Materials Science for Energy Technologies 3 (2020) 756–769

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Materials Science for Energy Technologies

CHINESE ROOTS
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Bactericidal activity of silver nanoparticles: A mechanistic review

Syed Anees Ahmad a, Sabya Sachi Das b, Ayesha Khatoon c, Mohammed Tahir Ansari d, Mohd. Afzal e,
Md Saquib Hasnain f,⇑, Amit Kumar Nayak g,⇑
a
Department of Pharmacology, Hygia Institute of Pharmaceutical Education and Research, Lucknow, U.P., India
b
Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835 215, Jharkhand, India
c
Molecular Cell Biology Laboratory, Integral Information and Research Centre-4 (IIRC-4), Department of Biosciences, Faculty of Science, Integral University, Kursi Road,
Lucknow 226026, India
d
School of Pharmacy, University of Nottingham Malaysia, Jalan Broga, Semenyih, Selangor 43500, Malaysia
e
Department of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia
f
Department of Pharmacy, Shri Venkateshwara University, NH-24, Rajabpur, Gajraula, Amroha 244236, U.P., India
g
Department of Pharmaceutics, Seemanta Institute of Pharmaceutical Sciences, Mayurbhanj 757086, Odisha, India

a r t i c l e i n f o a b s t r a c t

Article history: Metallic nanoparticles such as silver nanoparticles (AgNPs) have gained lots of attention due to the con-
Received 19 July 2020 tinuous upsurge in microbial infections and diseases, and also inefficient treatment. Also, due to rapid
Revised 9 September 2020 intensification in the antibiotic resistance in this period has revived the consideration of the researchers
Accepted 9 September 2020
and scientists to explore the therapeutic abilities of silver and its nanoparticulate systems as potential
Available online 29 September 2020
antimicrobial agents. Indeed, numerous studies suggested that AgNPs have exhibited significant antimi-
crobial actions, specifically against the bacterial infections. Ample of studies have been performed to
Keywords:
evaluate and estimate the antibacterial potentials of silver and its associated products, and it was noticed
Silver
Silver nanoparticles
that the they these Ag-particles triggers the oxidative stress, protein dysfunction, membrane and DNA
Bacterial resistance damage, leading to microbial cell damage. Although it has exhibited antimicrobial activities, but its
Antibacterial activity adverse effects over human health has been a major concern. Further, in this review we have summarized
Mechanism of action the significance of silver and AgNPs, various approaches for the preparation of AgNPs, antibacterial mech-
Toxicity profile anism and probable toxicity in the cell environment. Furthermore, this review has been focused to con-
sider the major mechanisms behind the bactericidal actions of the silver and silver nanoparticles-based
systems, followed by comprehensive ideas related to their toxic potentials. This review would open new
robust possibilities to develop silver nanoparticle-based antimicrobial systems with desired properties
for effective treatment of bacterial infections in humans.
Ó 2020 The Authors. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-
nd/4.0/).

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 757
2. Silver: an effective antibacterial agent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 757
2.1. Synthesis of silver nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 758
2.1.1. Physical method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 758
2.1.2. Chemical method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 759
2.1.3. Biological method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 759

⇑ Corresponding authors.
E-mail addresses: msaquibhasnain@gmail.com (M. Saquib Hasnain), amitkrnayak@yahoo.co.in (A. Kumar Nayak).
Peer review under responsibility of KeAi Communications Co., Ltd.

Production and hosting by Elsevier

https://doi.org/10.1016/j.mset.2020.09.002
2589-2991/Ó 2020 The Authors. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
S. Anees Ahmad, S. Sachi Das, A. Khatoon et al.
3. Antibacterial mechanism of AgNPs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.1. Antibacterial applications of AgNPs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4. Toxicity of AgNPs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5. Conclusion and future perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Declaration of Competing Interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Introduction
The metallic nanoparticles (NPs) are the most encouraging as
they show great antibacterial properties because of their extensive
surface range to volume proportion, which is coming up as the ebb
and flow enthusiasm for research because of the development of
microbial resistance against metallic particles, anti-toxins and
the advancement of safe strains [1]. Metallic particles in the
nanometre range exhibits physical properties which do not resem-
ble with both the particle and the mass material. This makes them
show astounding properties, for example, expanded reactant
movement because of morphologies with very dynamic aspects
[2]. Microorganisms, for example, microbes and organisms, now
assume a critical part in the remediation of poisonous metals
through the decrease of the metal particles [3]. Reaction surface
system (RSM) is an accumulation of measurable and scientific pro-
cedures helpful for creating, enhancing and streamlining forms [4].
RSM is an outstanding strategy connected in the streamlining of
medium constituents and other basic factors in charge of the cre-
ation of biomolecules [5,6]. Notwithstanding dissecting the
impacts of the autonomous factors, this test approach creates a sci-
entific model that precisely depicts the general procedure. It has
been effectively connected to advance the conditions in suste-
nance, compound and natural procedures [4,7].
The routine of single component streamlining by keeping up
different variables at an unspecified steady level does not portray
the joined impact of the considerable number of elements
included. The one component at once technique requires countless
to decide ideal levels, which is dreary and tedious. Streamlining all
the affecting parameters can dispense with these restrictions of a
solitary element enhancement prepare all in all by measurable test
configuration utilizing RSM [5,8]. Gamma-light amalgamation of
metallic NPs [9] has been additionally utilized as a standout
amongst the most encouraging techniques to deliver AgNPs
because of some imperative focal points. When contrasted with
ordinary synthetic/photochemical systems, the radiochemical pro-
cedure can be performed to diminish Ag+ particles at the encom-
passing temperature without utilizing over the top decreasing
operators or creating undesirable by-results of the reductant. In
addition, diminishing operator can be consistently disseminated
in the arrangement and AgNPs are delivered in exceptionally
immaculate and stable shape [10]. The advancement of novel
benign strains of microbes to develop anti-microbial agents have
showed significant potentials and thus thusly, there a strong moti-
vation has developed to establish new bactericidal agents [11,12].
2. Silver: an effective antibacterial agent
Silver (Ag) has been known to have a toxicity effect over an
extensive variety of small organisms [13], hence silver-based com-
binations have been widely exploited for its antibacterial applica-
tions [14,15]. A few salt types of Ag and their subtypes are
economically used as bactericidal agents. The bactericidal impact
of silver particles on microorganism’s is extremely notable; in
any case, the bactericidal system is just incompletely caught on.
Reports have demonstrated that the Ag+ ions firmly connects with
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Materials Science for Energy Technologies 3 (2020) 756–769
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763
764
764
765
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the thiol (-SH) links of crucial compounds and disables them [15].
Trials have showed that the replication capacity of the DNA gets
lost, when the microbes are treated with Ag-based particles. Differ-
ent reviews have demonstrated confirmation of basic alterations in
the cell layer and the arrangement of little electron-thick granules
shaped by silver and sulphur [16].
Ag-based particles have exhibited helpful and compelling
antibacterial applications, yet because of the remarkable activities
of nanotechnology based materials have given immense support to
improve the activities of Ag. Metallic particles with a size in
nanometre range have exhibited physical characteristics with
unique relation to both the particle and the mass material. This
makes them show astounding properties, for example, expanded
synergist action because of morphologies with profoundly
dynamic aspects [17–19]. A few electron microscopy strategies
could be applied to concentrate the system by which AgNPs inter-
face with these microbes. Also, a high point annular dull field
(HAADF) filtering transmission electron microscopy (STEM) could
be used, followed by the formation of a novel specimen planning
that maintains a strategic distance from the utilization of substan-
tial metal-based mixtures [2].
The advancement of new benign microbial strains to the pre-
sent anti-infective agents [20] has been a major issue in common
health systems; subsequently, there is a perquisite to develop
novel bactericidal agents [21]. The microbial strains have been
reported to exist with varied film assemblies which allows to rec-
ognize them as Gram-negative (G ve) or Gram positive (G+ve).
The main mechanism lies behind the conjugation with the main
sites of the layers of peptidoglycan (PG). G ve microorganisms
have a thin PG layer of 1–5 nm that exists between the external
layer and the cytoplasmic film, however the G+ve microscopic
organisms do not have the external film yet have a thick PG layer
of ~30 nm [2].
The complexes of Ag have likewise been utilized as a part of the
therapeutics to treat blazes and variety of diseases [16]. Also Ag
and its salt forms have been significantly utilized as a potential tool
as bactericidal agents for the treatment of various microbial infec-
tions [22]. Excellent endeavours have been performed to investi-
gate the bactericidal features of Ag-based materials through
electron microscopy and observed the possible interfaces of AgNPs
with microorganisms [23]. AgNPs have also been used as a material
medium for transportation of antibiotics [24], as a blending agent
to form composites used in purifications processes [25] and also as
casing material [24]. Although in any phase, the antibacterial prop-
erties of these AgNPs depends upon their steadiness in the system,
as this exhibits greater reaction time for the interaction between
the AgNPs and bacterial membranes. Thus, the stability of the
AgNPs in reaction medium plays a crucial role for hindering the
growth and progression of the microbes [2].
For a long time, Ag has been utilized by the people as an
antibacterial agent due to immense antibacterial properties against
a wide range of bacterial species. NPs, for the most time are pre-
ferred over the basic Ag-based materials due to the diverse quali-
ties of the NPs. The smaller size and shape of the AgNPs makes it
a potential bactericidal agent with enriched antibacterial impact.
Moreover, due to considerable surface area the AgNPs can loan
S. Anees Ahmad, S. Sachi Das, A. Khatoon et al.
antimicrobial impacts to many square meters of its host material
[26]. AgNPshave as of now been tried in different field of organic
science, medicate conveyance, water treatment and an antibacte-
rial compound against both G+ve and G ve microorganisms by dif-
ferent scientists. The greater part of the microscopic organisms has
yet created imperviousness to anti-microbial and in this view in
future it is expected to build up a substitute for anti-infection
agents. AgNPs are alluring as these are non-lethal to human body
at low fixation and having wide range antibacterial nature. AgNPs
repress the bacterial development at low fixation than anti-
infection agents and starting at now no reactions are accounted
for [26].
The acting system of Ag has been known in some cases. For
instance, Ag+ ions repress the phosphate uptake and growth of
Escherichia coli (E. coli) leading to efflux of aggregated phosphates,
glutamine, mannitol, proline, succinate. Besides, Ag particles
restrain oxidation of glucose, glycerol, fumarate, and succinate in
E. coli. The AgNPs demonstrate proficient bactericidal properties
contrasted with different salts due to greater degree of substantial
surface zone, which gives better contact microorganisms. It has
been observed that when the AgNPs enter into cell membrane of
bacteria, they frame a low sub-atomic weight within the cell. Con-
sequently, the microbes aggregate to shield the DNA from the
AgNPs. Thus, the AgNPs ideally assault the respiratory system, cel-
lular division for longer duration prompting to cell passing [27].
2.1. Synthesis of silver nanoparticles
AgNPs could be efficiently prepared through physical, chemical,
and biological approaches [28]. At present, top-down and bottom-
up are the two methods that have been mostly utilized for the syn-
thesis of AgNPs [29]. The top-down method is used to reduce the
size of the bigger structures into nanoscale range while preserves
their original characteristics without alterations ion the atomic or
sub-atomic levels [30]. The bottom-up method, also described as
molecular nanotechnology, includes the concept of assembling of
materials at atomic or molecular level by a procedure of assem-
bling or self-assembling [30]. Presently, the most of the technolo-
gies depends upon the top-down method, however, the bottom-
up method are frequently used for improvements in material prop-
erties [31–33], electronic engineering [34], energy and dynamics
[35–37], biotechnology-based material development [38–40]
medicines and healthcare systems [41–44]. In recent years, various
approaches have been reported for the blend of AgNPs by employ-
ing constituents, photochemical, physical and organic progresses.
Each approach has crucial facts and flaws with some common
problems, including expenditures, compliance, particle sizes and
distribution. Among the current techniques, the synthetic strate-
gies are mostly utilized for generation of AgNPs. Concoction
approaches provides a meek tactic to incorporate AgNPs in
arrangements. Mono-disperse tests of Ag-nanocubes were orches-
trated in huge quantities by treating silver nitrate (AgNO3) with
ethylene glycol surrounded by the polyvinylpyrrolidone (PVP)
[45]. It demonstrated that PVP amount and its molar ratio with
AgNO3, both exhibited significant impacts over the geometric
shape and size of material. Thus, it was possible regulate the mea-
sure of Ag-nanocubes by monitoring the various experimental
conditions.
Circular AgNPs with a manageable size and greater mono-
dispersity were incorporated by utilizing the polyol procedure
and an altered forerunner infusion method [46]. In the forerunner
infusion technique, the infusion rate and response temperature
were imperative components for delivering identical-sized AgNPs
with a lessened size. The infusion of the forerunner arrangement
within a warm arrangement was a crucial factor for quicker nucle-
ation within less time, guaranteeing the manufacture of AgNPs. In a
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study, mono-dispersed AgNPs were developed through oleylamine
and paraffin framework [47]. It was demonstrated that the
arrangement process of AgNPs could be parted into three phases:
development, brooding and Ostwald aging phases. In this tech-
nique, just three chemicals, including AgNO3, oleylamine and
paraffin, are utilized all through the entire procedure. The liquid
paraffin has higher melting point and this makes it usage more fea-
sible even at higher temperatures and thus are potentially used in
preparation of AgNPs at varying temperatures. Something else, the
extent of the colloidal AgNPs can be directed not just by altering
the warming temperature, or the growth time, additionally by
modifying the proportion of oleylamine to the Ag supernatants.
Most often the synthesizing procedure of AgNPs preparations does
not uses convoying three prime parts: (i) metal precursors, (ii)
diminishing specialists and (iii) settling/topping operators. The
generation of colloidal preparations from the decreased of Ag salts
comprises of two stages, nucleation and subsequent development.
Furthermore, the size and shape of the colloidal AgNPs mostly
depends upon the conditions of the two phase mentioned above.
Moreover, for the combination of monodispersed AgNPs with iden-
tical size distribution, all cores are prerequisite to form in the
interim. For this phase, each of the core have the similar or equiv-
alent size, followed by the development of similar sized NPs. The
underlying nucleation and subsequent development of initial cores
could be significantly regulated by monitoring the response fac-
tors, including temperature, pH, precursors, degeneration opera-
tors (glucose,ethylene glycol, etc.) and stabilizing agents
(polyvinyl alcohol, PVP etc.) [48–50].
2.1.1. Physical method
For a physical approach, the metallic NPs are mostly formed by
a robust method of evaporation followed by rapid condensation,
possibly performed by using a tube heater at climatic load. How-
ever, this approach has been reported with certain limitations,
including a substantial space of tube heater, incredible utilization
vitality for enhancing the ecological temperature across the base
material. Hence, different strategies for amalgamation of AgNPs
in view of the physical approaches have been produced. A thermal
disintegration technique was created to orchestrate AgNPs in pow-
dered shape [51]. The AgNPs were framed by decay of an Ag+-
oleate composite, formed by response with AgNO3 and sodium ole-
ate in aqueous media, at higher temperature (~290 °C). Normal
molecular size of the AgNPs was acquired of around 10 nm and
thus it showed that the AgNPs have an extremely limit measure
appropriation.
The physical methods have been reported with various advan-
tages for the development and establishment of high-quality
AgNPs. However, it is a low yield process, which often requires
high temperature and power consumption, thereby limiting their
application in the industrial sector. In contrast, AgNPs can be pro-
duced in large quantities through chemical and biological routes
due to their cost-effectiveness. In this respect, we focus mainly
on nanoparticle fabrication usingchemical and biological routes
in this section. The physical synthesis process generally employs
thermal, laser, or arc discharge power to form AgNPs with nearly
narrow size distribution. In this context, evaporation condensation
and laser ablation strategies are commonly adopted to form AgNPs.
The former approach is carried out by simply placing a source
metal, i.e., silver target inside the tube furnace, and then vaporized
silver into a carrier gas under atmospheric pressure at high tem-
peratures. The vapor is then condensed to form nanoparticles.
The drawbacks of this approach include high power consumption
and long heating time to reach thermal stability [28]. Jung et al.
modified this process by using a small ceramic heater with a local
heating area for vaporizing silver metal [52]. The temperature gra-
dient in the vicinity of the heater surface is very steep, such that
S. Anees Ahmad, S. Sachi Das, A. Khatoon et al.
the vapor can cool at a rapid rate, thereby condensing into spher-
ical AgNPs with diameters of 6.2–21.5 nm without agglomeration.
Alternatively, laser ablation can be used to synthesize AgNPs from
a silver target placed in a solution under laser beam irradiation.
The nanoparticle size of colloids depends on the laser wavelength,
ablation time, and duration of laser pulses [53–55]. The limitation
of this process is the high cost of laser facility.
2.1.2. Chemical method
The wet chemical route is by far the most economical and com-
monly used process for preparing nanosilver colloidal dispersions
in water or organic solvents. This route includes chemical reduc-
tion, microwave-assisted synthesis, microemulsion, photoreduc-
tion, electrochemical approach, etc. [56,57].
Chemical method of synthesis can be subdivided into chemical
reduction, electrochemical, irradiationassisted chemical and pyrol-
ysis methods [58]. Ag NPs synthesis in solution requires metal pre-
cursor, reducing agents and stabilizing or capping agent.
Commonly used reducing agents are ascorbic acid, alcohol, borohy-
dride, sodium citrate and hydrazine compounds. Sotiriou and Prat-
sinis [59] have shown that the Ag NPs supported on
nanostructured SiO2 were obtained by flame aerosol technology,
which allows close control of silver content and size. Also, silver/
silica nanoparticles with relatively narrow size distribution were
obtained by flame spray pyrolysis [59].
Among these, chemical reduction is a relatively simple, high
yield and cost-effective process through the chemical reduction
of silver salt in water or an organic solvent to form a colloidal sus-
pension. This strategy requires silver salt, reducing agent and sta-
bilizing/capping agent. Silver nitrate is the most widely used
silver salt precursor. Sodium borohydride (NaBH4), ascorbic acid,
glucose, hydrazine, sodium citrate, and ethylene glycol (EG) are
typical reductants for reducing silver ions [60,61].
Sodium borohydride is a strong reductant for forming fined and
monodispersed AgNPs. Weak reducing agents such as sodium
citrate, ascorbic acid, and glucose lead to the formation of rela-
tively large AgNPs, having a wider size distribution; sodiumcitrate
plays the role of a reducing and a stabilizing agent [61]. As recog-
nized, colloidal AgNPs tend to contact or link with each other to
form aggregates as a result of the attractive Van derWaals forces.
The agglomeration of colloidal AgNPs can be prevented by the
use of stabilizing agents. The stabilizing effect of polymer-based
capping agents or non-ionic surfactants of AgNPs suspensions is
based on the charge repulsion or steric hindrance to counteract
the van derWaals attraction between colloidal nanoparticles. As
such, electrostatic or steric stabilization of colloidal AgNPs is
achieved through adsorption of macromolecules or organic com-
pounds to the surfaces of the nanoparticles. Citrate-capped AgNPs
exhibit negative surface charge due to the carboxylic moiety of
citrate. This leads to electrostatic repulsion between AgNPs,
thereby preventing agglomeration of nanoparticles [62,63]. Typical
polymer-based capping agents are polyvinyl alcohol (PVA),
polyvinylpyrrolidone (PVP), polyethylene glycol (PEG) and
polysaccharides, while non-ionic surfactants including Brij, Tween,
and Triton X-100 are employed to stabilize AgNPs during the for-
mation process [63]. These stabilizers also play important roles
in controlling the size and shape of AgNPs. The properties and bac-
tericidal activities of AgNPs are greatly influenced by their size and
shape. Thus, researchers have spent much effort on the size- and
shape-controlled synthesis of AgNPs by using different capping
agents. Organic solvents have some advantages over aqueous solu-
tions such as high yield and narrow particle size distribution. In
certain cases, solvent itself can also serve as a reducing agent
[64]. As an example, the polyol process utilizing EG as both solvent
and reductant in the presence of PVP at 160 °C is known to be
effective to reduce silver nitrate to yield AgNPs [65]. In addition,
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Materials Science for Energy Technologies 3 (2020) 756–769
microwave irradiation is more energy efficient than thermal heat-
ing in the polyol process. Microwave irradiation offers fast and
homogeneous heating of the reaction medium, typically in a time
period of few seconds. As such, it provides uniform nucleation
and growth conditions for AgNPs [66].
2.1.3. Biological method
The limitations associated with both the physical and synthetic
strategies for the development of AgNPs includes expensive tech-
nique and usage of harmful, perilous chemicals, which might cause
impending ecological and biological hazards. Therefore, it becomes
necessary to establish methods which could possibly overcome
these limitations and produce stable and therapeutically active
AgNPs. This has led to the evolve of biological strategies, which
has encouraged the essential needs and potential usage of AgNPs
[67].
Integration of green science systems and philosophies into nan-
otechnology is of awesome intrigue which has increased much
consideration over the previous decade [68]. Green science which
is the utilization of science standards to decrease or take out utiliz-
ing of lethal reagents, has come about to noteworthy lessening in
the measure of unsafe deposits to social wellbeing and atmo-
sphere. Green science is characterized as science supported proce-
dures for contamination anticipation which can be reached out to
particular zones including green diagnostic science, naturally well-
disposed explanatory science and clean expository techniques [69].
Green union of AgNPs has pulled in extensive consideration as
of late. In such manner, plants concentrates and normal assets,
for example, microbes and proteins are observed to be of optional
components in AgNPs amalgamation. Using green constituents has
a few favourable circumstances including low vitality utilization
and direct process conditions (e.g. weight and temperature)
deprived of utilizing any lethal chemical [70]. Thus, green blend
strategies utilizing different natural living beings, for example,
yeast, form, green growth and microscopic organisms, and plant
extricates have been produced for NPs union [71]. When con-
trasted with the metallic components in mass state, metallic NPs
display irregular compound, optical, physical, and warm features
because of their higher surface area to volume proportion [72].
Consequently, these novel features make AgNPs (>100 nm) a
potential agent for a wide range of utilizations [73].
It is realized that Ag and its associated composites are very
effective against the real types of microbes and to the infections
spread by them [74–76]. Although the main mechanism behind
the antibacterial and antifungal activities of Ag and Ag-based
materials is still not clear, but studies have showed that the Ag
could restrain cell transduction and furthermore causes cell death
[67]. AgNPs, because of their surface design and little size which
thus, increment their surface to volume proportion, display stun-
ning bactericidal properties [77]. Antimicrobial exercises of silver
settles on it much intriguing decision for usages in various fields
including, industrial sectors, biomedical applications, tissue engi-
neering, food industries, safety concerns, environmental applica-
tions etc. [67,78].
A wide range of strategies have been created for union of AgNPs
including physical, synthetic and green (natural) methods (Fig. 1).
In all strategies, settled NPs are shaped by decreasing of the silver
particles to silver components utilizing lessening specialists took
after by nucleation and developing procedures [79–81]. In various
physical and synthetic strategies associated with the formation of
NPs, it is conceivable to get fabricated materials having desired
potentials. However, the utilization of costly and dangerous mate-
rials for their production trails them as unconvinced strategies
[82,83]. Green union of AgNPs by microorganisms and plant
removes as an option practical blend system which has increased
much consideration and application nowadays. Different plant-
S. Anees Ahmad, S. Sachi Das, A. Khatoon et al. Materials Science for Energy Technologies 3 (2020) 756–769

in the formation of NPs blend [68]. Utilizing plant concentrates can

likewise be beneficial over microorganisms for NPs blend, by end
of the distinguishing proof, confinement, and keeping up cell soci-
eties forms for microorganisms [87]. Some of the significant
approaches have been summarized in Tables 1 and 2.

3. Antibacterial mechanism of AgNPs

The antibacterial properties of AgNPs mostly depends upon the

Fig. 1. Various approaches for the synthesis and development of AgNPs.
based metabolites such as carbohydrates, alkaloids, terpenoids,
tannins, phenolic acids, flavonoids, proteins, and others, plays sig-
nificant role in the fabrication of AgNPs from the Ag materials [84].
The polyol parts, polysaccharides and aqueous-solvent hetero-
cyclic blends are the most important plant constituents that are
primarily responsible for the reduction of Ag particles, followed
by the formation of AgNPs. In green combination of AgNPs utilizing
plant separates, a few components including plant sources, sorts of
natural mixes in the rough leaf remove, convergence of beginning
silver particles, temperature and the sort and centralization of leaf
concentrate shades are the vital variables on the effectiveness of
AgNPs creation prepare [85]. In correlation with physical and con-
coction techniques, amalgamation of NPs by plant concentrates is
financially savvy and eco-accommodating strategy which allows
the objective of formation of NPs which are apt for human uses
[86]. This technique can be utilized as a monetary and significant
option for the huge scale creation of AgNPs. Moreover, separates
from plants might perform as reducing as well as stabilizing agents
size, pH and ionic strength of the medium, and also on the type of
capping agent. However, the specific mechanism of antibacterial or
toxicity activities by the AgNPs is still indefinite and has not been
completely explained. Perhaps, the AgNPs could frequently release
the silver ions (Ag+), which might be considered as one of the
mechanism behind the bactericidal activity of AgNPs [125]. The
positively charged Ag+ play a vital role to exhibit the antibacterial
or toxicity activities of the silver (Ag) and to maintain its antibac-
terial or toxicity activities, the Ag essentially should be in its ion-
ized state [126]. It has been noticed that the Ag+ ions forms
complexes with the nucleic acids and as compared to the phos-
phate groups, it specifically interacts with the nucleosides of
nucleic acids. Therefore, all types of silver or silver comprising
composites having antibacterial activities are ultimately the
sources of Ag+ ions [127,128]. In some of the works, the electro-
static attraction amongst the negatively charged microbial cells
and positively charged NP have been showed [129] and these
nanoparticulate systems have been proposed as the most apt bac-
tericidal agents [130,131]. Due to the electrostatic attractions and
affinity towards the sulfur proteins, the Ag+ ions adheres to the
cytoplasm and cell wall, and significantly enhances the permeabil-
ity; leading to the disruptions of bacterial casings [132]. As soon as
the free Ag+ ions are uptaken by the cells, the respiratory enzymes
gets deactivated, leading to the production of reactive oxygen spe-

Table 1
Antimicrobial activities of plant extracted silver nanoparticles.

Plant (extracts) Particle size (nm) Remark References

Brassica oleracea extract 42–83 Antibacterial action against Escherichia coli and Staphylococcus aureus [88]
Carica papaya extract 15 Antibacterial action against Escherichia coli [89]
Trianthemadecandra extract 10 Antibacterial action against Escherichia coli [90]
Garcinia mangostana extract 1–100 Antibacterial and antioxidant activity action against E. coli and S. aureus [91]
Withania somnifera extract 5–30 Antimicrobial activity against S. aureus, E. coli, Candida albicans, Aspergillus niger, [92]
and Aspergillus flavus
Acorus calamus extract 31.83 Antibacterial activity against Bacillus subtilis, Bacillus cereus, and S. aureus [93]
Ocimum tenuiflorum extract 25–40 Antibacterial activity against E. coli and B. subtilis [94]
Sensitivum portulacastrum 5–20 Antibacterial and antifungal activity against S. aureus, Listeria monocytogenes, and [95]
extract Penicilliumitalicum
Tribuluster restris extract 16–28 Antibacterial activity against B. subtilis, E. coli, and S. aureus [96]
Cocos nuciferain florescence 22 Antimicrobial activity against Salmonella paratyphi and B. subtilis [97]
extract
Lantana camara extract 12.55–12.99 Antibacterial activity against B. subtilis [98]
Cymbopogon citrates extract 32 Antibacterial effect against E. coli, Shigella flexneri, and S. Sonnei [99]
Boerhaavia diffusa extract 25 Antibacterial activity against Flavobacterium [100]
Cassia roxburghii extract 10–30 Antibacterial activity against B. subtilis [101]
Musa paradisiaca peel extract 23.7 antibacterial activity against B. subtilis, E. coli, and S. aureus [102]
Afzelia quanzensis bark extract 10–80 Antimicrobial activity of against E. coli and S. aureus [103]
Eucalyptus globules extract 1.9 to 4.3 and 5–25 Antimicrobial activity against E. coli and S. aureus [104]
Origanum vulgare extract 63–85 Antibacterial activity against E. coli, S. dysenteriae, S. typhi, and Shigellasonnei [105]
Pulicaria glutinosa extract 40–60 Antibacterial activity against E. coli and S. aureus [106]
Petroselinum crispum leaf extract 30–32 Antibacterial activity against E. coli and S. aureus [107]
Dioscorea bulbifera extract 8–20 Antibacterial activity against E. coli, B. subtilis, S. typhi, and S. aureus [108]
Mangosteen leaf extract 35 Antimicrobial activity against E. coli and S. aureus [109]
Prunus japonica leaves extract 26 Medicinal and pharmaceutical applications [110]
Rheum palmatum root extract 121 Antimicrobial activity against S. aureus and P. aeruginosa [111]
Phoenix dactylifera extract 15–40 Antibacterial activity against E. coli [112]
Phyllanthus emblica extract 40 Antibacterial activity against Acidovoraxoryzae strain RS-2 [113]
Rosa indica leaves 50–100 Antibacterial activity against P. aeruginosa and B.subtilis [114]
Taraxacum officinale leaf extract 15 Antibacterial activity against Xanthomona saxonopodis and P. syringae. [115]

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S. Anees Ahmad, S. Sachi Das, A. Khatoon et al. Materials Science for Energy Technologies 3 (2020) 756–769

Table 2
Antimicrobial activities of some microbes-mediated silver nanoparticles.

Bacterial Species Particle Major Outcomes References

size (nm)
Glucono bacterroseus 10 The AgNPs exhibited dose-dependent antiplatelet pattern against the ADP-induced activated blood platelets. [116]
The AgNPs conferred no toxicity.
Bacillus flexus 12–65 The synthesized AgNPs improved the efficiency of the antibacterial activity against multi-drug resistant [117]
(MDR) microbes.
Staphylococcus epidermidis 10–80 Metallic NPs synthesized from the supernatants of the bacterial cultures within 24 hours and the production [118]
rate was comparatively high at 50 °C.
CorynebacteriumSH09 10–15 The bio-sorption of the diamine Ag-complex was superior than that of Ag+ ions. [119]
Morganella species 10–40 As per study, the molecular mechanism of Ag resistance and its gene products (silE, silP and silS) showed a [120]
vital role in the entire synthesis procedure of AgNPs by Morganella sp.
Ureibacillus 10–100 The biosynthesis of AgNPs from the supernatants of bacterial strains were found to be maximum at the [121]
thermosphaericus raised temperatures and higherAg+ ion concentrations.
ShewanellaoneidensisMR-1 2–20 Results showed that the presence of bacterial cells was necessary for the development of AgNPs. Also, the [122]
reactions conditions effected the yield of AgNPs significantly, however did not effected the size very
effectively.
Geobacillus 5–35 Increased stability of the formed AgNPs was accredited to the release of certain capping proteins from the [123]
stearothermophilus bacterial cells present in the reactions mixture.
Bacillus safensis LAU 13 5–30 The AgNPs exhibited significant inhibitory activities against the clinical substrates of the bacterial strains of [124]
Escherichia coli. Also, the keratinase of the bacterial strain was found to be apt for the preparation of AgNPs.

cies (ROS) and interruption in adenosine triphosphate (ATP)
release [133].
ROS could be a vital agent in the aggravation of the disruption of
the cellular membrane and alteration in the deoxyribonucleic acid
(DNA). DNA majorly comprises of phosphorus and sulfur and when
its gets interacted with the Ag+ ions, could cause different issues
related to DNA, including DNA replication, cell propagation and
others (Fig. 2). Additionally, the Ag+ ions could efficiently hinder
the protein synthesis by denaturing cytoplasmic ribosomal compo-
nents [134]. Apart from the ability to release the Ag+ ions, the
AgNPs could themselves eradicate the microbes or bacteria. The
amassed AgNPs trigger denaturation of the cell membranes and
due to nanoscale size they have the capability to permeate through
the cell wall of bacteria and consequently modify the cell mem-
brane arrangements [135]. The organelles might get ruptured
due to denaturation of cell membrane, and also might cause cell
lysis. Also, the AgNPs could be included in microbial signal trans-
duction. The microbial signal transduction is impacted by phos-
phorylation of protein substrates, and the AgNPs could
potentially dephosphorylate the tyrosine residuals over the pep-
tide substrates. Furthermore, the disruption of microbial signal
transduction could significantly cause to cell apoptosis and inhibi-
tion of cell propagation (Fig. 3). One of the major limitation of the
currently available antibacterial or antimicrobial agents is resistant
of bacteria against these agents [136]. This is mainly due to anti-
genic alterations in the bacteria which are incompetently accom-
plished with the current treatments. The resistance to
antibacterial or antimicrobial agents by the bacteria or microbes
has turn out to be a severe issue and therefore, is has become very
important to develop novel therapeutic approaches. The research-
ers and formulators have explored the therapeutic potentials of Ag-
based nanoparticulate systems to overcome these issues. The main
mechanism behind the includes the interaction of Ag+ ions with
the disulphide bonds of the protein clusters or glycoproteins of
pathogens, leading to alterations in the three dimensional struc-
tures of the protein [137,138]. The antibacterial efficacy and mech-
anism of the AgNPs are affected by their dissolution profile in the
reaction media. The dissolution efficacy is highly dependent upon

Fig. 2. Probable mechanism of action of silver nanoparticles as antimicrobial agent [118] (Reproduced from Pareek et al., 2018).

761
S. Anees Ahmad, S. Sachi Das, A. Khatoon et al.
Fig. 3. Cell apoptosis in bacteria in presence of AgNPs [120] (Reproduced from Riaz Ahmed et al., 2017).
the synthesis and processing parameters, including intrinsic char-
acteristics of AgNPs and the dissolution media [139].
Apart from these, the size and shape of the AgNPs influences the
production of Ag+ ions and this phenomenon is described theoret-
ically by the Ostwald–Freundlich equation. According to it, the
AgNPs having small size and sphere-shaped or quasi-spherical
arrangement are more susceptible to the release, of Ag+ ions owing
to their greater surface area [140]. Thus, the aggregation of AgNPs
reduces the the release of Ag+ ions and this issue could be resolved
with the usage of capping agents, which effectively modifies the
surfaces of AgNPs, and thus could improve the dissolution activi-
ties of the AgNPs [141]. Addition to these inherent properties of
AgNPs, the surrounding media also influences the release of Ag+
ions. The existence of organic or inorganic constituents in the sur-
rounding media affects the dissolution of AgNPs by accumulating
with AgNPs or forming complexes with the Ag+ ions. Moreover,
as compared to the neutral media, the AgNPs releases the Ag+ ions
Fig. 4. Probable bactericidal mechanism of AgNPs in G+ve and G ve bacteria [127] (Reproduced from Duval et al., 2019).
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Materials Science for Energy Technologies 3 (2020) 756–769
more rapidly in the acidic media [142]. Studies have showed that
the gram-negative (G ve) bacteria are more liable to AgNPs than
the gram-positive (G+ve) bacteria. The cell wall of G-ve bacteria
is more tapered as compared to G+ve strains (Fig. 4). The thick cell
wall decrease the diffusion of the AgNPs into the cellular environ-
ment [143]. The diverse antibacterial activities of AgNPs over the
G ve and G+ve bacteria suggested that the uptake of AgNPs is
essential for effective antibacterial or antimicrobial action [139].
As above-mentioned, G+ve pathogens are composed of very thick
cell wall comprised pf various peptidoglycan coats, thus serves as
a barrier for the permeation of the Ag+ ions through cytoplasmic
membranes. However, G ve pathogens are mostly comprised of
only a single peptidoglycan coat, thus Ag+ ions easily penetrate
into the cytoplasm and causes cell lysis.
The antibacterial effects of AgNPs is also influenced by the pan-
icles properties such as shape, size, surface charge, dosing and dif-
fusion state [56,144–147]. It is usually recognized that AgNPs
S. Anees Ahmad, S. Sachi Das, A. Khatoon et al.
smaller than 10 nm could directly modify cell penetrability, go into
the bacterial cells and initiate cell lysis. Generally, the formation of
biofilm in the oral environment hinders the transport of Ag+ ions or
AgNPs and ultimately the bacteria gets protected from the effects
of Ag+ ions and AgNPs [148]. Apart from these, some other mech-
anisms are also reported, including interaction of Ag+ ions with
the biological macromolecules (enzymes and DNA), based on the
mechanism of electron-discharge or free radical generation [149].
As per the reported studies, AgNPs triggers the inhibition of both
protein synthesis and cell wall synthesis, evidenced by the amass-
ing of envelope protein precursor or disruption of the outer cellular
membrane, leading to ATP leakage [150].
3.1. Antibacterial applications of AgNPs
AgNPs have been showed wide applications in the treatment
and management of injuries, burns and microbial infections
[151,152]. Moreover, different salts of Ag and their by-products
are significantly used as bactericidal agents [153]. Abundant study
has been performed which reports the bactericidal activities of the
AgNPs. AgNPs have also been explored as a tool for the delivery of
antibiotics, production of complexes used as sterilizing filters and
encasing materials [138,154–156]. Most importantly, due to smal-
ler size and greater surface to volume proportions, the AgNPs holds
an extensive contact area with the microbes. These properties of
AgNPs significantly enhances their biological and chemical proper-
ties, and makes them a robust bactericidal material. The AgNPs also
have the capability to interrupt the cellular functions, including the
cell permeation and respiration. Additionally, the AgNPs when
reach within the cell membranes, potentially disrupts the cellular
components by reacting with the sulphur-mediated proteins and
phosphorus-mediated complexes like deoxyribonucleic acid
(DNA) [157–160].
Even though the AgNPs have exhibited potential bactericidal
activities, yet they have been also reported with certain limita-
tions, including toxicity against cells/tissues, particularly the mam-
malian cells [161–163]. Though, current studies have revealed that
the conjugation of AgNPs with bactericidal agents might decrease
the toxic effect towards the mammalian cells and simultaneously
improve their bactericidal activities synergistically [164–166]. Fur-
thermore, the amalgation of bactericidal agents with AgNPs in a
suitable fraction would reduce the loading amount of both the con-
stituents and thus with reduced dosage also they would be able to
show greater antibacterial efficacy. Also, the conjugation leads to
an increase in the amount of bactericidal agents or antibiotics at
the specific bacterial sites and thus enhances the therapeutic
potential of the antibiotics against the bacterial infections [167].
Apart from this, an alternative approach to overcome the toxic-
ity issues of the AgNPs is the potential usages of peptide/peptide-
based linkages with AgNPs. The interactions between the metallic
ions and the biomolecules such as proteins, peptides, amino acids
and others, have showed significant effects over the therapeutic
potential of the metallic NPs. These biomolecules also exhibit vital
role for the effective delivery of the conjugated metallic NPs
through various biological paths such as electron transmission
responses, metal transportation and storing. Furthermore, these
conjugates metallic systems significantly inhibit the enzymes
which play crucial role in bacterial metabolism. This process is car-
ried over by ligand interchange responses where the ligand exist-
ing with the loaded drug moiety is replaced by the specific
enzyme that acts as a primary source for various metal-mediated
systems. Thus, it has been reported as one of the most significantly
applied method in bio-inorganic chemistry [168–171].
Moreover, the modifications in AgNPs surface could also assist
in modifying their features to ensemble numerous applications
and govern the interactions of the constituents, and in this pro-
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Materials Science for Energy Technologies 3 (2020) 756–769
spect the surface modification of AgNPs through chemical func-
tionalization has gained much considerations. Functionalized NPs
could be useful in numerous areas such as medical, engineering,
and biological uses [172–180]. It could be categorized into two dis-
tinct groups, covalent and non-covalent type of binding physisorp-
tion. Although in the physisorption process, the conjugations are
merely weak where the ligands and the nanomaterials are conju-
gated through weak electrostatic bonds, hydrogen bonds and
hydrophobic interfaces. This property of the surface functionalisa-
tion is helpful for the formation of surface layers for stabilizing the
discrete NPs in the solution medium. However, the chemisorption
has showed greater potentials than the non-covalent bonding
developed by physisorption. Furthermore, the natural polysaccha-
rides could significantly improve the surface functionalization of
AgNPs [181–186]. Most of the surface functionalization approaches
are centred upon the formation of covalent bonds. This method
offers stronger bonds, allowing an increase in the stability of the
ligands attached with the surface of the NPs, thus makes the asso-
ciation stronger. Furthermore, the functional groups existing on
the ligands, reacts with the NPs and through chemisorption
approach attach to the surface of the NPs and yields self-
assembled arrangements [187,188]. Surface modifications of the
AgNPs might be helpful for the development of novel and fascinat-
ing bactericidal agents. Also, some of the studies have been
reported in which people have developed distinctive protein-
based natural antibacterial systems such as lysozyme-based and
peptide-based materials with improved efficacy to inhibit bacterial
growth [189,190]. These systems usually caused cell lysis in bacte-
ria and hence the bacteria find it perplexing to achieve resistance
against these developed and modified bactericidal agents.
AgNPs, due to their killing activities against bacteria, are recog-
nized for their remarkable antibacterial activities. Moreover, the
bactericidal activities of the AgNPs are mostly related with the
direct interaction of the NPs to the cell wall of bacteria, trailed
by permeating into the cytoplasmic fluid and this could damage
the membrane which causes leaking of the cellular component
and ultimately cellular death [191,192]. In one of the study, it
was represented the AgNPs (~10 nm) attached to the microbial cell
wall, thus interrupted the penetrability and cellular metabolic
pathways and caused cell death [191]. Moreover, the generation
of ROS has been found to be the major cause for bacterial death
as it promotes lipid peroxidation, however hinders the ATP gener-
ation and DNA replication. Also, the increased level of ROS in the
bacterial cells could lead to oxidative stress in these cells [193].
In general, the AgNPs that are finely dispersed in the physiological
media, exhibited more anti-bacterial efficiency than that of the
agglomerated AgNPs. Furthermore, it has been observed that the
killing effects of the AgNPs against G ve and G+ve bacteria
enhanced with a decrease in the size of the AgNPs [194,195]. In
another study, the anti-bacterial activity of the sphere-shaped
and rod-shaped AgNPs against G+ve and G ve bacterial strains
were investigated. Results showed that the antibacterial activity
of both the sphere-shaped and rod-shaped AgNPs followed a
dose- dependent and time-dependent pattern. Also, the sphere-
shaped AgNPs were found to be more efficient as compared to
rod-shaped AgNPs against the Klebsiella bacterial strain [196].
The antibacterial efficacy of the AgNPs is highly effected by the sur-
ficial charge over the NPs and in this context various studies have
been reported for the use of the capping agents as well as stabiliz-
ers which prevents accumulation of the AgNPs, and thus certainly
influences the surface charge over these NPs [197,198]. In one of
the study, the significant effect of surface charge of AgNPs coated
with polyvinyl pyrolidone (PVP), citrate (CT) and branched-
polyethyleneimine (BPEI) over the antibacterial efficacy against
the bacillus strains. Results revealed that the positively charged
AgNPs exhibited the maximum antibacterial activity against all
S. Anees Ahmad, S. Sachi Das, A. Khatoon et al.
the bacterial species, while negatively charged AgNPs exhibited the
least and neutrally-charged AgNPs showed transitional bacterici-
dal activity [199]. Apart from these, certain modification with car-
bon nanotubes and quantum dots have also improved the
therapeutic efficacy of these NPs [200–208]. The Ag-based disinfec-
tants have been widely used and has exhibited utmost potentials
in treating the resistance caused by the microbes against effective
antibacterial treatments. The Ag-based antiseptics have greater
reactivity and binding efficacy with the cellular proteins, so allows
for alterations inside the assembly of cellular membrane and
nuclear membrane, and finally causes disruptions and cell death
[208].
The AgNPs are also used in the food industries during the pro-
cess of packing, as they prevent destruction of the nutrients or
foodstuffs by the pathogens [209]. One of the most important
properties of the AgNPs or AgNPs-based biomaterials is that their
essential antibacterial activity is exhibited against both the plank-
tonic and biofilm prearranged microbes. Apart from this the pro-
gressive strategies to improve the bactericidal efficacy of the
AGNPs could be established by the method of bio-
functionalization by using some bactericidal peptides (like poly-
myxin B), bovine serum albumin (BSA), and others [210]. Bio-
functionalization improves the bactericidal activity, bioactivity
and protects the surface of the AgNPs from microbial attack [211].
The Ag-based nanocomposites have also showed significant
antibnacterial actions as that of AgNPs [212–214]. Chen et al.
developed a graphene oxide-silver nanocomposites (GO-Ag NCs)
and evaluated their antibacterial efficacy against multidrug-
resistant E. coli strains. The GO-Ag NCs exhibited synergistic acticv-
ity with improved antibacterial efficacy. Additionally, the pho-
tothermal effect for efficient sterilization was attained through
these nanocomposites [215]. The AgNPs adsorbed over graphene
or carbon nanotubes could efficiently enhance the antibacterial
activity of AgNPs [216–218]. In a study, a simplistic glucose-
mediated one-step approach was established for the production
AgNPs incorporated within carbon nanotubes (AgNPs-CNTs). The
nanocomposites were developed in the presence of CNTs (nano-
reactor), silver nitrite (precursor) and glucose (reductant). The
AgNPs were within the particle range of 6–10 nm and were uni-
formly assembled within the CNT channels. Furthermore, the
AgNPs-CNTs exhibited an improved antibacterial activity
against E. coli strains [219].
4. Toxicity of AgNPs
AgNPs are amongst the most extensively used metal NPs and
has played crucial role in different field of biomedical and pharma-
ceutical applications. The smaller size of the AgNPs allows them for
easy passage through the biological membranes and reach within
the cells, producing toxicity at various levels based upon the exag-
gerated microorganisms. The toxicity of the AgNPs is found to be
associated with its features like size, shape, amount, accumulation,
surface charge, and the methods applied for synthesis [220,221].
Also, the toxicity of AgNPs depends upon the category of targeted
microbe, which is correlated with the resistance mechanism of the
microbe used eradicate the unwanted complexes. Furthermore, the
bacterial response in the toxicity assessments is highly effected by
the culture media, in which the bacterial species are exposed [222–
224]. Primarily, both the AgNPs and Ag+ ions released from the
AgNPs are presumed to employ toxicity by stimulating membrane
impairment, ROS generation, oxidation and denaturation of pro-
teins, dysfunction of mitochondria, damage of DNA and obstruc-
tion of cell propagation [136,225].
Ema et al. reviewed toxicity mechanism of AgNPs in the mam-
mals, particularly the rabbits and rats, and described that the tox-
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Materials Science for Energy Technologies 3 (2020) 756–769
icity of AgNPs caused modifications in the organs of the mammals
that were related with their propagative and growth processes
[226]. They also reported that the oxidative stress and inflamma-
tion due to the formation of ROS were the intervening factors of
cytotoxicity. Moreover, the probable interaction of AgNPs with dif-
ferent environmental constituents might considerably alter the
toxicity profile of the AgNPs. Apart from this, toxicity of AgNPs
was found to be widely assessed amongst various microorganisms
of medical concern [136,227,228].
Studies have demonstrated that the cytotoxicity of AgNPs
mostly depends upon its physical and chemical properties, and
also the microorganism type against which the toxicity is assessed
[229]. AgNPs produced from the green methods are usually less
toxic than those attained from the non-green methods. Application
of green methods has abridged the usage of perilous chemical reac-
gents and enhanced the synthesis efficiency of AgNPs through
chemical processes [230–232]. Moreover, the toxicity of AgNPs is
generally observed due to the stimulation of oxidative stress or
production of reactive oxygen species (ROS) in the system [193].
AgNPs produced from the green methods are usually more toxic
than those attained from the non-green methods. Although, the
development and application of AgNPs has ensued in public cog-
nizance related to their toxicity and environmental impacts
[233,234]. Interestingly, a contrasting fact has been observed
related to the dose of AgNPs indorsing toxicity. In some studies,
the AgNPs of particle size >50 nm reduced the [235] sustainability
in the tested human mesenchymal cells at a lower dose of 10 lg/
mL, however in an another study no toxicity was reported even
at a higher dose of 100 lg/mL. Also, the stability of the samples
has showed significant role in an upsurge in toxicity by the stored
AgNPs (water for 6 months) which is correlated with the release of
Ag+ ions [236].
5. Conclusion and future perspectives
The potential advantages of nanotechnology in modern
biomedical applications are broadly acknowledged and have found
to be most encouraging segment for era in developing new bacte-
ricidal agents for treating bacterial infections. It is presently evi-
dent that AgNPs have a solid bactericidal and antiviral activities,
emphasized by a few reviews. AgNPs can collaborate with different
microorganisms, (for example, microscopic organisms) and fur-
thermore affect both the development of and develop bacterial bio-
films and, in this way, could be utilized as expansive range
bactericidal agents. Despite the fact that lipopolysaccharides are
made out of lipids covalently conjugated with the polysaccharides,
an absence of inflexibility of the general basic envelope is noticed.
Also, the negative charge over the lipopolysaccharides are pulled in
to the frail positive charges of AgNPs. Then again, the cell mass of
Gram+ve microbes is essentially made out of a thick peptidoglycan
layer comprised of chains of polysaccharides interlinked with short
peptides to frame three-dimensional inflexible structures. The
solidness and the broad cross-connecting not only decrease the
bacterial cell divider tying down destinations for AgNPs addition-
ally render the divider itself more troublesome to enter. A multi-
faceted system against microorganisms appears to be because of
NPs communications with the bacterial surfaces, and in addition
to their specific structure. These days, there is significant need
for establishment of specific instruments characterization of AgNPs
and their activities. Also, apt research is essentially required on the
biocompatibility and bioactivity of the AgNPs. This review on the
consolidated utilization of AgNPs with other antimicrobial opera-
tors could definitely help lessen the issue of lethality and to keep
away from the potential for improvement of resistance and, most
importantly, unequivocally upgrade the bactericidal impacts. The
S. Anees Ahmad, S. Sachi Das, A. Khatoon et al. Materials Science for Energy Technologies 3 (2020) 756–769

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