197-209

7/28/2019 197-209

http://slidepdf.com/reader/full/197-209 1/13

Nanoparticles and their potential application as antimicrobials

Ravishankar Rai V *and Jamuna Bai A

Department of Studies in Microbiology, University of Mysore, Manasagangotri, Mysore, India.

* Email: [email protected]

Emerging infectious diseases and the increase in incidence of drug resistance among pathogenic bacteria have made thesearch for new antimicrobials inevitable. In the current situation, one of the most promising and novel therapeutic agents

are the nanoparticles. The unique physiochemical properties of the nanoparticles combined with the growth inhibitorycapacity against microbes has led to the upsurge in the research on nanoparticles and their potential application as

antimicrobials. From centuries metals such as silver have been used for treating burns and chronic wounds, and copper has been used to make water potable. It is quite evident that some of the metallic compounds possess antimicrobial property.

Recently, the confluence of nanotechnology and biology has brought to fore metals in the form of nanoparticles as potential antimicrobial agents. Nanoparticles have unique and well defined physical and chemical properties which can bemanipulated suitably for desired applications. Moreover, their potent antimicrobial efficacy due to the large surface area to

volume ratio has provided them an edge over their chemical counterparts which are facing the problems of drug resistance.This review focuses on the properties of different types of metallic nanoparticles such as copper, aluminium, gold, silver,

magnesium, zinc and titanium nanoparticles. The mechanism of action of nanoparticles as bactericidal, antifungal and

antiviral agents will be highlighted in this study. The potential application of nanoparticles will be also reviewed. Theapplication of nanoparticles as antimicrobials is gaining relevance in prophylaxis and therapeutics, in medical devices,

food industry and textile fabrics. The problems related to toxicity of nanoparticles will be addressed in brief.

Keywords: Nanoparticles, antimicrobials agents, therapeutics, drug resistance.

1. Introduction

The emerging infectious diseases and the development of drug resistance in the pathogenic bacteria and fungi at analarming rate is a matter of serious concern. Despite the increased knowledge of microbial pathogenesis and applicationof modern therapeutics, the morbidity and mortality associated with the microbial infections still remains high [1].Therefore, there is a pressing demand to discover novel strategies and identify new antimicrobial agents from natural

and inorganic substances to develop the next generation of drugs or agents to control microbial infections.Prior to the extensive use of chemotherapeutics in modern health care system, inorganic antimicrobials such as silver

and copper were used since ancient times to treat microbial infections [2]. In the recent times, the advances in the fieldof nanosciences and nanotechnology has brought to fore the nanosized inorganic and organic particles which are findingincreasing applications as amendments in industrial, medicine and therapeutics, synthetic textiles and food packaging products [3].

Nanoparticles usually ranging in dimension from 1-100 nanometers (nm) have properties unique from their bulk equivalent. With the decrease in the dimensions of the materials to the atomic level, their properties change. The

nanoparticles possess unique physico-chemical, optical and biological properties which can be manipulated suitably for desired applications [4]. Moreover, as the biological processes also occur at the nanoscale and due to their amenability

to biological functionalization, the nanoparticles are finding important applications in the field of medicine [5]. Thenanoparticles are broadly grouped into organic and inorganic nanoparticles. The latter have gained significantimportance due to their ability to withstand adverse processing conditions [6]. Currently, the metallic nanoparticles are

thoroughly being explored and extensively investigated as potential antimicrobials. The antimicrobial activity of thenanoparticles is known to be a function of the surface area in contact with the microorganisms. The small size and thehigh surface to volume ratio i.e., large surface area of the nanoparticles enhances their interaction with the microbes to

carry out a broad range of probable antimicrobial activities. Metal nanoparticles with antimicrobial activity whenembedded and coated on to surfaces can find immense applications in water treatment, synthetic textiles, biomedicaland surgical devices, food processing and packaging [7]. Moreover, the composites prepared using metal nanoparticlesand polymers can find better utilization due to the enhanced antimicrobial activity.

In this review, we focus on the role of various metallic nanoparticles as potential antimicrobials and the possiblemechanism of their inhibitory actions. The increasing application of nanoparticles as antimicrobials in industries,

medicine, cosmetics, textiles and food packaging which requires the assessment of the toxicity and risks associated withthese particles will also be reviewed.

197©FORMATEX 2011

Science against microbial pathogens: communicating current research and technological advances

A. Méndez-Vilas (Ed.) _______________________________________________________________________________

7/28/2019 197-209


2. Properties of Nanoparticles

The dimension of matter important in nanoscience and nanotechnology is typically on the 0.2- to 100-nm scale(nanoscale). The properties of materials change as their size approaches the nanoscale. Further, the percentage of atomsat the surface of a material becomes more significant [8]. Bulk materials possess relatively constant physical propertiesregardless of their size, but at the nanoscale this is often not the case. As the material becomes smaller the percentage of

atoms at the surface increases relative to the total number of atoms of the material bulk. This can lead to unexpected properties of nanoparticles which are partly due to the surface of the material dominating over the bulk properties. Atthis scale, the surface-to-volume ratios of materials become large and their electronic energy states become discrete,leading to unique electronic, optical, magnetic, and mechanical properties of the nanomaterials. In general, as the size of inorganic and organic materials decreases towards the nanoscale, their optical and electronic properties largely variesfrom the bulk material at the atomic/molecular levels and is size and shape dependent. The various size dependent properties that can be observed are quantum confinement in semi-conductor particles, surface plasmon resonance in

noble metal particles and super paramagnetism in magnetic materials. Thus, the crystallographic surface structure andthe large surface to volume ratio make the nanoparticles exhibit remarkable properties. Moreover, the increased

catalytic activity due to morphologies with highly active facets and the tailoring of its synthesis as per the requirementmakes the nanoparticles an attractive tool to solve various technological problems [9-10].

In the field of medicine, nanoparticles are being explored extensively because of their size dependant chemical and physical properties. The size of nanoparticles is similar to that of most biological molecules and structures. This makes

them an interesting candidate for application in both in vivo and in vitro biomedical research. The result of their integration in the field of medicine has led to their application mainly in targeted drug delivery, imaging, sensing, and

artificial implants. Another interesting avenue for their exploration in medicine is their use as antimicrobials to targethighly pathogenic and drug resistant microbes. But, for the application of nanoparticles in biology, biocompatibility is ahighly desired trait. Biocompatibility is the materials ability to perform medically without exertion of undesired local or systemic effects [11].

3. Nanoparticles as antimicrobials

3.1 Antibacterial activity of nanoparticles

3.1.1 Silver nanoparticles

Silver compounds have been used to treat burns, wounds and infections [12]. Various salts of silver and their derivatives are used as antimicrobial agents [13-14]. Recent studies have reported that nanosized silver particles exhibitantimicrobial properties [15-16]. Nanoparticles of silver have been studied as a medium for antibiotic delivery, and tosynthesize composites for use as disinfecting filters and coating materials [17-19].Several mechanisms have been proposed to explain the inhibitory effect of silver nanoparticles on bacteria. It isassumed that the high affinity of silver towards sulfur and phosphorus is the key element of the antimicrobial effect.

Due to the abundance of sulfur-containing proteins on the bacterial cell membrane, silver nanoparticles can react withsulfur-containing amino acids inside or outside the cell membrane, which in turn affects bacterial cell viability. It was

also suggested that silver ions (particularly Ag+) released from silver nanoparticles can interact with phosphorus

moieties in DNA, resulting in inactivation of DNA replication, or can react with sulfur-containing proteins, leading to

the inhibition of enzyme functions [20-21]. The general understanding is that Ag nanoparticle of typically less than 20nm diameters get attached to sulfur-containing proteins of bacterial cell membranes leading to greater permeability of the membrane, which causes the death of the bacteria [22].

The dose dependent effect of silver nanoparticles (in the size range of 10-15 nm) on the Gram-negative and Gram- positive microorganisms has been studied [23]. At micromolar levels of Ag+ ions have been reported to uncouple

respiratory electron transport from oxidative phosphorylation, inhibit respiratory chain enzymes, or interfere with themembrane permeability to protons and phosphate [24-26]. In addition, higher concentrations of Ag+ ions have been

shown to interact with cytoplasmic components and nucleic acids [27-28].The effect of silver nanoparticles on the cell morphology of Escherichia coli and Staphylococcus aureus has been

studied using TEM, SEM and X-ray microanalyses [29-30]. It was revealed that treatment with the silver ions results insimilar morphological changes in both the Gram positive and Gram negative bacteria. The cytoplasmic membrane

detaches from cell walls and an electron-light region containing condensed deoxyribonucleic acid molecules appears inthe centre of the cell. The inhibitory activity of silver ions is higher in case of Gram negative bacteria. This might be

due to the thickness of the peptidoglycan layer in Gram-positive bacteria cell wall which may prevent to some extent,the action of the silver ions [29]. The formation of electron-dense granules containing silver ions and sulphur ions in thecytoplasm of the bacterial cell suggests that the possible mechanism of action of silver nanoparticles may be due to the

198 ©FORMATEX 2011


A. Méndez-Vilas (Ed.) ______________________________________________________________________________

7/28/2019 197-209


interaction of silver ions with nucleic acids and impairment of DNA replication which results in loss of cell viabilityand eventually resulting in cell death [31].

The bactericidal effect of silver nanoparticles typically ranging from 2 to 5 nm has been investigated using greenfluorescent protein (GFP)-expressing recombinant Escherichia coli [32]. Apart from the conventional viability tests, the

morphological changes of the fluorescent bacteria and electrophoretic analysis of cellular DNA and protein migration profiles were performed to establish the effect of silver nanoparticles on GFP bacteria. The silver nanoparticles of less

than 10 nm diameters attached to the bacterial cell wall causes perforation of the cell wall, which leads to the cell death.This study suggests that the mode of action of silver nanoparticles is that the NPs get attached to the sulfur-containing proteins on the bacterial cell wall, leading to increased permeability of the membrane, finally causing cell death [32].

There are also studies reporting that metal ions induce generation of intracellular reactive oxygen species in bacterialcells [33]. Ag ions released by active surfaces of silver nanoparticles and silver oxide present on the surfaces of thesenanoparticles are reported to be the actual biocidal agents [34]. The silver ions enter the bacterial cells, where they arereduced as the cell attempts to remove them from the cell interior, eventually leading to cell destruction [22]. It has been

recently demonstrated that silver nanoparticles of less than 10 nm diameter make pores on the bacterial cell walls. Thecytoplasmic content is released to the medium, which leads to cell death without affecting the intracellular and

extracellular proteins and nucleic acids of the bacterium [34].It has been demonstrated that composites of silver nanoparticles with polymer results in the improvement of

antimicrobial activities of silver nanoparticles at lower concentrations [35-37]. Among the polymers chitosan, a cationic polysaccharide composing randomly distributed (1,4)-linked 2-amino-2-deoxy-β-D-glucose units has been reported to

be used as such or in the form of composite with silver nanoparticles with high antimicrobial efficacies. It is generallyaccepted that polycationic chitosan can bind with negatively charged cell membranes, which will then lead to decreasein the osmotic stability of the cell, followed by subsequent leakage of intracellular constituents. The chitosan silver

nanoparticles have enhanced antimicrobial activity than its individual components i.e. chitosan and silver. In thecomposite, the essential function of the positively charged chitosan matrix was to capture negatively charged bacteriaon its surface, while small sized Ag NPs created pores on bacterial wall, thereby causing rapid disintegration of the bacteria [38].

A proteomic approach (two dimensional electrophoresis and proteins identification by mass spectrometry) was usedto investigate the mode of antibacterial action of nano-Ag against E. coli [39]. The proteomic studies revealed for thefirst time, several primary actions of nano-Ag in E. coli cells, namely in envelope protein processing, outer membrane permeability, plasma membrane potential and energization. The proteomic analyses revealed that just a short exposure

of E. coli cells to nano-Ag resulted in alterations in the expressions of a number of envelope proteins and heat shock proteins which are usually induced in a variety of stress conditions. The envelope proteins (OmpA, OmpC, OmpF,

OppA, and MetQ) are integral outer membrane or periplasmic components guarding against the entry of foreignsubstances. In particular, the expression of the heat shock proteins IbpA and IbpB is stimulated during the over expression of heterologous proteins that are associated inclusion bodies [40-43]. The treatment with nano-Agdestabilizes the outer membrane and disrupts the outer membrane barrier components such as lipopolysaccharide or

porins, culminating in the perturbation of the cytoplasmic membrane. The proteomic signatures of nano-Ag treated E.coli cells are characterized by an accumulation of envelope protein precursors. This indicates that nano-Ag may target

the bacterial membrane, leading to a dissipation of the proton motive force. Although the detailed mechanism by whichnanoparticles with a diameter of 10 nm can penetrate and disrupt the membranes remains to be elucidated, electronmicroscopy and optical imaging results suggest that nano-Ag penetrate the outer and inner membranes of the Gramnegative bacteria, with some nanoparticles found intracellularly [41]. Nano-Ag and Ag

+ ions share a similar membrane-

targeting mechanism of action. But the effective concentrations of nano-Ag and Ag+

ions are at nanomolar andmicromolar levels, respectively. Nano-Ag appears to be significantly more efficient than Ag+ ions in mediating their

antimicrobial activities [44].

Size-controlled silver colloid nanoparticles generated using a one-step modified Tollens process was assessed for antimicrobial activity against drug resistant pathogens [45]. The pH and type of reducing saccharide of the reactionsystem were found to influence the size of particles. A wide range of particle size, particularly 25-100 nm with narrowsize distributions were obtained using four different saccharides. Nanoparticles with size less than 25 nm have exhibitedminimum inhibitory concentration of 6.75-54 μg/mL whereas 25 nm size particles showed MIC in the range of 1.69-

13.5 μg/mL against including highly multiresistant bacteria such as methicillin-resistant Staphylococcus aureus,methicillin-resistant coagulase-negative staphylococci (e.g., Staphylococcus epidermidis), vancomycin-resistant Enterococcus faecium, and ESBL-positive Klebsiella pneumoniae. This is an important result, particularly whenantibiotic resistance among bacterial species is increasing at an alarming rate and very few alternative options areavailable to address the issue.

Silver nanoparticles have been evaluated for their antimicrobial activities against a wige range of pathogenic

organisms [46-51]. The highest sensitivity was observed against Methicillin resistant Staphylococcus aureus (MRSA)followed by Methicillin resistant Staphylococcus epidermidis (MRSE) and Streptococcus pyogenes. A moderate

antimicrobial activity was observed in case of the gram negative pathogens Salmonella typhi and Klebsiella pneumonia[52].

199©FORMATEX 2011


A. Méndez-Vilas (Ed.) _______________________________________________________________________________

7/28/2019 197-209


The size of the particle plays a central role in antimicrobial activity [22] The colloidal silver particles, with variable

sizes (44, 50, 35, and 25 nm), synthesized by the reduction of [Ag (NH3)2]+ complexes with carbohydrates were tested

for antimicrobial activity [45]. The antibacterial activity was particle size dependent. The silver nanoparticles alsoexhibit a shape-dependent interaction with the bacterial cells. The truncated triangular silver nanoplates displayed thestrongest biocidal action against E. coli, when than the spherical and rod-shaped nanoparticles [53].

Small particles exhibited higher antimicrobial activity than big particles. This result can be due to high particle

penetration when these particles have smaller sizes. The antibacterial properties are related to the total surface area of the nanoparticles. Smaller particles with larger surface to volume ratios have greater antibacterial activity [ 54-56].

3.1.2 Gold nanoparticles

The therapeutic use of gold can be traced back to the Chinese medical history in 2500 BC. Red colloidal gold is stillused in the Indian Ayurvedic medicine for rejuvenation and revitalization during old age under the name of SwarnaBhasma (“Swarna” meaning gold, “Bhasma” meaning ash) [57-58]. Gold also has a long history of use in the westernworld as nervine, a substance that could revitalize people suffering from nervous conditions. In the 16th century gold

was recommended for the treatment of epilepsy. In the beginning of the 19th century gold was used in the treatment of syphilis. Following the discovery of the bacteriostatic effect of gold cyanide towards the tubercle bacillus by Robert

Koch, gold based therapy for tuberculosis was introduced in 1920s [59]. The major clinical uses of gold compounds arein the treatment of rheumatic diseases including psoriasis, juvenile arthritis, planindromic rheutamitism and discoidlupus erythematosus [60].

Au particles are particularly and extensively exploited in organisms because of their biocompatibility [61-62]. Gold

nanoparticles (Au) generally are considered to be biologically inert but can be engineered to possess chemical or photothermal functionality. On near infrared (NIR) irradiation the Au-based nanomaterials, Au nanospheres, Au

nanocages, and Au nanorods with characteristic NIR absorption can destroy cancer cells and bacteria via photothermalheating. Au-based nanoparticles can be combined with photosensitizers for photodynamic antimicrobial chemotherapy.Au nanorods conjugated with photosensitizers can kill MRSA by photodynamic antimicrobial chemotherapy and NIR photothermal radiation [63-64]. A hydrophilic photosensitizer, toluidine blue O was conjugated on the surface of Aunanorods for photodynamic antimicrobial chemotherapy. The Au nanorods served as both photodynamic and photothermal agents and inactivated MRSA. The combined effect of PACT and hyperthermia has enhancedantimicrobial effect of gold nanoparticle. The study clearly showed that gold nanorods conjugated with a hydrophilic

photosensitizer such as toluidine blue O act as dual-function agents in photodynamic inactivation and hyperthermiaagainst methicillin-resistant Staphylococcus aureus [65-66]. Light absorbing gold nanoparticles conjugated with

specific antibodies have also been exploited to photothermally kill Staphylococcus aureus by using laser [67]. Recentstudies have focussed on functionalising the gold nanoparticles as phothermal agents for hyperthermically killing pathogens [68-70]

The efficacy of the antibacterial activity of gold nanoparticles can be increased by adding antibiotics [71].The

antimicrobial activity of the antibiotic vancomycin was enhanced on coating with gold nanoparticle against vancomycinresistant enterococci (VRE) [72]. The coating of aminoglycosidic antibiotics with gold nanoparticles has an

antibacterial effect on a range of Gram-positive and Gram-negative bacteria [73-74]. Cefaclor (a second-generation β-lactam antibiotic) reduced gold nanoparticles have potent antimicrobial activity on both Grampositive (S. aureus) andGram-negative bacteria ( E. coli) compared to cefaclor and gold nanoparticles alone. Cefaclor inhibits the synthesis of the peptidoglycan layer, making cell walls porous. Further, the gold nanoparticles generate holes in the cell wall,resulting in the leakage of cell contents and cell death. It is also possible that gold nanoparticles bind to the DNA of bacteria and inhibit the uncoiling and transcription of DNA [75].The Au nanoparticles can be used to coat a wide

variety of surfaces for instance implants, fabrics for treatment of wounds and glass surfaces to maintain hygienicconditions in the home, in hospitals and other places [76].

3.1.3 Magnesium oxide nanoparticles

Highly ionic nanoparticulate metal oxides can be prepared with extremely high surface areas and unusual crystalmorphologies having numerous edge/corner and reactive surface sites [77]. Magnesium oxide (MgO) prepared throughan aerogel procedure (AP-MgO) yields square and polyhedral shaped nanoparticles with diameters varying slightlyaround 4 nm, arranged in an extensive porous structure with considerable pore volume [78]. An interesting property of

AP-MgO nanoparticles is their ability to adsorb and retain for a long time (in the order of months) significant amountsof elemental chlorine and bromine [79]. The AP-MgO/X2 nanoparticles exhibited biocidal activity against certainvegetative Gram-positive bacteria, Gram-negative bacteria and the spores [80]. AP-MgO nanoparticles are found to possess many properties that are desirable for a potent disinfectant [81]. Because of their high surface area and

enhanced surface reactivity, the nanocrystals adsorb and carry a high load of active halogens. Their extremely small sizeallows many particles to cover the bacteria cells to a high extent and bring halogen in an active form in high

concentration in proximity to the cell [80]. Standard bacteriological tests have shown excellent activity against E.coli

200 ©FORMATEX 2011


A. Méndez-Vilas (Ed.) ______________________________________________________________________________

7/28/2019 197-209


and Bacillus megaterium and a good activity against spores of Bacillus subtilis [81]. The bioactivity of AP-MgO/X2nanoparticles is due to the positive charge they have in water suspension, opposite to those of the bacteria and sporecells, which enhances the total bactericidal effect. Confocal microscopy studies have shown that in water suspension theopposite charge brings the bacteria and nanoparticles together in aggregates composed of both AP-MgO nanoparticles

and bacteria. Atomic force microscopy and electron microscopy studies demonstrate that halogenated magnesium oxidehas a very strong influence on microorganisms and their membranes in particular. Overall, the halogen such as chlorine

and bromine treated MgO nanoparticles have a stronger and faster effect on the killing action of both bacteria andspores [81].

3.1.4 Copper oxide nanoparticles

Copper oxide (CuO) is a semiconducting compound with a monoclinic structure. It is the simplest member of the familyof copper compounds and exhibits a range of potentially useful physical properties such as high temperature,

superconductivity, electron correlation effects and spin dynamics. Therefore, it finds a wide application [82-83]. CuOcrystal also has photocatalytic or photovoltaic properties and photoconductive functionalities [84]. There is limited

information available about the antimicrobial activity of nano CuO. As CuO is cheaper than silver, easily mixes with polymers and relatively stable in terms of both chemical and physical properties, it finds a wide application [85]. It issuggested that highly ionic nanoparticulate metal oxides, such as CuO, may find potential application as antimicrobialagents as they can be prepared with extremely high surface areas and unusual crystal morphologies [77].

CuO nanoparticles were effective in killing a range of bacterial pathogens involved in hospital-acquired infections.But a high concentration of nano CuO is required to achieve a bactericidal effect [86]. It has been suggested that the

reduced amount of negatively charged peptidoglycans makes Gram-negative bacteria such as Pseudomonas aeruginosaand Proteus spp. less susceptible to such positively charged antimicrobials. However, in the time–kill experiments theGram-negative strains showed a greater susceptibility to nano CuO combined nano Ag. Studies have been conducted toassess the potential of nano CuO embedded in a range of polymer materials. A lower contact-killing ability was

observed in comparison with release killing ability against MRSA strains. This suggests that a release of ions into thelocal environment is required for optimal antimicrobial activity [86-87].

Copper nanoparticles have a high antimicrobial activity against B. subtilis. This may be attributed to greater abundanceof amines and carboxyl groups on cell surface of B. subtilis and greater affinity of copper towards these groups. Copper ions released may also interact with DNA molecules and intercalate with nucleic acid strands. Copper ions inside bacterial cells also disrupt biochemical processes [88]. The exact mechanism behind bactericidal effect of copper nanoparticles is not clear.

3.1.5 Aluminium nanoparticles

Aluminum oxide NPs have wide-range applications in industrial and personal care products. The growth-inhibitory

effect of alumina NPs over a wide concentration range (10–1000 μg/mL) on Escherichia coli have been studied [89].Fourier transform–infrared studies have shown differences in structure between nanoparticles treated and untreatedcells. Alumina nanoparticle have exhibited a mild growth-inhibitory effect, only at very high concentrations. This isattributed to surface charge interactions between the particles and cells. It is possible that the free-radical scavenging properties of the particles might have prevented cell wall disruption and drastic antimicrobial action [89].

Alumina is thermodynamically stable over a wide temperature range and has a corundum-like structure, with oxygen

atoms adopting hexagonal close packing and Al3+

ions filling two thirds of the octahedral sites in the lattice [90]. Thealumina nanoparticles carry a positive charge on its surface at near-neutral pH. The electrostatic interaction between thenegatively charged E. coli cells and the particles resulted in the adhesion of nanoparticles on the bacterial surfaces [91].

The adhesion increased with increase in concentration of the particles in the suspension, a negative effect on growthwas observed with respect to concentration. This electrostatic interaction between bacteria and particle surface, alongwith hydrophobic interactions and polymer bridging, may be responsible for the phenomenon of bacterial adhesion onto

the particles. The antimicrobial property of these metal oxides is attributed to the generation of reactive oxygen species(ROS) which causes disruption of cell wall and subsequntly cell death [88]. But alumina NPs may act as free radicalscavengers. These NPs are able to rescue cells from oxidative stress-induced cell death in a manner that appears to bedependent upon the structure of the particle but independent of its size within the range of 6–1000 nm [92].

3.1.6 Titanium dioxide nanoparticles

The inhibitory activity of TiO2 is due to the photocatalytic generation of strong oxidizing power when illuminated with

UV light at wavelength of less than 385 nm [93-95]. TiO2 particles catalyze the killing of bacteria on illumination bynear-UV light. The generation of active free hydroxyl radicals (

_ OH) by photoexcited TiO2 particles is probably

responsible for the antibacterial activity [96-98]. The antimicrobial effect of TiO2 photocatalyst on Escherichia coli inwater and its photocatalytic activity against fungi and bacteria has been demonstrated [99-102].

201©FORMATEX 2011


A. Méndez-Vilas (Ed.) _______________________________________________________________________________

7/28/2019 197-209


There are also studies on bactericidal activity of nitrogen-doped metal oxide nanocatalysts on E. coli biofilms and onthe photocatalytic oxidation of biofilm components on TiO2- coated surfaces [100]. In conclusion, the use of TiO2 photocatalysts as alternative means of self-disinfecting contaminated surfaces by further development may provide potent disinfecting solutions for prevention of biofilm formation. TiO2 photocatalysts can be used as effective biofilm

disinfectant in food processing industries [103-104]. Suspensions containing TiO2 are effective at killing Escherichiacoli. This has led to the development of photocatalytic methods for the killing of bacteria and viruses using TiO2 in

aqueous media [105-106].It has been suggested that nanostructured TiO2 on UV irradiation can be used as an effective way to reduce the

disinfection time, eliminating pathogenic microorganisms in food contact surfaces and enhance food safety [93]. Themajor disadvantage of using TiO2 is that UV light is required to activate the photocatalyst and initiate the killing of the bacteria and viruses. In recent years, visible light absorbing photocatalysts with Ag/AgBr/TiO2 has proved to besuccessful at killing S. aureus and E. coli [107-108].

3.1.7 Zinc oxide nanoparticles

Among the various metal oxides studied for their antibacterial activity, zinc oxide nanoparticles have been found to behighly toxic. Moreover, their stability under harsh processing conditions and relatively low toxicity combined with the potent antimicrobial properties favours their application as antimicrobials [77]. Many studies have shown that some NPs made of metal oxides, such as ZnO NP, have selective toxicity to bacteria and only exhibit minimal effect on

human cells, which recommend their prospective uses in agricultural and food industries [109-112].The antimicrobial activity of zinc oxide nanoparticles have been studied against the food related bacteria Bacillus

subtilis, Escherichia coli and Pseudomonas fluorescens [113]. ZnO NP could potentially be used as an effectiveantibacterial agent to protect agricultural and food safety from foodborne pathogens, especially E. coli O157:H7 [112].ZnO NPs possess antimicrobial activities against Listeria monocytogenes, Salmonella enteritidis and E. coli O157:H7 inculture media [113]. There are also other studies confirming the strong antimicrobial activity of ZnO nanoparticleswherein the nanoparticles could completely lyse the food-borne bacteria Salmonella typhimurium and Staphylococcusaureus [114]. In another study, ZnO nanoparticles (12 nm) inhibited the growth of E. coli by disintegrating the cellmembrane and increasing the membrane permeability [115].

The above findings suggest that ZnO nanoparticles can find applications in food systems and can be used to inhibitgrowth of pathogenic bacteria.

There are several mechanisms which have been proposed to explain the antibacterial activity of ZnO nanoparticles.The generation of hydrogen peroxide from the surface of ZnO is considered as an effective mean for the inhibition of

bacterial growth [116]. It is presumed that with decreasing particle size, the number of ZnO powder particles per unitvolume of powder slurry increases resulting in increased surface area and increased generation of hydrogen peroxide.Another possible mechanism for ZnO antibacterial activity is the release of Zn

2+ions which can the damage cell

membrane and interact with intracellular contents [109].

3.2 Antiviral studies on nanoparticles

The antibacterial property of metal nanoparticles has been extensively explored. But the anti-viral properties of metal

nanoparticles remain an undeveloped area [117]. The diseases caused by viruses present challenging problems withworldwide social and economic implications. Developing antiviral drugs which can target the virus and maintaininghost cell viability is challenging [118]. Metal NPs have been proposed as anti-viral systems taking advantage of the corematerial and/or the ligands shell [119].

Silver nanoparticles have proven to exert antiviral activity against HIV-1 at non-cytotoxic concentrations [120].

Using a number of in vitro assays, the mode of antiviral action of silver nanoparticles against HIV-1 was elucidated. Itwas revealed that silver nanoparticles exert anti-HIV activity at an early stage of viral replication, most likely as avirucidal agent or as an inhibitor of viral entry. Silver nanoparticles prevent CD4-dependent virion binding, fusion, andinfectivity, acting as an effective virucidal agent against both cell-free virus and cell-associated virus. Besides, silver nanoparticles inhibit post-entry stages of the HIV-1 life cycle. It can be concluded that these properties make them a broad-spectrum agent not prone to inducing resistance that could be used preventively against a wide variety of circulating HIV-1 strains [120].

Gold nanoparticles have also been explored for their anti-HIV activity [119]. The gold nanoparticles coated withmultiple copies of an amphiphilic sulfate-ended ligand bind the HIV envelope glycoprotein gp120 and inhibit the HIVinfection of T-cells at nanomolar concentrations in vitro. Nanoparticle-based presentation of multiple ligands creates ahigh local concentration of binding molecules which can assist the targeted biological interaction. It is suggested thatthe multivalent gold nanoparticles coated with sulfated ligands can be considered a novel alternative to the known anti-HIV systems for targeting the adsorption/fusion process of the virus infection. Depending on the ligand density, these

NPs can bind gp120 with high affinity [119]. The possibility of simultaneously tailoring on the same gold nanoplatform both sulfated ligands and other active molecules which target different stages of the HIV life cycle makes gold

202 ©FORMATEX 2011


A. Méndez-Vilas (Ed.) ______________________________________________________________________________

7/28/2019 197-209


nanoparticles an appealing scaffold which can contribute to the development of new multifunctional anti-HIV systems[121].

The use of gold nanoparticles with different anionic groups to inhibit influenza has also been reported [122]. Theanionic gold nanoparticles have shown effective inhibition properties against several influenza strains. The primary

mechanism of inhibition was due to the blocking of viral attachment to cell surface. The variation in the degree of inhibition with the anionic groups indicated that in the antiviral activity of the nanoparticles, the charge density and the

functional group itself has a role to play. The end groups present on the surface of the anionic gold functionalizedgroups may interact with the viruses by multivalent bonds. The small size of the gold nanoparticles (Au-NPs) enablesthem to enter the cell through the endosome vesicle allowing them to possibly interfere with the fusion step as well[123]. Several publications demonstrated low or no Au-NPs cytotoxicity, and their toxicity if present is dependent on

the particle’s surface charge, size and shape [124]. The NPs composed of an Au core and mercaptoethanesulfonate(MES) molecules bonded to its surface through the thiol group exhibited no cytotoxicity and inhibited different

influenza virus types and strains (including the recent pandemic swine influenza A (H1N1) strain), indicating that theinteraction is not limited to a specific strain. This property is crucial for antiviral compounds, which need to beunaffected by random viral genetic mutations.

There are also studies on the inhibition of Herpes simplex virus Type 1 infection by silver nanoparticles capped withmercaptoethane sulfonate [118]. These nanoparticles target the virus by competing for its binding to cellular heparansulfate through their sulfonate end groups. This results in the blockage of viral entry into the cell and prevention of

subsequent infection. Effective inhibition of HSV-1 infection in cell culture by the capped nanoparticles has been

demonstrated. There are no toxic effects of these nanoparticles on host cells. The capped nanoparticles can serve asuseful topical agents for the prevention of infections with pathogens dependent on heparan sulfate for entry.

There are also several studies which report the antiviral activity of silver nanoparticles against the hepatitis B virus,respiratory syncytial virus, HIV 1 and monkeypox virus [125-128].

These studies suggest that metal nanoparticles with functionalized groups have enhanced antiviral activity and may

possibly help in combating viral infections.

3.3 Antifungal activity of metal nanoparticles

In the recent years, severe fungal infections have significantly contributed to the increasing morbidity and mortality of immunocompromised patients who need intensive treatment including broad-spectrum antibiotic therapy [129].

There are limited studies on the antifungal activity of metal nanoparticles. The fungistatic and fungicidal effects of the silver NPs against selected pathogenic yeasts causing invasive life-threatening fungal infections in intensive care

patients has been studied. Silver NPs exhibit high antifungal activity against pathogenic Candida spp. at a concentrationof around 1 mg/L of Ag. Antifungal activity of the silver NPs is comparable with those of ionic silver [130].

The antifungal effects of spherical silver nanoparticles have been investigated against dermatophytes [131]. The Nano-Ag exhibited potent activity against clinical isolates and ATCC strains of Trichophyton mentagrophytes and

Candida species (IC80, 1-7 μg/ml). The activity of nano-Ag was comparable to that of amphotericin B and fluconazole.The antifungal activity of nano-Ag is attributed to its effects on the mycelia [131].

There are also reports of the application of nanosilver having antifungal activity in biostabilization of footwear materials, wherein, 1% solution inhibited the growth of the majority of yeast-like fungal and mold strains [132].

The mode of action of nano-Ag on fungi is by targeting the yeast cell membranes and disrupting membrane potential.

The transmission electron microscopy analysis has revealed that the interaction between nano-Ag and the membranestructure of C. albicans cells during nano-Ag exposure results in changes in the membranes of C. albicans, which can be observed as the “pits” on the membrane surfaces. The formation of pores subsequently leads to cell death [133].

4. Application of nanoparticles

It is evident that the metal based nanoparticles constitute an effective antimicrobial agent against common pathogenicmicroorganisms. Therefore, some of the nanoparticles such as silver, titanium dioxide and zinc oxide are receiving

considerable attention as antimicrobials and additives in consumer, health-related and industrial products [44]. As silver nanoparticles have a broad spectrum antimicrobial activity against several pathogens they are increasingly

incorporated into various matrices to extend their utility in materials and biomedical applications [50]. They are used asadditives in health related products such as bandages, catheters, and other materials to prevent infection, particularlyduring the healing of wounds and burns. An antibacterial Ag/Na carboxymethyl cotton burn dressing by the partialcation exchange of sodium with silver has been developed and these can find applications in surgical dressings. Theyare currently being added to many common household products such as bedding, washers, water purification systems,tooth paste, shampoo, fabrics, deodorants, filters, paints, kitchen utensils, toys, and humidifiers to impart antimicrobial

properties [55]. Nanoparticles of titanium dioxide are used in cosmetics, filters that exhibit strong germicidal properties and removeodors, and in conjunction with silver as an antimicrobial agent. Moreover, due to the photocatalytic activity, it has been

203©FORMATEX 2011


A. Méndez-Vilas (Ed.) _______________________________________________________________________________

7/28/2019 197-209


used in waste water treatment. It is considered non-toxic and has been approved by the American Food and DrugAdministration (FDA) for use in human food, drugs, cosmetics and food contact materials [134]. Nowadays titaniumdioxide nanoparticles are finding wide application as a self-cleaning and self-disinfecting material for surface coatingsin many applications and in food industries for disinfecting equipments [135].

Zinc oxide (ZnO) and copper oxide nanomaterials due to their antimicrobial property are being incorporated into avariety of medical and skin coatings. ZnO nanoparticles are used in the wallpapers in hospitals as antimicrobials. ZnO

powder is an active ingredient for dermatological applications in creams, lotions and ointments on account of itsantibacterial properties [90].

5. Toxicity of nanoparticles

It is evident from the above studies that metal nanoparticles due to their unique physico-chemical and biological

properties have far reaching industrial and medical applications. But there is a dearth of knowledge about the effect of the prolonged exposures to nanoparticle on human health and environment. The implication of nanoparticles on health

and environment needs to be assessed completely before their large-scale production and application in various fields[136-138]. Studies conducted on the NP-induced toxicity have revealed that the metal-based nanoparticles can affect the biological behavior at the organ, tissue, cellular, subcellular, and protein levels. The size of the nanoparticles is smalland these can easily access the skin, lungs, and brain and cause adverse affects [139-142]. For example, exposure of metal based nanoparticles to human lung epithelical cells leads to the generation of reactive oxygen species and result inoxidative stress and cellular damage. The toxicity of nanoparticles can be assessed by a number of in vitro and in vivo

studies. For example, the toxic effects of nanoparticles can be carried out using zebrafish as a model due to its fastdevelopment and transparent body structure. Cell culture based assays are used as a pre-screening tool to understand the biological effects of nanoparticles. However, along with the in vitro assays it is necessary to confirm the in vivo biological activities of nanoparticles in animal models to study the suitability of their application [143-144]. There is anincreasing use of microarray and real-time reverse transcription polymerase chain reaction for gene expression analysesas these are very sensitive and reliable methods to assess the changes in the expression levels of thousands of genes

simultaneously under a wide variety of experimental conditions [145].It is evident that metal based nanoparticles due to their biological and physiochemical properties are promising as

antimicrobials and therapeutic agents. They can be used to address a number of challenges in the field of nanomedicine.But it must be remembered that they can also possibly cause adverse biological effects at the cellular and subcellular levels. Therefore, after the cytotoxicity and clinical studies the nanoparticles can find immense application asantimicrobials in the consumer and industrial products.

Table 1 Antimicrobial activity of metal based nanoparticles.

Properties Mechanism of action Examples of nanoparticles

Antibacterial Interaction with phosphorus

moieties in DNA, resulting ininactivation of DNAreplication.Reacts with sulfur-containing

proteins, leading to theinhibition of enzymefunctions.

Silver nanoparticles have inhibitory activity against E. coli, B. subtilis, S. aureus, methicillin-resistant coagulase-negativestaphylococci, vancomycin-resistant Enterococcus faecium,ESBL-positive K. pneumonia, S. typhi, Vibri cholera[29, 30, 32, 45, 52].Gold nanoparticles have antibacterial activity against MRSA,VRE, E. coli, Pseudomonas aeruginosa [65-66, 72].MgO nanoparticles have excellent against E. coli, B.subtilis,

B.megaterium.[80,81]CuO strongly inhibits B.subtilis [86-88].

Aluminium oxide nanoparticles have growth inhibitory effect on E. coli [91].TiO2 nanoparticls are effective in killing E. coli, S.aureus, Listeriamonocytogenes [99-102, 107,108].ZnO nanoparticles inhibit food-borne bacteria E. coli0157:H7 ,B.subtilis, Pseudomonas fluorescens, L. monocytogenes,Salmonella enteritidis, S. aureus, S. typhimurium [113-115].

Antiviral Blocking of viral attachmentto cell surface.

Gold nanoparticles have anti-HIV activity and inhibit severalstrains of influenza virus [119-120].

Silver nanoparticles inhibit HIV-1, Influenza virus, HerpesSimplex virus, Respiratory syncytial virus, Monkey pox virus[118,120, 125-128].

Antifungal Disruption of cell membrane. Silver nanoparticles have fungicidal and fungistatic effects on the

dermatophytes Trichophyton mentagrophytes and Candida species[130-133].

204 ©FORMATEX 2011


A. Méndez-Vilas (Ed.) ______________________________________________________________________________

7/28/2019 197-209


References

[1] Kolar M, Urbanek K, Latal T. Antibiotic selective pressure and development of bacterial resistance. Int J Antimicrob Ag .2001;17:357–363.

[2] Moghimi SM. Nanomedicine: prospective diagnostic and therapeutic potential. Asia Pacific Biotech News. 2005;9:1072-

1077.[3] Gajjar P, Pettee B, Britt DW, Huang W, Johnson WP, Anderson J. Antimicrobial activities of commercial nanoparticles

against an environmental soil microbe, Pseudomonas putida KT2440. Journal of Biological Engineering . 2009;3:9-22.[4] Feynman R. There's plenty of room at the bottom. Science. 1991;254:1300-1301.[5] Parak WJ, Gerion D, Pellegrino T, Zanchet D, Micheel C, Williams CS, Boudreau R, Le Gros MA, Larabell CA, Alivisatos

AP: Biological applications of colloidal nanocrystals. Nanotechnology. 2003;14:15-27. [6] Whitesides GM. The 'right' size in Nanobiotechnology. Nature Biotechnology. 2003; 21:1161-1165.

[7] Gutierrez FM, Olive PL, Banuelos A, Orrantia E, Nino N, Sanchez EM, Ruiz F, Bach H, Gay YA. Synthesis,characterization, and evaluation of antimicrobial and cytotoxic effect of silver and titanium nanoparticles. Nanomedicine.2010;6:681-688.

[8] Eustis S, El-Sayed MA. Why gold nanoparticles are more precious than pretty gold: Noble metal surface plasmon resonanceand its enhancement of the radiative and nonradiative properties of nanocrystals of different shapes. Chemical Society

Reviews. 2006; 35:209-217. [9] Gupta AK, Gupta M. Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications.

Biomaterials. 2005; 26:3995-4021.[10] Jamieson T, Bakhshi R, Petrova D, Pocock R, Imani M, Seifalian AM. Biological applications of quantum dots.

Biomaterials.2007; 28: 4717-4732.[11] Samia ACS, Dayal S, Burda C. Quantum dot-based energy transfer: Perspectives and potential for applications in

photodynamic therapy. Photochemistry and Photobiology. 2006; 82:617-625.[12] Dunn K, Edwards-Jones V. The role of Acticoat with nanocrystalline silver in the management of burns. Burns. 2004;

30:1–9.[13] Russell AD, Hugo WB. Antimicrobial activity and action of silver. Prog. Med. Chem. 1994;31:351-370.

[14] Ip M, Lui SL, Poon VK, Lung I, Burd A. Antimicrobial activities of silver dressings: an in vitro comparison. J Med Microbiol . 2006; 55:59–63.

[15] Petica A, Gavriliu S, Lungu M, Buruntea N, Panzaru C. Colloidal silver solutions with antimicrobial properties. Mater Sci Eng . 2008;152:22–27.

[16] Rai M, Yadav A, Gade A. Silver nanoparticles as a new generation of antimicrobials. Biotechnol Adv. 2009; 27:76–83.[17] Kim JS, Kuk E, Yu KN, Kim JH, Park SJ, Lee HJ, Kim SH, Park YK, Park YH, Hwang CY, Kim YK, Lee YS, Jeong DH,

Cho MH. Antimicrobial effects of silver nanoparticles. Nanomedicine. 2007;3:95–101.

[18] Li P, Li J, Wu C, Wu Q, Li J. Synergistic antibacterial effects of β -lactam antibiotic combined with silver nanoparticles.

Nanotechnology. 2005;16:1912–1917.[19] Ruparelia JP, Duttagupta SP, Chatterjee AK, Mukherji SM. A comparative study on disinfection potential of nanosilver andnanonickel. Technical poster, Proceedings of the 9th Annual Conference of the Indian Environmental Association(Envirovision-2006), entitled ‘‘Advances in Environmental Management and Technology”, Goa, India, September 21–23,

2006.[20] Gupta A, Silver S. Silver as a biocide: will resistance become a problem? Nat Biotechnol . 1998;16:888-890.

[21] Matsumura Y, Yoshikata K, Kunisaki S, Tsuchido T. Mode of bactericidal action of silver zeolite and its comparison withthat of silver nitrate. Appl Environ Microbiol . 2003; 69:4278-4281.

[22] Morones JR, Elechiguerra JL, Camacho A, Holt K, Kouri JB, Yacaman MJ. The bactericidal effect of silver nanoparticles. Nanotechnology. 2005;16:2346–2353.

[23] Shrivastava S, Bera T, Roy A, Singh G, Ramachandrarao P, Dash D. Characterization of enhanced antibacterial effects of novel silver nanoparticles. Nanotechnology. 2007;18:1–9.

[24] Bard AJ, Holt KB. Interaction of Silver(I) Ions with the Respiratory Chain of Escherichia coli: An Electrochemical and

Scanning Electrochemical Microscopy Study of the Antimicrobial Mechanism of Micromolar Ag+. Biochemistry. 2005;44:13214-13223.

[25] Schreurs WJ, Rosenberg H. Effect of silver ions on transport and retention of phosphate by Escherichia coli. J. Bacteriol.1982, 152:7-13.

[26] Bragg PD, Rainnie DJ. The effect of silver ions on the respiratory chain of Escherichia coli. Can. J. Microbiol. 1974; 228:883-889.

[27] Semeykina AL, Skulachev VP. Submicromolar Ag+ increases passive Na+ permeability and inhibits the respiration-supported formation of Na+ gradient in Bacillus FTU vesicles. FEBS Lett. 1990; 269: 69-72.

[28] Dibrov P, Dzioba J, Gosink KK, Hase CC. Chemiosmotic mechanism of antimicrobial activity of Ag+ in Vibrio cholerae. Antimicrob. Agents Chemother. 2002; 46: 2668-2670.

[29] Feng QL, Wu J, Chen GQ, Cui FZ, Kim TN, Kim JO. A mechanistic study of the antibacterial effect of silver ions on Escherichia coli and Staphylococcus aureus. J Biomed Mater Res. 2000;52:662-668.

[30] Jung WK, Koo HC, Kim KW, Shin S, Kim SH, Park YH. Antibacterial activity and mechanism of action of the silver ionin Staphylococcus aureus and Escherichia coli. Appl. Environ. Microbiol. 2008; 74:2171-2178.

[31] Gogoi SK, Gopinath P, Paul A, Ramesh A, Ghosh SS, Chattopadhyay A. Green fluorescent protein-expressing Escherichiacoli as a model system for investigating the antimicrobial activities of silver nanoparticles. Langmuir 2006;22:9322–9328.

[32] Alexander S, Klabunde K J, George MR, Christopher MS. Biocidal activity of nanocrystalline silver powders and particles. Langmuir 2008;24:7457–7464.

[33] Stohs SJ, Bagchi D. Oxidative mechanisms in the toxicity of metal ions. Free Radic Biol Med . 1995;18:321–36.

205©FORMATEX 2011


A. Méndez-Vilas (Ed.) _______________________________________________________________________________

7/28/2019 197-209


[34] Sondi I, Salopek-Sondi B. Silver nanoparticles as antimicrobial agent: A case study on E. coli as a model for Gram-

negative bacteria. J Colloid Interface Sci. 2004;275:177–182.[35] Aymonier C, Schlotterbeck U, Antonietti L, Zacharias P, Thomann R, Tiller JC, Mecking S. Hybrids of silver

nanoparticles with amphiphilic hyperbranched macromolecules exhibiting antimicrobial properties. Chem. Commun. 2002;3018-3019.

[36] Melaiye A, Sun Z, Hindi K, Milsted A, Ely D, Reneker DH, Tessier CA, Youngs WJ. Silver(I)-imidazole cyclophane gem-

diol complexes encapsulated by electrospun tecophilic nanofibers: formation of nanosilver particles and antimicrobial

activity. J. Am. Chem. Soc. 2005; 127: 2285-2291.[37] Kumar R, Munstedt H. Silver ion release from antimicrobial polyamide/silver composites. Biomaterials. 2005; 26: 2081–

2088.

[38] Banerjee M, Mallick S, Paul A, Chattopadhyay A, Ghosh SS. Heightened Reactive Oxygen Species Generation in theAntimicrobial Activity of a Three Component Iodinated Chitosan-Silver Nanoparticle Composite. Langmuir . 2010; 26:

5901–5908.[39] Lok CN, Ho CM, Chen R, He QY, Yu WY, Sun H, Tam PK, Chiu JF, Che CM. Proteomic analysis of the mode of

antibacterial action of silver nanoparticles. J Proteome Res. 2006;5:916–924.

[40] Otani M, Tabata J, Ueki T, Sano K, Inouye S. Heat-shock induced proteins from Myxococcus xanthus. J. Bacteriol.

2001;183: 6282-6287.[41] Jakob U, Gaestel M, Engel K, Buchner J. Small heat shock proteins are molecular chaperones. J. Biol. Chem. 1993;268:

1517-1520.

[42] Kitagawa M, Matsumura Y, Tsuchido T. Small heat shock proteins, IbpA and IbpB, are involved in resistances to heat andsuperoxide stresses in Escherichia coli. FEMS Microbiol. Lett. 2000;184:165-171.

[43] Allen SP, Polazzi JO, Gierse JK, Easton AM. Two novel heat shock genes encoding proteins produced in response toheterologous protein expression in Escherichia coli. J. Bacteriol. 1992;174:6938-6947.

[44] Dibrov P, Dzioba J, Gosink KK, Hase CC. Chemiosmotic mechanism of antimicrobial activity of Ag (+) in Vibrio cholerae.

Antimicrob Agents Chemother . 2002;46:2668-2670.[45] Panacek A, Kvitek L, Prucek R, Kolar M, Vecerova R, Pizurova N, Sharma V K, Nevecna T and Zboril R. Silver colloid

nanoparticles: synthesis, characterization, and their antibacterial activity. J Phys Chem. 2006;110:16248-16253.

[46] Yamanaka M, Hara K, Kudo J. Bactericidal actions of a silver ion solution on Escherichia coli, studied by energy-filteringtransmission electron microscopy and proteomic analysis. Appl Environ Microbiol . 2005;71:7589–7593.

[47] Lara HH, Nilda VA, Turrent LCI, Padilla CR. Bactericidal effect of silver nanoparticles against multidrug-resistant bacteria. World J Microbiol Biotechnol . 2010;26:615–621.

[48] Shahverdi AR, Fakhimi A, Shahverdi HR, Minaian S. Synthesis and effect of silver nanoparticles on the antibacterialactivity of different antibiotics against Staphylococcus aureus and Escherichia coli. Nanomed: Nanotechnol. Biol Med

2007;3:168–171.[49] Yoon K, Byeon JH, Park J, Hwang J. Susceptibility constants of Escherichia coli and Bacillus subtilis to silver and copper

nanoparticles. Sci Total Environ. 2007;373:572–575.

[50] Sarkar S, Jana AD, Samanta SK, Mostafa G. Facile synthesis of silver nanoparticles with highly efficient anti-microbial property. Polyhedron. 2007;26:4419–4426.

[51] Shrivastava S, Bera T, Roy A, Singh G, Ramachandrarao P, Dash D. Characterization of enhanced antibacterial effects of novel silver nanoparticles. Nanotechnology. 2007;18:1–9.

[52] Nanda A, Saravanan M. Biosynthesis of silver nanoparticles from Staphylococcus aureus and its antimicrobial activity

against MRSA and MRSE. Nanomedicine. 2009;5:452-456.[53] Pal S, Tak YK, Song JM. Does the antimicrobial activity of silver nanoparticles depend on the shape of the nanoparticle? A

study of the gram-negative bacterium Escherichia coli. Appl Environ Microbiol . 2007;73:1712–1720.

[54] Cho KH, Park JE, Osaka T, Park SG. The study of antimicrobial activity and preservative effects of nanosilver ingredient. Electrochim. Acta. 2005;51:956–960.

[55] Baker C, Pradhan A, PakstisL, Pochan DJ, Shah SI. Synthesis and antibacterial properties of silver nanoparticles. J. Nanosci. Nanotechnol. 2005;5,244-249.

[56] Martínez-Castañón GA, Niño-Martínez N, Martínez-Gutierrez F, Martínez-Mendoza JR, Ruiz F. Synthesis andantibacterial activity of silver nanoparticles with different sizes. J Nanoparticle Res. 2008;10:1343-1348.

[57] Mahdihassan S. Cinnabar-gold as the best alchemical drug of longevity, called Makaradhwaja in India. Am. J. Chin. Med.1985;13:93–108.

[58] Higby GJ. Gold in medicine: a review of its use in the West before 1900. Gold Bull . 1982;15:130–140.

[59] Shaw IC. Gold-based therapeutic agents. Chem. Rev. 1999;99:2589–2600.[60] Felson DT, Anderson JJ, Meenan RF. The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis.

Results of two meta analyses, Arthritis. Rheum. 1990; 33:1449–1461.

[61] Bhattacharya R, Mukherjee P. Biological properties of “naked” metal nanoparticles. Advanced Drug Delivery Reviews.2008;60:1289–1306.

[62] Daniel MC, Astruc D. Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, andapplications toward biology, catalysis, and nanotechnology. Chem. Rev. 2004;104:293–346.

[63] Kuo WS. Antimicrobial gold nanorods with dual-modality photodynamic inactivation and hyperthermia. Chem. Commun.2009;32:4853–4855.

[64] Pissuwan D, Cortie CH, Valenzuela SM, Cortie MB. Functionalised gold nanoparticles for controlling pathogenic bacteria.Trends in Biotechnology. 2009; 28:207-213.

[65] Gil-Tomas J. Lethal photosensitisation of Staphylococcus aureus using a toluidine blue O–tiopronin–gold nanoparticleconjugate. J. Mater. Chem. 2007;17:3739–3746.

206 ©FORMATEX 2011


A. Méndez-Vilas (Ed.) ______________________________________________________________________________

7/28/2019 197-209


[66] Perni S. The antimicrobial properties of light-activated polymers containing methylene blue and gold nanoparticles.

Biomaterials. 2009;30:89–93.[67] Zharov VP. Photothermal nanotherapeutics and nanodiagnostics for selective killing of bacteria targeted with gold

nanoparticles. Biophys. J . 2006;90:619–627.[68] Norman RS. Targeted photothermal lysis of the pathogenic bacteria, Pseudomonas aeruginosa, with gold nanorods. Nano

Lett . 2008;8:302–306.

[69] Simon-Deckers A. Impact of gold nanoparticles combined to X-Ray irradiation on bacteria. Gold Bull. 2008;41:187–193.

[70] Huang WC. Functional gold nanoparticles as photothermal agents for selective-killing of pathogenic bacteria. Nanomedicine. 2007;2:777–787.

[71] Burygin, G.L. On the enhanced antibacterial activity of antibiotics mixed with gold nanoparticles. Nanoscale Res. Lett.

2009;4:794–801.[72] Gu, H, Ho P L , Edmond Tong, Ling Wang, Bing Xu. Presenting vancomycin on nanoparticles to enhance antimicrobial

activities. Nano Lett . 2003;3:1261–1263.[73] Grace NA, Pandian K. Antibacterial efficacy of aminoglycosidic antibiotics protected gold nanoparticles—A brief study.

Colloids Surf. A Physicochem. Eng. Asp. 2007; 297: 63–70.

[74] Saha, B. In vitro structural and functional evaluation of gold nanoparticles conjugated antibiotics. Nanoscale Res. Lett. 2007; 2:614–622.

[75] Rai A, Prabhune A, Perry CC. Antibiotic mediated synthesis of gold nanoparticles with potent antimicrobial activity and

their application in antimicrobial coatings. J. Mater. Chem. 2010;20:6789-6798.[76] Das SK. Gold nanoparticles: microbial synthesis and application in water hygiene management. Langmuir . 2009; 25: 8192–

8199.

[77] Stoimenov PK. Metal oxide nanoparticles as bactericidal agents. Langmuir . 2002;18:6679-86.[78] Klabunde KJ, Stark J, Koper O, Mohs C, Park D, Decker S, Jiang Y, Lagadic I, Zhang D. Nanocrystals as Stoichiometric

Reagents with Unique Surface Chemistry J. Phys. Chem. 1996;100:12142-12153.

[79] Huang L. Controllable preparation of Nano-MgO and investigation of its bactericidal properties. J Inorg Biochem. 2005;99:986-993.

[80] Richards R, Li W, Decker S, Davidson C, Koper O, Zaikovski V, Volodin A, Rieker T, Klabunde K. Consolidation of

Metal Oxide Nanocrystals. Reactive Pellets with Controllable Pore Structure That Represent a New Family of Porous,Inorganic Materials J. Am. Chem. Soc. 2000;122:4921-4925.

[81] Koper O, Klabunde J, Marchin G, Klabunde KJ, Stoimenov P, Bohra L. Nanoscale Powders and Formulations withBiocidal Activity Toward Spores and Vegetative Cells of Bacillus Species, Viruses, and Toxins. Current Microbiology.2002;44:49-55.

[82] Cava RJ. Structural chemistry and the local charge picture of copper oxide superconductors. Science. 1990;247:656–62.[83] Tranquada JM, Sternlieb BJ, Axe JD, Nakamura Y, Uchida S. Evidence for stripe correlations of spins and holes in copper

oxide superconductors. Nature. 1995;375:561-565.[84] Kwak K, Kim C. Viscosity and thermal conductivity of copper oxide nanofluid dispersed in ethylene glycol. Korea–

Australia Rheol J . 2005;17:35–40.

[85] Xu JF, JiW, Shen ZX, Tang SH, Ye XR, Jia DZ, Xin X Q Preparation and characterization of CuO nanocrystals. J Solid State Chem. 1999;147:516–519.

[86] Ren G, Hu D, Cheng EWC, Vargas-Reus MA, Reip P, Allaker RP. Characterisation of copper oxide nanoparticles for antimicrobial applications. International Journal of Antimicrobial Agents. 2009;33:587–590.

[87] Cioffi N, Torsi L, Ditaranto N, Tantillo G, Ghibelli L, Sabbatini L. Copper nanoparticle/polymer composites withantifungal and bacteriostatic properties. Chem Mater . 2005;17:5255–5262.

[88] Rupareli JP, Chatterjee AK, Duttagupta SP, Mukherji S. Strain specificity in antimicrobial activity of silver and copper

nanoparticles. Acta Biomaterialia. 2008;4:707-771.

[89] Sadiq M, Chowdhury B, Chandrasekaran N, Mukherjee A. Antimicrobial sensitivity of Escherichia coli to aluminananoparticles. Nanomedicine: Nanotechnology, Biology, and Medicine. 2009;5:282–286.

[90] Martínez Flores E, Negrete J, Torres Villaseñor G. Structure and properties of Zn-Al-Cu alloy reinforced with alumina particles. Mater Des. 2003;24:281-286.

[91] Li B, Logan BE. Bacterial adhesion to glass and metal oxide surfaces. Colloids Surf B. 2004;36:81-90.

[92] Mohammad G, Mishra VK, Pandey HP. Antioxidant properties of some nanoparticles may enhance wound healing inT2DM patient. Digest J Nanomater Biostruct . 2008;3:159-62.

[93] Chorianopoulos NG, Tsoukleris DS, Panagou EZ, Falaras P, Nychas G-JE. Use of titanium dioxide (TiO2) photocatalysts

as alternative means for Listeria monocytogenes biofilm disinfection in food processing. Food Microbiology. 2011;28:164-170.

[94] Fujishima A, Honda K. Electrochemical photocatalysis of water at semiconductor electrode. Nature. 1972;238:27-38.

[95] Fujishima A, Hashimoto K, Watanabe T. TiO2 Photocatalysis: Fundamentals and Applications. Japan. BKC Inc., 1992.[96] Wei C, Lin WY, Zainal Z, Williams NE, Zhu K, Kruzic AP, Smith RL, Rajeshwar K. Bactericidal activity of TiO2

photocatalyst in aqueous media: toward a solar-assisted water disinfection system. Environ. Sci. Technol. 1994;28:934-938.[97] Pham HN, McDowell T, Wikins E. Photocatalytically-mediated disinfection of water using TiO 2 as a catalyst and spore-

forming Bacillus pumilus as a model. J. Environ. Sci. Health A. 1995;30:627-636.

[98] Ireland JC, Klostermann P, Rice EW, Clark RM. Inactivation of Escherichia coli by titanium dioxide photocatalyticoxidation. Appl. Environ. Microbiol . 1993;59:1668-1670.

[99] Matsunaga T, Tomada R, Nakajima T, Wake H. Photochemical sterilization of microbial cells by semiconductor powders.

FEMS Microbiol. Lett. 1998;29:211-214.[100] Matsunga T, Tomoda R, Nakajima T, Nakamura N, Kmine T. Continuous-sterilization system that uses photosemiconductor powders. Appl.Environ.Microbiol. 1988;54:1330-1333.

207©FORMATEX 2011


A. Méndez-Vilas (Ed.) _______________________________________________________________________________

7/28/2019 197-209


[101] Kim B, Kim D, Cho D, Cho S. Bactericidal effect of TiO2 photocatalyst on selected food-borne pathogenic bacteria.

Chemosphere. 2003;52:277-281.[102] Chawengkijwanich C, Hayata Y. Development of TiO2 powder-coated food packaging film and its ability to inactivate

Escherichia coli in vitro and in actual tests. Int. J. Food Microbiol. 2008;123:288-292.[103] Liu Y, Li J, Qiu XF, Burda C. Bactericidal activity of nitrogen-doped metal oxide nanocatalysts and the influence of

bacterial extracellular polymeric substances (EPS). J. Photochem. Photobiol. A: Chem.2007;190:94-100.

[104] Wolfrum EJ, Huang J, Blake DM, Maness PC, Huang Z, Fiest J, Jacoby WA. Photocatalytic oxidation of bacteria,

bacterial and fungal spores, and model biofilm components to carbon dioxide on titanium dioxide-coated surfaces. Environ.Sci. Technol. 2002;36:3412-3419.

[105] Saito T, Iwase T, Morioka T. Mode of photocatalytic bactericidal action of powdered semiconductor TiO 2 on mutans

streptococci. Journal of Photochemistry and photobiology. 1992;14:369–379.[106] Duffy EF, Touati FA, Kehoe SC, McLoughlin OA, Gill LW, Gernjak W, Oller I, Maldonado MI, Malato S, Cassidy J,

Reed RH, McGuigan KG.A novel TiO2-assisted solar photocatalytic batch-process disinfection reactor for the treatment of biological and chemical contaminants in domestic drinking water in developing countries. Solar Energy. 2002;77:649-655.

[107] Sunada K, Kikuchi Y, Hashimoto K, Fujishima A. Bactericidal and detoxification effects of TiO 2 thin film photocatalysts.

Environmental Science & Technology. 1998;32:726–728.[108] Hu C, Lan Y, Qu J, Hu X, Wang A. Ag/AgBr/TiO2 visible light photocatalyst for destruction of azodyes and bacteria. J

Phys Chem B. 2006;110:4066–4072.

[109] Brayner R, Ferrari-Iliou R, Brivois N, Djediat S, Benedetti MF, Fievet F. Toxicological impact studies based on Escherichia coli bacteria in ultrafine ZnO nanoparticles colloidal medium. Nano Lett . 2006;6:866–870.

[110] Thill A, Zeyons O, Spalla O, Chauvat F, Rose J, Auffan M, Flank AM. Cytotoxicity of CeO2 nanoparticles for

Escherichia coli physico-chemical insight of the cytotoxicitymechanism. Environ. Sci. Technol. 2006;40:6151–6156.[111] Reddy KM, Feris K, Bell J, Wingett DG, Hanley C, Punnoose A. Selective toxicity of zinc oxide nanoparticles to

prokaryotic and eukaryotic systems. Appl. Phys. lett. 2007;90: 2139021–2139023.

[112] Zhang LL, Jiang YH, Ding YL, Povey M, York D. Investigation into the antibacterial behaviour of suspensions of ZnOnanoparticles (zno nanofluids). J.Nanopart. Res. 2007;9:479–489.

[113] Jiang W, Mashayekhi H, Xing B. Bacterial toxicity comparison between nano- and micro-scaled oxide particles. Environ. Pollut. 2009;157:1619–1625.

[114] Liu Y, He L, Mustapha A, Li H, Hu ZQ, Lin M. Antibacterial activities of zinc oxide nanoparticles against Escherichia

coli O157:H7. J.Appl.Microbiol. 2009;107:1193–1201. [115] Jin T, Sun D, Su Y, Zhang H, Sue HJ. Antimicrobial efficacy of zinc oxide quantum dots against Listeria monocytogenes,

Salmonella enteritidis and Escherichia coli O157:H7. J. Food Sci. 2009;74:46–52.

[116] Yamamoto O. Influence of particle size on the antibacterial activity of zinc oxide. Int. J. Inorg. Mater. 2001;3:643–646.[117] Sun RW, Rong C, Chung NPY, Ho CM, Lin CLS, Che CM. Silver nanoparticles fabricated in Hepes buffer exhibit a

cryoprotective activities toward HIV-1 infected cells. Chem Commun. 2005:5059-5061.[118] Pinto DB, Shukla S, Perkas N, Gedanken A, Sarid R. Inhibition of Herpes Simplex Virus Type 1 Infection by Silver

Nanoparticles Capped with Mercaptoethane Sulfonate Bioconjugate Chem. 2009;20:1497–1502

[119] Giancivincenzo PD, Marradi M, Martinez-Avila OM, Bedoya LM, Alcami J, Penades S. Gold nanoparticles capped withsulfate-ended ligands as anti-HIV agents. Bioorganic & Medicinal Chemistry Letters. 2010;20:2718–2721

[120] Lara HH, Ayala-Nunez NV, Turrent LI, Padilla CR. Mode of antiviral action of silver nanoparticles against HIV-1. Journal of Nanobiotechnology. 2010 8:1-9.

[121] Bowman MC, Ballard TE, Ackerson CJ, Feldheim DJ, Margolis DM, Melander C. Inhibition of HIV fusion withmultivalent gold nanoparticles. J. Am. Chem.Soc. 2008;130:6896–6897.

[122] Sametband M, Shukla S, Meningher T, Hirsh S, Mendelson E, Sarid R, Gedanken A, Mandelboim M. Effective multi-

strain inhibition of influenza virus by anionic gold nanoparticles. Med. Chem. Commun. 2011;2:421-423.[123] Verma A, Stellaci F. Effect of surface properties on nanoparticle-cell interactions. Small . 2010;6:12-21.[124] Simpson CA, Huffman BJ, Gerdon AE, Cliffel DE. Unexpected Toxicity of Monolayer Protected Gold Clusters

Eliminated by PEG-Thiol Place Exchange Reactions. Chem. Res. Toxicol. 2010;23:1608–1616.[125] Lu L, Sun RW, Chen R, Hui CK, Ho CM, Luk JM, Lau GK, Che CM. Silver nanoparticles inhibit hepatitis B virus

replication. Antivir Ther . 2008;13:253-262.

[126] Sun L, Singh AK, Vig K, Pillai SR, Singh SR. Silver Nanoparticles Inhibit Replication of Respiratory Syncytial Virus. J Biomed Biotechnol . 2008;4:149-158.

[127] Elechiguerra JL, Burt JL, Morones JR, Camacho-Bragado A, Gao X, Lara HH, Yacaman MJ. Interaction of silver

nanoparticles with HIV-1. J. Nanobiotechnol.2005;3:6-10.[128] Rogers JV, Parkinson C V, Choi YW, Speshock JL, Hussain SM. A preliminary assessment of silver nanoparticle

inhibition of monkeypox virus plaque formation. Nanoscale Res. Lett. 2008;3:129–133.

[129] Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clinical Microbiology Reviews. 2007;20:133–163.

[130] Kim KJ, Sung WS, Moon SK, Choi JS, Kim JG, Lee DG. Antifungal effect of silver nanoparticles on dermatophytes. Journal of Microbiology and Biotechnology. 2008;18:1482–1484.

[131] Kim KJ, Sung WS, Suh BK, Moon SK, Choi JS, Kim JG. Antifungal activity and mode of action of silver nano-particles

on Candida albicans. Biometals. 2009;22:235-242.[132] Falkiewicz-Dulik M, Macura AB. Nanosilver as substance biostabilising footwear materials in the foot mycosis

prophylaxis. Mikologia Lekarska. 2008;15:145-150.

[133] Gajbhiye M, Kesharwani J, Ingle A, Gade A, Rai M. Fungus-mediated synthesis of silver nanoparticles and their activityagainst pathogenic fungi in combination with fluconazole. Nanomedicine: Nanotechnology, Biology and Medicine.

2009;5:382-386.

208 ©FORMATEX 2011


A. Méndez-Vilas (Ed.) ______________________________________________________________________________

7/28/2019 197-209


[134] Wist J, Sanabria J, Dierolf C, Torres W, Pulgarin C. Evaluation of photocatalytic disinfection of crude water for drinking-

water production. Journal of Photochemistry and Photobiology. A, Chemistry. 2004;147:241–246.[135] Yoshimura M, Namura S, Akamaysu H, Horio T. Antimicrobial effects of phototherapy and photochemotherapy in vivo

and in vitro. British Journal of Dermatology. 1994;135: 528–532.[136] Sharma VK, Yngard RA, Lin Y. Silver nanoparticles: Green synthesis and their antimicrobial activities. Advances in

Colloid and Interface Science. 2009;145:83–96.

[137] Canesi L, Ciacci C, Betti M, Fabbri R, Canonico B,Fantinati A, Marcomini A, Poiana G. Immunotoxicity of carbon black

nanoparticles to blue mussel hemocytes. Environ Int . 2008;34:1114-1118.[138] Finney LA, O’Halloran TV. Transition metal speciation in the cell: insights from the chemistry of metal ion receptors.

Science. 2003;300:931–936.

[139] Huster D, Purnat TD, Burkhead LL, Ralle M, Fiehn O, Stuckert F, Olson NE, Teupser D, Lutsekno SJ. High copper selectively alters lipid metabolism and cell cycle machinery in the mouse model of Wilson disease. J Biol Chem.

2007;282:8343–8355.[140] Kennedy DC, Lyn RK, Pezacki JP. Cellular lipid metabolism is influenced by the coordination environment of copper. J

Am Chem Soc. 2009;131:2444–2445.

[141] Lanone S, Rogerieux F, Geys F, Dupont A, Maillot-Marechal E, Boczkowski J, Lacroix G, Hoet P. Comparative toxicityof 24 manufactured nanoparticles in human alveolar epithelial and macrophage cell lines. Part Fibre Toxicol . 2009;6:14– 25.

[142] Braydich-Stolle L, Hussain SM, Schlager J, Hofmann MC. In vitro cytotoxicity of nanoparticles in mammalian germlinestem cells. Toxicol Sci. 2005;88:412–419.

[143] Asharani PV, Wu YL, Gong Z, Valiyaveettil S. Toxicity of silver nanoparticles in zebrafish models. Nanotechnology.

2008;19:255102-255110.[144] Shaw SY, Westly EC, Pittet MJ, Subramanian A, Schreiber SL, Weissleder R. Perturbational profiling of nanomaterial

biologic activity. Proc Natl Acad Sci. 2008; 105:7387–7392.[145] Schrand AM, Rahman MF, Hussain SM, Schlager JJ, SmithDA, Syed AF. Metal-based nanoparticles and their toxicity

assessment Nanomed Nanobiotechnol . 2010;2:544–568.

209©FORMATEX 2011


A. Méndez-Vilas (Ed.) _______________________________________________________________________________

Documents

197-209