterial captureE. coliOwing to the multiple functions of the hydrogel, the antibacterial therapeutic effect and wound healing efficacy can be significantly enhanced.[70]
    MoS2@TA/Fe-PVA/Dex hydrogelsPOD/CAT like catalysis + PTT + tannic acid anti-inflammatoryE. coli, S. aureus[122]
    Tannic acid chelated-Ag hydrogelPOD-like catalysis + Ag + tannic acid anti-inflammatoryStaphylococcus epidermidis, E. coli.[124]
    CNT@MoS2 hydrogelsPOD/SOD/CAT-like catalysis + PTTE. coli, S. aureus[125]
    Nanozymes without enhancementsHRPPOD-like activity11.632.758[66]
    Fe3O4 NPsPOD-like activity150.50.292[63]
    Nano-CeO2OXD-like activity0.420 (TMB)0.100 (TMB)[130]
    NM-88POD-like activity0.91321.3[58]
    MSN-AuNPsPOD-like activity15.8117.30[78]
    Pt-PCNPOD-like activity7.3620.252[131]
    MoS2POD-like activity60.87[43]
    CuSPOD-like activity264.112.6[84]
    CoSPOD-like activity114.55.9[84]
    Pd cubesPOD-like activity0.076.5[85]
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  • 收稿日期:  2022-04-18
  • 录用日期:  2022-05-16
  • 修回日期:  2022-05-12
  • 刊出日期:  2022-06-28

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