纳米酶: 对抗细菌的新策略

doi:10.15541/jim20200273

摘要/Abstract

摘要：

由细菌引发的相关疾病和环境污染等问题引起了人们的高度重视, 同时随着抗生素的使用, 细菌的耐药性逐渐增强, 人们急需开发新型抗菌剂。诸如溶菌酶、髓过氧化物酶等天然酶具有显著的抗菌能力, 但其作为抗菌剂存在保质期短、生产成本高等缺点, 很难大规模生产。因此, 人们正探索寻求天然酶的替代品。纳米酶是新一代人工模拟酶, 兼具纳米材料独特的理化性质和类酶催化活性, 因其结构稳定、生产成本低等优点受到广泛关注。本文综述了纳米酶的抗菌机制和近期抗菌纳米酶的主要研究进展, 并对未来该领域的研究进行展望。

关键词: 纳米酶, 过氧化物酶, 氧化物酶, 卤代过氧化物酶, 脱氧核糖核酸酶, 抗菌, 综述

Abstract:

Bacteria-related diseases, environmental pollution and other issues have attracted enough attention. Meanwhile, with the use of antibiotics, bacteria evolved strong drug resistance forcing people to develop new antibacterial agents urgently. Natural enzymes such as lysozyme and myeloperoxidase have significant antibacterial ability. However, natural enzymes own limitations such as short shelf life and high production costs. Besides, they are difficult in applying to large-scale production. Therefore, people are seeking alternatives to natural enzymes. Nanozymes are a new generation of artificial enzymes which have unique physical and chemical properties of nanomaterials and enzyme-like catalytic activity. Because of structural stability and low production cost, they are widely explored. This article reviews the antimicrobial mechanism and the recent progress of nanozymes in antibacterial research, and, finally, gives some prospects for future research.

Key words: nanozyme, peroxidase, oxidase, haloperoxidase, deoxyribonuclease, antibacterial, review

中图分类号:

Q811

傅佳骏, 沈涛, 吴佳, 王成. 纳米酶: 对抗细菌的新策略[J]. 无机材料学报, 2021, 36(3): 257-268.

FU Jiajun, SHEN Tao, WU Jia, WANG Chen. Nanozyme: a New Strategy Combating Bacterial[J]. Journal of Inorganic Materials, 2021, 36(3): 257-268.

图/表 10

图1 含有类卤代过氧化物酶活性的防污装置中活性物质的工作机理[29]

Fig. 1 Principle of active substances incorporated in an antifouling device with haloperoxidase-like activity[29]

图2 信号分子对海洋细菌QS系统的调节机制[29]

Fig. 2 Regulation mechanism of signaling molecules on marine bacterial QS system[29] AHL: Acylated homoserine lactones

图3 (a)eDNA作为桥梁及(b)由DNase破坏EPS中eDNA成分[41]

Fig. 3 (a) eDNA acting as a bridge, and (b) disruption of EPS by DNase attacking the eDNA component of the EPS[41]

图4 (a, b)MSN-AuNPs在不同放大倍数下的TEM照片; 不同(c)pH和(d)温度条件下MSN-AuNPs的酶活性; 不同条件处理的(e)大肠杆菌和(f)金黄色葡萄球菌的生长密度[43]

Fig. 4 (a,b)TEM images of the MSN-AuNPs under different magnifications, enzyme activity of MSN-AuNPs under different (c) pH and (d) temperature conditions, and growth densities of (e) E. coli and (f) S. aureus under different conditions[43]

图5 (a)ZIF-8结构框架和(b)碳纳米球PMCS结构模型, (c)ZIF-8和(d)PMCS的TEM照片, (e)对照和PMCS处理的铜绿假单胞菌存活分析和(f)拟定的PMCS催化机理图[46]

Fig. 5 (a) ZIF-8 structural framework and (b) PMCS structural model, TEM images of (c) ZIF-8 and (d) PMCS, (e) apoptosis analysis of P. aeruginosa treated with PMCS, and (f) proposed catalytic mechanism of PMCS[46]

图6 (a)Cit-MoS2的合成路线; (b)光调节Cit-MoS2酶活性以实现革兰氏选择性抗菌性能; 不同(c) pH和(d)光照时间下细菌的存活率[49]

Fig. 6 (a) Synthesis route of Cit-MoS2, and (b) illustration of light regulating Cit-MoS2 enzyme activity to achieve Gram-selective antibacterial potential, and bacterial viabilities under different (c) pH and (d) irradiation time[49]

图7 (a)抗菌平台的制备及其(b)抗菌示意图, 不同浓度抗坏血酸处理的(c)金黄色葡萄球菌和(d)大肠杆菌的存活率[52]

Fig. 7 (a) Preparation of the antibacterial platform, and its (b) schematic diagram of antibacterial, and survival rates of (c) S. aureus and (d) E. coli treated with different concentrations of ascorbic acid[52]

图8 (a)DMAE的制备; 组装在核/壳颗粒表面的金纳米颗粒的(b)SEM、(c)TEM和(d, e)放大的TEM照片; (f)生物膜生长情况和(g)形成生物膜的平均厚度[64]

Fig. 8 (a) Preparation of DMAE and its (b) TEM and (c) SEM images, as well as magnified (d, e) TEM images of Au NPs confined on the surface of core/shell particles, and (f) growth of biofilms and (g) average thickness of the biofilms[64]

图9 CeO2-x纳米棒的(a)TEM和(b)HRTEM照片, (c)海洋挂板实验, (d)拟定的CeO2-x纳米棒催化溴化机理[72]

Fig. 9 (a) TEM and (b) HRTEM images of CeO2-x NPs, (c) ocean hanging board experiment, and (d) proposed catalytic bromination mechanism of the CeO2-x NPs[72]

图10 (a)纳米纤维垫的制备及防污示意图, (b)未填充和(c)填充CeO2-x纳米棒的PVA垫抑菌SEM照片, (d)22wt%填充PVA垫的细菌附着对比[73]

Fig. 10 (a) Schematic diagram of preparation and anti-fouling of nanofibrous, SEM images of PVA (b) without and (c) with CeO2-x NRs after incubation, and (d) comparison of bacterial adhesion between 22wt% filled and unfilled PVA nanofibrous[73]

参考文献 74

[1]	RIZZELLO L, POMPA P P. Nanosilver-based antibacterial drugs and devices: mechanisms, methodological drawbacks, and guidelines. Chemical Society Reviews, 2014,43(5):1501-1518. DOI URL PMID
[2]	WANG LI-SHENG, GUPTA A, ROTELLO V M. Nanomaterials for the treatment of bacterial biofilms. ACS Infections Dieases, 2015,2(1):3-4.
[3]	YANG LIANG, LIU YANG, WU HONG. Combating biofilms. Fems Immunology & Medical Microbiology, 2012,65(2):146-157. DOI URL PMID
[4]	SIMOES MANUEL. Antimicrobial strategies effective against infectious bacterial biofilms. Current Medicinal Chemistry, 2011,18(14):2129-2145. DOI URL PMID
[5]	GAO LI-ZENG, ZHUANG JIE, LENG NIE, et al. Intrinsic peroxidase-like activity of ferromagnetic nanoparticles. Nature Nanotechnology, 2007,2(9):577-583. URL PMID
[6]	YAN XI-YUN. Nanozyme: a new type of artificial enzyme. Progress in Biochemistry and Biophysics, 2018,45(2):101-104.
[7]	WEI HUI, WANG ERKANG. Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes. Chemical Society Reviews, 2013,42(14):6060-6093. DOI URL PMID
[8]	TANG YAN, QIU ZHI YUE, XU ZHUO BING. Antibacterial mechanism and applications of nanozymes. Progress in Biochemistry and Biophysics, 2018,45(2):118-128.
[9]	JIANG DA-WEI, NI DA-LONG, ROSENKRANS Z T. Nanozyme: new horizons for responsive biomedical applications. Chemical Society Reviews, 2019,48(14):3683-3704. DOI URL PMID
[10]	LIANG MIN-MIN, YAN XI-YUN. Nanozyme: from new concepts, mechanisms, and standards to applications. Accounts of Chemical Research, 2019,52(8):2190-2200. DOI URL PMID
[11]	LAURENTS D V, BALDWIN R L. Characterization of the unfolding pathway of hen egg with white lysozyme. Biochemistry, 1997,36(6):1496-1504. DOI URL PMID
[12]	FATMA V, DE M W C M A, PINAR A, et al. Antimicrobial strategies centered around reactive oxygen species-bactericidal antibiotics, photodynamic therapy, and beyond. FEMS Microbiology Reviews, 2013,37(6):955-989. DOI URL PMID
[13]	HOU YA-XIN, ZHANG RUO-FEI, YAN XI-YUN, et al. Nanozymes: a new choice for disease treatment. Science Sinica(Vitae), 2020,50(3):311-328.
[14]	NELSON D, ROSA M A, ALESSANDRO D, et al. Applications of laccases and tyrosinases (phenoloxidases) immobilized on different supports: a review. Enzyme & Microbial Technology, 2002,31(7):907-931.
[15]	ZUO PENG, YU SHAO-MING, YANG JIE-RU, et al. Research progress in support material for immobilization of horseradish peroxidase. Materials Review, 2007,21(11):46-49.
[16]	VEITHC N C. Horseradish peroxidase: a modern view of a classic enzyme. Phytochemistry (Amsterdam), 2004,65(3):249-259.
[17]	WU JIANG-JIEXING, WANG XIAO-YU, WANG QUAN, et al. Nanomaterials with enzyme-like characteristics (nanozymes): next- generation artificial enzymes (Ⅱ). Chemical Society Reviews, 2019,48(4):1004-1076. URL PMID
[18]	JIANG BING, FANG LONG, WU KONG-MING, et al. Ferritins as natural and artificial nanozymes for theranostic. Theranostics, 2019,10(2):687-706. DOI URL PMID
[19]	CHEN ZHAO-WEI, WANG ZHEN-ZHEN, REN JINSONG, et al. Enzyme mimicry for combating bacterial and biofilms. Accounts of Chemical Research, 2018,51(3):789-799. DOI URL PMID
[20]	MURRAY P J, WYNN T A. Protective and pathogenic functions of macrophage subsets. Nature Reviews Immunology, 2011,11(11):723-737. DOI URL PMID
[21]	LOO A E K, WANG Y T, HO R J, et al. Effects of hydrogen peroxide on wound healing in mice in relation to oxidative damage. PLOS One, 2012,7(11):49215.
[22]	RAGG R, TAHIR M N, TREMEL W. Solids go bio: inorganic nanoparticles as enzyme mimics. European Journal of Inorganic Chemistry, 2016(13/14):1906-1915.
[23]	ASATI ATUL SANTRA, SANTIMUKUL KAITTANIS, CHARALAMBOS NATH, et al. Oxidase-like activity of polymer- coated cerium oxide nanoparticles. Angewandte Chemie International Edition, 2009,48(13):2308-2312. URL PMID
[24]	ASATI A, KAITTANIS C, SANTRA S, et al. pH-tunable oxidase- like activity of cerium oxide nanoparticles achieving sensitive fluorigenic detection of cancer biomarkers at neutral pH. Analytical Chemistry, 2011,83(7):2547-2553. DOI URL PMID
[25]	FATMA V, DE M W C M A, PINAR A, et al. Antimicrobial strategies centered around reactive oxygen species-bactericidal antibiotics, photodynamic therapy, and beyond. FEMS Microbiology Reviews, 2013,6(6):955-989.
[26]	HOFLER G T, BUT A, HOLLMANN. , Haloperoxidase as catalysts in organic synthesis. Orgainc & Biomolecular Chemistry, 2019,17(42):9267-9274.
[27]	SHAW P D, HAGER L P. Choroperoxidase: a component of the β-ketoadipate chlorinase system. Journal of Biological Chemistry, 1961,236(6):1626-1630.
[28]	TIMMINS A, VISSER S P D. Enzymatic halogenases and haloperoxidases: computantional studies on mechanism and function. Advances in Protein Chemistry & Structural Biology, 2015,100:113-151. DOI URL PMID
[29]	KAROLINE H, HAJO F, FELIX P, et al. Functional enzyme mimics for oxidative halogenation reactions that combat biofilm formation. Advanced Materials, 2018,30(36):1701703.
[30]	THOMAS E L. Myeloperoxidase-hydrogen peroxide-chloride antimicrobial system: effect of exogenous amines on antibacterial action against Escherichia Coli. Infection & Immunity, 1979,25(1):110-116. DOI URL PMID
[31]	REIS P A, MARTINS M L, ARAUJO E F, et al. AiiA quorum- sensing quenching controls proteolytic activity and biofilm formation by enterobacter cloacae. Current Microbiology, 2012,65(6):758-763. DOI URL PMID
[32]	ZHANG JING-JING, FENG TAO, WANG JIA-YI, et al. The mechanisms and applications of quorum sensing (QS) and quorum quenching (QQ). Journal of Ocean University of China, 2019,18(6):1427-1442.
[33]	BEZEK K, KURINI M, KNAUDER E, et al. Attenuation of adhesion, biofilm formation and quorum sensing of campylobacter jejuni by euodia ruticarpa. Phytotherapy, 2016,30(9):1527-1532.
[34]	TAUNK A, CHEN R, ISKANDER G, et al. Dual-action biomaterial surfaces with quorum sensing inhibitor and nitric oxide to reduce bacterial colonization. ACS Biomaterials Science & Engineering, 2018,4(12):4174-4182. URL PMID
[35]	CORDONNIER C, BERNARDI G. A comparative study of acid deoxyribonucleases extracted from different tissues and species. Canadian Journal of Biochemistry, 1968,46(8):989-995. DOI URL PMID
[36]	MEHTA H J, BISWAS A, PENLEY A M, et al. Management of intrapleural sepsis with once daily use of tissue plasminogen activator and deoxyribonuclease. Respiration, 2016,91(2):101-106. DOI URL PMID
[37]	GRUBER B, KATAEV E, ASCHENBRENNER J, et al. Vesicles and micelles from amphilic zinc(Ⅱ)-cyclen complexes as highly potent promoters of hydrolytic DNA cleavage. Journal of American Chemical Society, 2011,133(5):20704-20707.
[38]	BRANUM M E, TIPTON A K, ZHU SHOU-RONG, et al. Double-strand hydrolysis of plasmid DNA by dicerium complexes at 37 ℃. Journal of American Chemical Society, 2001,123(9):1898-1904.
[39]	FABRIZIO M, LEONARD P, PAOLO P, et al. Hydrolytic metallo- nanozymes: from micelles and vesicles to gold nanoparticles. Molecules, 2016,21(8):1014.
[40]	JENNINGS L K, STOREK K M, LEDVINA H E, et al. Pel is a cationic exopolysaccharide that cross-link extracellular DNA in the pseudomonas aeruginosa biofilm matrix. Proceeding of the National Academy of Science, 2015,112(36):11353-11358.
[41]	SWARTIES J, DAS T, SHARIFI S, et al. A functional DNase I coating to prevent adhesion of bacteria and the formation of biofilm. Advanced Functional Materials, 2013,23(22):2843-2849.
[42]	HU WEN-CHAO, YOUNIS M R, ZHOU YUE, et al. In situ fabrication of ultrasmall gold nanoparticles/2D MOFs hybrid as nanozyme for antibacterial therapy. Small, 2020,16(23):200553.
[43]	XI JU-QUN, WEO GEN, AN LAN-FANG, et al. Copper/carbon hybrid nanozyme: tuning catalytic activity by the copper state for antibacterial therapy. Nano Letter, 2019,19(11):7645-7654.
[44]	TAO YU, JU EN-GUO, REN JIN-SONG, et al. Bifunctionalized mesoporous silicasupported gold nanoparticles: intrinsic oxidase and peroxidase catalytic activities for antibacterial applications. Advanced Materials, 2015,27(6):1097-1104. DOI URL PMID
[45]	SHAN JING-YANG, LI XIAO, YANG KAI-LI, et al. Efficient bacteria killing by Cu₂WS₄ nanocrystals with enzyme-like properties and bacteria-binding ability. ACS Nano, 2019,13(12):13797-13808. DOI URL PMID
[46]	XU BO-LONG, WANG HUI, WANG WEI-WEI, et al. A single-atom nanozyme for wound disinfection applications. Angewandte Chemie International Edition, 2019,58(15):4911-4916. URL PMID
[47]	HUANG LIANG, CHEN JIN-XING, GAN LIN-FENG, et al. Single-atom nanozymes. Science Advances, 2019, 5(5): eaav5490. DOI URL PMID
[48]	FANG GE, LI WEI-FENG, SHEN XIAO-MEI, et al. Differential Pd-nanocrystal facets demonstrate distinct antibacterial activity against gram-positive and gram-negative bacteria. Nature Communications, 2018,9:129. DOI URL PMID
[49]	NIU JING-SHENG, SUN YU-HUAN, WANG FA-MING, et al. Photomodulated nanozyme used for a Gram-selective antimicrobial. Chemistry of Materials, 2018,30(20):7027-7033.
[50]	NATAN M, EDIN F, PERKAS N, et al. Two are better than one: combating ZnO and MgF₂ nanoparticles reduces streptococcus penumoniae and staphylococcus aures biofilm formation on cochlear implants. Advanced Functional Materials, 2016,26(15):2473-2481.
[51]	YIN WEN-YAN, YU JIE, LV FENG-TING, et al. Functionalized nano-MoS₂ with peroxidase catalytic and near-infrared photothermal activities for safe and synergetic wound antibacterial applications. ACS Nano, 2016,10(12):11000-11011. DOI URL PMID
[52]	JI HAI-WEI, DONG KAI, YAN ZHENG-QIN, et al. Bacterial hyaluronidase self-triggered prodrug release for chemo-photothermal synergistic treatment of bacterial infection. Small, 2016,12(45):6200-6206. DOI URL PMID
[53]	ZOU XUE-FENG, ZHANG LI, WANG ZHAO-JUN, et al. Mechanisms of the antimicrobial activities of graphene material. J. Am. Chem. Soc., 2016,138(7):2064-2077.
[54]	PERELSHTEIN I, LIPOVSKY A, PERKAS N, et al. The influence of the crystalline nature of nano-metal oxides on their antibacterial and toxicity properties. Nano Res., 2015,8(2):695-707.
[55]	DICKINSON B C, CHANG CJ J. Chemistry and biology of reactive oxygen species in signaling or stress responses. Nat. Chem. Biol., 2011,7(8):504-511.
[56]	WANG WAN-SHUN, LI BING-LIN, YANG HUI-LI, et al. Efficient elimination of multidrug-resistant bacteria using copper sulfide nanozymes anchored to graphene oxide nanosheets. Nano Res., 2020,13(8):2156-2164.
[57]	LEVY S. Antibacterial resistance worldwide: causes, challenges and responses. Nature Medicine, 2004,10(S12):S122-129.
[58]	WU HONG, MOSER C, WANG HENG-ZHUANG, et al. Strategies for combating bacterial biofilm infections. International Journal of Oral Science, 2015,1:1-7.
[59]	ARCIOLA C R, CAMPOCCIA D, SPEZIALE P, et al. Biofilm formation in staphylococcus implant infections: a review of molecular mechanisms and implications for biofilm-resistant materials. Biomaterials, 2012,33(26):5967-5982. DOI URL PMID
[60]	LEBEAUX D, GHIGO J M, BELOIN C. Biofilm-related infections: bridging the gap between clinical management and fundamental aspects of recalcitrance toward antibiotics. Microbiology & Molecular Biology Reviews, 2014,78(3):510-543. DOI URL PMID
[61]	GAO LI-ZENG, GIGLIO K M, NELSON J L, et al. Ferromagnetic nanoparticles with peroxidase-like activity enhance the cleavage of biological macromolecules for biofilm elimination. Nanoscale, 2014,6(5):2588. DOI URL PMID
[62]	GAO LI-ZENG, LIU YUAN, KIM D, et al. Nanocatalysts promote streptococcus mutans biofilm matrix degradation and enhance bacterial killing to suppress dental caries in vivo. Biomaterials, 2016,101:272-284. DOI URL PMID
[63]	NAHA P C, LIU YUAN, HWANG G, et al. Dextran-coated iron oxide nanoparticles as biomimetic catalysts for localized and pH-activated biofilm disruption. ACS Nano, 2019,13(5):4960-4971. DOI URL PMID
[64]	CHEN ZHAO-WEI, JI HAI-WEI, LIU CHAO-QUN, et al. A multinuclear metal complex based DNase-mimetic artificial enzyme: matrix cleavage for combating bacterial biofilms. Angewandte Chemie International Edition, 2016,55(36):10732-10736. DOI URL PMID
[65]	LIU ZHENG-WEI, WANG FA-MING, REN JIN-SONG, et al. A series of MOF/Ce-based nanozymes with dual enzyme-like activity disrupting biofilms and hindering recolonization of bacteria. Biomaterials, 2019,208:21-31. DOI URL PMID
[66]	LEJARS M, MARGAILLAN A, BRESSY C. Fouling release coatings: a nontoxic alternative to biocidal antifouling coatings. Chemical Reviews, 2012,112(8):4347-4390. DOI URL PMID
[67]	GAO ZHI-GIANG, JIANG SHEN-MING, ZHANG QI-FU, et al. Advances in research of marine antifouling fluorine resin coatings with low surface energy. Electroplating & Finishing, 2017,36(6):273-279.
[68]	陈吉 . 船舶纳米防污涂料的研究与应用. 武汉: 武汉大学硕士学位论文, 2015.
[69]	NATALIO F, ANDRE R, HARTOG A F, et al. Vanadium pentoxide nanoparticles mimic vanadium haloperoxidases and thwart biofilm formation. Nature Nanotechnology, 2012,7(8):530-535. DOI URL PMID
[70]	ANDRE R, NATALIO F, HUMANES M, et al. V₂O₅ nanowires with an intrinsic peroxidase-like activity. Advanced Functional Materials, 2011,21(3):501-509.
[71]	ASSENM F L, LEVY S. A review of current toxicological concerns on vanadium pentoxide and other vnadium compounds: gaps in knowledge and directions for future research. Journal of Toxicology & Environment, 2009,12(4):289-306.
[72]	HERGET K, HUBACH P, PUSH S, et al. Haloperoxidase mimicry by CeO_2-_x nanorods combats biofouling. Advanced Materials, 2017,29(4):1603823.
[73]	HU MING-HAN, KORSCHELT K, VIEL MELANIE, et al. Nanozymes in nanofibrous mats with haloperoxidase-like activity to combat biofouling. ACS Applied Materia HOUUls & Interfaces, 2018,10(51):44722-44730.
[74]	ZHAO YU-YUN, TIAN YUE, CUI YAN, et al. Small molecule-capped gold nanoparticles as potent antibacterial agents that target Gram- negative bacterial. J. Am. Chem. Soc, 2010,132(35):12349-12356. DOI URL PMID