纳米银的制备及其生物活性研究进展

陈 嵘,荣凯峰,吕 中,曾琦斐，丘奕怡,梁惠强,余响林

(1.武汉工程大学绿色化工过程省部共建教育部重点实验室,湖北省新型反应器与绿色化学工艺重点实验室,湖北 武汉 430074;2.湖南环境生物职业技术学院，湖南 衡阳 421005；3.香港大学牙医学院,香港)

0 引 言

随着纳米技术的迅猛发展,纳米材料因其独特的量子效应、小尺寸效应以及大的比表面积而显现出特有的性质,引起人们广泛的研究兴趣.二十世纪九十年代以来,研究人员在纳米材料的制备、表征上做了大量工作,取得了丰硕的研究成果.近年来,人们已越来越多的把目光集中在纳米材料的性质及其应用上[1-2],而不是仅仅局限在材料的合成与制备.人类很早就认识到了银具有广谱的抗菌作用,银及其化合物,已广泛应用于日常生活和生物医药领域[3].而近年来,纳米银的研究更是取得了极为丰富的研究成果.在众多的纳米材料中,无论从制备、性质,还是应用,纳米银无疑是一种研究最为广泛、深入的材料.在已报道的文献中,人们已经通过不同的方法合成出不同粒径和不同形貌的纳米银颗粒以及多种一维纳米结构,如银纳米线、纳米棒和具有一定空间结构的树枝状的纳米银等.在纳米银的活性研究中,人们发现其不但具有显著的抗菌活性[4-9],还具有抗病毒[10-11],抗肿瘤[12-13]等生物活性.正是这些显著的生物活性,使得纳米银在生物医药和纺织上得到广泛的应用[14],并且已有多种关于纳米银的产品市场化.本文简要综述了不同粒径和形貌的纳米银的各种制备方法,及其抗菌、抗病毒、抗肿瘤等生物活性和其产业化应用.

1 纳米银的制备

在不同形貌和大小的银纳米结构的制备方法中,根据所用还原剂或还原方法的不同,主要分为三类:化学还原法、物理还原法、生物还原法.

1.1 化学还原法

化学还原法是制备纳米银最简单也最常用的方法.一般指在液相条件下,将Ag+还原为单质银,所用还原剂常有硼氢化钠、柠檬酸钠、乙二醇、抗坏血酸、葡萄糖等.不同的还原剂和分散剂对纳米银的形貌和大小有很大的影响,在纳米银颗粒的合成中,人们通过控制不同的反应条件,分别得到了不同粒径大小的纳米银颗粒(如图1所示).例如,Logar等以NaBH4为还原剂,制备得到颗粒大小为7 nm左右的纳米银颗粒[15].Lee课题组报道了利用1,2-二羟基十六烷还原Ag+得到晶种并通过银纳米粒子的自组装,得到粒径为10 nm左右的单分散纳米银颗粒[16].殷亚东课题组还报道了使用多羟基还原的方法,以乙二醇为溶剂和还原剂,并且使用聚丙烯酸(PAA)为表面活性剂,得到了粒径为20 nm的银纳米颗粒[17].夏幼南课题组在引入少量NaCl的条件下,以乙二醇为溶剂和还原剂,可得到粒径为30 nm左右的银纳米颗粒及其二聚体[18].还有报道直接用柠檬酸钠还原硝酸银,可制备出了30～50 nm的银纳米颗粒[19]. 陈代荣课题组使用抗坏血酸还原氯化银可得到50 nm的银纳米颗粒[20].Pyatenko等采用晶种技术,首先生成纳米银种子颗粒,然后合成纳米银溶胶,再经多步合成过程,便可得到80 nm左右的纳米银颗粒[21].Quaroni等使用乳液聚合作用,制备了尺寸均一、稳定、粒径为100 nm的纳米银颗粒[22].

图1 不同粒径的纳米银颗粒透射电镜图

目前,除了用各种方法制备出不同粒径的银纳米颗粒外,人们也制备出了银纳米线[23-25]、纳米立方[26-27]、纳米棒[28-29]、纳米球[30]、纳米三角片[31]、纳米双锥体[32]等不同形貌结构(如图2所示).

图2 不同形貌的纳米银扫描电镜图

夏幼南课题组报道在PVP存在下,用乙二醇还原AgNO3,以Pt或Ag的小粒径的纳米颗粒作为晶种,合成出长度50 μm,直径30～40 nm的银纳米线[23-24].夏幼南课题组还报道了使用多羟基还原的方法,在PVP存在条件下,通过改变PVP与AgNO3的摩尔比,可控合成了平均粒径为80±7 nm的银纳米立方结构[26].该课题组还使用多羟基还原的方法,通过控制纳米银种子晶型来控制最终产物的形貌,选择性的合成出不同形状的银纳米结构,如纳米三角、纳米双锥体、纳米棒、纳米线、纳米束、纳米立方体、纳米球等结构,并通过调节AgNO3浓度,PVP与AgNO3的比例等因素也可来改变纳米银的粒径和形貌[31-33].在此基础上,Yam课题组使用水热法,以葡萄糖为还原剂还原[Ag(NH3)2]+得到边长为55±5 nm的银纳米立方结构[27].钱逸泰课题组使用水热法,并以氯化银作为前驱体反应生成银的纳米线,其长度可达500 μm,平均直径约为100 nm[25].Maiyalagan利用多元醇方法通过改变AgNO3与PVP的比例,得到不同长径比的银纳米棒[28].Pietrobon等采用水热法,并以柠檬酸为还原剂,将单分散的纳米银颗粒,自组装成银的纳米棒结构[29].Liang等采用水热法,使用聚乙二醇(PEG)作为还原剂和溶剂,通过控制PVP与AgNO3的摩尔比,制备出了单分散的银纳米球结构[30].李亚栋课题组通过溶剂热法,合成三角片、球型、立方体形状的纳米银[34].化学还原法操作简单,容易控制,常使用表面活性剂(如PVP、CTAB、PEG、SDS等)防止纳米银颗粒聚集,并诱导其晶体生长.

1.2 物理还原法

物理还原法主要是指借助于物理手段或方法等辅助条件将Ag+还原为单质银的方法,主要有:紫外光照射法、电子束辐射法、微波还原法等.Giovanna等使用紫外光照射的方法制备出2～4 nm的纳米银颗粒[35].在聚乙烯醇(PVA)存在下,通过电子束辐射,可将AgNO3还原制得稳定的银纳米粒子[36-37].而微波法由于具有加热速度快、加热均匀、无温度梯度、无滞后效应等特点,近年来也被广泛应用于纳米银颗粒的制备.在乙二醇溶剂里,通过微波加热可制备得到粒径为10 nm左右的纳米银颗粒[38].俞书宏课题组发现在AgNO3中加入一定比例的氨基酸、淀粉,通过微波加热也可合成出平均粒径约为26 nm的纳米银颗粒[39].Baruwati等人还报道了在谷胱甘肽促进下,水溶液中微波合成粒径为5～10 nm的纳米银颗粒[40].

1.3 生物还原法

随着人们对环境友好型技术的逐渐重视,研究人员发现利用微生物体系也可来制备纳米银颗粒.生物还原法主要有:细菌还原法、真菌还原法、植物还原法等[3].1999年,Klaus等首次报道了利用施氏假单胞菌合成银的纳米颗粒,高浓度AgNO3在施氏假单胞菌中被还原成颗粒大小为200 nm左右的银纳米晶体[41](如图3所示).随后不同研究小组分别报道了用肺炎克雷伯杆菌[42]、地衣芽孢杆菌[43-44]、烟曲霉菌[45]、黄曲霉[46]、黑曲霉[47]、木霉菌[48]、白腐真菌[49]、尖孢镰刀菌[50]等与Ag+作用得到不同粒径的纳米银颗粒.除细菌、真菌外,印度学者还报道了用植物还原法合成纳米银.研究发现天竺葵叶提取物在较短时间内,可将银离子还原成粒径为16～40 nm的银纳米颗粒[51].李清彪课题组也报道了利用香樟叶合成粒径约为55～80 nm的银纳米颗粒[52].生物还原法具有原料来源广、价廉易得、绿色环保、反应条件温和等优点,可能引领一种简易的生物合成纳米银方法的新发展,但其还原能力较弱,寻找新的具有较强还原能力的生物源是此法的主要突破口.

图3 施氏假单胞菌细胞的超薄切片的高分辨透射电子显微镜照片

2 纳米银的生物活性

2.1 纳米银的抗菌活性

人类很早就认识到银具有广谱杀菌作用,并用银来杀菌消毒.近年来,随着纳米技术的发展,纳米级无机抗菌剂的应用日益广泛.其中纳米银系列抗菌剂是研究最为广泛和深入的纳米抗菌材料,有关纳米银的抗菌活性的报道层出不穷,研究发现,纳米银对大肠杆菌、金黄色葡萄球菌有较好的抑制作用[6-7,53-60],不同研究小组还分别报道了纳米银对枯草芽孢杆菌[8,61]、铜绿假单胞菌[62-63],鼠伤寒少门氏杆菌[64]、真菌[65]等的抗菌作用.随后Hernández-Sierra等报道了其对口腔细菌:致龋菌变形链球菌的抑制作用[9,66].Arora等研究了纳米银颗粒经细胞毒性实验、动物实验,证明纳米银基本属无生物毒性的纳米材料,其具有高效抗菌活性并且使用安全[67-68].支志明课题组系统研究了纳米银对大肠杆菌的抑制作用,并探讨了其抗菌机制,说明纳米银可能是通过破坏细菌细胞膜,从而消耗其质子驱动力,这样来达到其抗菌效果[69-71].Sondi等在前人研究的基础上总结了银系抗菌剂的抗菌机理,他们指出纳米银颗粒可以直接进入微生物体内,中断DNA的复制,通过阻断细菌的呼吸酶系统,杀灭细菌,从而阻止微生物繁殖,杀灭各种致病细菌[7,72].

2.2 纳米银的抗病毒活性

人们对银的抗病毒活性研究起步较晚,随着纳米科技的快速发展,近年,人们对纳米银的抗病毒活性研究越来越多.2005年,Yacaman课题组和支志明课题组相继报道了纳米银对HIV病毒的抑制作用,研究表明粒径在1～30 nm的纳米银颗粒均能起到杀灭HIV病毒的作用,阻止其HIV病毒的繁殖[10,73].2008年,支志明课题组和Rogers课题组又相继报道了纳米银对乙型肝炎病毒[11]和腥红热病毒[74]的抑制作用.张若愚等人还报道了纳米银颗粒对禽流感病毒也有较好的抑制作用[75].

2.3 纳米银的抗肿瘤活性

尽管纳米银在抗肿瘤活性方面的研究不及抗菌活性方面的研究广泛,但也有不少研究小组对其抗肿瘤活性做了相关报道.Gopinath 等报道了纳米银可以使细胞内线粒体膜通透性发生改变,从而促进肿瘤细胞凋亡[76].Verma等也研究了纳米银具有较好的抗癌活性[77].Otrock等报道了纳米银的靶向治疗,在杀死癌细胞时,对正常细胞没有损伤[78].Youngs等报道了纳米银对乳腺癌细胞的抑杀作用[12].在预防和治疗与细胞凋亡缺陷有关的疾病方面(如恶性肿瘤等),纳米银的作用值得进一步深入研究.

3 纳米银产品

由于纳米银具有广谱抗菌性,且其有抗菌活性高、毒性低等特点,载银纳米无机抗菌材已成为目前应用最广泛的无机抗菌材料.国内外研究人员研制出的相应的纳米银产品已应用于各领域.例如:香港安信纳米科技公司率先研发的纳米银速效抗菌颗粒,已通过香港大学、中国科学院、中国医学院等权威机构的认证并投产.除此以外,安信公司还研制开发了纳米抗菌袜、纳米银创可贴等纳米产品.江苏瑞德纳米材料技术有限公司推出的宣氏纳米银抗菌凝胶(烧伤用),其产品具有超强的抗菌活性,能促进组织修复与再生,加快创面愈合,减少疤痕组织的形成.中山市国宇医疗器械有限公司开发研制的纳米银痔疮净、沈阳高名医药科技有限公司的纳米银前列宝、济南龙邦生物科技有限公司的纳米银脚癣净、西安华康生物科技有限公司妇科千金(纳米银)凝胶、上海沪正纳米科技有限公司的纳米银牙膏以及深圳清华源兴纳米医药科技有限公司研制开发的纳米银制剂阿希米都已经产业化.

4 总结与展望

随着纳米科技的发展,纳米银在人类生活中有着举足轻重的作用.近年来通过化学还原法和物理还原法可以合成出不同大小、不同形貌的纳米银.以细菌、真菌以及植物为原料的生物还原法也是具有很大的潜力的绿色合成方法.未来的纳米银制备方法将向低成本、低能耗、环境友好的方向发展.纳米银对常见革兰氏阴性菌和革兰氏阳性菌都有较好的抗菌作用,其抗菌活性高、抗菌谱广且毒性较低等,其且对HIV病毒、腥红热病毒及禽流感病毒均有较好的抑制作用.纳米银还可通过靶向治疗促使肿瘤细胞凋亡.随着人们对其抗菌、抗病毒、抗肿瘤原理及其活性与生物稳定性研究的进一步深入,将开发出更多安全、有效的纳米银制剂.由于纳米银在生物医学等方面有着广泛的应用,其产业化引起了人们的高度重视,并且许多成果已经开始产业化.真正全面实现纳米银的产业化,造福人类,也是当前科技工作者努力的方向.

参考文献：

[1]刘善堂.扫描探针加工和自组装技术相结合的研究进展——表面图形可控的功能纳米结构的制备[J].武汉工程大学学报,2007,29(4):1-4.

[2]陈嵘,程刚,吴际良,等.含铋复合材料对幽门螺杆菌的多联治疗的研究[J].武汉工程大学学报,2009,31(1):5-9.

[3]Vaidyanathan R,Kalishwaralal K,Gopalram S,et al.Nanosilver-the burgeoning therapeutic molecule and its green synthesis[J].Biotechnol Adv,2009,27:924-937.

[4]Alta V,Bechertb T,Steinrückeb P,et al.An in vitro assessment of the antibacterial properties and cytotoxicity of nanoparticulate silver bone cement[J].Biomaterials,2004,25:4383-4391.

[5]Lee D,Cohen R E,Rubner M F.Antibacterial properties of Ag nanoparticle loaded multilayers and formation of magnetically directed antibacterial microparticles[J].Langmuir,2005,21:9651-9659.

[6]Li W R,Xie X B,Shi Q S,et al.Antibacterial activity and mechanism of silver nanoparticles on escherichia coli[J].Appl Microbiol Biotechnol,2010,85:1115-1122.

[7]Sondi I,Salopek-Sondi B.Silver nanoparticles as antimicrobial agent:a case study on E. coli as a model for gram-negative bacteria[J].J Colloid Interface Sci,2004,275:177-182.

[8]Yoon K Y,Byeon J H,Park J H,et al.Antimicrobial characteristics of silver aerosol nanoparticles against bacillus subtilis bioaerosols[J].Environ Eng Sci,2008,25(2):289-293.

[9]Hernández-Sierra J F,Ruiz F,Pena DCC,et al.The antimicrobial sensitivity of streptococcus mutans to nanoparticles of silver, zinc oxide, and gold[J].Nanomedicine,2008,4:237-240.

[10]Sun R W Y,Chen R,Chung N P Y.Silver nanoparticles fabricated in hepes buffer exhibit,cytoprotective activities toward HIV-1 infected cells[J].Chem Commun,2005:5059-5061.

[11]Lu L, Sun R W Y, Chen R.Silver nanoparticles inhibit hepatitis B virus replication[J].Antiviral Therapy,2008,13(2):253-262.

[12]Youngs W J,Robishaw N,Panzner M J.Treatment of breast cancer with silver antitumor drugs encapsulated in biodegradable polymeric nanoparticles[J].Nanotech Conference & Expo,2009,2:5-8.

[13]Okada H,Mak T W.Pathways of apoptotic and non-apoptotic death in tumour cells[J].Nat Rev Cancer,2004,4:592-603.

[14]Chen X,Schluesener H J.Nanosilver:a nanoproduct in medical application[J].Toxicol Lett,2008,176:1-12.

[15]Logar M,Jancar B,Suvorov D,et al.In situ synthesis of Ag nanoparticles in polyelectrolyte multilayers[J].Nanotechnology,2007,18:325601-325607.

[16]Zhang Q,Xie J,Yang J,et al.Monodisperse icosahedral Ag, Au, and Pd nanoparticles:size control strategy and superlattice formation[J].ACS Nano,2009,3(1):139-148.

[17]Hu Y, Ge J, Lim D, et al.Size-controlled synthesis of highly water-soluble silver nanocrystals[J].J Solid State Chem,2008,181:1524-1529.

[18]Li W,Camargo P H C,Lu X,et al.Dimers of silver nanospheres:facile synthesis and their use as hot spots for surface-enhanced raman scattering[J].Nano lett,2009,9(1):485-490.

[19]Khanna P K,Singh N,Kulkarni D,et al.Water based simple synthesis of re-dispersible silver nano-particles[J].Mater Lett,2007,61:3366-3370.

[20]Chen B, Jiao X, Chen D.Size-controlled and size-designed synthesis of nano/submicrometer Ag particles[J].Cryst Growth Des,2010,10(8):3378-3386.

[21]Pyatenko A, Yamaguchi M, Suzuki M.Synthesis of spherical silver nanoparticles with controllable sizes in aqueous solutions[J].J. Phys. Chem. C,2007,111:7910-7917.

[22]Quaroni L,Chumanov G.Preparation of polymer-coated functionalized silver nanoparticles[J].J Am Chem Soc,1999,121:10642-10643.

[23]Sun Y,Gates B,Mayers B,et al.Crystalline silver nanowires by soft solution processing[J].Nano Lett,2002,2(2):165-168.

[24]Sun Y,Mayers B,Herricks T,et al.Polyol synthesis of uniform silver nanowires:a plausible growth mechanism and the supporting evidence[J].Nano Lett,2003,3(7):955-960.

[25]Wang Z,Liu J,Chen X,et al.A simple hydrothermal route to large-scale synthesis of uniform silver nanowires[J].Chem Eur J,2005,11:160-163.

[26]Sun Y,Xia Y.Shape-controlled synthesis of gold and silver nanoparticles[J].Science,2002,298:2176-2179.

[27]Yu D,Yam W W V.Controlled synthesis of monodisperse silver nanocubes in water[J].J Am Chem Soc,2004,126:13200-13201.

[28]Maiyalagan T.Synthesis,characterization and electrocatalytic activity of silver nanorods towards the reduction of benzyl chloride[J].Appl Catal A,2008,340:191-195.

[29]Pietrobon B,McEachran M,Kitaev V.Synthesis of size-controlled faceted pentagonal silver nanorods with tunable plasmonic properties and self-assembly of these nanorods[J].ACS Nano,2009,3(1):21-26.

[30]Liang H,Wang W,Huang Y.Controlled synthesis of uniform silver nanospheres[J].J Phys Chem C,2010,114:7427-7431.

[31]Washio I,Xiong Y,Yin Y.Reduction by the end groups of poly(vinyl pyrrolidone): A new and versatile route to the kinetically controlled synthesis of Ag triangular nanoplates[J].Adv Mater,2006,18:1745-1749.

[32]Wiley B,Sun Y,Xia Y.Synthesis of silver nanostructures with controlled shapes and properties[J].Acc Chem Res,2007,40(10):1067-1076.

[33]Wiley B,Sun Y,Mayers B,et al.Shape-controlled synthesis of metal nanostructures:the case of silver[J].Chem Eur J,2005,11:454-463.

[34]Xu R,Wang D,Zhang J,et al.Shape-dependent catalytic activity of silver nanoparticles for the oxidation of styrene[J].Chem Asian J,2006,1:888-893.

[35]Giovanna M,Marisa M B,Adriano F F.Silver nanoparticles obtained in PAH/PAA-based multilayers by photochemical reaction[J].J Phys Chem C,2009,113(44):19005-19010.

[36]Pattabi M,Pattabi R M,Sanjeev G.Studies on the growth and stability of silver nanoparticles synthesized by electron beam irradiation[J].J Mater Sci-Mater Electron,2009,20:1233-1238.

[37]Vostokov A V,Ignatev A I,Nikonorov N V,et al.Effect of electron irradiation on the formation of silver nanoclusters in photothermorefractive glasses[J].Tech Phys Lett,2009,35(9):812-814.

[38]Zhu J F,Zhu Y J.Microwave assisted one step synthesis of polyaerylamide metal(M=Ag,Pt,Cu)nanocomposites in ethylene glycol[J].J Phys Chem B,2006,110(17):8593-8597.

[39]Hu B,Wang S B,Wang K.Microwave-assisted rapid facile “green” synthesis of uniform silver nanoparticles:self-assembly into multilayered films and their optical properties[J].J Phys Chem C,2008,112:11169-11174.

[40]Baruwati B,Polshettiwar V,Varma R S.Glutathione promoted expeditious green synthesis of silver nanoparticles in water using microwaves[J].Green Chem,2009,11:926-930.

[41]Klaus T,Joerger R,Olsson E,et al.Silver-based crystalline nanoparticles,microbially fabricated[J].P Natl Acad Sci USA,1999,96(24) :13611-13614.

[42]Ahmad R S,Sara M,Hamid R S,et al.Rapid synthesis of silver nanoparticles using culture supernatants of enterobacteria:a novel biological approach[J].Process Biochem,2007,42:919-923.

[43]Kalimuthu K,Babu R S,Venkataraman D,et al.Biosynthesis of silver nanocrystals by bacillus licheniformis[J].Colloids Surf B,2008,24:604-610.

[44]Kalishwaralal K,Deepak V,Ramkumarpandian S,et al.Extracellular biosynthesis of silver nanoparticles by the culture supernatant of bacillus licheniformis[J].Mater Lett,2008,62:4411-4413.

[45]Bhainsa K C,D’Souza S F.Extracellular biosynthesis of silver nanoparticles using the fungus aspergillus fumigatus[J].Colloids Surf B,2006,47:160-164.

[46]Vigneshwaran N,Ashtaputre N M,Varadarajan P V,et al.Biological synthesis of silver nanoparticles using the fungus aspergillus flavus[J].Mater Lett,2007,66:1413-1418.

[47]Gade A K,Bonde P,Ingle A P,et al.Exploitation of aspergillus niger for synthesis of silver nanoparticles[J].J Biobased Mat Bioenergy,2008,3:123-129.

[48]Mukherjee P,Roy M,Mandal B P,et al.Green synthesis of highly stabilized nanocrystalline silver particles by a non-pathogenic and agriculturally important.fungus T asperellum[J].Nanotechnology,2008,19:075103(7 pp).

[49]Vigueshwaran N,KatheA A,Varadarajan P V,et a1.Biomimetics of silver nanoparticles by white rot fungus, phaenerochaete chrysosporium[J].Colloids Surf B,2006,53:55-59.

[50]Ahmad A,Mukherjee P,Senapati S,et al.Extracellular biosynthesis of silver nanoparticles using the fungus fusarium oxysporum[J].Colloids Surf B,2003,28:313-318.

[51]Shankar S S,Ahmad A,Sastry M.Geranium leaf assisted biosynthesis of silver nanoparticles[J].Biotechnol Prog,2003,19:1627-1631.

[52]Huang J,Li Q,Sun D,et al.Biosynthesis of silver and gold nanoparticles by novel sundried cinnamomum camphora leaf[J].Nanotechnology,2007,18:105104-105115.

[53]Sanpui P, Murugadoss A, Prasad P,et al.The antibacterial properties of a novel chitosan-Ag-nanoparticle composite[J].Int J Food Microbiol,2008,124:142-146.

[54]Raffi M, Hussain F, Bhatti TM,et al.Antibacterial characterization of silver nanoparticles against E.Coli ATCC-15224[J].J Mater Sci Technol,2008,24(2):192-196.

[55]Le A T,Tam PD,Huy TQ,et al.Synthesis of oleic acid-stabilized silver nanoparticles and analysis of their antibacterial activity[J].Mater Sci Eng,2010,30:910-916.

[56]Dung T T N,Buu N Q,Quang D V,et al.Synthesis of nanosilver particles by reverse micelle method and study of their bactericidal properties[J].J Phys:Conference Series,2009,187:012054(8 pp).

[57]Wang H,Wei Q,Wang X,et al.Antibacterial properties of PLA nonwoven medical dressings coated with nanostructured silver[J].Fiber Polym,2008,9(5):556-560.

[58]Dorjnamjin D,Ariunaa M,Shim YK.Synthesis of silver nanoparticles using hydroxyl functionalized ionic liquids and their antimicrobial activity[J].Int J Mol Sci,2008,9:807-820.

[59]Jain J,Arora S,Rajwade JM,et al.Silver nanoparticles in therapeutics:development of an antimicrobial gel formulation for topical use[J].Mol Pharmaceut,2009,6(5):1388-1401.

[60]Kemp M M,Kumar A,Clement D,et al.Hyaluronan- and heparin-reduced silver nanoparticles with antimicrobial properties[J].Nanomedicine,2009,4(4):421-429.

[61]Yoon K Y,Byeon J H,Park J H,et al.Susceptibility constants of escherichia coli and bacillus subtilis to silver and copper nanoparticles[J].Sci Total Environ,2007,373:572-575.

[62]Birla S S,Tiwari V V,Gade A K,et al.Fabrication of silver nanoparticles by Phoma glomerata and its combined effect against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus[J].Lett Appl Microbiol,2009,48:173-179.

[63]Trana H V,Tranb L D,Bac C T,et al.Synthesis, characterization, antibacterial and antiproliferative activities of monodisperse chitosan-based silver nanoparticles[J].Colloids Surf A,2010,360:32-40.

[64]Patil S S,Dhumal R S,Varghese M V,et al.Synthesis and antibacterial studies of chloramphenicol loaded nano-silver against Salmonella typhi[J].Synth React Inorg Met Org Chem,2009,39(2):65-72.

[65]Jo Y K,Kim B H,Jung G,et al.Antifungal activity of silver ions and nanoparticles on phytopathogenic fungi[J].Plant Dis,2009,93(10):1037-1043.

[66]Espinosa-Cristóbal L F,Martínez-Castaón G A,Martínez-Martínez R E,et al. Antibacterial effect of silver nanoparticles against streptococcus mutans[J].Mater Lett,2009,63:2603-2606.

[67]Arora S,Jain J,Rajwade JM,et al.Cellular responses induced by silver nanoparticles: In vitro studies[J].Toxicol Lett,2008,179:93-100.

[68]钟金栋,夏雪山,张若愚,等.纳米银材料抗菌效果研究及其安全性初步评价[J].昆明理工大学学报:理工版,2005,30(5):91-98.

[69]Lok C N,Ho C M,Chen R,et al.Proteomic analysis of the mode of antibacterial action of silver nanoparticles[J].J Proteome Res,2006,5:916-924.

[70]Lok C N,Ho C M,Chen R,et al.Proteomic identification of the cus system as a major determinant of constitutive escherichia coli silver resistance of chromosomal origin[J].J Proteome Res,2008,7:2351-2356.

[71]Lok C N,Ho C M,Chen R,et al.Silver nanoparticles:partial oxidation and antibacterial activities[J].J Biol Inorg Chem,2007,12(4):527-534.

[72]Li Q,Mahendra S,Delina Y,et al.Antimicrobial nanomaterials for water disinfection and microbial control: Potential applications and implications[J].Water Res,2008,42:4591-4602.

[73]Elechiguerra J L,Burt J L,Morones J R,et al.Interaction of silver nanoparticles with HIV-1[J].J Nanobiotechnol,2005,3:1-10.

[74]James V,Christopher R,Parkinson V,et al.A preliminary assessment of silver nanoparticle inhibition of monkeypox virus plaque formation[J].Nanoscale Res Lett,2008,3:129-133.

[75]张若愚,夏雪山,胡亮,等.Ag/Diatomite复合材料及其对禽流感病毒的杀灭研究[J].贵金属,2004,25(2):28-32.

[76]Gopinath P,Gogoi S K,Chattopadhyay A,et al.Implications of silver nanoparticle induced cell apoptosis for in vitro gene therapy[J].Nanotechnology,2008,19:075104.

[77]Verma S K,Mani P,Sharma N R,et al.Histidylated lipid-modified sendai viral envelopes mediate enhanced membrane fusion and potentiate targeted gene delivery[J].J Biol Chem,2005,280:35399-35409.

[78]Otrock Z K,Makarem J A,Shamseddine A I.Vascular endothelial growth factor family of ligands and receptors:review[J].Blood Cells Mol Diseases,2007,38:258-268.