Topic Review Article: The antimicrobial activity of metal nanoparticles: present situation

and prospects for the future.

Abstract

Mostly infections are due to bacterial pathogens that use to get resistant against the over exposure
of antibacterial medicines. Nanoparticles smaller than 10 nm are antibacterial and their antibiotic
properties are being used in many disciplines of life. Nanoparticles make reactive oxygen species
or ions to induce the reactions that ultimately cause the destruction of bacterial pathogens. These
reactive oxygen species or ions adopt three types of mechanisms to kill the bacteria like of
discharged metallic ions that causes alteration in permeably of membrane, non-oxidative
mechanism that decreases metabolism of bacteria and the mechanism of oxidative pressure that
breaks all vital polypeptides of bacteria. Different kinds of metal nanoparticles show different
action mechanisms to eradicate bacterial strains like gold nanoparticles tend to prevent the
translation of mRNA, magnesium nanoparticles stop transcription of some genes in bacteria,
nanoparticles of silver create hindrance in development of biofilms around bacterial cells and
titanium nanoparticles breach the outer barrier of bacterial cell. Due to their antibacterial property
nanoparticles are being used in different fields of like in making products bacteria free or less
prone to bacteria like in bone adhesive material, wall dyes, root canal filling and braces, packaging
for milk and edible materials and as covering on human implants. There are many more aspects of
nanoparticles yet the antibacterial feature is of immense importance and there are many ways to
use antibacterial metal nanoparticles for instance in environmental protection, water purification,
surface disinfection and for treating diseases emerged through drinking contaminated water.

Introduction

Bacteria are the reason behind most of infectious diseases all over the world that are usually cured
by a conventional means of using antibiotics over the period of many years. Many of the researches
conducted in this perspective have revealed that extensive consumption of antibiotics have
developed such types of bacteria that are not affected by various or almost all antibiotic drugs
because of a gene products that make them resistance to all medicines used against that bacterium
over and over again [1]. This characteristic of bacteria developing resistance against antibiotics
has put people’s health at risk worldwide [2-4]. The action mechanisms of antibacterial medicines
are mainly of three types: i) these antibacterial medicines inhibit the production of bacterial cell
wall, ii) either these medicines hinder the proteins associated with bacterial DNA replication or
iii) these antibacterial medicines damage the bacterial translational proteins. Even than bacteria
have the ability to generate resistance against all these conventional mechanisms of antibacterial
medicines [5].

Nanoparticles are those materials or substances which hold the size in the range of nanometers [6].
Due to the exceptional qualities of nanoparticles, particles having size less than nanometers are
being generated now a days to apply them in various fields of life to fulfil many purposes for
example saving lives [7,8]. Metallic nanoparticles greatly differ in mass, form and chemical
properties but their activity is mainly due to their mass or size [9-12]. Small sized nanoparticles
have been reported through many studies to have antibiotic properties [13]. Metal nanoparticles
hold and display a wide variety of antibacterial characteristics. For instance, zinc oxide and silver
nanoparticles have been known to hinder the growth of S. aureus and E. coli and P. aeruginosa,
respectively [14]. There are many ways in which metal nanoparticles can affect or inhibit the
bacterial growth and continued existence such as silver nanoparticles quickly remove the charge
of membrane thereby alter the number of molecules entering or leaving the cell [15]. Nanoparticle
technology is quickly emerging and there has been generated innovative nanoparticles having
unique characteristic properties and these unique characteristics are being used in different fields
of life such as biomedical sciences as well as social sciences for environmental protection and in
generating environmental friendly devices [16-19].

1) Nanoparticles to get through bacterial outer surfaces

1.1) Nanoparticles produce reactive oxygen species that diffuse through the external
surfaces:

Few nanoparticles, most probably the metal oxides, have tendency to produce reactive oxygen
species that have the propensity to diffuse through the external surfaces of bacterial membrane and
by way of entering the cell these reactive oxygen species cause metabolic changes leading to
bacterial cell death. For example, reactive oxygen species produced by silicon, silver and gold
nanoparticles. Studies have shown that diffusion time of reactive oxygen species in E. coli is about
107 seconds whereas the approximate lifetime of reactive oxygen species is about 105 to
106 seconds [20]. Silver nanoparticles having size less than 10 nanometers display potential to
cross the bacterial cell membrane by means of the pores present in it therefore they have been
proved to be efficient antibacterial nanoparticles thereby killing the bacteria more efficiently than
the other nanoparticles [21].

1.2) Nanoparticles make metallic ions that get stuck to bacterial cell wall and cell membrane:

Metallic ions nanoparticles get stuck to bacterial cell wall and cell membrane due to negative
charge present in polypeptide units of cell membrane and each metallic ion differs in terms of its
actions as well, for instance nanoparticles of zinc ions have great attraction for the Sulphur atoms
present in cysteine, an amino acid in polypeptide of cell membrane, and its binding damages the
cell membrane resulting in passing away of bacterium [22]. Other researches have proved that gold
nanoparticles having charges on their surface can massively impact the adsorptive property
nanoparticles to bacterial cellular membrane thereby changing the regularity of membrane that
consequence in bacterial death [23].

2) Types of antibacterial mechanisms displayed by nanoparticles

The growing applications of nanoparticles in the field of medical sciences have directed the
increased research about the possible actions of nanoparticles against bacteria [24]. Such as the
metallic nanoparticles tend to alter the metabolism of target bacterium [25]. These action
mechanisms of nanoparticles against bacteria have been mostly studied in recent researches, for
example the mechanism of discharged metallic ions [26], non-oxidative mechanism [27] and the
mechanism of oxidative pressure [28].

2.1) Mechanism of discharged metallic ions:

Metallic oxides tend to gradually release metallic ions which get engulfed by the cellular
membrane of bacteria after their contact with the side chains of amino acids in polypeptides present
in the bacterial membranes and this contact causes destruction of enzymatic actions hence end
result is the alteration in cellular functions and configuration eventually preventing and impairing
the bacterial existence. But the influence of metallic ions on the pH within vesicular bodies
containing lipid is very less, hence it is not an effective mechanism against bacteria [29]. Recent
researches have proved ions of iron oxide having magnetic properties can straightly enter the
bacterial cells and disturb the transfer of electrons through the cell membrane of bacteria, as
consequence the bacterial cell is destroyed [30].

2.2) Mechanism of non-oxidative nanoparticles:

Some recent researchers have proved that some non-oxidative particles are also able to generate
antibacterial effects and they have proved it through using certain efficient processes like three
kind of magnesium oxide nanoparticles have proved to be effect against bacteria. The mechanism
of action of magnesium oxide nanoparticles is different from oxidative nanoparticles as
magnesium oxide nanoparticles tend to remarkably decrease some important metabolic pathways
that are crucial for cell survival, hence by targeting and damaging the functions of the bacterial
cell they prove to be detrimental for the survival of bacteria [27].

2.3) Mechanism of oxidative pressure:

The oxidative pressure created through any of the four reactive oxygen species such as super oxide,
having robust reducing capacity, is significant action mechanism of nanoparticles in contradiction
of bacteria [31]. Many studies, in this regard, have proved that oxidative pressure produced by
reactive oxygen species causes alteration in permeability and hence destruction of bacterial outer
membrane which results in decease of bacteria [32]. Additionally, the reactive oxygen species
produced by many nanoparticles have the capacity of out-breaking all the polypeptides plus the
enzymatic activities involved in sustaining regular functions of bacterium [22].

Systemic Academic Review

1) Actions of nanoparticles against bacteria

1.1) Nanoparticles cause prevention of transcription of some genes in bacteria:

Nanoparticles have generally two mechanisms to disturb many bacterial metabolic pathways by
regulating the transcription of many genes such as mechanisms of reactive oxygen species and a
metallic ion discharge [22, 29]. Magnesium oxide nanoparticles deregulate the synthesis of many
vital polypeptides involved in some important pathways in metabolism of bacterium thereby
controlling and disturbing the cellular functions of bacterial cell which ultimately induce death of
the bacterial cell [27].

1.2) Nanoparticles cause prevention of translation in bacteria:

A study have shown that copper oxide nanoparticles affect the replication a translation of a vital
polypeptide necessary for the nitrogen fixation pathway and some other vital pathways that are
mandatory for the survival and growth of the bacterial cell [33]. Another research based on gold
nanoparticles have showed that gold nanoparticles kill bacteria in two ways. One way of action is
that gold nanoparticles inhibit the binding of transfer RNA to the ribosomal complex hence stop
the translation of mRNA into polypeptide [34].

1.3) Nanoparticles hinder the development of biofilms around bacterial cells:

Biofilms are the protective layers around bacteria that protects it from many toxic substances
present in environment hence essential for survival of bacteria [35]. Nanoparticles of titanium
dioxide have been known to decrease the formation of biofilms around bacteria which results in
the eradication of bacteria [36, 37]. Moreover, as the nanoparticles of magnesium regulate or
disturb most of the metabolism of bacterial cells thereby affecting the formation of biofilms and
making the bacterial cells more predisposed to the harmful chemicals outside it that results in
ultimate death of bacteria [38].

1.4) Interference of nanoparticles with outer surfaces of bacterial cell:

Bacterial cell is protected and safeguarded by its outer protective surfaces that are cell membrane
and cell wall which efficiently regulate many of bacterial passageways for the exchange of material
between cell and the surroundings [39]. Nanoparticles easily get into gram positive bacteria as
their cell wall have many negative charges [40]. The action of nanoparticles against bacteria
depends on conformation and organization of bacterial cell as well as the width of the cell wall of
the bacteria [41]. A study set that titanium dioxide nanoparticles can stick to the external layer of
bacteria and yield reactive oxygen species to destruct the structural configuration and arrangement
of their plasma membranes, thereby interfering with the function of the cell membrane and causing
leakage of cellular contents, resulting in bacterial death [42].
2) Review of antibacterial properties of some types of nanoparticles

2.1) Magnesium nanoparticles

The action of magnesium oxide nanoparticles is diverse than oxidative nanoparticles as per
magnesium oxide nanoparticles have a tendency to extraordinarily decrease some important and
essential polypeptides of metabolic pathways that are crucial for cell continued existence [27].
Magnesium oxide nanoparticles inhibit the translation of many vital polypeptides involved in some
important pathways in metabolism of bacterium. So they induce death of the cell [27]. They also
interfere in the formation of bacterial biofilms hence stop the bacterial growth and death [43].

2.2) Iron oxide nanoparticles

Oxides of metal elements have a tendency to progressively discharge the relevant metallic ions,
having positive or negative charges on them, that are in capacity to cross the outer membrane
boundary of bacterial cells whenever they come to interact with the side chains of amino acid
residues of polypeptide chains existing in the bacterial outer membranes and this interaction
originates the demolition of enzymatic actions henceforth termination all these activities is the
amendment in tasks and alignment of bacterial cell which in the long run harm plus stop the
bacterial way of life. On the other hand the power of metallic ions on the concentration of hydrogen
ions contained by vesicular organelle encompassing fatty acid molecules is in lesser amount,
therefore it is not considered very active mechanics to eradicate bacterial strains [29]. Latest
investigations have evidenced that ions produced from iron oxide show magnet like forces through
which they straightly cross the threshold of the bacterial cell membranes as a result get in the way
the electrons transmission from inside out and vice versa in the exterior plasma membrane of
bacterial cells, this destruction of membrane barrier consequences in the death and eradication of
bacterial cells [30].

2.3) Silver nanoparticles

There are certain ways in which silver nanoparticles can distress or obstruct the bacterial
progression and existence like silver nanoparticles swiftly confiscate the charge present on
bacterial cell membrane and in this manner modify the quantity of molecules moving in and out
the bacterial cell that ultimately make the cell prone to death [44]. Nanoparticles generated from
silver metal with the size that is even smaller than 10 nanometers have as much propensity so as
to cross the plasma membrane barrier of bacterial cell through means of the openings existent in
its membrane consequently they have been demonstrated to be competent nanoparticles against
bacteria in that way these nanoparticles destroy the bacterial cells with great proficiency than all
the other known types of nanoparticles [21].

2.4) Zinc oxide nanoparticles

Negative charge presence on metallic ions nanoparticles caused them to become immovable at
bacterial cell wall and cell membrane by attaching with the polypeptide molecules of cell
membrane and every metallic ion nanoparticle is different from rest of the relevant nanoparticles
in relation to its activities as well. Zinc ions nanoparticles possess excessive magnetism for the
Sulphur atoms existing in cysteine an amino acid residues of polypeptide chains of plasma
membrane and binding of zinc ions nanoparticles injures the cell membrane resulting in subsequent
death of bacterial cell [22].

2.5) Gold nanoparticles

Current researches have shown that gold nanoparticles can eradicate bacteria by two techniques
and through one of these technique, they obstruct the binding of tRNA to the ribosomal subunits
complex thereby discontinue the translation of messenger RNA into polypeptides resulting in the
death of bacteria [34]. Some researchers have ascertained that gold nanoparticles display charges
that can tremendously control the adsorption of these nanoparticles into cell through outer
membrane hence imbalance the normal functioning of bacterial cell resulting in massive cell
destruction [23].

2.6) Nanoparticles of titanium dioxide

Bacteria make biofilms around them that are basically the defending covers around bacteria that
protects it from many venomous or harmful constituents present in environment that can harm the
bacteria growth, its structure or survival [35]. Through some researches, nanoparticles of titanium
dioxide are known to decrease the formation of biofilms around bacteria as a result the bacteria
are prone to the toxic substances around them and bacterial survival is put to risk hence bacteria
are dead [36, 37]. Research have declared that cell surface of bacterial plasma membrane increases
after its dealing with nanoparticles of titanium dioxide with the bacterial cell size and it results in
the formation honeycomb like structures in the cell membrane which originates the seepage of
cytoplasm[45].

2.7) Copper oxide nanoparticles

Recent research on copper oxide nanoparticles have revealed that these nanoparticles affect the
replication of genes or the translation of their mRNAs related to a vital polypeptide that is
compulsory for the process of nitrogen fixation pathway and some other vital pathways crucial for
bacterial survival [33].

2.8) Diamond nanoparticles

A group of researchers named Wehling and co-workers explored the antibacterial action of
diamond nanoparticles in numerous external configurations using diverse reactive species and
established that these nanoparticles have ability to make covalent links to neighboring
polypeptides and fragments present at cell walls of bacteria. In combination to intracellular
constituents that supplementary lock up fundamental enzymes and polypeptides, triggering the
malfunctioning of the microbial metabolic rate and, in conclusion, death of bacteria. Hence
diamond nanoparticles have capacity to extinguish the cell membrane of bacteria in order to
accomplish the antibacterial task [46].

2.9) Mixed nanoparticles

Mixed nanoparticles have ability to increase their powers despite the fact that decrease the flaws
of the distinct categories of nanoparticles. For instance, researches have proved that greater
effectiveness into real cell transfer of nanoparticles can be accomplished by way of using mixture
of lipid and polymer nanoparticles associated by means of transport lacking polymer nanoparticles
or by means of lipid nanoparticles [47].

2.10) Other types of nanoparticles

Studies have shown that many nanoparticles can prevent or overcome biofilm formation, including
NO nanoparticles [48, 49] and YF nanoparticles [50]. Greater prevention of biofilms is achieved
by a smaller size and higher surface area-to-mass ratio, and the particle shape of NPs also has a
remarkable effect on biofilm destruction that means nanoparticles having bar resembling form tend
to show extra operational activity than nanoparticles having figure like a sphere [49].

4) Uses of and forthcoming aspects of metal nanoparticles

4.1) Antibacterial nanoparticles in bandages:

A bandage must be like the skin in terms of properties shown by skin so as to cover and heal the
wound by decreasing the scab development, stimulating the propagation and relocation of cells
like fibroblasts, and speeding up the establishment of epithelial tissues as well as having the
capacity to kill the invading bacteria, there are several types of bandages having antibacterial
properties in them so that the wound do not get attacked by the pathogenic bacteria and the healing
process can be completed soon [51].

4.2) Actions of nanoparticles to eradicate pathogenic fungus:

In a study, it has been found that silver nanoparticles poses the property to eradicate fungus by
interfering its plasma membrane structure plus the mechanism of bud formation [52].

4.3) Nanoparticles in bone adhesive material:

Bone adhesive material is a type of cementing material which is made up of poly-methyl

methacrylate and methyl methacrylate. It is usually applied to repair joints like knee and hip by
repairing cracks of cavities in them. Recent research have shown that poly-methyl methacrylate
material with antibacterial agents have zero percent chances of developing bacterial infections
[53]. Poly-methyl methacrylate centered bone adhesive material plus silver nanoparticles
extensively decrease the production of biofilms [54]. Silver nanoparticles are an efficient substitute
of antibiotics in the production of antimicrobial bone adhesive material [55].

4.4) Wall dyes containing antibacterial silver nanoparticles

For safeguarding human wellbeing and the surrounding atmosphere, there has been a great
attentiveness and demand for the wall dyes having antibacterial nanoparticles. Amongst all the
available dyes in market, there is specific attention paid towards those having silver nanoparticles
in them due to the fact that silver nanoparticles are most efficient in killing the bacteria. These can
be used on timber, crystal, steel and various synthetic polymers [56].

4.5) Root canal filling and braces covered with metal nanoparticles:

Most of the oral cavity diseases are caused by plaque that increases the chances of invasion of
other bacteria in mouth. Root canal filling with amoxicillin and gutta-percha reduces the remaining
bacteria [57]. Braces covered with copper oxide and zinc oxide nanoparticles efficiently hinder the
development of S. mutans, though, the coverings also effect the presence of braces [58].

4.6) Antibacterial packaging for milk and edible materials:

There is enormous trend of canned food and milk to make food available all over the world. For
this purpose the packing material could be loaded with silver nanoparticles so as to decrease the
growth of bacterial in and outside of the packaging [59].

4.7) Nanoparticle covering on human implants:

Human implants like heart valves and teeth are the structures that are covered with material
containing antibacterial metal nanoparticles [60] to prevent the bacterial sticking and development
[61]. Tubes or pipes used in surgeries between veins can also develop bacteria in them and to
prevent bacterial growth antibacterial material, containing nanoparticles, is used in making those
tubes and pipes [61, 62].

Discussion

Metal nanoparticles are of immense significance as being antibacterial and eradicating the gram-
negative and gram-positive strains of bacterial pathogens. Pathogenic strains of bacteria are unable
to develop confrontation to counter metal nanoparticles because their way of action is far different
from that of antibiotic medicines. In this review article, antibacterial property of metal
nanoparticles has been thoroughly discussed along with their mechanism of action, their
applications in various areas of life such as in medical, surgery, human implantable devices, in
dyes to restrain the bacterial development. From previous researches, it has been suggested that
metal nanoparticles could be used to protect environment, water, electrical instruments and
products of sanitization in cosmetic of medicine from pathogenic strains of bacteria. To gain
maximum benefit of metal nanoparticles and their antibacterial potential, it is necessary to develop
more researches on metal nanoparticles and analytically use them for different antibacterial
purposes. Additionally there must be further exploration that is required to conclude in what
manner to securely propose the structure and applications of products comprehending metal
nanoparticles in a way that there remains no chance of building a new danger or health hazard for
human being or to the atmosphere.

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