CHAPTER FIFTEEN

Green synthesized silver

nanoparticles and their
therapeutic applications
Samson Oluwagbemiga Alayandea,*, Anuoluwa Abimbola Akinsikub,
Oyesolape Basirat Akinsipo (Oyelaja)c, Esther Oluwasayo Ogunjinmia,
and Enock Olugbenga Darea,d
a
Department of Physical Sciences, First Technical University, Ibadan, Oyo State, Nigeria
b
Department of Chemistry, Covenant University, Ota, Ogun State, Nigeria
c
Department of Chemical Sciences, Tai Solarin University of Education, Ijebu Ode, Ogun State, Nigeria
d
Department of Chemistry, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
*Corresponding author: e-mail address: samson.alayande@tech-u.edu.ng

Contents
1. Introduction 585
1.1 Bacteria-mediated synthesis of NMs 587
1.2 Algae-mediated synthesis of NMs 587
1.3 Fungi-mediated synthesis of NMs 588
1.4 Plant-mediated synthesis of NMs 588
1.5 Green synthesis of NMs for therapeutic applications 589
1.6 Factors influencing the plant-based green synthesis of AgNPs 589
1.7 Reaction conditions for the biosynthesis of AgNPs 591
1.8 Mechanism of reaction 592
1.9 Green AgNPs 593
1.10 Therapeutic applications 594
1.11 Mechanistic profile followed by AgNP 602
2. Conclusions 604
References 605

1. Introduction
The concept of nanotechnology was introduced by Norio Taniguchi
at the international conference on industrial production in Tokyo in 1974,
defined as advanced materials. It is the development of materials within
nanometre range (10
9 m). This idea was taken up by Feynman, and
Drexler later developed it. Structure or object whose dimension is in the

Comprehensive Analytical Chemistry, Volume 94 Copyright # 2021 Elsevier B.V. 585

ISSN 0166-526X All rights reserved.
https://doi.org/10.1016/bs.coac.2021.01.009
586 Samson Oluwagbemiga Alayande et al.

range between 1 and 100 nm (nanoscale) are called nanomaterials (NMs) [1].
The NMs may exist as particles, fibres, flakes, wires, composites, films,
and tubes. Nanostructured materials like quantum dots, clusters, nano-
crystals, nanowires and nanotubes represent various NMs. The nanocrystals
exist in groups as assemblies, arrays, and superlattices of a discrete nanostruc-
ture [2]. Classifications of NMs are: zero-dimensional (nanoparticles),
1-dimensional (nanorods and nanotubes), 2-dimensional (nanofilms) and
nanolayers [3]. Due to size confinement and superior surface of these mate-
rials at the nanoscale, they are incredibly useful and of exceptional perf-
ormance in many fields of applications including medicine, electronics,
photonics, bioceramics, biotechnology and agriculture. NMs exhibit quite
different properties from their bulk counterparts, which account for the
unique feature they possess which includes a large surface to volume ratio,
specific physicochemical and biological properties [4].
Two approaches are well-established for the fabrication of nano-
materials: top-down (break down) and bottom-up (build-up). The top-
down method breaks a solid bulk to small size. This includes solid-phase
techniques: mechanical alloying, grinding, and mechanochemical transfor-
mation. A bottom-up approach creates nanoparticles by building up of
atoms based on their atomic charges. This method involves solid-phase
method (chemical and physical techniques), and physical-phase procedure
(liquid/liquid and sedimentation methods). Liquid/liquid procedure invol-
ves solvothermal, supercritical, spray pyrolysis, indirect reduction, chemical
reduction and green synthesis. Green synthesis is also known as biosynthesis.
It is the synthesis of nanomaterials through the use of microorganisms, plant
extracts, protein and DNA [5,6]. The approach applies the 12 principles
of green chemistry, as it requires little or no toxic substance to health and
environment, minimal separation, mild solvent, conduction of experiment
at ambient pressure and temperature and the use of renewable materials [7].
It is worthy to note that the green synthesis is classified as the sustainable
approach which has gained global attention. This method is non-toxic,
eco-friendly, affordable, fast, safe, and abundant. This approach involves
the use of benign solvents, low energy, renewable feedstock, less hazardous
chemicals, prevent waste, design for degradation, and chemical accident
free [8,9]. It is a bio-reduction process. Generally, there are two main
methods in green synthesis, namely, microbe and plant mediated synthesis.
Both approaches have associated merits. For instance, microbes are readily
available, requires low energy, and no complex calculations, also, it can be
duplicated [10]. Microbe mediated approach is gaining global attention in
Green synthesized silver nanoparticles 587

the field of Nanobiotechnology. Bio-reduction of metal ions into metallic/

oxide nanoparticles have been achieved with bacteria, algae, and fungi [11].
The resultant products have been utilized for various therapeutic applica-
tions. Microbes have been proven to survive and multiply even at relatively
high concentrations of the metal ion during bio-reduction process, exhibi-
ting poly-dispersity and relative stability. This category is divided into three
main groups, which are described below.

1.1 Bacteria-mediated synthesis of NMs

In this method, the organic moieties on the cell wall of bacteria are major
player which aid reduction of metallic ions by intracellular and extracellular
mechanism, leading to the formation of nanoparticles. For instance, Acinetobacter
sp. was used in the fabrication of crystalline nanoparticles [12]. Several strains of
bacteria have been used for biosynthesis of silver nanoparticles (AgNPs),
these include Serratia nematodiphila, Bacillus stearothermophilus Bacillus strain,
Exopolysaccharide-producing strain, Leuconostoc lactis Escherichia coli, Streptomyces
hygroscopicus, Pediococcus pentosaceus, Enterococcus faecium, Lactococcus garvieae
Bacillus cereus, Bacillus subtilis, Escherichia coli, Enterobacter cloacae, Klebsiella pneu-
monia, Lactobacillus acidophilus, Staphylococcus aereus, Pseudomonas aeruginosa,
Morganella morganii Quasispherical Pseudomonas proteolytica, Arthrobacter gan-
gotriensis, Pseudomonas antarctica, Pseudomonas meridiana, Arthrobacter kerguelensis,
Bacillus indicus, Bacillus cecembensis, Staphylococcus aureus, Bacillus brevis and
Bacillus subtilis [10,13,14]. The morphology ranges from spherical, quasi-
spherical, irregular, etc. [14].

1.2 Algae-mediated synthesis of NMs

Rapid production of NMs is associated with the use of algae because algae
cells are negatively charged, and this makes nucleation and growth of
nanoparticles fast compared with other microbes. It is worth noting that
the culture media of bacteria secrete metabolites which aid reduction of
metallic ions. The protocol is cheap and fast. Size control is essential in
the fabrication of NMs and this could be achieved by the use of polysaccha-
rides of algae species [15]. For instance: Pterocladia capillacae, Jania rubins,
Ulva fasciata, Colpmenia sinusa. AgNPs with various shapes were produced
using: Shewanella algae, Sargassum wightii Greville (spherical), Chlorella vulgari
(triangular, truncated triangular, hexagonal) [13]. Others organism with
great potential for synthesis include Caulerpa racemose, Chaetomorpha linum,
Chaetoceros calcitran, Chlorella salina, Isochrysis galbana and Tetraselmis gracilis.
588 Samson Oluwagbemiga Alayande et al.

1.3 Fungi-mediated synthesis of NMs

The ability to produce in large scale favoured extracellular biosynthesis of
nanoparticles using fungi. Metal-bioaccumulation and tolerance are proper-
ties that make fungal strains preferred over bacterial strains [14]. Also,
enzymes and proteins present in fungi is notable for reduction and stabilizing
agents during formation of many nanoparticles. Penicillium italicum, a soil
fungus, was used to produce nanoparticle, which was very active against
multi-drug resistance pathogens [16]. Fungi are known to secrete diverse
proteins and enzymes which results in a higher yield of NMs, compared
with bacteria [17]. The synthesis of AgNPs has recorded several success using
several fungal species, namely: Fusarium oxysporum, Aspergillus fumigatus,
Verticillium, Penicillium fellutanum, Aspergillus flavus, Fusarium semitectum,
Alternaria alternata, Rhizopus stolonifer, and Phanerochaete chrysosporium [14].

1.4 Plant-mediated synthesis of NMs

The approach of plant mediated synthesis have numerous merits, namely:
broad polydispersity, high stability, abundant phytochemicals to aid the
bio-reduction processes, presence of bio-molecules which serve as capping
or reducing agents and faster rate of the bio-reduction process [10,18].
Also, elaborate processes of intracellular synthesis, cell culture, and multiple
purification steps are eliminated in plants-mediated synthesis. It has gained
huge attention due to its non-toxic characteristics, simplicity, and eco-
friendliness. Hence, the plant-mediated biosynthesis found extensive appli-
cations [18]. It could be an alternative to chemical method for the synthesis
of nanoparticles owing to complimentary features of capping agents.
Bio-reduction process is aided through phytochemicals, some of the mech-
anisms are discussed in this review. Notable phytochemicals including ter-
penoids, polyols, carbohydrates, protein, flavonoids, saponins and alkaloids
have been reported for the synthesis of several nanoparticles [10,18].
Among different biosynthetic methods, the use of medicinal plants
offers more advantages than the use of microbes particularly for therapeutic
application. This is due to the elimination of complicated procedures. Also,
multi-step stages involving culture media, culture maintenance, isolation,
purification, among others are not necessary. Further, the phytochemicals
present in the medicinal plants have healing values, and of such, many parts
of the plants are considered as reducing/stabilising agents for the pro-
duction of nanoparticles. Nanomaterials derived from medicinal plants
have been affirmed with therapeutic properties/activities like anticancer,
Green synthesized silver nanoparticles 589

antimicrobial, antioxidant, antidiabetics, insecticidal, wound healing,

immunomodulatory, etc. Fields like nanomedicine, diagnostics, biomedical
and drug delivery take advantage of the non-contaminated biosynthesised
NMs [19].
Bio-synthesized nanoparticles are identified to possess several pro-
perties than the NMs obtained via conventional methods [11]. Silver
nanoparticles synthesized using the leaf part of Tribulus terrestris exhibited
antibacterial activity in a similar manner with cinnamon [20]. Silver-nickel
bimetallic nanoparticles from Canna indica have proved to be an antibacterial
agent against Escherichia coli, Streptococcus pyogenes while synthesis with
Candida albicans resulted in antifungal agent [21,22]. Silver nanoparticles
from Senna occidentalis displayed antibacterial activity against Staphylococcus
aureus and Streptococcus pyogenes [18]. Phyto-synthesized NMs are reported
to inhibit the adult stage of mosquitoes, thus proving the mosquitocidal
properties of the NMs [23,24]. AgNPs from Feronia elephantum plant have
been studied to possess larvicidal activity against Culex quinquefasciatus,
Aedes aegypti and the third instar larvae of Anopheles stephensi [25].

1.5 Green synthesis of NMs for therapeutic applications

Algae, enzymes and secondary metabolites present in the plant extract act
as reducing agents essential for the development of nanomaterials during
green synthesis. Each organism involved in the biosynthesis react differently
with metallic ions, and the formation of the nanoparticles depends on the
temperature and pH of the reaction medium. Unlike the nanoparticles
synthesized by physical and chemical methods, green synthesized nanomat-
erials are non-toxic, and this qualifies them to be suitable for biomedical
and therapeutic applications, especially for the complimentary phytochem-
icals from medicinal plants. These are also eco-friendly, sustainable, safe to
humans and environment, and need no sophisticated equipment [26].
Another merit is nanomaterials produced from plants containing antioxi-
dants are potential candidates as anticancer agents. Table 1 is the compilation
of some therapeutic applications of green-synthesized nanomaterials.

1.6 Factors influencing the plant-based green synthesis

of AgNPs
It is worth mentioning that the therapeutic activity of the NPs is influenced
or controlled by factors like morphology of particle, particle size, particle
reactivity in solution, agglomeration, dissolution rate, organism cell type,
Table 1 Therapeutic applications of AgNP.
Biomass source Nanoparticle Material Therapeutic properties Size (nm) Shape References

Gelidium AgNP Algae Antibacterial 20–40 Not determined [27]

corneum
Fusarium AgNP Fungus Antibacterial and anticancer 8–40 Spherical and [28]
oxysporum Triangular
Phyllantus niruri AgNP Leaf Mosquitocidal 35–55 spherical and cubic [29]
Trapa natans AgNP Leaf Anticancer activity against A431 human skin cancer 30–90 Almost spherical [30]
cells
Turbinaria AgNP Leaf Cardioprotective and liver protective agent 50–100 Not determined [31]
conoides
Parkia speciose AgNP Leaf Antibacterial antioxidant 22–43 Spherical [32]
Polysaccharide AgNP Polysaccharide Anticancer activity in human hepatocellular 17–50 Spherical [33]
chitosan carcinoma Hep G2 cells
Teucrium polium AgNP Leaf Anticancer against MNK45 in human gastric cancer 70–100 Spherical/near spherical [34]
cell line
Oxalis corniculata AgNP Leaf Antioxidant, antimicrobial, cytotoxic and apoptotic 21.22 Almost spherical [35]
effects on human colon carcinoma cell line (HT29)
and healthy fibroblast cells (L929)
Iboza Riparia AgNP Leaf Cytotoxicity on human embryonic kidney cells 156 [36]
Ilex Mitis Root bark 50
Callistemon AgNP Leaf, flower, Antimalaria, antitrypanosomal and antibacterial 29 Triangular spherical [37]
citrinus Seed
Azadirachta AgNP Leaf Antibacterial and cytotoxic effects on human acute 20 Spherical [38]
indica lymphoblastic leukaemia cells
Prosopis juliflora AgNP Leaf Antibacterial, antibiofilm and wound healing 10–20 Spherical [39]
Momordica AgNP Stem leaf Antimicrobial Not Not determined [40,41]
charantia determined
Green synthesized silver nanoparticles 591

nature of the bio-reducing agent, among others. Moreover, the geometry

of the NPs controls the optical, chemical, physical, electronic properties
of bio-synthesized materials [42]. NPs with small sizes and uniform mor-
phologies are known to be active with diverse applications, especially in bio-
medical uses. Synthesis parameters are optimized during the biosynthesis of
NPs in order to control morphology and size. Reaction conditions includ-
ing pH, concentration, temperature, concentration and volume of pre-
cursors, reaction time, etc. need to be controlled to obtain uniform-sized
NPs and to prevent aggregation [43].

1.7 Reaction conditions for the biosynthesis of AgNPs

The under-listed are the factors influencing the green synthesis of the
AgNPs:
1. The concentration of reducing agent/precursor solution
2. The reaction temperature
3. The pH of solution

1.7.1 The concentration of the reduction agent/precursor solution

Concentrations of reducing agents and metal ion solution during the biosyn-
thesis of NPs results in different sizes, shapes, optical properties, and mor-
phology. A direct relationship has been established between the precursor
concentration with the size of NPs. Higher is the concentration, larger is
the size of the NPs. As the metal ion association increases, larger particles
are formed. The collision of small particles in solution may also result in
aggregation of particles [44]. It was reported that the concentration of
phytochemicals in a plant is not evenly distributed. Hence, NPs prepared
with different parts of the plant result in diverse morphology and sizes
[45,46]. One of the evidences of nanoparticle formation during synthesis
is a change in colour of the reaction mixture, and the effect of reducing agent
is noticed during the absorbance measurement of the bio-synthesized
NPs. The change in colour is a result of collective oscillation of metal
nanoparticles resulting in the appearance of Surface Plasmon Resonance
(SPR) ensuring the absorption beyond the ultraviolet region, measured
using a UV–Vis spectrophotometer.

1.7.2 Reaction temperature

Like any other chemical reaction, the fabrication of AgNPs is a temperature-
dependent process. Also, morphologies, shapes and sizes of NP are fine-
tuned at varied reaction temperatures. Ordinarily, reaction rates are raised
at elevated temperatures. As the heat of a reaction increases, the formation
592 Samson Oluwagbemiga Alayande et al.

of nucleation centres also increases. Aspect ratio and the relative amount of
NPs are controlled by the variation in temperature. Increase in temperature
lowers the activation energy of the reaction. In general, the formation of
NPs are faster at elevated temperatures as the kinetic energy of the reaction
is raised which speed up the rate of collisions between metal ions and the
biomolecules. Furthermore, more crystalline NPs are formed at higher
temperatures compared with the reactions at lower temperatures [47].

1.7.3 pH of the reaction solution

The pH of the reaction medium has been reported to have direct impact on
the shape, sizes and the rate of phyto-synthesis of the NPs [48]. Variation in
the pH of the reaction medium leads to a change in the ionic charges on
the secondary metabolites that influences their ability to adsorb metal ions.
Also, the solution pH affects the activity of phytochemicals which act as
reduction agents. Smaller metal oxide NPs are generally produced under
alkaline condition compared to the acidic medium. This account for the less
aggregation of the NPs at a higher pH, it is expected that more moieties are
present for binding to the metal ions resulting in a greater stability of the
NPs. Size of the NPs can be controlled by varying the pH of the reaction
media. According to Zikalala et al. [49], phyto-synthesis of metal oxide
NPs was found to be spontaneous in an alkaline pH medium.

1.8 Mechanism of reaction

Some reaction mechanisms are proposed for the interaction between metal-
lic ions and bio-reducing agents during the formation of nanoparticles.
Phytochemicals/secondary metabolites in plants are regarded as reducing
agents in the green synthesis. For instance, Scheme 1: saponins present in
the plant extract interact with the Ag+ ions through the hydroxyl groups
present in saponins, leading to the formation of silver nanoparticles, also
providing stability for the newly formed nanoparticles [4]. Flavonoids inter-
act with the metallic ions via carbonyl functional groups present in the
extract, liberating the reactive hydrogen, which then converts the enol in
the flavonoid to keto form leading to the Ag0 formation [50]. More so,
in the formation of AgNPs from Parkia speciose leaf extract, enol form is pre-
sent in phenolic and flavonoid is capable of releasing electrons from the
OdH group for the reduction of Ag+ to Ag0 and then cap the nanoparticles
formed [32]. Some proposed bio-reduction mechanism for AgNPs by
phytochemicals are illustrated in Schemes 1–3.
Green synthesized silver nanoparticles 593

O O OHC O O HOOC O O
HO Ag+
+ Ag0
HO OH HO OH
HO OH
OH OH
OH
+
Scheme 1 Phytoreduction of Ag to AgNP by saponins [4].

+
Ag
+ Ago
OH
O-H+
O-H+ O

Scheme 2 Phytoreduction of Ag+ to AgNP by terpenoids [21].

R1
R1
R1
OH O H
O
HO O
HO O
HO O +
Ago
Ag+
OH OH
OH O OH O
OH

OH O

Scheme 3 Phytoreduction of Ag+ to AgNP by flavonoids [18].

The redox reaction for the formation of silver nanoparticles is illustrated as:
AgNO3 ! Ag+ + NO

3
Ag+ + plantchemicals ! Ago , E o ¼ +0:80 V

1.9 Green AgNPs

Researchers have been able to explore numerous potential applications
of green nanomaterials within the medical, biomedical, healthcare, drug
and gene delivery, cosmetics, drug and gene delivery, agricultural, photo-
electronic, and environmental industries. This can be attributed to its less
troublesome preparation procedure and unique properties including small
droplet size, structural orientation, size distribution, and most importantly,
their environmental friendliness and relatively fewer toxicity concerns.
594 Samson Oluwagbemiga Alayande et al.

Interestingly, silver nanoparticles have found tremendous applications in the

biomedical industry including biosensing, antimicrobial, anticancer, anti-
diabetic, antioxidant, and antimalarial applications. This is because recent
advances in the design and restructuring of nanomaterials have strongly
proven AgNPs to possess unique physicochemical properties via their shape,
size, concentration, and stability in the colloidal state [51–54]. In addition,
AgNPs have been reported to possess the highest electrical and thermal
conductivity compared to the other metallic NPs. It is endowed with
extraordinary properties like chemical stability, high conductivity, catalytic,
and biological activities. These unique properties of silver nanoparticles make
them extensively considered by researchers over the other metallic nano-
particles for biomedical and therapeutic applications, viz., antimicrobial, ant-
iviral, anticancer, antifungal and anti-inflammatory activities [55]. Green
synthesized silver nanoparticles had been found to be relevant in the biomed-
ical field, especially in the development of antimicrobial applications [56,57].

1.10 Therapeutic applications

This section presents an overview of the therapeutic applications of the
green AgNPs as antimicrobial, antimalarial, and anticancer agents.

1.10.1 Antimicrobial
Based on the usual high surface-area-to-volume ratio of nanoparticles, the
potential of the AgNPs as a remarkable antimicrobial agent cannot be under-
estimated. Since the increasing need for an antimicrobial agent that can over-
whelm the growing microbial resistance, multidrug resistance (MDR) and
non-multidrug resistance (non-MDR) of pathogenic microorganism against
antibiotics, the development of appropriate resistant strains has been the cry-
ing need of the researchers in the microbiology. For the purpose, several
metallic nanoparticles have been extensively explored [53,58]. AgNPs dem-
onstrate a broad spectrum of antibacterial and antifungal activities, since the
reducing activity of the AgNPs tends to be comparatively lower than that
of the silver ions. Interestingly, AgNPs of high surface-area to volume ratio
having their size below 100 nm are of major interest as they are believed to
render high antimicrobial capabilities against microbial pathogens including
Gram-positive and Gram-negative bacteria [59], viruses, and other eukary-
otic microorganisms when compared to other NMs. Additionally, AgNPs
exhibit potential antimicrobial effects against multidrug susceptibles as
well as multidrug-resistant strains, viz., Pseudomonas aeruginosa, methicillin-
resistant Staphylococcus aureus, erythromycin-resistant Streptococcus pyogenes,
Green synthesized silver nanoparticles 595

ampicillin-resistant Escherichia coli and vancomycin-resistant Staphylococcus

aureus (VRSA) [57,60]. AgNPs synthesized with Boerhaavia diffusa plant
extract were tested for antibacterial activity against three fish bacterial patho-
gens including Aeromonas hydrophila, Pseudomonas fluorescens and Flavobacterium
branchiophilum [61]. The antibacterial activity of the Boerhaavia diffusa plant
extract synthesized AgNPs was evaluated for its Minimum Inhibitory
Concentration (MIC) that is required to inhibit the growth of the three
test pathogens selected for the study. Antibacterial activity of rifampicin
antibiotics and bulk silver nitrate (AgNO3) were also studied for cross-
examination by these authors. The biosynthesized AgNPs of varying
dilution (3.12–100 μg/mL) were prepared and each bacterial pathogen
was inoculated with MHA media in different petri dishes. Biosynthesized
AgNPs of six different dilutions were introduced into six wells made into
solidified agar and the zone of inhibition formed at the minimum dilution
for each pathogen was noted [61]. It was observed that 50 μg/mL inhibitory
dilution concentration was constant for all the three test pathogens, there-
fore, a further test using AgNO3, biosynthesized AgNP, and Rifampicin
antibiotics were carried out by the authors. Biosynthesized AgNPs showed
the highest zone of inhibition of about 15 mm for Flavobacterium branchio-
philum, 14 mm for Aeromonas hydrophila and 12 mm for Pseudomonas fluorescens.
Whereas the zone reported for AgNO3 was lower compared to AgNPs
and Boerhaavia diffusa plant extract showed no zone of inhibition [61].
Antimicrobial activity of green AgNPs was also examined in representative
microorganisms of gram-positive bacteria (Bacillus subtilis local isolate;
Staphylococcus aureus) and gram-negative bacteria (Pseudomonas aeruginosa;
P. fluorescens local isolate; Escherichia coli) including yeast (Candida albicans).
Also, AgNPs with spherical shape and monodisperse having an average
particle size of 23.7 nm were synthesized with banana peel extract [62].
Bacterial strains and yeast which were maintained on nutrient agar slants
and potato-dextrose agar were exposed to green AgNPs. The MIC and min-
imum bactericidal concentration (MBC) were determined. The inhibition
zone was measured and compared with that of levofloxacin, AgNO3 solu-
tion, and silver nanoparticles individually. AgNPs demonstrated antibacterial
activity against various strains of pathogenic bacteria. Antimicrobial activi-
ties of the AgNPs increased gradually [62]. AgNPs produced using the
inflorescence of Cocos nucifera significantly inhibited the growth of Vibrio
alginolyticus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacillus subtilis,
and Plesiomonas shigelloides and the results were confirmed microscopically
confirming the binding of the AgNPs to the bacterial cell wall [63].
596 Samson Oluwagbemiga Alayande et al.

Synthesis of bimetallic nanoparticles of silver with culture supernatant of

Staphylococcus aureus was also reported and its antimicrobial activity was
evaluated against different pathogenic organisms including Salmonella
typhi, Staphylococcus epidermidis, Staphylococcus aureus, Streptococcus pyogenes
and Klebsiella pneumoniae [64]. The most sensitive activity observed was
against S. aureus followed by Staphylococcus epidermidis and Streptococcus pyogenes.
Only moderate antimicrobial activity was seen against the Salmonella typhi
and Klebsiella pneumonia [64]. Also organisms such as Salmonella typhi
and Staphylococcus aureus known for multi-drug resistance were inhibited
by AgNPs biosynthesized with Bacillus brevis [65]. Trichoderma viride, a
non-pathogenic, fast growing and environmentally friendly fungus had
also shown reducing capability for silver ions as its use for the synthesis of
biogenic silver nanoparticles [66]. Trichoderma viride synthesized AgNPs
was studied for its antimicrobial behaviour by evaluating it against
methicillin-resistant Staphylococcus aureus (MRSA) and four gram-negative
bacteria (Shigella boydii, Acinetobacter baumannii, Shigella sonnei and
Salmonella typhimurium). The tested bacteria were grown on a nutrient broth
medium for 48 h. The AgNPs demonstrated inhibition of gram-negative
bacteria, compared to the antibiotics control. A significant inhibition of
the MRSA growth was displayed by AgNPs [66]. Previous studies have asso-
ciated the stability and biocompatibility of AgNPs for suitability in multiple
clinical and therapeutic applications to their physicochemical properties.
The shape of nanoparticles was reported to be one of the properties that
uniquely influenced its activities, whereas, the AgNPs were confirmed to
interact with fungi, bacteria, and viruses in a shape-dependent manner
[53,54,67]. It was reportedly shown that AgNPs with different morphol-
ogies and similar surface area exhibited varying bactericidal activity.
Significantly, the size of nanoparticles is another important physicochemical
property responsible for their applicability as antimicrobial agent with a
typical size not exceeding 50 nm. Particles of size between 5 and 10 nm dem-
onstrated both bactericidal and bacteriostatic effects against bacterial patho-
gens including Staphylococcus aureus and MRSA [68]. It was also found that
the antibacterial activity increased with the decrease of particle size when
the potential of different-sized AgNPs was tested against Streptococcus
mutants. The interesting mechanistic action of nanoparticles towards their
antibacterial activity may be attributed to their small size. The small size
nanoparticles have a pronounced tendency to alter the lipid bilayers of
microbes, after the NPs attachment to the cell wall by promoting a huge
Green synthesized silver nanoparticles 597

membrane permeability, damage to the microbes, and finally cell death [69].
AgNPs were evaluated for their antiviral potency against HIV-1 and found
to display antiviral activity in a size-dependent manner. It was reported that
AgNPs with particle size of 1–10 nm interact with the causative organism of
HIV-1, forming a strong bond with the disulphide groups present in the gly-
coproteins of the viral envelope [53,70,71]. A summary is presented in
Table 2.

1.10.2 Antimalarial
Malaria represents a common infectious disease which continue to pose
critical public health concern and its wide spread is mostly found in the
Sub Saharan Africa [81]. The main cause of malaria is the Plasmodium par-
asites and these parasites spread through exposure to infected female
Anopheles mosquitoes, called “malaria vectors”. Among the five most signif-
icant parasite species that cause malaria in humans, Plasmodium falciparum and
Plasmodium vivax represent the most significant species that pose the greatest
threat. In 2018, Plasmodium falciparum accounted for 99.7% of estimated
malaria cases in the Africa, 50% of cases in the South-East Asia, 71% of cases
in the Eastern Mediterranean and 65% in the Western Pacific. P. vivax is the
most widespread specie. According to the latest world malaria report
released in December 2019, there were 228 million cases of malaria in
2018 [82]. The estimated number of malaria deaths stood at 405,000 in
2018, Africa accounted for 93% of malaria cases and 94% of malaria deaths.
In the same year (2018), six countries accounted for more than half of all
malaria cases worldwide including Nigeria (25%), the Democratic Republic
of the Congo (12%), Uganda (5%), C^ ote d’Ivoire (4%), Mozambique (4%)
and Niger (4%) [82]. Previous reports concerning the resistance of antimalarial
drugs including Chloroquine and sulfadoxine–pyrimethamine were emerging
in artemisinin-based combination therapy (ACT) as its resistance-associated
k13 mutation in Africa. Meanwhile, the use of insecticides in malaria endemic
areas was encouraged for protection against the disease since the vector trans-
mission rate is extremely high but insecticide resistance including its toxicity to
human health and the environment are other concerns [81,83].
Nanomaterials and the metal nanoparticles have potential benefits
towards the management of malaria, especially, the green nanoparticles
may be more useful. As previously mentioned, metal nanoparticles, parti-
cularly the biosynthesized AgNPs have demonstrated anti-plasmodial
activities, which have been widely used against mosquito vectors [84].
Table 2 Antimicrobial, antimalarial and anticancer uses of the green AgNPs.
Size /
Biomedical Nature of the morphology
application Green entity entity obtained Method Test microorganism References

Antimicrobial Boerhaavia diffusa Plant 25 nm Twofold symmetry Aeromonas hydrohilia, Pseudomonas [61]
plant Spherical flourescens, Flavobacterium branchiophilum
Antimicrobial Banana peel extract Plant 23.7 nm Agar well diffusion assay Staphylococcus aureus, Pseudomonas [62]
Spherical aeruginosa, Escherichia coli, Candida
albicans
Antimicrobial Cocos nucifera Plant 22 nm Agar well diffusion Klebsiella pneumoniae, Bacillus subtilis, [63]
Spherical method Pseudomonas aeruginosa, and Salmonella
paratyphi
Antimicrobial Staphylococcus aureus Microorganism 160–180 nm Well diffusion method methicillin-resistant Staphylococcus [64]
Spherical aureus, Staphylococcus epidermidis
Streptococcus pyogenes, Salmonella typhi,
Klebsiella pneumonia, and Vibrio cholerae
Antimicrobial Bacillus brevis Microorganism 41 nm Standard Nathan’s Agar Clinical isolates of Staphylococcus aureus [65]
Spherical Well Diffusion (NAWD) and Salmonella typhi
and Kirby-Bauer Disc
Diffusion Methods
Antimicrobial Chitosan/Glucose Polymer 20 nm Viable cell-counting Escherichia coli [72]
method
Antimicrobial Ziziphus zizyphus Plant/leaf 30 nm Radial diffusion assay Escherichia coli [73]
leaf extract Spherical Microdilution plate assay Candida albicans
Antimicrobial Lingonberry and Plant/Fruit 30–50 nm Agar well diffusion Staphylococcus aureus, Salmonella [74]
cranberry juices Spherical typhimurium, Listeria monocytogenes,
Bacillus cereus, Escherichia coli, Bacillus
subtilis, Candida albicans and Bacillus
cereus
Antimicrobial Trichoderma viride Microbe-fungus 1–50 nm Agar well diffusion Methicillin-resistant Staphylococcus [66]
aureus (MRSA) and four
Gram-negative bacteria (Shigella boydii,
Acinetobacter baumannii, Shigella sonnei
and Salmonella typhimurium)
Antimalarial Callistemon citrinus Plant-fruit/leaf/ 29 nm Larvacidal bioassay Plasmodium falciparum [37]
seed Spherical
Antimalarial Murraya koenigii Plant-Leaf 29.42 nm Plasmodium falciparum [75]
Spherical
Antimalarial Syzygium jambos Plant-leaf and 8.51 nm Plasmodium falciparum [76]
bark
Antimalarial Mukia Plant-leaf 64 nm Larvacidal bioassay Aedes aegypti and Culex quinquefasciatus [77]
maderaspatana
Antimalarial Sterculia foetida L. Plant-seed 24.6 nm Larvacidal Bioassay Anopheles stephensi [78]
Aedes egypti (L.)
Culex quinquefasciatus
Anticancer Sterculia foetida L. Plant-seed 24.6 nm MTT assay Cervical carcinoma cell lines [78]
Anticancer Rheum ribes Plant-leaf 18.2 nm MTT cell viability assay MDA-MB-231 breast cancer cells [79]
Anticancer Cucurbita maxima Plant-petals, 76.10 nm MTT cell viability assay A431 epidermoid carcinoma cell lines [80]
(petals), Moringa leaves, rhizome 94.17 nm
oleifera (leaves) and 59.02 nm
Acorus calamus
(rhizome)
600 Samson Oluwagbemiga Alayande et al.

Plant mediated biosynthesized AgNPs using crude leaf, flower and seed
extract of Callistemon citrinus plant, having spherical shape and an average size
of 29 nm exhibited a pronounced anti-plasmodial effect [37]. Chloroquine
or artemisinin was used as positive controls and AgNPs were subjec-
ted to in vitro screening of anti-plasmodial activity against the malaria
parasites (Plasmodium falciparum strain 3D7). A considerable decrease in
the viability of Plasmodium falciparum was exhibited by the use of green
AgNPs. In addition, the seed-synthesized AgNPs also showed considerable
decrease in the viability against the same Plasmodium falciparum strain at
(1.192  4.38%) [37].
Biosynthesized antiplasmodial AgNPs involving the use of β-caryophyllene
extracted from the leaf extract of Murraya koenigii were used in the chloro-
quine sensitive strain 3D7 of Plasmodium falciparum by Kamaraj et al. [75].
The strain was reared and used in in vitro blood stage culture in order to
test the anti-malarial efficacy of β-caryophyllene and the AgNPs. Murraya
koenigii synthesized AgNPs yielded a spherical nanosilver with an average
size of 29.42 nm and a promising antiplasmoidal activity on chloroquine-
sensitive Plasmodium falciparum (3D7) (IC50: 2.34  0.07 μg/mL) was repor-
ted by the same group of authors [75]. The β-caryophyllene synthesized
AgNPs were further recommended for consideration as a promising source
for the development of cost effective and safer alternative drugs towards
malaria treatment [75]. Dutta et al.’s [76] investigations using Syzygium
jambos L., a traditional plant of nutritional importance, reported excellent
reducing and capping ability on Ag+ ions into silver nanoparticles, which
were tested for antimalarial activity. AgNPs synthesized with the bark and
leaves of phenol rich Syzygium jambos extract gave a spherical morphology
with an average size of 8.51  1.63 nm and 5.58  1.84 nm, respectively.
Study on the anti-malarial potential of the synthesized nanoparticles against
both chloroquine (CQ)-sensitive (3D7) strains of Plasmodium falciparum
revealed a significant (P < 0.05) inhibition with IC50 values of 24.22 and
28.97 μg mL
1. Following the anti-plasmodial activity of Syzygium jambos
leaf, the bark of the plant was used for the preparation of biosynthesized
AgNPs. Activity of the resultant AgNPs against CQ resistant (Dd2) strain
of Plasmodium falciparum was significantly high (P < 0.05). Anti-plasmodial
activity with IC50 values of 29.09 and 34.49 μg mL
1 was recorded by these
authors [76]. Silver nanoparticles play an important role in controlling
the mosquito population as well as multi drug resistant pathogens without
causing much harm to humans. AgNP was synthesized using leaf aqueous
extract Mukia maderaspatana while larvicidal potential was evaluated on
Green synthesized silver nanoparticles 601

fourth instar larvae of Aedes aegypti and Culex quinquefasciatus [77]. The green
AgNPs show-cased higher larvicidal activity on Aedes aegypti relative to
Culex quinquefasciatus.

1.10.3 Anticancer
AgNP has shown numerous capabilities and promising results in cancer
diagnostics and therapeutics. The attributed improvements that are endorsed
towards the application of metal NP over the conventional therapy has
been interesting. Meanwhile, the conventional drugs currently assigned
for use as an anti-cancer agent are toxic to the body, thereby, producing both
projected and unexpected side effect capable of disturbing the body’s normal
physiology. Other effects include development of drug resistance, quick
drug metabolism and clearance from the patient’s body decreasing effective
treatment time etc. Green synthesized AgNP provide safe and effective ther-
apeutic response for cancer treatment. This class of material demonstrated
unique properties against various cancer cells [85].
Studies on anticancer applications of green AgNP can be understood
from a recent one-step and eco-friendly process which capped the silver with
protein-lipid. The resultant composite was silver functionalized protein-lipid
nanoparticle (Ag-PLNP) with core– shell morphology. The synthesis was
achieved using seed extract from Sterculia foetida (L.) (Sterculiaceae). Using
the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide]
assay to determine the cell viability with treated Ag-PLNP. The cytotoxi-
city study was presented as the MTT assay confirmed in vitro toxicity of
Ag-PLNP synthesized using S. foetida seed extract against HeLa cell lines
[78]. The Ag-PLNP reduced viability of HeLa cell line while dose was varied.
Meanwhile, HeLa cell proliferation was significantly inhibited even at low
concentration [78]. Whereas, the control and original AgNP did not exhibit
any toxicity to the HeLa cells [78].
Furthermore, anti-carcinogenic properties of green AgNP was studied
using the extract of Rheum ribes (R. ribes), a medicinal plant that belongs
to Polygonaceae, as the reducing and capping agent for bio-reduction
process. MDA-MB-231 breast cancer cells was studied using MTT cell via-
bility test for cytotoxicity assay and evaluation of cell survival was achieved
on MDA-MB-231 cells treated with variable concentrations of AgNP for
24 and 48 h. AgNP showed cytotoxic effect against cancer cells. Based
on MTT cell viability assay results, the survival rate of MDA-MB-231 cells
were 60% and 40% after treatment for 24 and 48 h respectively. Also, IC50
602 Samson Oluwagbemiga Alayande et al.

values of AgNP was calculated as 165.6 and 98.96 μg/mL [79]. Another
study on green AgNP using plants mediated route from different origin
Cucurbita maxima (petals), Moringa oleifera (leaves) and Acorus calamus (rhizome).
AgNP demonstrated strong anticancer property against A431 skin cancer cell
line. The IC50 values of 82.39  3.1, 83.57  3.9 and 78.58  2.7μg/mL
were calculated for AgNP synthesized from Cucurbita maxima, Moringa oleifera
and Acorus calamus respectively [80].

1.11 Mechanistic profile followed by AgNP

1.11.1 Antimicrobial mechanism of action of AgNP
Based on previous reports, the mechanism of action of AgNP in terms of
its toxicity to microbial cells can be attributed to the release of silver ions
and/or deposition of nanoparticles inside the cell. The comprehensive
mechanisms of action of AgNP can be majorly attributed to “Reactive
Oxygen Species” (ROS) generation, cellular membrane damage, disruption
of energy metabolism, and disruption of gene transcription [86]. AgNP
exhibits synergistic effect that occurs when they combine with natural or
synthetic compounds. This can be explained from the large area of contact
created by AgNP for bacteria. The ratio of particle size to surface area
enables AgNP to attach to the cell membrane, thereby penetrating the bac-
teria easily. Hence, a smaller-sized nanoparticles give a better cell-particle
resulting in biocidal effect [87]. The mechanism of AgNP mediated from
plant can be understood from the generation of free radical species (ROS
e.g. OH%) and superoxide anions (O2
) that leads to radical-induced mem-
brane destruction. Secondly, silver ions can further make new bonds with
sulphydryl groups that encounters the denaturation of bacterial proteins.
In addition, the silver ions released can travel into the bacterial cell wall
to severely damage the bacteria and cause cell death [87,88]. Study suggest
that the effect on membrane proteins and the oxidative stress induced by
AgNP are the main mechanism responsible for the antimicrobial activity
(Scheme 4).
Furthermore, the mechanistic action of AgNP on microorganism can
be understood using a proteomics related study. This shows that AgNP
directly affects proteins and ROS-related proteins and this is expected
to lead to membrane damage, oxidative stress, and possibly cell death.
Pseudomonas aeruginosa (a model for Gram-negative bacteria) was treated
with AgNP and its proteomic response was comprehensively studied to
elucidate the antimicrobial mechanism. In total, 59 silver-regulated proteins
(27 up-regulated and 32 down-regulated proteins) and 5 silver-binding
Green synthesized silver nanoparticles 603

cytoplasm

AgNPs
Bacteria
Cell membrane
distruction

Dead bacteria cells

Scheme 4 Plausible mechanism of antimicrobial activity of AgNP. Modified after
B.K. Mandal, Silver nanoparticles: potential as insecticidal and microbial biopesticides, in:
Ed: O. Koul (Ed.), Nano-Biopesticides Today and Future Perspectives, Chapter 12, Academic
Press, 2019, pp. 281–302. ISBN 9780128158296, https://doi.org/10.1016/B978-0-12-815829-
6.00012-7.

proteins were identified. Result of molecular function and biological

processes of silver-regulated proteins indicated that the pattern of membrane
proteins regulated by AgNP was similar to that found for silver ions. In
addition, the same proteins could bind with both AgNP and silver ions.
These indicated that AgNP probably interact with cell membrane, then react
with proteins which result to release of silver ions. Nevertheless, a com-
parison of protein expression levels in Pseudomonas aeruginosa showed that
AgNP caused more intense alterations than silver ions. On the other hand,
a number of differentially expressed proteins were found only in the
AgNP-treated group, which reflects a particle-specific effect. Except for
the 16 common regulated proteins, 12 proteins were specifically regulated
in the AgNO3-treated groups, which is due to the different effective con-
centration of particles and ions. Furthermore, intracellular ROS generation
in Pseudomonas aeruginosa was significantly induced solely by AgNP. This was
attributed to higher bioaccumulation of AgNP than silver ions. The regu-
lation of ROS-related proteins and the generation of oxidative stress by
AgNP can mainly be ascribed to the nano characteristics of the particles [86].

1.11.2 Mechanism of anticancer activities of AgNP

Due to the small size of AgNP, they are either taken up by the mammalian
cell in the form of aggregates through endocytosis or they crosses the blood
604 Samson Oluwagbemiga Alayande et al.

brain barrier. Afterwards, intracellular trafficking of AgNP to the cytoplasm

and nucleus takes place. Although, variation in their physicochemical prop-
erties such as size and shape can encourage different cellular processes for
different cells. Generally, AgNP exercises toxicity towards cancerous cells
by reducing mitochondrial function, decreasing ROS production, releasing
lactate dehydrogenase (LDH), cell cycle deregulation, induction of apopto-
tic genes like Bax, formation of micronuclei, chromosome aberration and
DNA damage [89]. Another pathway to consider is inflammatory induction
caused by AgNP to the treated cell. The engulfment of AgNP by macro-
phages initiates inflammatory responses in cancer cells. While this happens,
the inflammation-activated macrophages releases ROS, TNF-α, inflam-
matory cytokines including interleukins (IL-6) [90]. In addition, size of
nanoparticles represent an important property that significantly exert size-
dependent toxicity to cancerous cells. The smaller-sized nanoparticles tend
to efficiently produce more ROS than the larger-sized particles, hence,
more toxic. Anti-angiogenic and anti-proliferative effect of AgNP show
that PI3K/Akt (phosphatidylinositol-3-kinase/protein kinase B) signalling
pathway-“an important intracellular pathway that regulates normal cell
processes” becomes activated when vascular endothelial growth factor binds
to endothelial receptors in order to activate angiogenesis in normal tissue
cells. AgNP plays an anti-angiogenic role by inhibiting the phosphorylation
of PI3K/AKT pathway, thereby deactivating angiogenesis since PI3K/AKT
signalling pathway cannot be completed. This mechanistic route deprive the
cell of oxygen and causes apoptotic tumour cell death [91]. AgNP also exerts
its anti-proliferative potential via DNA damage and chromosome disruption
[92]. These mediate disturbed gene, disrupts the homeostasis of calcium
and finally induce cell injury and death, afterwards, anti-proliferative effect
of AgNP arises against cancer cells [85,92–95].

2. Conclusions
Silver is the most popular green nanoparticle. Green AgNPs
with numerous morphology and sizes have been successfully synthesized
using ecologically friendly routes. These routes include bacteria, algae, fungi
and plant mediated synthesis. The general operating principle is the bio-
reduction process. The plant mediated synthesis have additional merits over
the microbe mediated route, due to the complimentary role of the phyto-
chemicals present in plants which capped the AgNPs. For therapeutic
Green synthesized silver nanoparticles 605

applications in antimicrobial; anti-malaria; cancer; plant mediated synthesis

prevails. Abundance of bio-diversity will continue to aid flourishing green
AgNP and their applications.

References
[1] S. Krishnamurthy, S. Vijayasarathy, Applications of Nanobiomaterials, Nanobiomaterials
in Dentistry, 11, Elsevier BV, 2016, pp. 211–240. https://doi.org/10.1016/B978-0-323-
42867-5.00009-6.
[2] H. Ghadimi, A.B. Sulaiman, G. Amiri, Carbon-based electrodes and their uses in syn-
thesis and sensors, in: Electrochemistry of Dihydroxybenzene Compounds, 2017,
pp. 1–30. https://doi.org/10.1016/B978-0-12-813222-7.00001-2.
[3] M.A. Elkodous, G.S. El-Sayyad, I.Y. Abdelrahman, et al., Therapeutic and diagnostic
potential of nanomaterials for enhanced biomedical applications, Colloids Surf.
B Biointerfaces 180 (2019) 411–428.
[4] A.A. Akinsiku, K.O. Ajanaku, E.O. Dare, Green synthesis of pseudo-cubic Ag/Ni
bimetallic nanoparticles using Senna occidentalis leaf extract, J. Phys. Conf. Ser. 1299
(2019), 012133. https://doi.org/10.1088/1742-6596/1299/1/012133.
[5] I. Khan, K. Saeed, I. Khan, Nanoparticles: properties, applications and toxicities, Arab.
J. Chem. 7 (2019) 908–931.
[6] W. Wei, F. Bai, H. Fan, Surfactant-assisted cooperative self-assembly of nanoparticles
into active nanostructures, Science 11 (2018) 272–293.
[7] Twelve Principles of Green Chemistry, 2020. Retrieved on April 9, 2020, from https://
www.acs.org/content/acs/en/greenchemistry/principles/12-principles-of-
green-chemistry.html.
[8] K. Emmanuel, Green Synthesis of Silver Nanoparticles for Post-Harvest Management
of Spices, MSc Dissertation, Obafemi Awolowo University, Nigeria, 2018.
[9] P.T. Anastas, J.C. Warner, Green Chemistry: Theory and Practice, Oxford University
Press, New York, 2000.
[10] R.K. Omole, N. Torimiro, S.O. Alayande, E. Ajenifuja, Silver nanoparticles synthe-
sized from Bacillus subtilis for detection of deterioration in the post-harvest spoilage
of fruit, Sustain. Chem. Pharm. 10 (2018) 33–40, https://doi.org/10.1016/j.scp.
2018.08.005.
[11] S.O. Alayande, T.V. Adeseluka, B.J. Odewunmi, N. Torimiro, K. Sodeinde,
O.B. Daramola, D. Ighodaro, A. Ofudje, J.A. Ajao, Evaluation of microbial inhibition
properties of green and chemically synthesized ZnO nanoparticles, Bull. Mater. Sci.
42 (2019) 101. https://doi.org/10.1007/s12034-019-1761-0.
[12] S.P. Suriyaraj, G. Ramadoss, K. Chandraraj, R. Selvakumar, One-pot facile green
synthesis of crystalline bio-ZrO2 nanoparticles using Acinetobacter sp. KCSI1 under room
temperature, Mater. Sci. Eng. C 105 (2019) 110021. https://doi.org/10.1016/
j. msec.2019.110021.
[13] M. Sengania, A.M. Grumezescu, V.D. Rajeswari, Recent trends and methodologies in
gold nanoparticle synthesis—a prospective review on drug delivery aspect, Open Nano
2 (2017) 37–46. https://doi.org/10.1016/j.onano.2017.07.001.
[14] A. Shabir, S. Munir, N. Zeb, A. Ullah, B. Khan, J. Ali, M. Bilal, M. Omer, M. Alamzeb,
S.M. Salman, Saqib Ali Green nanotechnology: a review on green synthesis of silver
nanoparticles—an ecofriendly approach, Int. J. Nanomedicine 14 (2019) 5087–5107.
[15] H.M. El-Rafie, M.H. El-Rafie, M.K. Zahran, Green synthesis of silver nanoparticles
using polysaccharides extracted from marine macroalgae, Carbohydr. Polym.
96 (2013) 403–410. https://doi.org/10.1016/j.carbpol.2013.03.071.
606 Samson Oluwagbemiga Alayande et al.

[16] B.K. Nayak, A. Nanda, V. Prabhakar, Biogenic synthesis of silver nanoparticle from
wasp nest soil fungus, Penicillium italicum and its analysis against multidrug-resistant path-
ogens, Biocatal. Agric. Biotechnol. 16 (2018) 412–418. https://doi.org/10.1016/j.
bcab.2018.09.014.
[17] K.B. Narayanan, N. Sakthivel, Biological synthesis of metal nanoparticles by microbes,
Adv. Colloid Interface Sci. 156 (2010) 1–13.
[18] A.A. Akinsiku, E.O. Dare, K.O. Ajanaku, J.A. Adekoya, S.O. Alayande,
A.O. Adeyemi, Synthesis of silver nanoparticles by plant-mediated green method: opti-
cal and biological properties, J. Bionanosci. 10 (2016) 171–180. doi.org/10.1166/jbns.
2016.1361.
[19] M. Mailafiya, K. Abubakar, A. Danmaigoro, S. Chiroma, E.B. Abdul Rahim,
A.M. Moklas, A.Z. Zakaria, Cockle shell-derived calcium carbonate (aragonite) nano-
particles: a dynamite to nanomedicine, Appl. Sci. 9 (2019) 2897.
[20] J. Premkumar, T. Sudhakar, A. Dhakal, J.B. Shrestha, S. Krishnakumar,
P. Balashanmugam, Synthesis of silver nanoparticles (AgNP) from cinnamon against
bacterial pathogens, Biocatal. Agric. Biotechnol. 15 (2018) 311–316.
[21] A.A. Akinsiku, E.O. Dare, K.O. Ajanaku, O.O. Ajani, J.A.O. Olugbuyiro, T.O.
Siyanbola, O. Ejilude, E.E. Emetere, Modelling and synthesis of Ag and Ag/Ni allied
bimetallic nanoparticles by green method: optical and biological properties, Int.
J. Biomater 2018 (2018) 9658080. 17 pages. https://doi.org/10.1155/2018/9658080.
[22] A.A. Akinsiku, E.O. Dare, O.O. Ajani, J.A. Adekoya, A.O. Adeyemi, O. Ejilude, K.O.
Oyeyemi, Dataset on the evaluation of antimicrobial activity and optical properties of
green synthesized silver and its allied bimetallic nanoparticles, Data Brief
21 (2018) 989–995. https://doi.org/10.1016/j.dib.2018.10.054.
[23] N. Soni, S. Prakash, Green nanoparticles for mosquito control, Sci. World J. 6 (2014).
https://doi.org/10.1155/2014/496362.
[24] G. Benelli, Plant-mediated biosynthesis of nanoparticles as an emerging tool against
mosquitoes of medical and veterinary importance: a review, Parasitol. Res. 115
(2016) 23–34.
[25] K. Veerakumar, M. Govindarajan, M. Rajeswary, U. Muthukumaran, Low-cost and eco-
friendly green synthesis of silver nanoparticles using Feronia elephantum (Rutaceae) against
Culex quinquefasciatus, Anopheles stephensi, and Aedes aegypti (Diptera: Culicidae), Parasitol.
Res. 113 (2014) 2363–2373.
[26] H. Chandra, P. Kumari, E. Bontempi, S. Yadav, Medicinal plants: treasure trove for
green synthesis of metallic nanoparticles and their biomedical applications, Biocatal.
Agric. Biotechnol. 24 (2020) 101518. https://doi.org/10.1016/j.bcab.2020.101518.
€ urk, B.Y. G€
[27] B.Y. Ozt€ ursu, I_ . Dag, Antibiofilm and antimicrobial activities of green syn-
thesized silver nanoparticles using marine red algae Gelidium corneum, Process Biochem.
89 (2020) 208–219. https://doi.org/10.1016/j.procbio.2019.10.027.
[28] S.M. Husseiny, T.A. Salah, H.A. Anter, Biosynthesis of size-controlled silver nano-
particles by Fusarium oxysporum, their antibacterial and antitumor activities, Beni-
Suef Univ. J. Basic Appl. Sci. 4 (2015) 225–231. https://doi.org/10.1016/j.bjbas.
2015.07.004.
[29] U. Suresh, K. Murugan, G. Benelli, M. Nicoletti, D.R. Barnard, C. Panneerselvam,
P.M. Kumar, J. Subramaniam, D. Dinesh, B. Chandramohan, Tackling the growing
threat of dengue: Phyllanthus niruri-mediated synthesis of silver nanoparticles and their
mosquitocidal properties against the dengue vector Aedes aegypti (Diptera: Culicidae),
Parasitol. Res. 114 (2015) 1551–1562.
[30] M.M. Sabera, S.B. Mirtajanic, K. Karimzadeh, Green synthesis of silver nanoparticles
using Trapa natans extract and their anticancer activity against A431 human skin cancer
cells, J. Drug Deliv. Sci. Technol. 47 (2018) 375–379. https://doi.org/10.1016/j.jddst.
2018.08.004.
Green synthesized silver nanoparticles 607

[31] M.S. Ali, V. Anuradha, N. Yogananth, S. Krishnakumar, Heart and liver regeneration in
zebrafish using silver nanoparticle synthesized from Turbinaria conoides—in vivo, Biocatal.
Agric. Biotechnol. 17 (2019) 104–109. https://doi.org/10.1016/j.bcab.2018.10.013.
[32] V. Ravichandran, S. Vasanthi, S. Shalini, S.A.A. Shah, M. Tripathy, N. Paliwal, Green
synthesis, characterization, antibacterial, antioxidant and photocatalytic activity of Parkia
speciosa leaves extract mediated silver nanoparticles, Results Phys. 15 (2019) 102565.
https://doi.org/10.1016/j.rinp.2019.102565.
[33] K. Priya, M. Vijayakumar, B. Janani, Chitosan-mediated synthesis of biogenic silver
nanoparticles (AgNPs), nanoparticle characterisation and in vitro assessment of anticancer
activity in human hepatocellular carcinoma HepG2 cells, Int. J. Biol. Macromol. 149
(2020) 844–852. https://doi.org/10.1016/j.ijbiomac.2020.02.007.
[34] S.F. Hashemi, N. Tasharrofi, M.M. Saber, Green synthesis of silver nanoparticles using
Teucrium polium leaf extract and assessment of their antitumor effects against MNK45
human gastric cancer cell line, J. Mol. Struct. Theochem. 1208 (2020) 127889.
https://doi.org/10.1016/j.molstruc.2020.127889.
[35] K. Karimzadeh, E. Sharifi, N. Bakhshi, M. Ramzanpoor, Biogenic silver nanoparticles
using Oxalis corniculata characterization and their clinical implications, J. Drug Deliv. Sci.
Technol. 54 (2019) 101263. https://doi.org/10.1016/j.jddst.2019.101263.
[36] M.I. Sabela, T. Makhanya, S. Kanchi, M. Shahbaaza, D. Idress, K. Bisetty,
One-pot biosynthesis of silver nanoparticles using Iboza Riparia and Ilex Mitis for cyto-
toxicity on human embryonic kidney cells, J. Photochem. Photobiol. B 178 (2018)
560–567.
[37] R. Larayetan, M.O. Ojemaye, O.O. Okoh, A.I. Okoh, Silver nanoparticles mediated
by Callistemon citrinus extracts and their antimalaria, antitrypanosoma and antibacterial
efficacy, J. Mol. Liq. 273 (2019) 615–625. https://doi.org/10.1016/j.molliq.
2018.10.020.
[38] M. Asimuddin, M.R. Shaik, S.F. Adil, M.R.H. Siddiqui, A. Alwarthan, K. Jamil,
M. Khan, Azadirachta indica based biosynthesis of silver nanoparticles and evaluation
of their antibacterial and cytotoxic effects, J. King Saud Univ. Sci. 32 (2020)
648–656. https://doi.org/10.1016/j.jksus.2018.09.014.
[39] G. Arya, R.M. Kumari, N. Sharma, N. Gupta, A. Kumar, S. Chatterjee, S. Nimesh,
Catalytic, antibacterial and antibiofilm efficacy of biosynthesised silver nanoparticles using
Prosopis juliflora leaf extract along with their wound healing potential, J. Photochem.
Photobiol. 190 (2019) 50–58. https://doi.org/10.1016/j.jphotobiol.2018.11.005.
[40] A.A. Akinsiku, K.O. Ajanaku, A.A. Adebisi, A. Edobor-Osoh, O. Aladesuyi,
O.S. Taiwo, E.O. Dare, Momordica charantia stem extract mediated biogenic synthesis
of silver nanoparticles: optical and antimicrobial efficacy, Mater. Sci. Eng. C 509
(2019) 012019. https://doi.org/10.1088/1757-899X/509/1/012019.
[41] A.A. Akinsiku, E.O. Dare, K.O. Ajanaku, J.A. Adekoya, O.S. Taiwo, J. Ayo-Ajayi,
A.O. Adeyemi, Room temperature phytosynthesis of silver nanoparticles using leaf
extract of Momordica charantia: optical and antimicrobial properties, Mater. Sci. Eng.
C 509 (2019), https://doi.org/10.1088/1757-899X/509/1/012019, 012019.
[42] H. Kim, Y. Seo, K. Kim, J.W. Han, Y. Park, S. Cho, Concentration effect of
reducing agents on green synthesis of gold nanoparticles: size, morphology, and growth
mechanism, Nanoscale Res. Lett. 11 (2016) 230, https://doi.org/10.1186/s11671-016-
1393-x.
[43] X.-F. Zhang, Z.-G. Liu, W. Shen, S. Gurunathan, S. Nanoparticles, Synthesis, charac-
terization, properties, applications, and therapeutic approaches-review, Int. J. Mol. Sci.
17 (2016) 1534. https://doi:10.3390/ijms17091534.
[44] A. Abedini, A.R. Daud, A.A. Hamid, N.K. Othman, E. Saion, A review on
radiation-induced nucleation and growth of colloidal metallic nanoparticles, Nanoscale
Res. Lett. 8 (2013) 474. http://www.nanoscalereslett.com/content/8/1/474.
608 Samson Oluwagbemiga Alayande et al.

[45] J. Mittal, A. Batra, A. Singh, M.M. Sharma, Phytofabrication of nanoparticles through

plant as nanofactories, Adv. Nat. Sci. Nanosci. Nanotechnol. 5 (2014) 1–10.
[46] Y. Zheng, L. Fu, F. Han, A. Wang, W. Cai, J. Yu, J. Yang, F. Peng, Green biosynthesis
and characterization of zinc oxide nanoparticles using Corymbia citriodora leaf extract and
their photocatalytic activity, Green Chem. Lett. Rev. 8 (2015) 59–63.
[47] L. Pereira, F. Mehboob, A.J.M. Stams, M.M. Mota, H.H.M. Rijnaarts, M.M. Alves,
Metallic nanoparticles: microbial synthesis and unique properties for biotechnological
applications, bioavailability and biotransformation, Crit. Rev. Biotechnol. 35 (2015)
114–128.
[48] K. Vijayaraghavan, T. Ashokkumar, Plant-mediated biosynthesis of metallic nanopar-
ticles: a review of literature, factors affecting synthesis, characterization techniques
and applications, J. Environ. Chem. Eng. 5 (2017) 4866–4883.
[49] N. Zikalala, K. Matshetshe, S. Parani, O.S. Oluwafemi, Biosynthesis protocols for
colloidal metal oxide nanoparticles, Nano-Struct. Nano-Obj. 16 (2018) 288–299.
[50] A.C. Lokhande, P.T. Babar, V.C. Karade, J.S. Jang, V.C. Lokhande, D.J. Lee,
I.C. Kim, S.P. Patole, I.A. Qattan, C.D. Lokhande, J.H. Kim, A viable green route
to produce Ag nanoparticles for antibacterial and electrochemical supercapacitor appli-
cations, Mater. Today Chem. 14 (2019) 100181. https://doi.org/10.1016/j.mtchem.
2019.07.003.
[51] X. Chen, H.J. Schluesener, Nanosilver: a nanoproduct in medical application, Toxicol.
Lett. 176 (1) (2008) 1–12, https://doi.org/10.1016/j.toxlet.2007.10.00.
[52] J.S. Kim, E. Kuk, K.N. Yu, J.H. Kim, S.J. Park, H.J. Lee, S.H. Kim, Y.K. Park, Y.H.
Park, C.Y. Hwang, Y.K. Kim, Y.S. Lee, D.H. Jeong, M.H. Cho, Antimicrobial
effects of silver nanoparticles, Nanomed. Nanotechnol. Biol. Med. 3 (1) (2007)
95–101.
[53] T.C. Dakal, A. Kumar, R.S. Majumdar, V. Yadav, Mechanistic basis of antimicrobial
actions of silver nanoparticles, Front. Microbiol. 7 (2016) 183, https://doi.org/10.
3389/fmicb.2016.01831.
[54] M.A. Raza, Z. Kanwal, A. Rauf, A.N. Sabri, S. Riaz, S. Naseem, Size- and
shape-dependent antibacterial studies of silver nanoparticles synthesized by wet chemical
routes, Nanomaterials (Basel) 6 (4) (2016) 74. https://doi.org/10.3390/nano6040074.
PMID: 28335201; PMCID: PMC5302562.
[55] K.C. Hembram, R. Kumar, L. Kandha, P.K. Parhi, C.N. Kundu, B.K. Bindhani,
Therapeutic prospective of plant-induced silver nanoparticles: application as antimicro-
bial and anticancer agent, Artif. Cells Nanomed. Biotechnol. 46 (Suppl. 3) (2018)
S38–S51, https://doi.org/10.1080/21691401.2018.1489262.
[56] M. Rai, A. Yadav, A. Gade, Silver nanoparticles as a new generation of antimicrobials,
Biotechnol. Adv. 27 (1) (2009) 76–83. https://doi.org/10.1016/j.biotechadv.2008.
09.002.
[57] A. Roy, O. Bulut, S. Some, A.K. Mandal, M.D. Yilmaz, Green synthesis of silver
nanoparticles: biomolecule-nanoparticle organizations targeting antimicrobial activity,
RSC Adv. 9 (2019) 2673–2702. https://doi.org/10.1039/C8RA08982E.
[58] S. Ahmed, M. Ahmad, B.L. Swami, S. Ikram, A review on plants extract mediated syn-
thesis of silver nanoparticles for antimicrobial applications: a green expertise, J. Adv.
Res. 7 (1) (2016) 17–28. https://doi.org/10.1016/j.jare.2015.02.007.
[59] S. Gurunathan, J.W. Han, D.N. Kwon, J.H. Kim, Enhanced antibacterial and anti-
biofilm activities of silver nanoparticles against Gram-negative and Gram-positive
bacteria, Nanoscale Res. Lett. 9 (1) (2014) 373. https://doi.org/10.1186/1556-
276X-9-373.
[60] M.K. Rai, S.D. Deshmukh, A.P. Ingle, A.K. Gade, Silver nanoparticles: the powerful
nanoweapon against multidrug-resistant bacteria, J. Appl. Microbiol. 112 (5) (2012)
841–852, https://doi.org/10.1111/j.1365-2672.2012.05253.x.
Green synthesized silver nanoparticles 609

[61] P.P.N. Vijay Kumar, S.V.N. Pammi, P. Kollu, K.V.V. Satyanarayana, U. Shameem,
Green synthesis and characterization of silver nanoparticles using Boerhaavia diffusa plant
extract and their antibacterial activity, Ind. Crop Prod. 52 (2014) 562–566. https://doi.
org/10.1016/j.indcrop.2013.10.050.
[62] H.H.M. Ibrahim, Green synthesis and characterization of silver nanoparticles using
Banana Peel extract and their antimicrobial activity against representative microorgan-
isms, J. Radiat. Res. Appl. Sci. 8 (2015) 265–275. https://doi.org/10.1016/j.jrras.
2015.01.007.
[63] R. Mariselvam, A.J.A. Ranjitsingh, A. Usha Raja Nanthini, K. Kalirajan,
C. Padmalatha, P. Mosae Selvakumar, Green synthesis of silver nanoparticles from
the extract of the inflorescence of Cocos nucifera (Family: Arecaceae) for enhanced
antibacterial activity, Spectrochim. Acta A Mol. Biomol. Spectrosc. 129 (2014)
537–541, https://doi.org/10.1016/j.saa.2014.03.066.
[64] A. Nanda, M. Saravanan, Biosynthesis of silver nanoparticles from Staphylococcus aureus
and its antimicrobial activity against MRSA and MRSE, Nanomedicine 5 (4) (2009)
452–456, https://doi.org/10.1016/j.nano.2009.01.012.
[65] M. Saravanan, S.K. Barik, D. MubarakAli, P. Prakash, A. Pugazhendhi, Synthesis of
silver nanoparticles from Bacillus brevis (NCIM 2533) and their antibacterial activity
against pathogenic bacteria, Microb. Pathog. 116 (2018) 221–226. https://doi.org/
10.1016/j.micpath.2018.01.038.
[66] A.M. Elgorban, A.N. Al-Rahmah, S.R. Sayed, A. Hirad, A.A.F. Mostafa, A.H. Bahkali,
Antimicrobial activity and green synthesis of silver nanoparticles using Trichoderma viride,
Biotechnol. Biotechnol. Equip. 30 (2) (2016) 299–304. https://doi.org/10.1080/
13102818.2015.1133255.
[67] S.H. Kim, H.S. Lee, D.S. Ryu, S.J. Choi, D.S. Lee, Antibacterial activity of
silver-nanoparticles against Staphylococcus aureus and Escherichia coli, Korean J. Microbiol.
Biotechnol. 39 (1) (2011) 77–85.
[68] M.A. Ansari, H.M. Khan, A.A. Khan, A. Malik, A. Sultan, M. Shahid, F. Shujatullah,
A. Azam, Evaluation of antibacterial activity of silver nanoparticles against MSSA and
MRSA on isolates from skin infections, Biol. Med. 3 (2) (2011) 141–146.
[69] J. Li, K. Rong, H. Zhao, F. Li, Z. Lu, R. Chen, Highly selective antibacterial activities
of silver nanoparticles against bacillus subtilis, J. Nanosci. Nanotechnol. 13 (10) (2013)
6806–6813. 10.1166jnn.2013.7781.
[70] J.L. Elechiguerra, J.L. Burt, J.R. Morones, A. Camacho-Bragado, X. Gao, H.H. Lara,
M.J. Yacaman, Interaction of silver nanoparticles with HIV-1, J Nanobiotechnol. 3
(2005) 6. https://doi.org/10.1186/1477-3155-3-6.
[71] R.W.Y. Sun, R. Chen, N.P.Y. Chung, C.M. Ho, C.L.S. Lin, C.M. Che, Silver
nanoparticles fabricated in HEPES buffer exhibit cytoprotective activities toward
HIV-1 infected cells, Chem. Commun. 40 (2005) 5059–5061. https://doi.org/10.1039/
B510984A.
[72] A.M. Abdelgawad, S.M. Hudson, O.J. Rojas, Antimicrobial wound dressing nano-
fiber mats from multicomponent (chitosan/silver-NPs/polyvinyl alcohol) systems,
Carbohydr. Polym. 100 (2014) 166–178. https://doi.org/10.1016/j.carbpol.
2012.12.043.
[73] A.A.A. Aljabali, Y. Akkam, M.S. Al Zoubi, K.M. Al-Batayneh, B. Al-Trad,
O.A. Alrob, A.M. Alkilany, M. Benamara, D.J. Evans, Synthesis of gold nanoparticles
using leaf extract of ziziphus zizyphus and their antimicrobial activity, Nanomaterials 8
(3) (2018) 174. https://doi.org/10.3390/nano8030174.
[74] J. Puišo, D. Jonkuviene, I. Macioniene, J. Šalomskiene, I. Jasutiene, R. Kondrotas,
Biosynthesis of silver nanoparticles using lingonberry and cranberry juices and their anti-
microbial activity, Colloids Surf. B Biointerfaces 121 (2014) 214–221. https://doi.org/
10.1016/j.colsurfb.2014.05.001.2014.
610 Samson Oluwagbemiga Alayande et al.

[75] C. Kamaraj, G. Balasubramani, C. Siva, M. Raja, V. Balasubramanian, R.K. Raja,

S. Tamilsevan, G. Benelli, P. Peruma, Ag nanoparticles synthesized using β-caryophyllene
isolated from Murraya koenigii: antimalarial (Plasmodium falciparum 3D7) and anticancer
activity (A549 and HeLa cell lines), J. Clust. Sci. 28 (2017) 1667–1684. https://doi.
org/10.1007/s10876-017-1180-6.
[76] P.P. Dutta, M. Bordoloi, K. Gogoi, S. Roy, B. Narzary, D.R. Bhattacharyya, P.K.
Mohapatra, B. Mazumder, Antimalarial silver and gold nanoparticles: green synthesis,
characterization and in vitro study, Biomed. Pharmacother. 91 (2017) 567–580.
https://doi.org/10.1016/j.biopha.2017.04.032.
[77] G. Chitra, G. Balasubramani, R. Ramkumar, R. Sowmiya, P. Peruma, Mukia mad-
eraspatana (Cucurbitaceae) extract-mediated synthesis of silver nanoparticles to control
Culex quinquefasciatus and Aedes aegypti (Diptera: Culicidae), Parasitol. Res. 114
(2015) 1407–1415. https://doi.org/10.1007/s00436-015-4320-7;.
[78] P. Rajasekharreddy, P.U. Rani, Biofabrication of Ag nanoparticles using Sterculia foetida
L. seed extract and their toxic potential against mosquito vectors and HeLa cancer cells,
Mater. Sci. Eng. C 39 (2014) 203–212. https://doi.org/10.1016/j.msec.2014.03.003.
[79] A. Ayg€ un, F. G€ ulbagça, M.S. Nas, M.H. Alma, M.H. Çalımlı, B. Ustaoglu,
Y.C. Altunoglu, M.C. Baloglu, K. Cellat, F. Şen, Biological synthesis of silver nano-
particles using Rheum ribes and evaluation of their anticarcinogenic and antimicrobial
potential: a novel approach in phytonanotechnology, J. Pharm. Biomed. Anal. 179
(2020), 113012. https://doi.org/10.1016/j.jpba.2019.113012.
[80] D. Nayak, S. Pradhan, S. Ashe, P.R. Rauta, B. Nayak, Biologically synthesised silver
nanoparticles from three diverse family of plant extracts and their anticancer activity
against epidermoid A431 carcinoma, J. Colloid Interface Sci. 457 (2015) 329–338.
https://doi.org/10.1016/j.jcis.2015.07.012.
[81] L.P. Kojom Foko, F. Eya’ane Meva, C.E. Eboumbou Moukoko, A.A. Ntoumba,
M.I. Ngaha Njila, P. Belle Ebanda Kedi, L. Ayong, L.G. Lehman, et al., A systematic
review on anti-malarial drug discovery and antiplasmodial potential of green synthesis
mediated metal nanoparticles: overview, challenges and future perspectives, Malar. J. 18
(2019) 337. https://doi.org/10.1186/s12936-019-2974-99.
[82] WHO, World Malaria Report 2019, 2019, [Internet]. Available from www.who.int/
malaria/publications/world-malaria-report-2019/en/%0D.
[83] M. Rai, A.P. Ingle, P. Paralikar, I. Gupta, S. Medici, C.A. Santos, Recent advances
in use of silver nanoparticles as antimalarial agents, Int. J. Pharm. 526 (1–2) (2017)
254–270. https://doi.org/10.1016/j.ijpharm.2017.04.042.
[84] A. Jaganathan, K. Murugan, C. Panneerselvam, P. Madhiyazhagan, D. Dinesh, C.
Vadivalagan, A.T. Aziz, B. Chandramohan, U. Suresh, R. Rajaganesh, J. Subramaniam,
M. Nicoletti, A. Higuchi, A.A. Alarfaj, M.A. Munusamy, S. Kumar, G. Benelli,
Earthworm-mediated synthesis of silver nanoparticles: a potent tool against hepatocellular
carcinoma, Plasmodium falciparum parasites and malaria mosquitoes, Paramed. Int.
65 (3) (2016) 276–284, https://doi.org/10.1016/j.parint.2016.02.003.
[85] H. Chugh, D. Sood, I. Chandra, V. Tomar, G. Dhawan, R. Chandra, Role of gold and
silver nanoparticles in cancer nano-medicine, Artif. Cells, Nanomed. Biotechnol.
46 (sup1) (2018) 1210–1220, https://doi.org/10.1080/21691401.2018.1449118.
[86] X. Yan, B. He, L. Liu, G. Qu, J. Shi, L. Hu, G. Jiang, Antibacterial mechanism of silver
nanoparticles in: Pseudomonas aeruginosa: proteomics approach, Metallomics 10 (2018)
557–564. https://doi.org/10.1039/C7MT00328E.
[87] M.S. Mufamadi, R.B. Mulaudzi, Green engineering of silver nanoparticles to
combat plant and foodborne pathogens: potential economic impact and food quality,
in: R. Prasad (Ed.), Plant Nanobionics, Nanotechnology in the Life Sciences,
Springer, Cham, 2019, ISBN: 978-3-030-16378-5. https://doi.org/10.1007/978-
3-030-16379-2_16.
Green synthesized silver nanoparticles 611

[88] S. Rajeshkumar, L.V. Bharath, Mechanism of plant-mediated synthesis of silver

nanoparticles—a review on biomolecules involved, characterisation and antibacterial
activity, Chem. Biol. Interact. 0009-2797, 273 (2017) 219–227. https://doi.org/10.
1016/j.cbi.2017.06.019.
[89] C. Greulich, J. Diendorf, T. Simon, G. Eggeler, M. Epple, M. K€ oller, Uptake and intra-
cellular distribution of silver nanoparticles in human mesenchymal stem cells, Acta
Biomater. 7 (1) (2011) 347–354. https://doi.org/10.1016/j.actbio.2010.08.003.
[90] E.J. Park, J. Yi, Y. Kim, K. Choi, K. Park, et al., Toxicol. In Vitro 0887-2333,
24 (3) (2010) 872–878. https://doi.org/10.1016/j.tiv.2009.12.001.
[91] S. Gurunathan, K.J. Lee, K. Kalishwaralal, S. Sheikpranbabu, R. Vaidyanathan,
S.H. Eom, Antiangiogenic properties of silver nanoparticles, Biomaterials 30 (31)
(2009) 6341–6350, https://doi.org/10.1016/j.biomaterials.2009.08.008.
[92] P.V. AshaRani, M.P. Hande, S. Valiyaveettil, Anti-proliferative activity of silver
nanoparticles, BMC Cell Biol. 10 (2009) 65, https://doi.org/10.1186/1471-
2121-10-65.
[93] S.K. Verma, A.K. Das, M.K. Patel, A. Shah, V. Kumar, S. Gantait, Engineered
nanomaterials for plant growth and development: a prospective analysis, Sci. Total
Environ. 630C (1413) (2018) 1435. https://doi.org/10.1016/j.scitotenv.2018.02.313.
[94] T. Khare, U. Oak, V. Shriram, S.K. Verma, V. Kumar, Biologically synthesized nano-
materials and their antimicrobial potentials, Compr. Anal. Chem. 87 (2019) 263–289.
https://doi.org/10.1016/bs.coac.2019.09.002.
[95] G. Tan, S. I_ lk, E. Ezgi, S. Mesut, A. Serap, B. Emre, A. Elif, Y. Ozfer, S.K. Verma,
G. Ekrem, S. Necdet, Green synthesis and biogenic materials, characterization, and their
applications, in: R. Prasad (Ed.), Microbial Nanobionics. Nanotechnology in the Life
Sciences, Springer, Cham, 2019. https://doi.org/10.1007/978-3-030-16383-9_2.