Graphical Abstract
![](https://wqketang.oss-cn-beijing.aliyuncs.com/zip-unzip/zip-0042eed3-37c6-4e1f-a9e8-3c6b0191805c/nr-15-2-1446/files/nr-15-2-1446-FE1.jpg?Expires=1725756170&OSSAccessKeyId=STS.NSssK71aLjDMY9SbRgGRGskMT&Signature=NUJY5BckZWIH9Vz0epxxKG8Y8Z0%3D&security-token=CAISywJ1q6Ft5B2yfSjIr5DGOPGD3L5t3YamWx%2FihlIyS91rnK7mtjz2IHtKenhsBOsbtfk1mG5W5%2FgZlqJ9SptIAEfJa9d99Myjb%2F9FltCT1fau5Jko1beHewHKeTOZsebWZ%2BLmNqC%2FHt6md1HDkAJq3LL%2Bbk%2FMdle5MJqP%2B%2FUFB5ZtKWveVzddA8pMLQZPsdITMWCrVcygKRn3mGHdfiEK00he8TouufTinpHMskGA1Aell7Mvyt6vcsT%2BXa5FJ4xiVtq55utye5fa3TRYgxowr%2Fwo0v0YpGya5YzHXwcPskvdKZbo78UqLQlla6w%2BGqFJqvPxr%2Fp8t%2Fx5fWJKAezhVgs8cVM8JOjIqKOscIsixo262SmqFV55c8Fdm%2BgUooJVgIMhTnduUfAPJAGOxzJitP%2BUVGGphr60TEnBL4rB5MUctfzRpwT64j3UTzDnGoABhFRSspTLrn9GrEN9pQYzC6eepGdfWDQh3fr5hA1VnwVUJMCz%2BNQEDWKceF%2FnEjWVMtfbvqYxuyhSCmIMMyh5bEREEKEiD%2BFVv4ZfsqnV7hQy5w6HhIkN8kZzP6L0zPvPgkBLOtdMDeDxhf8dVPrCSG4etXHjxcwUaRVb3ZR7Yu8gAA%3D%3D)
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The abuse of conventional antibiotics leads to increasing bacterial resistance. Nanozyme is a new kind of ultra-efficient and safe nanomaterial with intrinsic enzyme-like activities, showing remarkable potential as a next generation nanobactericide. Graphdiyne (GDY) is a burgeoning two-dimensional (2D) carbon allotrope with intriguing physicochemical properties, holding a great promise as a metal-free nanozyme. In this study, a boron doped GDY nanosheet (B-GDY) was constructed to simulate the performance of peroxidase (POD). By promoting the decomposition of H2O2 to produce reactive oxygen species (ROS), the bactericidal efficacies against both Gram-positive and Gram-negative bacteria were substantially enhanced attributed to the extremely high catalytic activity of B-GDY. In-depth density functional theory (DFT) calculations illuminate that doping of boron can introduce more active B-defect sites as well as lower Gibbs free energy during the H2O2 decomposition reaction. Notably, B-GDY contributes to significant wound healing and excellent biocompatibility, reducing the biological burden. The design of this nanozyme opens a new avenue for the development of alternative antibiotics.
Reverter, M.; Sarter, S.; Caruso, D.; Avarre, J. C.; Combe, M.; Pepey, E.; Pouyaud, L.; Vega–Heredía, S.; de Verdal, H.; Gozlan, R. E. Aquaculture at the crossroads of global warming and antimicrobial resistance. Nat. Commun. 2020, 11, 1870.
Lakemeyer, M.; Zhao, W. N.; Mandl, F. A.; Hammann, P.; Sieber, S. A. Thinking outside the box—novel antibacterials to tackle the resistance crisis. Angew. Chem., Int. Ed. 2018, 57, 14440–14475.
Van Boeckel, T. P.; Gandra, S.; Ashok, A.; Caudron, Q.; Grenfell, B. T.; Levin, S. A.; Laxminarayan, R. Global antibiotic consumption 2000 to 2010: An analysis of national pharmaceutical sales data. Lancet Infect. Dis. 2014, 14, 742–750.
Willyard, C. Drug–resistant bacteria ranked: World Health Organization hopes list will drive development of much-needed antibiotics. Nature 2017, 543, 15.
Ding, X. K.; Duan, S.; Ding, X. J.; Liu, R. H.; Xu, F. J. Versatile antibacterial materials: An emerging arsenal for combatting bacterial pathogens. Adv. Funct. Mater. 2018, 28, 1802140.
Gupta, A.; Mumtaz, S.; Li, C. H.; Hussain, I.; Rotello, V. M. Combatting antibiotic-resistant bacteria using nanomaterials. Chem. Soc. Rev. 2019, 48, 415–427.
Wang, Y.; Yang, Y. N.; Shi, Y. R.; Song, H.; Yu, C. Z. Antibiotic– free antibacterial strategies enabled by nanomaterials: Progress and perspectives. Adv. Mater. 2020, 32, 1904106.
Kotov, N. A. Inorganic nanoparticles as protein mimics. Science 2010, 330, 188–189.
Wei, H.; Wang, E. Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes. Chem. Soc. Rev. 2013, 42, 6060–6093.
Lin, Y. H.; Ren, J. S.; Qu, X. G. Catalytically active nanomaterials: A promising candidate for artificial enzymes. Acc. Chem. Res. 2014, 47, 1097–1105.
Wu, J. J. X.; Wang, X. Y.; Wang, Q.; Lou, Z. P.; Li, S. R.; Zhu, Y. Y.; Qin, L.; Wei, H. Nanomaterials with enzyme-like characteristics (nanozymes): Next-generation artificial enzymes (Ⅱ). Chem. Soc. Rev. 2019, 48, 1004–1076.
Wang, H.; Wan, K. W.; Shi, X. H. Recent advances in nanozyme research. Adv. Mater. 2019, 31, 1805368.
Gao, L. Z.; Fan, K. L.; Yan, X. Y. Iron oxide nanozyme: A multifunctional enzyme mimetic for biomedical applications. Theranostics 2017, 7, 3207–3227.
Ye, H. H.; Xi, Z.; Magloire, K.; Xia, X. H. Noble–metal nanostructures as highly efficient peroxidase mimics. Chem. Nano. Mat. 2019, 5, 860–868.
Sun, H. J.; Zhou, Y.; Ren, J. S.; Qu, X. G. Carbon nanozymes: Enzymatic properties, catalytic mechanism, and applications. Angew. Chem., Int. Ed. 2018, 57, 9224–9237.
Jiang, D. W.; Ni, D. L.; Rosenkrans, Z. T.; Huang, P.; Yan, X. Y.; Cai, W. B. Nanozyme: New horizons for responsive biomedical applications. Chem. Soc. Rev. 2019, 48, 3683–3704.
Huang, Y. Y.; Ren, J. S.; Qu, X. G. Nanozymes: Classification, catalytic mechanisms, activity regulation, and applications. Chem. Rev. 2019, 119, 4357–4412.
Zhang, X. L.; Li, G. L.; Chen, G.; Wu, D.; Zhou, X. X.; Wu, Y. N. Single-atom nanozymes: A rising star for biosensing and biomedicine. Coord. Chem. Rev. 2020, 418, 213376.
Xu, B. L.; Wang, H.; Wang, W. W.; Gao, L. Z.; Li, S. S.; Pan, X. T.; Wang, H. Y.; Yang, H. L.; Meng, X. Q.; Wu, Q. W. et al. A single- atom nanozyme for wound disinfection applications. Angew. Chem., Int. Ed. 2019, 58, 4911–4916.
Xi, J. Q.; Wei, G.; An, L. F.; Xu, Z. B.; Xu, Z. L.; Fan, L.; Gao, L. Z. Copper/carbon hybrid nanozyme: Tuning catalytic activity by the copper state for antibacterial therapy. Nano Lett. 2019, 19, 7645– 7654.
Shan, J. Y.; Li, X.; Yang, K. L.; Xiu, W. J.; Wen, Q. R.; Zhang, Y. Q.; Yuwen, L. H.; Weng, L. X.; Teng, Z. G.; Wang, L. H. Efficient bacteria killing by Cu2WS4 nanocrystals with enzyme-like properties and bacteria–binding ability. ACS Nano 2019, 13, 13797–13808.
Xiao, S. J.; Wang, L. Z.; Yuan, M. Y.; Huang, X. H.; Ding, J. H.; Zhang, L. Peroxidase-mimetic and fenton-like activities of molybdenum oxide quantum dots. ChemistrySelect 2020, 5, 10149–10155.
Wang, W. S.; Li, B. L.; Yang, H. L.; Lin, Z. F.; Chen, L. L.; Li, Z.; Ge, J. Y.; Zhang, T.; Xia, H.; Li, L. H. et al. Efficient elimination of multidrug-resistant bacteria using copper sulfide nanozymes anchored to graphene oxide nanosheets. Nano Res. 2020, 13, 2156– 2164.
Shan, J. Y.; Yang, K. L.; Xiu, W. J.; Qiu, Q.; Dai, S. L.; Yuwen, L. H.; Weng, L. X.; Teng, Z. G.; Wang, L. H. Cu2MoS4 nanozyme with NIR–Ⅱ light enhanced catalytic activity for efficient eradication of multidrug-resistant bacteria. Small 2020, 16, 2001099.
Wang, L. W.; Gao, F. N.; Wang, A. Z.; Chen, X. Y.; Li, H.; Zhang, X.; Zheng, H.; Ji, R.; Li, B.; Yu, X. et al. Defect-rich adhesive molybdenum disulfide/rGO vertical heterostructures with enhanced nanozyme activity for smart bacterial killing application. Adv. Mater. 2020, 32, 2005423.
Ma, L.; Jiang, F. B.; Fan, X.; Wang, L. Y.; He, C.; Zhou, M.; Li, S.; Luo, H. R.; Cheng, C.; Qiu, L. Metal–organic-framework-engineered enzyme-mimetic catalysts. Adv. Mater. 2020, 32, 2003065.
Zhang, Y.; Li, D. X.; Tan, J. S.; Chang, Z. S.; Liu, X. Y.; Ma, W. S.; Xu, Y. H. Near-infrared regulated nanozymatic/photothermal/ photodynamic triple-therapy for combating multidrug-resistant bacterial infections via oxygen-vacancy molybdenum trioxide nanodots. Small, 2021, 17, 2005739.
Wang, T.; Bai, Q.; Zhu, Z. L.; Xiao, H. L.; Jiang, F. Y.; Du, F. L.; Yu, W. W.; Liu, M. H.; Sui, N. Graphdiyne-supported palladium-iron nanosheets: A dual-functional peroxidase mimetic nanozyme for glutathione detection and antibacterial application. Chem. Eng. J. 2021, 413, 127537.
Okazoe, S.; Yasaka, Y.; Kudo, M.; Maeno, H.; Murakami, Y.; Kimura, Y. Synthesis of zero-valent iron nanoparticles via laser ablation in a formate ionic liquid under atmospheric conditions. Chem. Commun. 2018, 54, 7834–7837.
Nugraha, A. D.; Wulandari, I. O.; Rahayu, L. B. H.; Riva'i, I.; Santojo, D. J. D. H.; Sabarudin, A. One-pot synthesis and surface modification of Fe3O4 nanoparticles using polyvinyl alcohol by coprecipitation and ultrasonication methods. IOP Conf. Ser.: Mater. Sci. Eng. 2018, 299, 012066.
Arami, H.; Khandhar, A.; Liggitt, D.; Krishnan, K. M. In vivo delivery, pharmacokinetics, biodistribution and toxicity of iron oxide nanoparticles. Chem. Soc. Rev. 2015, 44, 8576–8607.
Zhao, F.; Zhao, Y.; Liu, Y.; Chang, X. L.; Chen, C. Y.; Zhao, Y. L. Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials. Small 2011, 7, 1322–1337.
Li, G. X.; Li, Y. L.; Liu, H. B.; Guo, Y. B.; Li, Y. J.; Zhu, D. B. Architecture of graphdiyne nanoscale films. Chem. Commun. 2010, 46, 3256–3258.
Li, Y. J.; Xu, L.; Liu, H. H.; Li, Y. L. Graphdiyne and graphyne: From theoretical predictions to practical construction. Chem. Soc. Rev. 2014, 43, 2572–2586.
Huang, C. S.; Li, Y. J.; Wang, N.; Xue, Y. R.; Zuo, Z. C.; Liu, H. B.; Li, Y. L. Progress in research into 2D graphdiyne-based materials. Chem. Rev. 2018, 118, 7744–7803.
Jia, Z.; Li, Y.; Zuo, Z.; Liu, H.; Huang, C.; Li, Y. Synthesis and properties of 2D carbon-graphdiyne. Acc. Chem. Res. 2017, 50, 2470–2478.
Gao, X.; Liu, H. B.; Wang, D.; Zhang, J. Graphdiyne: Synthesis, properties, and applications. Chem. Soc. Rev. 2019, 48, 908–936.
Yu, H. D.; Xue, Y. R.; Li, Y. L. Graphdiyne and its assembly architectures: Synthesis, functionalization, and applications. Adv. Mater. 2019, 31, 1803101.
Long, M. Q.; Tang, L.; Wang, D.; Li, Y. L.; Shuai, Z. G. Electronic structure and carrier mobility in graphdiyne sheet and nanoribbons: Theoretical predictions. ACS Nano 2011, 5, 2593–2600.
Zhang, S. S.; Cai, Y. J.; He, H. Y.; Zhang, Y. Q.; Liu, R. J.; Cao, H. B.; Wang, M.; Liu, J. J.; Zhang, G. J.; Li, Y. L. et al. Heteroatom doped graphdiyne as efficient metal-free electrocatalyst for oxygen reduction reaction in alkaline medium. J. Mater. Chem. A 2016, 4, 4738–4744.
Lv, Q.; Si, W. Y.; Yang, Z.; Wang, N.; Tu, Z. Y.; Yi, Y. P.; Huang, C. S.; Jiang, L.; Zhang, M. J.; He, J. J. et al. Nitrogen-doped porous graphdiyne: A highly efficient metal-free electrocatalyst for oxygen reduction reaction. ACS Appl. Mater. Interfaces 2017, 9, 29744– 29752.
Wang, N.; Li, X. D.; Tu, Z. Y.; Zhao, F. H.; He, J. J.; Guan, Z. Y.; Huang, C. S.; Yi, Y. P.; Li, Y. L. Synthesis and electronic structure of boron-graphdiyne with an sp-hybridized carbon skeleton and its application in sodium storage. Angew. Chem., Int. Ed. 2018, 57, 3968–3973.
Yu, H. D.; Xue, Y. R.; Hui, L.; Zhang, C.; Zhao, Y. J.; Li, Z. B.; Li, Y. L. Controlled growth of MoS2 nanosheets on 2D N-doped graphdiyne nanolayers for highly associated effects on water reduction. Adv. Funct. Mater. 2018, 28, 1707564.
Zhao, Y. S.; Wan, J. W.; Yao, H. Y.; Zhang, L. J.; Lin, K. F.; Wang, L.; Yang, N. L.; Liu, D. B.; Song, L.; Zhu, J. et al. Few-layer graphdiyne doped with sp-hybridized nitrogen atoms at acetylenic sites for oxygen reduction electrocatalysis. Nat. Chem. 2018, 10, 924–931.
Gu, J. X.; Magagula, S.; Zhao, J. X.; Chen, Z. F. Boosting ORR/OER activity of graphdiyne by simple heteroatom doping. Small Methods 2019, 3, 1800550.
Zhao, J.; Chen, Z.; Zhao, J. X. Metal-free graphdiyne doped with sp-hybridized boron and nitrogen atoms at acetylenic sites for high-efficiency electroreduction of CO2 to CH4 and C2H4. J. Mater. Chem. A 2019, 7, 4026–4035.
Chen, X. Z.; Ong, W. J.; Kong, Z. Z.; Zhao, X. J.; Li, N. Probing the active sites of site-specific nitrogen doping in metal-free graphdiyne for electrochemical oxygen reduction reactions. Sci. Bull. 2020, 65, 45–54.
Liu, J. M.; Chen, C. Y.; Zhao, Y. L. Progress and prospects of graphdiyne-based materials in biomedical applications. Adv. Mater. 2019, 31, 1804386.
Jiang, B.; Duan, D. M.; Gao, L. Z.; Zhou, M. J.; Fan, K. L.; Tang, Y.; Xi, J. Q.; Bi, Y. H.; Tong, Z.; Gao, G. F. et al. Standardized assays for determining the catalytic activity and kinetics of peroxidase-like nanozymes. Nat. Protoc. 2018, 13, 1506–1520.
Gao, L. Z.; Zhuang, J.; Nie, L.; Zhang, J. B.; Zhang, Y.; Gu, N.; Wang, T. H.; Feng, J.; Yang, D. L.; Perrett, S. et al. Intrinsic peroxidase-like activity of ferromagnetic nanoparticles. Nat. Nanotechnol. 2007, 2, 577–583.
Cleland, W. W. Derivation of rate equations for multisite Ping-Pong mechanisms with Ping-Pong reactions at one or more sites. J. Biol. Chem. 1973, 248, 8353–8355.
Berglund, G. I.; Carlsson, G. H.; Smith, A. T.; Szöke, H.; Henriksen, A.; Hajdu, J. The catalytic pathway of horseradish peroxidase at high resolution. Nature 2002, 417, 463–468.
Li, J. N.; Liu, W. Q.; Wu, X. C.; Gao, X. F. Mechanism of pH– switchable peroxidase and catalase-like activities of gold, silver, platinum and palladium. Biomaterials 2015, 48, 37–44.
Kim, M. S.; Cho, S.; Joo, S. H.; Lee, J.; Kwak, S. K.; Kim, M. I.; Lee, J. N- and B-codoped graphene: A strong candidate to replace natural peroxidase in sensitive and selective bioassays. ACS Nano 2019, 13, 4312–4321.
Wang, X. W.; Fan, L. X.; Cheng, L.; Sun, Y. B.; Wang, X. Y.; Zhong, X. Y.; Shi, Q. Q.; Gong, F.; Yang, Y.; Ma, Y. et al. Biodegradable nickel disulfide nanozymes with GSH-depleting function for high-efficiency photothermal-catalytic antibacterial therapy. iScience 2020, 23, 101281.
Wu, B. B.; Li, Y.; Su, K.; Tan, L.; Liu, X. M.; Cui, Z. D.; Yang, X. J.; Liang, Y. Q.; Li, Z. Y.; Zhu, S. L. et al. The enhanced photocatalytic properties of MnO2/g-C3N4 heterostructure for rapid sterilization under visible light. J. Hazard. Mater. 2019, 377, 227–236.
Winterbourn, C. C. Reconciling the chemistry and biology of reactive oxygen species. Nat. Chem. Biol. 2008, 4, 278–286.
Steinberg, B. E.; Grinstein, S. Unconventional roles of the NADPH oxidase: Signaling, ion homeostasis, and cell death. Science's STKE 2007, 2007, pe11.
Tu, Y. S.; Lv, M.; Xiu, P.; Huynh, T.; Zhang, M.; Castelli, M.; Liu, Z. R.; Huang, Q.; Fan, C. H.; Fang, H. P. et al. Destructive extraction of phospholipids from Escherichia coli membranes by graphene nanosheets. Nat. Nanotechnol. 2013, 8, 594–601.
Zhu, Z. L.; Bai, Q.; Li, S.; Li, S. H.; Liu, M. H.; Du, F. L.; Sui, N.; Yu, W. W. Antibacterial activity of graphdiyne and graphdiyne oxide. Small 2020, 16, 2001440.