JBIC Journal of Biological Inorganic Chemistry (2019) 24:929–941

https://doi.org/10.1007/s00775-019-01717-7

MINI REVIEW

Antimicrobial activities of biologically synthesized metal

nanoparticles: an insight into the mechanism of action
Parveen Nisar1 · Nasir Ali1 · Lubna Rahman1 · Muhammad Ali1 · Zabta Khan Shinwari1,2,3

Received: 22 February 2019 / Accepted: 28 August 2019 / Published online: 12 September 2019
© Society for Biological Inorganic Chemistry (SBIC) 2019

Abstract
Increasing antimicrobial resistance is a clinical crisis worldwide. Recent progress in the field of green synthesis has fascinated
scientists and researchers to explore its potentials against pathogenic microbes. Bioinspired-metal-based nanoparticles (silver,
copper, gold, zinc, etc.) have been reported to be tested against both Gram-positive and Gram-negative bacteria such as B.
subtilis, E. coli, Staphylococcus aureus, etc., as well as some pathogenic fungi including A. niger, F. oxysporum, A. fumigatus,
etc., and are testified to exhibit inhibitory effects against pathogenic microbes. The possible modes of action of these metal
nanoparticles include: (a) excess production of reactive oxygen species inside microbes; (b) disruption of vital enzymes in
respiratory chain via damaging microbial plasma membranes; (c) accumulation of metal ions in microbial membranes; (d)
electrostatic attraction between metal nanoparticles and microbial cells which disrupt metabolic activities; and (e) inhibition
of microbial proteins/enzymes by increased production of H ­ 2O2. Although these pathways are interconnected, information
on potential mechanism of most of these biogenic nanoparticles is still limited. Further exploration of these mechanisms
could help in tackling the burning issue of antibiotics resistance.

Keywords  Green synthesis · Metal nanoparticles · Antimicrobial activity · Antimicrobial mode of action

Introduction The burden of microbial infectious diseases is a serious

Nanoparticles are the particles with one dimension (at least)
in the size range of 10–100 nm [1]. They can be synthesized
by physical and chemical methods [2]. However, these meth-
ods have potential hazards due to manipulation of certain
stabilizing agents, high radiation, and high concentrated
reductants [3]. An alternative way to develop ecofriendly,
non-toxic, and reliable methods is based on biological syn-
thesis of nanoparticles. The safest of these methods is the
one that uses medicinal plants [4]. Another class of biologi-
cal synthesis is hybrid methods that combine organic and
inorganic compounds [2].
* Muhammad Ali
alibiotech01@gmail.com
1 metabolism processes [8] resulting in microbial death.
Molecular Systematics and Applied Ethnobotany
Laboratory, Department of Biotechnology, Quaid-i-Azam
University, Islamabad 45320, Pakistan
2
National Council for Tibb (NCT), Islamabad, Pakistan
3 is one of the common water pollutants released by paper and
Pakistan Academy of Sciences, Islamabad, Pakistan
health issue and economic burden around the globe. Due
to antimicrobial-resistant microorganisms, the number and
severity of infections have increased; and in USA alone;
annually, a cost of extra $125 billion increase has been
resulted in hospital charges [5, 6].
There are tons of nanoparticle-based products marketed
for bacterial diagnosis, medical devices, and antibiotic
delivery. Various organic and inorganic nanoparticles with
their unique physicochemical characteristics are playing
important role in rapid, sensitive, and selective detection of
infections. In addition, some of these biosynthesized metal
nanoparticles have the potential to heal microbial infections
involving multidrug-resistant pathogens. Thus, popular to
combat microbial infections [7].
There are various metal nanoparticles that can be used
as antimicrobial agents, e.g., ZnO and ­TiO2 nanocrystals.
These nanoparticles may alter microbial cell integrity and
Along with antimicrobial properties of ZnO nanoparticles,
it can also exhibit a photocatalytic activity under the sun-
light towards the degradation of rhodamine-B (RhB). RhB

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textile industries [9]. Similarly, CdSe nanoparticles exhibit
antibacterial potential against a vast variety of bacterial spe-
cies; E. coli, Staphylococcus aureus, E. hermannii, and P.
vulgaris. Among these P. vulgaris are more susceptible to
these nanoparticles [10].
Among other methods, “green synthesis” of metallic nan-
oparticles is popular because of their harmless procedure.
Several studies have shown green biosynthesis of different
metallic nanoparticles (such as copper, silver, gold, iron
oxide, zinc oxide, etc.) from various plants. We have sum-
marized the studies of plant-inspired synthesis of metallic
nanoparticles in Tables 1 and 2. The plants extracts used by
these methods exhibit various antimicrobial properties [11].
Table 1 shows green synthesis of various metallic nanoparti-
cles from different plants, their sizes, and nature of activity.
Table 2 shows the summary of studies conducted on green
synthesis of metallic particles, the plants extracts used, NPs
sizes, and their possible mechanisms.
Although the précised mechanism of nanoparticles action
against microbes is still under investigation; some of the
important proposed possibilities exist which include free
metal ion toxicity generating from dissolution from the sur-
face of synthesized nano-metals, and oxidative stress arising
from the reactive oxygen species (ROS) on the surface of
nanoparticles [39].
Several articles are available dealing with antimicrobial
activities of biosynthesized nanoparticles. Most of these
reports are limited to specific type of metals or biological
source or pathogen. Comprehensive data (based on the dec-
ade 2009–2018) from the peer reviewed journals indexed
by web of knowledge regarding plant-mediated synthesis
and green synthesis of different metallic nanoparticles
are shown in Figs. 1 and 2, respectively. It is worth noting
that in the literature, both key terms “synthesis and green
synthesis” are used alternatively for biological synthesis
methods. Therefore, we have shown that both key terms
search results in different figures. Silver and gold nanopar-
ticles have remained in the focus of most researchers due
to their numerous biomedical applications. These biogenic-
metal nanoparticles have been extensively manipulated for
in vitro and in vivo biological screening with multifarious
antimicrobial applications. However, very limited informa-
tion is available on the mechanism of bioinspired-metal NPs
action. In this study, we have discussed possible mechanism
of antimicrobial activities of different biosynthesized metal
nanoparticles.
Metal nanoparticles and their antimicrobial
potency
Metals have been used as antimicrobial agent for centuries
in several countries. In 1500 BP, the Egyptians have used
the copper salt as a constringent. The Greek, Egyptians,
Persians, Romans, and Indians have used silver and copper
to disinfect water and for food preservation [40, 41]. Small
size and larger surface area of metal nanoparticles have
shown improved antimicrobial activities. By the advent
of nanotechnology, several studies have been conducted
to synthesize and investigate metal nanoparticles with
better antimicrobial properties [42]. ZnO are reported
to be significantly efficient against pathogenic microbes
and viruses. However, ZnONPs are much more efficient
against pathogens as compared to zinc oxide due to their
small size. Tabernaemontana divaricata-based zinc oxide
nanoparticles have a promising photocatalytic activity for
methylene blue dye degradation under sunlight [43]. Due
to the selective nature of rare-earth metal oxides (REMO),
it can widely be used in certain fields: energy, ecological,
and biomedical. Cerium oxide ­(CeO2) is one of the most
accessible earth metal oxides meant for the excitation via
light-harvesting performance. ­C eO 2 nanostructure has

Table 1  Antimicrobial potential NPs type Plant Size Activity References

of green-synthesized metallic
nanoparticles from various AgNPs Abutilon indicum 50–100 nm Antimicrobial [12]
plants’ extracts
Cleome viscosa L. 20–50 nm Antimicrobial [13]
Shikakai and Reetha 20–40 nm Detection of Mycobacte- [14]
rium tuberculosis
Talinum triangulare (Jacq.) Not given Antimicrobial [15]
Datura stramonium 15–20 nm Antibacterial [16]
Banana (Musa paradisiaca) 23.7 nm Antimicrobial [17]
Azadirachtaindica 34 nm Antimicrobial [17]
AuNPs Panax ginseng 10–40 nm Antibacterial [18]
ZnONPs Aloe vera 8–18 nm Biofilm inhibition [19]
L. aculeate 12 nm Antifungal [20]
Aloe vera 8–18 nm Biofilm inhibition [21]
CuONPs Citrus medica 20 nm Antimicrobial [22]

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Table 2  Selected studies reporting potential mechanism of antimicrobial activity of metal nanoparticles

NPs type Plant Size (nm) Activity Antimicrobial mechanisms References

AgNPs Ocimum gratissimum 31 nm Antibacterial

Acacia rigidula
Syngonium podophyllum
Acalyphaindica
AuNPs Galaxaura elongate
Ananascomosus
CuO NPs Aloe vera
Gloriosa superba L.
Citrus medica Linn. (Idilimbu) 20 nm
Pam-ZnO Plectranthus amboinicus
Excess production of ROS by damaging plasma [22]
membrane that prevent electron transport and disrupt
respiratory chain enzymes; eventually cause cell
death
15 and 25 nm Antibacterial Release of ­Ag+ ions, production of ROS, and free [23]
radicals may interact with cell wall components
which produce toxicity; thus inhibit bacterial growth
by damaging bacterial cell wall
10.41 nm Antifungal Silver ions and nucleic acid complexes, interact with [24]
proteins/nucleosides; or A ­ g+ that may accumulate
in membrane, penetrate into microbial cell, interact
with nitrogen bases and as a result denature the DNA
20–30 nm Antibacterial Proteins and other elements in a cell that contain [25]
sulphur or phosphorus; such as sulphur-containing
proteins in membranes or within the cells; and other
biomolecules like DNA are the favorite reactive
sites for binding silver nanoparticles. Silver ions
disrupt the function of membrane bound enzymes
(vital enzymes in respiratory chain) and respiratory
enzymes that cause the complete destruction of
bacterial cell
3.85–77.13 nm Antibacterial Inhibit bacterial growth by reaction of Au ions with [26]
SH groups of protein by uncoupling respiratory
electron transport from oxidative phosphorylation;
as a result disruption of respiratory chain enzymes or
interruption of membrane permeability to phosphate
and proton
Similarly, impairment of DNA replicated strands by
interacting with nucleic acids
16 nm Antibacterial Antibacterial mechanism of AuNPs depends upon the [27]
morphology and physiology of cell. As electrostatic
attraction occurs between AuNPs and bacterial cell;
Au ions are released which penetrate in bacterial cell
wall. These ions further disrupt the metabolic activi-
ties eventually cause cell death
20 nm Antibacterial CuNPs rupture the bacterial cell wall by releasing Cu [28]
ions that bind negatively charged cell wall, attach-
ment of Cu ions with DNA molecule through forma-
tion of cross-linking strands with nucleic acids; thus
disorganization of DNA helical strand (denaturation
of protein) leads to cell death.It also interrupt bio-
chemical process of bacterial cell
5–10 nm Antibacterial Due to electrostatic attraction; released Cu ions cause [29]
disruption of biochemical activities of bacterial cell
and transformation of helical structure of DNA by
interacting between and within nucleic acids
Antimicrobial Metal nanoparticles release ions; and accumulation of [30]
these ions and nanoparticles on cell surface form pits
in the membrane; cause leakage of cellular compo-
nents. Furthermore, CuNPs penetrate in microbial
cell and inhibit their enzymes/proteins by increasing
production of H ­ 2O2 that finally cause cell death
It may also show antibacterial activity by interacting
of Cu ions with SH group; by producing ROS; and
by disorganizing DNA helical structure
20–50 nm Antibacterial Diffusion and penetration into the exopolysaccharide [31]
and deep inside the layers. Thus, removes the MRSA
ATCC 33591 biofilms and bacterial cells are reduced

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Table 2  (continued)
NPs type Plant Size (nm) Activity Antimicrobial mechanisms References

Cu NPs Acalyphaindica 26–30 nm Antimicrobial Copper nanoparticles can inhibit cellular growth by [32]
destroying cell wall and as a consequently interrupt
the activity of cellular enzyme
Gloriosa superba L. 5–10 nm Antibacterial
Cu has high affinity towards carboxyl and amine [33]
groups present on cell surface. The released Cu ions
may bind with DNA and disrupt the helical structure
via cross-linking between nucleic acid strands. It
also disrupt the biochemical processes of bacterial
cell
ZnONPs Azadirachtaindica (L.) 18 nm Antimicrobial The antimicrobial activities of ZnO NPs are due to [34]
the increase production of ­H2O2; able to penetrate
the cell membrane that eventually causes microbial
death
Mostly metal oxide nanoparticles are associated with
larger band gap and this cause unfavourable condi-
tions for recombination of excitons. As a result,
higher concentration of reactive oxygen species,
enhance antimicrobial activity
Aloe 40–25 nm Antimicrobial ROS react with H ions to generate hydrogen perox- [35]
ide, which can enter bacterial cell wall and cause
bacterial death. Furthermore, nanoparticles attach to
SH groups of bacterial protein present on cell wall,
which decreases cell permeability and leads to cell
lysis
This damage also leads to leakage of proteins, genetic
material and minerals which cause cell death
Nyctanthes arbor-tristis 12–32 nm Antifungal ZnONPs change the permeability of outer surface of [36]
plasma membrane; help nanoparticles enter to the
cytoplasm and inhibit cell growth by interfering with
biochemical process within cell
Production of ­H2O2 and ROS (singlet oxygen and
hydroxyl radicals) also lead to the fungal cell death
Ongamia pinnata 100 nm Antibacterial ZnONPs generate reactive oxygen species, which enter [37]
into cell through small pores present in cell. These
ROS when enter to the cell; kill bacterial cell due
to leakage of minerals, proteins and some cellular
components from the cell
Trifolium pratense < 100–190 nm Antibacterial Mechanism of antibacterial activity of ZnO involves [38]
the disruption of bacterial cell membrane and leak-
age of cytoplasmic components due to the produc-
tion of ROS which eventually cause bacterial cell
lysis
Azadirachtaindica (L.) Not given Antimicrobial Generation of free radical such as ­H2O2 molecules that [34]
enter the cell membrane which leads to the bacterial
cell death

become an attractive material, since there is less energy
difference among higher ­(Ce4+) and lower ­(Ce3+) ions in
ceria using their storage capacity and superior oxygen
mobility. Nowadays, erbium-doped ceria nanoparticles are
found to be beneficial for the decomposition of RhB dye
in aquatic industrial pollution [44]. Nanostructured metal
oxides (MnO, ZnO, ­MoO3, ­Co3O4, etc.) are increasingly
in-demand for their application as low-cost sensors due to
their properties of semi conductivity and good compat-
ibility. Mainly, cobalt oxide is a p-type antiferromagnetic
semiconductor, shows bio-sensing, electronic gas sens-
ing, and electro-catalysis properties. Both cobalt oxide
and their synthesized nano-composites have potential
applications in electrical, dielectric, and biosensors fields.
Furthermore, these nano-composites have been reported
with antibacterial activity when tested for Gram-positive
and Gram-negative bacteria [45]. Biosynthesis of differ-
ent metal nanoparticles (AgNPs, AuNPs, ZnONPs, and
CuNPs) from several plants and their potential antimicro-
bial activities are discussed below. In addition, chemical

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200
AgNPs AuNPs ZnONPs CuNPs Silver nanoparticles (AgNPs)
180
160 Among nanoparticles, silver nanoparticles are mostly
Number of publicaons

140 exploited against various microbes due to its fast produc-

120 tion and toxic nature to bacterial cell [46]. Biosynthesis of
100 silver nanoparticles from biological sources (mostly from
80 plants) is a single step technique which involves the reduc-
60 tion and stabilization of silver ions through combination
40 of biomolecules (enzymes, polysaccharides, amino acids,
20 tannins, alkaloids, terpeniods, phenolic, and vitamins)
0 derived from medicinal plants [47].
2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 Different plant extracts have been reported for the syn-
Year thesis of silver nanoparticles used against several micro-
bial activities. Kumar et al. [47] reported spherical-shaped
Fig. 1  Number of publications dealing with synthesis of metallic nan- silver nanoparticles biosynthesized using an aqueous mix-
oparticles from different plants. The literature search is based on the ture of Alternanthera dentate extract. These bioinspired
key term “Synthesis of AgNps, AuNps, and CuNps from plants”. The
x-axis represents years of publication (from 2009 to 2018) and y-axis
silver nanoparticles had potential antimicrobial activity
represents the number of articles published for each nanoparticle syn- against E. coli, Enterococcus facial, Pseudomonas aer-
thesis method uginosa, and Klebsiella pneumonia [48]. Reduction of
silver ions to nanoparticles using extract of Disodium
trifolium has been attributed to the presence of ascorbic
acids, hydrogen ions, and N ­ AD+ in the extract [49]. Study
reported by Anbazhagan et  al. [49] demonstrated that
AgNPs also exhibit broad spectrum antimicrobial activi-
300
ties against both Gram-negative and Gram-positive bacte-
250 AgNPs AuNPs ZnONPs CuNPs ria such as B. subtilis, E. coli, and S. aureus [50].
Number of publicaons

AgNPs have also been known to have inhibitory prop-

200
150
100
50
0 pneumoniae, and S. typhi. Of these bacteria, methicillin-
2009 2010 2011 2012 2013 2014 2015 2016 2017 2018
Year
Fig. 2  Number of publications dealing with green synthesis of metal-
lic nanoparticles from different plants. The literature search is based
on the key term “Green synthesis of AgNps, AuNps, and CuNps from
plants”. The x-axis represents years of publication (from 2009 to
2018) and y-axis represents the number of articles published for each
nanoparticle synthesis method
structure of metal nanoparticles stabilized with various
plant’s phytochemicals is schematically presented below
(Fig. 3).
erties biosynthesized from S. aureus through a bioreduc-
tion of aqueous ­Ag+ ion with the culture supernatants of
S. aureus. These AgNPs were tested for their antimicro-
bial activities against certain infectious microbes such
as methicillin-resistant S. aureus, methicillin-resistant
Staphylococcus epidermidis, Streptococcus pyogenes, K.
resistant S. aureus, S. pyogenes, and methicillin-resistant
S. epidermidis showed more sensitivity to AgNPs treat-
ment [50]. Maiti et al. [51] reported the antibacterial activ-
ity of AgNPs (biosynthesized from an aqueous extract of
red tomato; Lycopersicon esculentum) against a model
bacterium E. coli. For antibacterial evaluation, the E. coli
was inoculated on Luria broth agar plate in the presence
of various amounts of AgNPs. Zones of inhibition showed
bactericidal activity at high concentrations while bacterio-
static at low concentrations [51].
Variations in concentrations of biosynthesized AgNPs
lead to the investigation for assessing the antifungal prop-
erties of silver nanoparticles against pathogenic fungi Tri-
chosporon asahii. For this purpose, T. asahii was grown
on potato dextrose agar medium having various concen-
trations of silver nanoparticles and the antifungal effect
was determined using minimum inhibitory concentration
(MIC) [52]. Xia et al. [52] reported that although MIC

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Fig. 3  Schematic diagram of bioactive compounds within Nicotiana tabacum and Aleo vera with the proposed mechanism of reaction. During
this process, NPs’ structures are stabilized with plant’s phytochemicals
for silver nanoparticles was lower than other antifungal
drugs (used commonly in clinical practices); however, it
can inhibit the fungal growth more efficiently. They also
mentioned the mechanism that inhibits the growth of T.
asahii which involves invading the fungal cell, damaging
its cell wall, and other basic cellular components.
Antimicrobial mechanism of silver
nanoparticles (AgNPs)
Though the exact antimicrobial mechanism of silver nano-
particles remains unclear, still, there are certain theories
regarding antimicrobial mechanism of silver nanoparticles
[24, 53]. AgNPs have the ability to attach on the surface of
microbial cell wall, penetrate and disturb the structure of cell
membrane and ultimately cause cell death. The formation
of ‘pits’ on treated bacterial cell surface shows the altera-
tion and cell membrane damage [54]. The production of free
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JBIC Journal of Biological Inorganic Chemistry (2019) 24:929–941
radicals by the silver nanoparticles is believed to be another
mechanism which results in cell death. The electron spin
resonance spectroscopy studies suggested that the formation
of free radicals occurs in the contact of silver nanoparticles
with bacterial cell. Hence, these free radicals can damage
the cell membrane and make it porous that eventually lead
to cell death [55].
Reactive oxygen species are metabolic products gener-
ating from numerous cells; two cellular organelles, endo-
plasmic reticulum and mitochondria, involved in their gen-
eration and metabolism. ROS are highly reactive molecules
with the capability to oxidize cellular structures and bio-
molecules, and as a result cause DNA denaturation, pro-
tein modifications, and lipid peroxidation that leads to cell
death. Nanoparticles can produce ROS in the cell and con-
sequently cause oxidative stress to cellular structures. Das
et al. [56] have demonstrated that the production of ROS
may contribute to silver nanoparticles triggered cytotoxic-
ity in microbes. To monitor intracellular ROS production,
JBIC Journal of Biological Inorganic Chemistry (2019) 24:929–941 935
2,7-dichlorofluorescin-diacetate ­(DCFH2-DA) was used for
the silver nanoparticles treated bacterial cells. After treat-
ment with silver nanoparticles, cells were stained with
­DCFH2-DA. It was observed that nanoparticles treated bac-
teria became DCF+ which indicates ROS production. These
nanoparticles attached to the cell membrane and penetrate
inside the cell and produce ROS. The ROS productions
destabilize plasma membrane integrity and decrease level
of intracellular ATP, damaging cellular respiratory chain
(cellular enzymes) and DNA damage consequently cause
cell lysis and death [56].
Prabhu and Poulose [53] described the antibacterial
mechanism of silver nanoparticles that involves the release
of nanoparticles’ silver ions which can inactivate many vital
enzymes by the interaction of their thiol groups. When silver
ions contact with bacterial cell, they inhibit various basic
functions in the cell. Such alteration of cellular function can
damage the cells, and as a result, generating ROS due to
the inhibition of cellular respiratory enzymes, can trigger
microbial cell self-destruction [54].
Another fact is that phosphorous and sulphur are the vital
components of DNA. As these sulphur and phosphorous are
soft bases, while silver is soft acid, they have natural ten-
dency to react with each other. Nanoparticles can destroy
DNA by interrupting these soft bases which can cause tar-
geted cell death. The interaction between silver nanopar-
ticles with sulphur and phosphorous of the DNA can also
cause DNA replication complications in the pathogens. It
has also been noticed that nanoparticles can influence signal
transduction in the bacterial cell by the phosphorylation of
protein substrates and can alter the phosphotyrosine profile
of bacterial peptides. The NPs dephosphorylate the peptide
substrates on tyrosine residues of Gram-negative bacteria. It
stops the bacterial growth by signal transduction inhibition
(Fig. 4) [57].
Another antibacterial mechanism of biosynthesized sil-
ver nanoparticle involves the denaturation of bacterial pro-
tein. Several studies have stated that the electrostatic forces
between the nanoparticles and cell membrane of microbes
are vital for antimicrobial effects. Microorganisms such as
bacteria, fungi, and viruses have negatively charged surface
membranes, while nanoparticles often have positive charge
on their surface. AgNPs (due to large surface areas) have the
ability to bind with functional group (–SH) of proteins and
consequently cause protein denaturation [58].
According to earlier studies, AgNPs might inhibit fungal
cell growth by proton pump damaging and cause fungal sur-
face protein denaturation. It influences protein lipid bilayer
or membrane permeability and consequently disrupts cell
membrane. Silver nanoparticles (Fig. 5) also initiate the
accumulation of silver ions, efflux of intracellular ions,
blocking respiration, and metabolism process by damaging
the electron transport system [59].
Gold nanoparticles (AuNPs)
Gold nanoparticles have unique and tunable surface plas-
mon resonance (SPR) with various applications in differ-
ent fields of science especially in biomedical sciences and
research [60]. Several studies have reported antimicrobial
activities of gold nanoparticles. MubarakAli et al. [61]
biosynthesized gold nanoparticles from plant extracts
(leaves) of Mentha peperita (Lamiaceae). Nanoparti-
cles’ synthesis was studied under UV–Vis spectroscopy
and characterized by SEM equipped with EDS and FTIR.
The diameter of these biosynthesized nanoparticles was
reported to be 150 nm in size that exhibited strong bacte-
ricidal effects against pathogenic bacteria, E. coli and S.
aureus [61].
Green-based gold nanoparticles were also synthesized
using benign (saponin with no capping or any other special
reducing agents) solvent isolated from Trianthema decandra.
Stable gold nanoparticles were rapidly produced by treat-
ment of aqueous solutions containing ­AgNO3 or chloroauric
acid with a saponin solution. Ultraviolet–visible spectros-
copy was used to analyze the reduction of gold nanoparticles
formed in various shapes (hexagonal, spherical, and cubi-
cal). The Kirby–Bauer method was employed to examine
the antimicrobial activity of AuNPs. These nanoparticles
exhibited excellent bactericidal effects against S. aureus,
E. coli, P. vulgaris, S. faecalis, and Y. enterocolitica [34].
Vijayan et al. [62] conducted study on the synthesis of gold
nanoparticles from medicinal plant Indigofera tinctoria.
Different techniques including UV–Vis spectroscopy, EDX,
XRD, TEM, FTIR spectroscopy, and AFM were used for
the confirmation and characterization of biosynthesized
gold nanoparticles. Biosynthesized AuNPs showed high
antimicrobial activity against certain pathogenic strains
including S. aureus, B. pumilis, E. coli and Pseudomonas
species, A. niger, and A. fumigatus [62]. Jayaseelan et al.
[63] also reported biosynthesis of AuNPs using the extract
of Abelmoschus esculentus. The crystalline nature of the bio-
synthesized AuNPs (size; 62 nm) was confirmed through
XRD. The results confirmed that these nanoparticles pos-
sessed high antifungal efficacy against Candida albicans and
P. graminis with significant potential in the preparation of
certain antifungal drugs as well [63].
Antimicrobial mechanism of gold
nanoparticles
Cui et al. [64] illustrated the antibacterial mechanism of
AuNPs by elucidating the proteomic and transcriptomic
approaches. AuNPs use their antimicrobial capabilities
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Fig. 4  Illustration of possible antibacterial mechanism of action of biosynthesized metal nanoparticles
against multidrug-resistant (Gram-negative) bacteria
through two approaches: degrading membrane potential
to decrease the ATP level by inhibiting the activity of
ATPase, and inhibiting the binding of ribosome subunit
with tRNA. AuNPs induce the ATP level (oxidative phos-
phorylation pathway), down-regulation of F-type ATP
synthase and ribosome pathways, resulting in transient
upregulation of chemotaxis. The results also showed that
4,6-diaminopyrimidine thiol-modified AuNPs have the
ability to affect protein synthesis through inhibiting the
function of bacterial tRNA [64]. The modifier of AuNPs,
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JBIC Journal of Biological Inorganic Chemistry (2019) 24:929–941
4,6-diaminopyrimidine thiol is an analogue of bacterial
tRNA base. Hence, it can potentially inhibit bacterial
tRNA function [65] and eventually lead to cessation of
microbial growth.
The ATP synthesis in the terminal step of oxidative phos-
phorylation pathway is catalyzed by F-type ATP synthase.
F-type ATP synthase also works in a reverse manner as
an ATPase to produce the transmembrane proton electro-
chemical gradient which are essential for molecular trans-
location [66]. AuNPs down-regulate the F-type synthase
activity which leads to the decreased ATP levels as reported
JBIC Journal of Biological Inorganic Chemistry (2019) 24:929–941 937
Fig. 5  Effect of AgNPs on the activity of proton pump in fungal cell
can lead to cell death
Fig. 6  Possible antifungal mechanism of AuNPs. Interaction of fun-
gal cell and AuNPs, (1) can result in bursting of fungal cell wall (2)
in E. coli; and consequently cause metabolism failure. The
transcriptome analysis confirmed that gold nanoparticles
can up-regulate genes involved in the flagellar motility and
chemotaxis pathway [67].
Figure 6 shows the schematic diagram of the possible
mechanism of interaction between AuNPs and fungi cell
components. The fungicidal effect of gold nanoparticles is
spontaneous and irreversible. AgNPs affect hydrogen ion
extrusion through plasma membrane H ­ +-ATPase. AuNPs-
treated candida cells showed the inhibition of proton
pumping (transmembrane ­H+-ATPase). Glucose-induced
acidification of the external medium using yeast cells is a
suitable measure of H­ +-ATPase-mediated proton pumping.
The enzymes might be in various conformational states in
both situations. It was also observed that vanadate could
completely inhibits ­H+-efflux; however, fluconazole had no
substantial effect on ­H+-ATPase. Therefore, AuNPs might
interact directly with enzymes present in regulation of the
proton gradients through plasma membrane. H ­ +-ATPase is
one of the ATP-driven enzyme and its function is to convert
the energy of ATP hydrolysis to electro-chemical potential
differences of protons across diverse biological membranes
by primary active transport of ­H+. Sequentially, these can
be used to drive various secondary active transport systems
through ­H+-dependent antiporters, symporters, and channel-
mediated transport systems. Interactions involving AuNPs
and microbial enzyme (ATPases) might change their normal
conformations, resulting in loss of their function and eventu-
ally leading to cell death [68].
Antifungal activities of nanoparticles have been reported
associated with particle size, smaller the particle size higher
its antifungal potency. This property of nanoparticle can be
attributed to larger surface area of these nanoparticles result-
ing in higher/increased interaction with the target sites on
plasma membranes. In addition, nanoparticles with smaller
particle size can easily penetrate through cell membrane.
Gold (soft acid) has greater tendency to react with sulphur
and phosphorus containing soft bases. Therefore, AuNPs
possibly interact with the phosphorus containing bases in
the DNA or the sulphur-containing proteins in the mem-
brane. These interactions could cause interruption in normal
functioning of DNA such as repair mechanism, replication,
and synthesis of new strands and ultimately cause cell death
[69]. However, the process needs further elaboration that
could lead to understanding of specific pathway associated
with antifungal activity of nanoparticles.
Zinc oxide nanoparticles (ZnONPs)
There are various reported studies about the synthesis of sev-
eral types of inorganic metal oxides such as ZnO, ­TiO2, and
CuO. Among these, ZnO has gained much interest because
of low expenses on production, ease preparation, and safe
handling [70].
ZnO is an n-type semiconductor metal oxide with broad
range of nanostructures and significant antimicrobial prop-
erties [71].
Zinc oxide in nanoscale has also indicated various antimi-
crobial properties and potential applications in food preser-
vations. ZnONPs have been integrated in polymeric matrices
to improve packaging and provide antimicrobial activity to
the packaging materials [72]. For food industry and custom-
ers, antimicrobial packaging is very important, since these
packaging can retard microbial growth, maintain food safety,
and extend product shelf life [73].
Several nanoparticles have been synthesized success-
fully employed for food safety applications including zinc
oxide, silver oxide, and magnesium oxide nanoparticles [74].
ZnONPs have shown effective activities against food-borne
pathogens such as L. plantarum, E. coli, B. subtilis, and S.
aureus [75]. ZnONPs have also many promising bacteri-
cidal potentials against a wide variety of both Gram-positive
and Gram-negative bacteria including other multifarious
13

938
properties such as stability, mechanical strength, and bar-
rier properties [76, 77].
Researchers have also tested the in vitro antibacterial
action of zinc oxide; utilizing nanoparticles suspension
called nanofluids or pure nanoparticles. ZnO shows signifi-
cant obstruction in bacterial growth on a wide range of bac-
teria, particularly by the catalysis of ROS formation from
water and oxygen. ZnO nanofluids are ideal formulation for
antibacterial agents in liquid phases, but due to the hydro-
phobic nature of ZnONPs, it tends to aggregate into large
flocculates in aqueous media and, therefore, cannot interact
with microorganisms effectively. Gordon and co-workers
combined FeO with ZnO to generate magnetic composite
nanoparticles with enhanced colloidal suspension ability and
antibacterial activity. Results of the study showed that bio-
genic nano-composites had comparatively higher antibacte-
rial activity for S. aureus than E. coli. However, antibacterial
action of composite nanoparticles depends on the ratio of
Zn and Fe [78].
Parthenium hysterophorus is an annual herbaceous nox-
ious weed, native to North and South America, West Indies
America, Asia, Africa, and Australia. The weed is known
for its vigorous growth toxicity to humans and livestock.
However, despite all the problems related with this noxious
weed, recent studies suggested their pharmacological prop-
erties. P. hysterophorus confers several health benefits such
as anticancer, antioxidant, antimicrobial, anti-inflammatory,
antitrypanosomal, antimalarial, skin diseases, urinary tract
infection, and much more. Furthermore, the weed can be
used as pesticides, herbicides, insecticides, and phyto-reme-
dial agent for metal and dye removal from industrial waste.
It is a rich source of minerals such as P, N, K, Mn, Fe, Zn,
and Cu. It is also used as spice in several parts of the world,
useful as low-cost substrate for oxalic acid production, xyla-
nase production, and edible protein. In addition, its use in
nano-medicine is being carried out with some initially suc-
cess [79].
Zinc oxide nanoparticles also possess significant antifun-
gal activities. Gunalan et al. [34] biosynthesized ZnONPs
from P. hysterophorus L., and the study was based on the
comparison between chemically synthesized ZnO nanoparti-
cles and plant-based synthesis of ZnO nanoparticles. Results
of the study showed that green ZnO nanoparticles enhanced
fungicidal activity against certain fungal pathogens includ-
ing: R. stolonifera, A. nidulans, T. harzianum, and A. flavus
as compared to chemically synthesized ZnONPs [35]. More-
over, P. hysterophorus-based ZnO nanoparticles showed
antifungal activity against pathogenic fungi: F. oxysporium,
A. flavus, A. fumigatus, and A. niger. Thus, green-synthe-
sized ZnONPs can inhibit the growth and exert biocidal
effect for plant pathogenic fungi and bacteria [80].
In another study, antifungal efficacy of zinc oxide nan-
oparticles was examined against two pathogenic fungal
13
JBIC Journal of Biological Inorganic Chemistry (2019) 24:929–941
species, P. expansum and F. oxysporum. The zinc oxide
nanoparticles with size of ~ 70 nm showed notable inhibitory
effects against pathogenic fungi P. expansum and B. cinerea
in a concentration-dependent manner. These nanoparticles
may cause inhibition of fungal hyphae. Hence, it might be
used as effective fungicide in agriculture and food preserva-
tion applications [81]. Phytosynthesis-based ZnONPs (size
ranging from 12 to 32 nm) were synthesized from an aque-
ous extract of Nyctanthes arbor-tristis and were reported
with high fungicidal activities against fungal pathogens
including P. expansum, B. cinerea, A. alternata, F. oxyspo-
rum, and A. niger, indicating that these ZnONPs could be
efficient fungicidal agents in field of agriculture [36].
Antimicrobial mechanism of ZnONPs
The bactericidal activity of ZnONPs may be contributed to
the size of NPs, their shapes, and surface-capping agents.
Previous literature has reported that the smaller size of
ZnONPs is associated with greater antibacterial efficacy
[82]. Xie et al. [82] elucidated that the bactericidal mecha-
nism of ZnONPs is attributed to increased levels of oxidative
stress exerted in bacterial cells. As the majority of bacte-
rial virulence genes were observed to be down regulated by
applying NPs; proposing that bacterial virulence is weaken
by ZnONPs’ treatment [83].
ZnONPs showed remarkable bactericidal and toxic effects
against Campylobacter jejuni even at low concentrations.
ZnONPs showed considerable increase (up to 52 fold) in
the expression of oxidative stress gene, measurable mem-
brane leakage, and morphological differences in C. jejuni.
In view of these phenomena and cell responses, a conceiv-
able mode of ZnO-induced microbial inactivation includes
directly interaction between ZnONPs and cell surfaces.
These interactions influence membrane permeability and
allow nanoparticles to enter and incite oxidative stress in
bacterial cells which inhibit bacterial cell growth and ulti-
mately cause microbial cell death.
The antifungal mechanism of ZnONPs has not been yet
fully understood. However, an investigation of ZnONPs’
effects against the fungi B. cinerea and P. expansum dem-
onstrated inhibition of conidial development by distortion
of conidiophores of P. expansum. Conidia of P. expansum
was completely inhibited and conidial development was sup-
pressed by ZnONPs. While the inhibition of B. cinerea is
due to the deformation of fungal hyphae [84], this deforma-
tion may be due to higher accumulation of carbohydrates
and nucleic acids. ZnONPs can affect cell function by
the production of excessive amount of nucleic acids. The
increased level of nucleic acid in fungal hyphae may be due
to the NP-mediated stress response. Similarly, the increase
in carbohydrates level can be considered as self-protection
JBIC Journal of Biological Inorganic Chemistry (2019) 24:929–941 939
mechanism from ZnONPs, which could lead to deformed
hyphal cells structures and eventually cause cell death. Thus,
these investigations suggest that ZnO nanoparticles have dif-
ferent mechanisms of action than that of antibacterial activ-
ity [72]. It was also found that various fungi are known for
their mycotoxin production, i.e., patulin and fusaric acid. It
was determined that inhibition rate of these mycotoxin is
gradually decreased with an increase in the concentration
of ZnONPs. These inhibitions of mycotoxin production may
be due to the inactivation of specific enzymes involved in
biosynthesis pathway of these toxins by ZnONPs [85].
Copper nanoparticles (CuNPs)
Metal nanoparticles have potential applications in various
disciplines including nano-devices, nano-sensors, catalysis,
nano-electronics, and information storage. Among different
nanoparticles, copper nanoparticles have also gained special
attention due to their potential applications in antimicrobial
and other activities [86]. Cioffi et al. [86] have explained
the effective antibacterial and antifungal activities of cop-
per nanoparticles. Stable copper nanoparticles (size ranging
from 40 to 100 nm) were successfully synthesized using
Mangolia virginiana leaf extract treated with the aqueous
solution of ­CuSO4.5H2O as reducing agent with higher anti-
bacterial potentials [87]. The antibacterial test carried out
against E. coli and showed remarkable antibacterial activity
[88]. Another plant, citron juice (Citrus medica Linn.) was
used to synthesize biogenic nanoparticles (size; 10–60 nm).
These copper nanoparticles showed antimicrobial impact
against certain human and plant pathogens. The results
exhibited a substantial inhibitory activity against various
bacteria including K. pneumoniae, E. coli, S. aureus, P. vul-
garis, Shigella flexneri, Propionibacterium acnes, S. typhi, P.
aeruginosa, and E. faecalis. Among these pathogens, E. coli
and E. faecalis were reported with high sensitivity towards
CuO nanoparticles [89].
Sivaraj et al. [31] conducted a study elucidating both anti-
fungal and antibacterial activities of biosynthesized, highly
stable CuONPs using aqueous extract of Acalyphaindica
leaf. The size of the biosynthesized nanoparticles ranged
from 26 to 30 nm. These biosynthesized nanoparticles were
reported with significant antifungal effects against C. albi-
cans as well as noteworthy antibacterial activity against P.
fluorescens and E. coli [32].
Antimicrobial mechanism of CuNPs
Early research on the antimicrobial capabilities of CuNP-
­ u2+ ions can change local conductivity
described release of C
and pH. This salvation of C­ u2+ ions into the solution is able
to disturb bacterial cell membrane and localize in the cell to
disrupt cellular enzyme functions and cause inactivation or
death of bacterial cells [89].
Figure 7 shows fungicidal activity of metal nanoparticles
against A. niger. Electrospun cellulose acetate (CA) com-
plexes having copper and silver nanoparticles supported
in mesoporous silica and sepiolite were prepared and used
as fungistatic membranes. The size of nanoparticles for
mesoporous silica is range in 5–8 nm and the size of sepio-
lite (3–50 nm) and both are well dispersed inside the fiber.
Large aggregates in µm range are used and allowed a con-
trolled release of metals to make a fungistatic environment.
The finding showed that when spores were incubated either
in direct contacts with nanoparticles or included CA com-
plex membrane; the silver and copper nanoparticles resulted
in impaired growth of fungi. The fungistatic effect against A.
niger occurred in germinating spores before the formation
of hyphae growth conidiophore. Sepiolite containing copper
has been reported to effect the fungal growth by a decreas-
ing its metabolic activity. These metal-loaded nanoparticles
work as reservoirs for the controlled release of metals ions
that eventually effect fungal growth [90]. Shende et al. [29]
showed likely mechanism of copper nanoparticles in fungi
which is based on changes that occur in the function and
structure of fungal cell. In addition, it can cause cell death
by affecting its DNA and disrupt its replication and tran-
scription mechanisms. Moreover, CuNPs could inactivate
proteins by interacting with its –SH (sulfhydryl) groups and
may cause growth cessation. Another concept suggests that
CuNP-mediated oxidative stress inside microbes could result
in their cell death [30]. However, further studies are needed
Fig. 7  Possible antifungal mechanism of metal nanoparticles. The
illustration shows copper and silver nanoparticles supported in
mesoporous silica and sepiolite. Metal ions and nanoparticles are
slowly released from these complexes and effect growth of microbes.
(1) metal loaded particles (represented by black dots), (2) damaged
spores, (3) Aspergillus niger, (4) spores, (5) metal releasing mat
13

940
to understand molecular mechanisms for CuNP-mediated
inhibition of microbial growth.
Conclusion and future prospects
Green synthesis of metallic nanoparticles has rapidly cap-
tured scientists’ attention thanks to its involvement in the
utilization of various biological entities for a variety of effi-
cient antimicrobial properties. Several green-based metal
and metal oxide (gold, silver, copper, and zinc oxide) nano-
particles possessing substantial antimicrobial features have
been successfully generated from various biological sources
of which plants are the most prominent. These bio-nano-
materials have been proved to be most effective against dif-
ferent strains of (plant and human) pathogenic bacteria and
fungi. However, the precise mechanism of antimicrobial
characteristics for biogenic-metal nanoparticles needs fur-
ther experimental support and systematic and clinical trials.
References
1. Thakkar KN, Mhatre SS, Parikh RY (2010) Nanomed Nanotech-
nol Biol Med 6:257–262
2. Liu J, Qiao SZ, Hu QH, Lu GQ (2011) Small 7:425–443
3. Parveen K, Banse V, Ledwani L (2016) AIP conference proceed-
ings. AIP Publishing, New York, p 020048
4. Li X, Xu H, Chen Z-S, Chen G (2011) J Nanomater
2011(270974):1–16
5. Gao W, Thamphiwatana S, Angsantikul P, Zhang L (2014) Wiley
Interdiscip Rev Nanomed Nanobiotechnol 6:532–547
6. Grass G, Rensing C, Solioz M (2011) Appl Environ Microbiol
77:1541–1547
7. Wilson BA, Salyers AA, Whitt DD, Winkler ME (2011) Bacte-
rial pathogenesis: a molecular approach. American Society for
Microbiology (ASM), Washington, D.C.
8. Kaviyarasu K, Geetha N, Kanimozhi K, Magdalane CM, Sivaran-
jani S, Ayeshamariam A, Maaza M (2017) Mater Sci Eng C
74:325–333
9. Kaviyarasu K, Magdalane CM, Kanimozhi K, Kennedy J, Sid-
dhardha B, Reddy ES, Mola GT (2017) J Photochem Photobiol B
173:466–475
10. Kaviyarasu K, Kanimozhi K, Matinise N, Magdalane CM, Mola
GT, Kennedy J, Maaza M (2017) Mater Sci Eng C 76:1012–1025
11. Govindaraju K, Basha SK, Kumar VG, Singaravelu G (2008) J
Mater Sci 43:5115–5122
12. Lakshmanan G, Sathiyaseelan A, Kalaichelvan P, Murugesan K
(2018) Karbala Int J Mod Sci 4:61–68
13. Sur UK, Ankamwar B, Karmakar S, Halder A, Das P (2018) Mater
Today Proc 5:2321–2329
14. Ojo OA, Oyinloye BE, Ojo AB, Afolabi OB, Peters OA, Olaiya
O, Fadaka A, Jonathan J, Osunlana O (2017) J Bionanosci
11:292–296
15. Singh P, Kim YJ, Yang DC (2016) Artif Cells Nanomed Biotech-
nol 44:1949–1957
16. Ali K, Dwivedi S, Azam A, Saquib Q, Al-Said MS, Alkhedhairy
AA, Musarrat J (2016) J Colloid Interface Sci 472:145–156
17. Ibrahim HM (2015) J Radiat Res Appl Sci 8:265–275
13
JBIC Journal of Biological Inorganic Chemistry (2019) 24:929–941
18. Gomathi M, Rajkumar P, Prakasam A, Ravichandran K (2017)
Resour Effic Technol 3:280–284
19. Narendhran S, Sivaraj R (2016) Bull Mater Sci 39:1–5
20. Ahmed S, Ahmad M, Swami BL, Ikram S (2016) J Radiat Res
Appl Sci 9:1–7
21. Das B, Dash SK, Mandal D, Ghosh T, Chattopadhyay S, Tripathy
S, Das S, Dey SK, Das D, Roy S (2017) Arab J Chem 10:862–876
22. Escárcega-González CE, Garza-Cervantes J, Vázquez-Rodríguez
A, Montelongo-Peralta LZ, Treviño-González M, Castro EDB,
Saucedo-Salazar E, Morales RC, Soto DR, González FT (2018)
Int J Nanomed 13:2349
23. Yasir M, Singh J, Tripathi MK, Singh P, Shrivastava R (2018)
Pharmacogn Mag 13:S840
24. Krishnaraj C, Jagan E, Rajasekar S, Selvakumar P, Kalaichelvan
P, Mohan N (2010) Colloids Surf B 76:50–56
25. Abdel-Raouf N, Al-Enazi NM, Ibraheem IB (2017) Arab J Chem
10:S3029–S3039
26. Bindhu M, Umadevi M (2014) Mater Lett 120:122–125
27. Kumar PV, Shameem U, Kollu P, Kalyani R, Pammi S (2015)
BioNanoScience 5:135–139
28. Naika HR, Lingaraju K, Manjunath K, Kumar D, Nagaraju G,
Suresh D, Nagabhushana H (2015) J Taibah Univ Sci 9:7–12
29. Shende S, Ingle AP, Gade A, Rai M (2015) World J Microbiol
Biotechnol 31:865–873
30. Dobrucka R, Długaszewska J (2016) Saudi J Biol Sci 23:517–523
31. Sivaraj R, Rahman PK, Rajiv P, Narendhran S, Venckatesh
R (2014) Spectrochim Acta Part A Mol Biomol Spectrosc
129:255–258
32. Elumalai K, Velmurugan S (2015) Appl Surf Sci 345:329–336
33. Sundrarajan M, Ambika S, Bharathi K (2015) Adv Powder Tech-
nol 26:1294–1299
34. Gunalan S, Sivaraj R, Rajendran V (2012) Prog Nat Sci Mater Int
22:693–700
35. Jamdagni P, Khatri P, Rana J (2018) J King Saud Univ Sci
30:168–175
36. Vijayakumar S, Vinoj G, Malaikozhundan B, Shanthi S, Vasee-
haran B (2015) Spectrochim Acta Part A Mol Biomol Spectrosc
137:886–891
37. Chandirika JU, Annadurai G (2018) Glob J Biotechnol Biochem
13:07–11
38. Besinis A, De Peralta T, Handy RD (2014) Nanotoxicology
8:1–16
39. Lemire JA, Harrison JJ, Turner RJ (2013) Nat Rev Microbiol
11:371
40. Gold K, Slay B, Knackstedt M, Gaharwar AK (2018) Adv Ther
1:1700033
41. Jeon H-J, Yi S-C, Oh S-G (2003) Biomaterials 24:4921–4928
42. Klueh U, Wagner V, Kelly S, Johnson A, Bryers J (2000) J Biomed
Mater Res 53:621–63143
43. Raja A, Ashokkumar S, Marthandam RP, Jayachandiran J, Khati-
wada CP, Kaviyarasu K, Swaminathan M (2018) J Photochem
Photobiol B Biol 181:53–58
44. Magdalane CM, Kaviyarasu K, Raja A, Arularasu MV, Mola
GT, Isaev AB, Maaza M (2018) J Photochem Photobiol B
185:275–282
45. Amanulla AM, Shahina SJ, Sundaram R, Magdalane CM, Kavi-
yarasu K, Letsholathebe D, Maaza M (2018) J Photochem Photo-
biol B 183:233–241
46. Roy S, Das T (2015) J Appl Spectrosc 82:598–606
47. Kumar DA, Palanichamy V, Roopan SM (2014) Spectrochim
Acta Part A Mol Biomol Spectrosc 127:168–171. https​://doi.
org/10.1016/j.saa.2014.02.058
48. Ahmad N, Sharma S, Singh V, Shamsi S, Fatma A, Mehta B
(2011) Biotechnol Res Int 2011(454090):1–8
49. Anbazhagan S, Azeez S, Morukattu G, Rajan R, Venkatesan K,
Thangavelu KP (2017) 3 Biotech 7:333
JBIC Journal of Biological Inorganic Chemistry (2019) 24:929–941 941
50. Nanda A, Saravanan M (2009) Nanomed Nanotechnol Biol Med
5:452–456. https​://doi.org/10.1016/j.nano.2009.01.012
51. Maiti S, Krishnan D, Barman G, Ghosh SK, Laha JK (2014) J
Anal Sci Technol 5:40
52. Xia Z-K, Ma Q-H, Li S-Y, Zhang D-Q, Cong L, Tian Y-L, Yang
R-Y (2016) J Microbiol Immunol Infect 49:182–188
53. Prabhu S, Poulose EK (2012) Int Nano Lett 2:32
54. Sondi I, Salopek-Sondi B (2004) J Colloid Interface Sci
275:177–182
55. Danilczuk M, Lund A, Sadlo J, Yamada H, Michalik J (2006)
Spectrochim Acta Part A Mol Biomol Spectrosc 63:189–19157
56. Das B, Dash SK, Mandal D, Ghosh T, Chattopadhyay S, Tripathy
S, Roy S (2017) Arab J Chem 10(6):862–876
57. Shrivastava S, Bera T, Roy A, Singh G, Ramachandrarao P, Dash
D (2007) Nanotechnology 18:225103
58. Kim J, Lee J, Kwon S, Jeong S (2009) J Nanosci Nanotechnol
9:1098–1102
59. Du H, Lo T-M, Sitompul J, Chang MW (2012) Biochem Biophys
Res Commun 424:657–662
60. Huang S-H (2006) Clin Chim Acta 373:139–143
61. MubarakAli D, Thajuddin N, Jeganathan K, Gunasekaran M
(2011) Colloids Surf B Biointerfaces 85:360–365. https​://doi.
org/10.1016/j.colsu​rfb.2011.03.009
62. Vijayan R, Joseph S, Mathew B (2018) Artif Cells Nanomed Bio-
technol 46:861–871
63. Jayaseelan C, Ramkumar R, Rahuman AA, Perumal P (2013) Ind
Crops Prod 45:423–429
64. Cui Y, Zhao Y, Tian Y, Zhang W, Lü X, Jiang X (2012) Biomateri-
als 33:2327–2333
65. Carbon J, David H, Studier MH (1968) Science 161:1146–1147
66. Zharova TV, Vinogradov AD (2004) J Biol Chem
279:12319–12324
67. Wani IA, Ahmad T (2013) Colloids Surf B 101:162–170
68. Ahmad T, Wani IA, Lone IH, Ganguly A, Manzoor N, Ahmad A,
Al-Shihri AS (2013) Mater Res Bull 48(1):12–20
69. Tan YN, Lee KH, Su X (2011) Anal Chem 83:4251–4257
70. Jayaseelan C, Rahuman AA, Kirthi AV, Marimuthu S, Santho-
shkumar T, Bagavan A, Gaurav K, Karthik L, Rao KB (2012)
Spectrochim Acta Part A Mol Biomol Spectrosc 90:78–84
71. Szabó T, Németh J, Dékány I (2003) Colloids Surf A 230:23–35
72. Espitia PJP, Soares NDFF, dos Reis Coimbra JS, de Andrade
NJ, Cruz RS, Medeiros EAA (2012) Food Bioprocess Technol
5:1447–1464
73. Neethirajan S, Jayas DS (2011) Food Bioprocess Technol 4:39–47
7 4. Jones N, Ray B, Ranjit KT, Manna AC (2008) FEMS Microbiol
Lett 279:71–76
75. Jin T, Gurtler J (2011) J Appl Microbiol 110:704–712
76. Seil JT, Webster TJ (2011) Acta Biomater 7:2579–2584
77. Vicentini DS, Smania A Jr, Laranjeira MC (2010) Mater Sci Eng
C 30:503–508
78. Gordon T, Perlstein B, Houbara O, Felner I, Banin E, Margel S
(2011) Colloids Surf A 374:1–8
79. Rajiv P, Rajeshwari S, Venckatesh R (2013) Spectrochim Acta
Part A Mol Biomol Spectrosc 112:384–387
80. Patel S (2011) 3 Biotech 1(1):1–9
81. He L, Liu Y, Mustapha A, Lin M (2011) Microbiol Res
166:207–215
82. Xie Y, He Y, Irwin PL, Jin T, Shi X (2011) Appl Environ Micro-
biol 77:2325–2331
83. Abbasi BH, Anjum S, Hano C (2017) RSC Adv
7(26):15931–15943
84. Huang Z, Cui F, Kang H, Chen J, Zhang X, Xia C (2008) Chem
Mater 20:5090–5099
85. Yehia RS, Ahmed OF (2013) Afr J Microbiol Res 7:1917–1923
86. Cioffi N, Torsi L, Ditaranto N, Tantillo G, Ghibelli L, Sabbatini L,
Bleve-Zacheo T, D’Alessio M, Zambonin PG, Traversa E (2005)
Chem Mater 17:5255–5262
87. Lee H-J, Lee G, Jang NR, Yun JH, Song JY, Kim BS (2011)
Nanotechnology 1:371–374
88. Ahamed M, Alhadlaq HA, Khan M, Karuppiah P, Al-Dhabi NA
(2014) J Nanomater 2014:17
89. Ren G, Hu D, Cheng EW, Vargas-Reus MA, Reip P, Allaker RP
(2009) Int J Antimicrob Agents 33:587–590
90. Quirós J, Gonzalo S, Jalvo B, Boltes K, Perdigón-Melón JA, Rosal
R (2016) Sci Total Environ 563:912–920
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