孙昊宇,
龙茜,
林志芬
污染控制与资源化研究国家重点实验室, 同济大学环境科学与工程学院, 上海 200092
作者简介: 王孟珍(1995-),女,硕士研究生,研究方向为微生物毒理学,E-mail:1525230568@qq.com.
基金项目: 同济大学污染控制与资源化研究国家重点实验室自主研究(重点)项目(PCRRK16007)；水体污染控制与治理科技重大专项(2018ZX07109-1)；上海市科学技术委员会科研计划课题资助项目(17DZ1200103，14DZ2261100)；环境化学与生态毒理学国家重点实验室开放基金课题资助项目(KF2016-11)；111工程资助项目；上海“超级博士后”激励计划项目(2019194)；博士后创新人才支持计划资助项目(BX20190247)；中国博士后科学基金资助项目(2019M661624)中图分类号: X171.5
Combined Antibacterial Property and Mechanism of Nanosilver Composites and Antibiotics against Bacteria
Wang Mengzhen,Sun Haoyu,
Long Xi,
Lin Zhifen
State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China
CLC number: X171.5
-->
摘要
HTML全文
图
参考文献
相关文章
施引文献
资源附件
访问统计
摘要:抗生素的滥用导致细菌耐药问题日益严重，人类迫切需要开发出新的抗菌药物以减少细菌耐药问题。基于纳米银制备而成的纳米银复合材料在兼顾纳米银抗菌性能的同时不仅能够克服单一纳米银释放速度快、不稳定等缺点，还能缓解细菌耐药的问题，因此被认为是一类具有广泛应用前景的新型抗菌剂。已有研究表明，单一纳米银与某些抗生素的联合使用可以达到协同抗菌效果，但目前尚缺乏对纳米银复合材料与抗生素的联合抗菌性能及机制的研究。本文首先制备出3种不同结构的纳米银复合材料，包括二氧化硅-聚多巴胺-纳米银复合材料(SiO2-PD-AgNPs)、纳米银@二氧化硅复合材料(AgNPs@SiO2)和纳米银@二氧化硅-聚多巴胺-纳米银复合材料(AgNPs@SiO2-PD-AgNPs)。随后测定了纳米银复合材料对大肠杆菌(Escherichia coli, E. coli)和枯草芽孢杆菌(Bacillus subtilis, B. subtilis)的单一毒性效应。结果显示，AgNPs@SiO2-PD-AgNPs复合材料对2种菌的单一毒性均大于其余2种纳米银复合材料。因此，笔者以AgNPs@SiO2-PD-AgNPs作为代表，测定了纳米银复合材料与硫酸卡那霉素(kanamycin sulfate, KS)/盐酸土霉素(oxytetracycline hydro-chloride, OH)的二元联合抗菌性能，发现AgNPs@SiO2-PD-AgNPs与KS联合可以对E. coli产生协同效应。协同效应产生的主要原因可能是：AgNPs@SiO2-PD-AgNPs释放出的纳米银会和KS发生键合反应生成KS-纳米银复合物，导致纳米银释放出大量的Ag+增加了细胞膜的通透性，从而使得进入细菌内的Ag+和KS比单独作用时进入胞内的抗菌剂增多，产生更强的抗菌性能，从而表现出协同抗菌效应。本研究基于新型纳米银复合材料与抗生素的联合抗菌性能实验探究了纳米银复合材料与特定抗生素联合用药的最佳组合和相关机制，为今后开发新型抗菌材料提供了新思路并为相关联合用药提供参考。
关键词: 纳米银复合材料/
抗生素/
大肠杆菌/
枯草芽孢杆菌/
联合抗菌性能
Abstract:The abuse of antibiotics has caused increasingly serious problem of bacterial resistance, thus it is urgent to develop new antibacterial drugs to alleviate this problem. The nanosilver composites that was synthesized from single nanosilver can not only overcome the shortcomings of nanosilver, such as the rapid release rate of Ag+ and unstable physicochemical property, but also reduce the bacterial resistance, which are regarded as a new kind of antibacterial agents with broad application prospects. Previous studies have showed that the combination of single nanosilver and some antibiotics could exhibit the synergistic antibacterial effect. However, little information is available on the performance and mechanism of nanosilver composites combined with antibiotics. In this paper, three kinds of nanosilver composites with different structures were synthesized: silica-polydopamine-nanosilver (SiO2-PD-AgNPs), nanosilver@silica (AgNPs@SiO2) and nanosilver@silica-polydopamine-nanosilver (AgNPs@SiO2-PD-AgNPs). Subsequently, the single toxicity of nanosilver composites to Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis) was determined. The results showed that the toxicity of AgNPs@SiO2-PD-AgNPs to the two kinds of bacteria were greater than that of the other two nanosilver composites. Therefore, AgNPs@SiO2-PD-AgNPs was selected as the representative to determine its combined antibacterial property with KS (kanamycin sulfate)/OH (oxytetracycline hydrochloride), and it was found that the combination of AgNPs@SiO2-PD-AgNPs and KS could display synergistic effect on E. coli/. The nanosilver released by AgNPs@SiO2-PD-AgNPs could react with KS to form the KS-nanosilver complex, resulting in a large amount of Ag+ released from nanosilver. The increase of Ag+ enhanced the permeability of cell membrane, so the amount of Ag+ and KS entering the bacteria were more than that of the antibacterial agents when acting alone, which resulted in greater antibacterial property and a synergistic effect. This study explores the optimal combination and related mechanism of new nanosilver composite and specific antibiotics based on the combined toxicity experiments, which will provide new insight into the development of new antibacterial materials and give a reference for the related combination application of drugs.
Key words:nanosilver composite/
antibiotic/
Escherichia coli/
Bacillus subtilis/
combined antibacterial property.
| Goldman E. Antibiotic abuse in animal agriculture:Exacerbating drug resistance in human pathogens[J]. Human and Ecological Risk Assessment, 2004, 10(1):121-134 |
| Morones J R, Elechiguerra J L, Camacho A, et al. The bactericidal effect of silver nanoparticles[J]. Nanotechnology, 2005, 16(10):2346-2353 |
| Kim J S, Kuk E, Yu K N, et al. Antimicrobial effects of silver nanoparticles[J]. Nanomedicine:Nanotechnology, Biology and Medicine, 2007, 3(1):95-101 |
| 姚雪,张亚会,吕菊波,等.纳米银/聚合物复合材料的合成及其抑菌性研究进展[J].化学通报, 2016, 79(6):496-502Yao X, Zhang Y H, Lv J B, et al. Syntheses and antibacterial properties of Ag/polymer composites[J]. Chemistry, 2016, 79(6):496-502(in Chinese) |
| Cai X, Lin M, Mai W, et al.The use of polyethyleneiminemodified reduced graphene oxide as a substrate for silver nanoparticles to produce a material with lower cytotoxicity and long-term antibacterial activity[J]. Carbon, 2012, 50(10):3407-3415 |
| Babu K F, Dhandapani P, Maruthamuthu S, et al. One pot synthesis of polypyrrole silver nanocomposite on cotton fabrics for multifunctional property[J]. Carbohydrate Polymers, 2012, 90(4):1557-1563 |
| Tang J, Chen Q, Xu L, et al. Grapheneoxide-silver nanocomposite as a highly effective antibacterial agent with species-specific mechanisms[J]. Applied Materials & Interfaces, 2013, 5(9):3867-3874 |
| Zhou Y, Deng Y, He P, et al. Antibacterial zeolite with a high silver-loading content and excellent antibacterial performance[J]. RSC Advances, 2014, 4(10):5283-5288 |
| 杨标,章家立,郭赞如,等.碳纳米管增强纳米银复合材料应用进展[J].工程塑料应用, 2016, 44(9):121-125Yang B, Zhang J L, Guo Z R, et al. Application progress of silver composite enhanced by carbon nanotubes[J]. Engineering Plastics Application, 2016, 44(9):121-125(in Chinese) |
| 王林变,赵英虎,高莉,等.氧化石墨烯-纳米银复合材料的应用研究进展[J].化工新型材料, 2019, 47(3):1-5Wang L B, Zhao Y H, Gao L, et al. Research progress on application of graphene oxide-silver nanoparticle[J]. New Chemical Materials, 2019, 47(3):1-5(in Chinese) |
| Yang H, Liu Y, Shen Q, et al. Mesoporous silica microcapsule-supported Ag nanoparticles fabricated via nanoassembly and its antibacterial properties[J]. Journal of Materials Chemistry, 2012, 22(45):24132-24138 |
| 袁丽,王蓓娣,唐倩倩,等.介孔二氧化硅纳米粒子应用于可控药物传输系统的若干新进展[J].有机化学, 2010, 30(5):640-647Yuan L, Wang B D, Tang Q Q, et al. New progress in the applications of mesoporous silica nanoparticles to controlled drug delivery system[J]. Chinese Journal of Organic Chemistry, 2010, 30(5):640-647(in Chinese) |
| 任小宁,罗志强,李昱,等.多孔二氧化硅微球在药物控释载体中的应用(连载二)[J].医药导报, 2018, 37(7):785-793Ren X N, Luo Z Q, Li Y, et al. Application of porous silica spheres carriers for controlled drug delivery system[J]. Herald of Medicine, 2018, 37(7):785-793(in Chinese) |
| Gill I, Ballesteros A. Encapsulation of biologicals within silicate, siloxane, and hybrid sol-gel polymers:An efficient and generic approach[J]. Journal of the American Chemical Society, 1998, 120(34):8587-8598 |
| Li P, Li J, Wu Q, et al. Synergistic antibacterial effects of beta-lactam antibiotic combined with silver nanoparticles[J]. Nanotechnology, 2005, 16(9):1912-1917 |
| Naqvi S Z H, Kiran U, Ali M I, et al. Combined efficacy of biologically synthesized silver nanoparticles and different antibiotics against multidrug-resistant bacteria[J]. International Journal of Nanomedicine, 2013, 8(1):3187-3195 |
| 郭春兰,席祖洋,戴德兰.纳米银敷料结合抗生素用于慢性伤口感染干预效果的研究[J].中国医药导报, 2017, 14(28):60-64Guo C L, Xi Z Y, Dai D L. Research on intervention effect of nano silver dressing in combination with antibiotics for chronic wound infection[J]. China Medical Herald, 2017, 14(28):60-64(in Chinese) |
| 宋笑,刘涛,董丽华,等.夹心层结构的纳米银复合粒子的缓释抑菌性[J].纳米技术, 2014, 4:17-22 Song X, Liu T, Dong L H, et al. Prolonged antimicrobial activity of unique sandwich-structured silver nanocomposites[J]. Hans Journal of Nanotechnology, 2014, 4:17-22(in Chinese) |
| 苏冰梅,王婷,方淑霞,等.喹诺酮类与磺胺类药物对枯草芽孢杆菌与大肠杆菌的联合毒性及其机制初探[J].环境化学, 2015, 34(11):1975-1980Su B M, Wang T, Fang S X, et al. The combined toxicity of quinolones and sulfonamides on Bacillus subtilis and Escherichia coli[J]. Environmental Chemistry, 2015, 34(11):1975-1980(in Chinese) |
| 孟庆俊,肖昕.不同方法对联合毒性作用的评价[J].污染防治技术, 2004, 17(1):33-35Meng Q J, Xiao X. Asessment of combined toxicity using different methods[J]. Pollution Control Technology, 2004, 17(1):33-35(in Chinese) |
| 高继军,张力平,马梅.应用淡水发光菌研究二元重金属混合物的联合毒性[J].上海环境科学, 2003, 22(11):772-775Gao J J, Zhang L P, Ma M. Study on combined toxicity of binary mixture of heavy metals by applying freshwater luminescent bacteria Vibrio qinghaiensis[J]. Shanghai Environmental Sciences, 2003, 22(11):772-775(in Chinese) |
| Broderius S J, Kahl M D, Hoglund M D. Use of joint toxic response to define the primary mode of toxic acton for diverse industrial organic chemicals[J]. Environmental Toxicology and Chemistry, 1995, 14(9):1591-1605 |
| Yue L, Wang Q Q, Zhang X M, et al. Synthesis of Ag/TiO 2 core/shell nanoparticles with antibacterial properties[J]. Bulletin of the Korean Chemical Society, 2011, 32(8):2607-2610 |
| Fayaz A M, Balaji K, Girilal M, et al. Biogenic synthesis of silver nanoparticles and their synergistic effect with antibiotics:A study against Gram-positive and Gram-negative bacteria[J]. Nanomedicine:Nanotechnology, Biology and Medicine, 2010, 6(1):103-109 |
| Tom R T, Nair A S, Singh N, et al. Freely dispersible Au@TiO2, Au@ZrO2, Ag@TiO2, and Ag@ZrO2 core-shell nanoparticles:One-step synthesis, characterization, spectroscopy, and optical limiting properties[J]. Langmuir, 2003, 19(8):3439-3445 |
| Kim Y H, Lee D K, Kang Y S. Synthesis and characterization of Ag and Ag-SiO2 nanoparticles[J]. Colloids and Surfaces A:Physicochemical and Engineering Aspects, 2005, 257:273-276 |
| Zhou Y, Yang J, He T, et al. Highly stable and dispersive silver nanoparticle-graphene composites by a simple and low-energy-consuming approach and their antimicrobial activity[J]. Small, 2013, 9(20):3445-3454 |
| 刘鑫,任艳,周子军,等.纳米银抗菌机理及应用研究进展[J].安徽农业大学学报, 2017, 44(4):702-708Liu X, Ren Y, Zhou Z J, et al. Antimicrobial mechanism and application of nano-silver material[J]. Journal of Anhui Agricultural University, 2017, 44(4):702-708(in Chinese) |
| Hsueh Y H, Lin K S, Ke W J, et al. The antimicrobial properties of silver nanoparticles in Bacillus subtilis are mediated by released Ag+ ions[J]. Plos One, 2015, 10(12):e0144306 |
| Li W R, Xie X B, Shi Q S, et al. Antibacterial activity and mechanism of silver nanoparticles on Escherichia coli[J]. Applied Microbiology and Biotechnology, 2010, 85(4):1115-1122 |
| Sotiriou G A, Pratsinis S E. Antibacterial activity of nanosilver ions and particles[J]. Environmental Science & Technology, 2010, 44(14):5649-5654 |
| 王洁,孟翔峰.纳米银的抗菌机制研究[J].现代口腔医学杂志, 2013, 27(5):304-308 |
| Ovington L G. Nanocrystalline silver:Where the old and familiar meets a new frontier[J]. Wounds:A Compendium of Clinical Research and Practice, 2001, 13(2):5-10 |
| Yun H, Kim J D, Choi H C, et al. Antibacterial activity of CNT-Ag and GO-Ag nanocomposites against Gram-negative and Gram-positive bacteria[J]. Bulletin of the Korean Chemical Society, 2013, 34(11):3261-3264 |
| 郑卫.氨基糖苷类抗生素研究的新进展[J].四川生理科学杂志, 2003, 25(4):178-179 |
| 戴俊,凌静,郭文.氨基糖苷类抗生素的发展现状与机遇[J].中国抗生素杂志, 2019, 44(11):1307-1311Dai J, Ling J, Guo W. Development status and opportunities of aminoglycoside antibiotics[J]. Chinese Journal of Antibiotics, 2019, 44(11):1307-1311(in Chinese) |
| 贺德春,许振成,吴根义,等.四环素类抗生素的环境行为研究进展[J].动物医学进展, 2011, 32(4):98-102He D C, Xu Z C, Wu G Y, et al. Progress on residues and environmental behaivor of tetracycline antibiotics[J]. Progress in Veterinary Medicine, 2011, 32(4):98-102(in Chinese) |
| Deng H, McShan D, Zhang Y, et al. Mechanistic study of the synergistic antibacterial activity of combined silver nanoparticles and common antibiotics[J]. Environmental Science & Technology, 2016, 50(16):8840-8848 |
| Zhang W, Yao Y, Sulivan N, et al. Modeling the primary size effects of citrate-coated silver nanoparticles on their ion release kinetics[J]. Environmental Science & Technology, 2011, 45(10):4422-4428 |
| Duran N, Duran M, Jesus M, et al. Silver nanoparticles:A new view on mechanistic aspects on antimicrobial activity[J]. Nanomedicine:Nanotechnology, Biology and Medicine, 2016, 12(3):789-799 |
| Xiong M H, Li Y J, Bao X Z, et al. Bacteria-responsive multifunctional nanogel for targeted antibiotic delivery[J]. Advanced Materials, 2012, 24(46):6175-6180 |
| 范铭琦,赵敏,范瑾. 30S核糖体的结构及其与氨基糖苷类抗生素相互作用的新进展[J].中国新药杂志, 2006, 15(9):676-682Fan M Q, Zhao M, Fan J. Recent advances on the structure of 30S ribosomal subunit and interaction of 30S ribosome with aminoglycosides[J]. Chinese Journal of New Drugs, 2006, 15(9):676-682(in Chinese) |
| 孟迪,薛罡,陈红.典型PPCPs与纳米银颗粒在水溶液中理化性质的交互影响研究[J].广东化工, 2016, 43(7):5-7Meng D, Xue G, Chen H. Interaction effects of typical PPCPs and silver nanoparticles on physical-chemical properties in aqueous solution[J]. Guangdong Chemical Industry, 2016, 43(7):5-7(in Chinese) |
| Wan G, Ruan L, Yang T, et al. Effects of silver nanoparticles in combination with antibiotics on the resistant bacteria Acinetobacter baumannii[J]. International Journal of Nanomedicine, 2016, 11:3789-3800 |
