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Materials Today: Proceedings

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A review on the toxicity of silver nanoparticles on human health

Tamanna Jaswal, Jasmine Gupta
Department of Chemistry, University Institute of Science, Chandigarh University, Mohali, Chandigarh, Punjab 140413, India

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

Article history: Silver nanoparticles are generally used in various products due to their distinctive and antibacterica
Available online xxxx activities. Nanosilver are used in electronics bio-sensing, clothing, cosmetics, sunscreen and medical
devices but a large numbers of in vitro shows that AgNPs has toxic effects on various cultured mammalian
Keywords: cells. In this paper I reviewed about the toxicity effect of silver nanoparticles(AgNPs) on humans Health.
Nanoparticles In addition we studied to which content the silver ion fraction contribute the toxicity to cells. However by
Silver nanoparticles green formation of silver nanoparticles(AgNPs) the toxicity of silver nanoparticles can be reduced. More
Green synthesis
studies and research is required that confer AgNPs at lower toxicity only then their use would be proved
Human health
useful in several industry biomedical contexts and for human health also. The ambition or goal of this
review is to estimate the literature on the toxicity of silver nanoparticles. The aim of this review to inspire
more studies in the field of toxicity of nanoparticles of silver or silver nanoparticles.
Ó 2021 Elsevier Ltd. All rights reserved.
Selection and peer-review under responsibility of the scientific committee of the International Virtual
Conference on Sustainable Materials (IVCSM-2k20).

1. Introduction nanoparticles used in dental work, surgery applications,wounds,h

Nanoparticles are defined as particles with structural dimen-
sion of 100 nm or less[12] Use of nanoparticles are increasing
day by day because of its unique and physicochemical properties
but there are many research and evidence which show the adverse
effect of nanoparticles towards human health and environment[3].
In today’s era the use of nanotechnology increase nanoparticles
technology also used in food system to increase the nutritional
value but it also have some adverse effects diagrammatic view of
benefits and adverse effect of nanotechnology fig: 1[4]
some studies shows that nanoparticles can pass the cell mem-
branes and also interact with the biological system due to the
strong oxidative activity[5] silver nanoparticles (AgNPs) after pass-
ing the cell membranes and release ther ions of silver into the cell
these ions has side effects on the biological system these ions
induced genotoxicity[6] ,cyctotoxicity[76] and even death of the
cell.A study tells that the nanoparticles of TiO2Induce ROS which
leads protein dysfunt ,degradational of DNA and oxidative damage
in the mouse brain[5]. Therfore the toxicity of nano particles
became a matter of concern for human health and environment
that is why there is a need of research and some procedure to
ensure the saftey from nanoparicles.Silver nanoparticles (AgNPs)
are used most generally used due to its antibacterial or antimi-
crobal activity (Jun Sun [8,1].Application of nanoparticles of silver
are in environmental, biomedical and industrial area (S.P [9]. silver
oudeshold appliances ,odor resistant textials , food procressing,
food packaging, food safety, cosmetic and various biomedical
devices [10,11,12]. but there is some adverse effect of silver nano
particles.Some studies shows that liver and lungs are main destina-
tion or target tissue for prolonged AgNPs exposure [13].
AgNPs can damage the cell viability of human hepatoma cell
[14].Lungs can easily damage by nanoparticles. The process by
which AgNPs enter to the cell is endocytosis and diffusion .Oxida-
tive stress caused because inside the cell, in the cytoplasm the sil-
ver nanoparticles ionized Ag± And start formation of ROS and these
species caused oxidative stress [5]AgNPs cause DNA damage, apop-
tosis, genotoxicity and chromosome aberration. In a study it is
found that silver nanoparticle can have genotoxic effects. In vitro
and in vivo studies both gave positive result on genotoxicity[15]
some studies also examined that silver nanoparticles are also
harmful for environment (C.A. [16] because of its reactivity and
surface area when it exposure to environment then various trans-
formation occur which is difficult for environment.[17].
2. Synthesis of silver nanoparticles
Nanoparticles or nanomaterials are synthesized by chemicals
physicals and biological method.AgNPs used widely due to the anti
bacterical properties of silver. For the preperation of silver

https://doi.org/10.1016/j.matpr.2021.04.266
2214-7853/Ó 2021 Elsevier Ltd. All rights reserved.
Selection and peer-review under responsibility of the scientific committee of the International Virtual Conference on Sustainable Materials (IVCSM-2k20).

Please cite this article as: T. Jaswal and J. Gupta, A review on the toxicity of silver nanoparticles on human health, Materials Today: Proceedings, https://doi.
org/10.1016/j.matpr.2021.04.266
T. Jaswal and J. Gupta
nanoparticles there are two method first one is top to down
approach and one more approach is bottom to top[18],[19],20 .
Nanoparticles and nanosilver are synthesized by taking bulk mate-
rial in top to bottom approach where as in bottom to top method
nanoparticles are synthesized on the basis of their packing of par-
ticles[2122].by phyochemicals methods AgNPs can also be pre-
pared. AgNPs can be prepared by photochemical reduction,
microwave, electrochemicals and by chemicals reduction however
there is limitation in both physical and chemicals methods of for-
mation of AgNPs because the synthesized NPs are very short lived
and the process of formatation is very costly[23]. Over physical and
chemical methods the green synthesis of silver nanoparticlesis
more advanced and.green synthesis is environmental friendly ,less
costly as compare to the both chemical and physical methods. In
green synthesis of silver nanoparticles there is no requirement of
high pressure, maximum temperature and harmfull chemical So
many articles has been reported till now on the green synthesisof-
nanosilver (AgNPs). In Biological synthesis microorganism includ-
ing fungi bacteria or plants are used for the making of silver
nanoparticles because of their reducing proprerties. These reduc-
ing properties are capable for the reduction of metals compounds
into nonaparticles ,Due to the non– toxicity or low biohazard and
process of cell culture maintaining .Plant extract is used is used
for this process over microoraginism .Various biomolecules which
are present in plant extract like Amino acids ,enzymes ,alkaloids,
tannins phenolics, proteins , vitamins and polysaccharides increase
the medicinal values of silver nanoparticles during the process of
reduction and stabilization of ions by plant extracts[24]. silver
nanoparticles synthesized by Acorus Calamus has antibacterical
antioxidant and anticancer effects[25].Nanoparticles of silver can
be produced by Seaweed (Gracilariabiridial)and these nanoparticles
has antibacterial effect[26].There are several benefits of silver
nanoparticles which are synthesized by plants extract, these bene-
fits are protection of environment and human health ,less costly
and energy efficiency[27] Fig. 1. is the green or biological synthesis
of nanoparticles (silver nanoparticles) [28] Figs. 2 and 3.
3. Cytotoxicity of silver naoparticles
Humans exposed to AgNPs by dermal contact ,inhalation, oral
administration and blood circulation[29], (Niels [13] For in vivo
and in vitro experiments of toxicity of nanoparticles there are many
paper and publication are published which show that the toxicity
of silver nanoparticles upon there concentrations environmental
factors, size and expsore time[5].Larger silver nanoparticles is less
cytotoxic as compare to small silver nanoparticles because of its
Fig. 1. Uses and risks of nanotechnology (Noel.N, 2020).
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higher surface area per unit mass and due to the higher realese
of Ag± ion the cytotoxity of silver nanoparticle at sizer lager than
10 nm dominate by the direct interaction of silver nanoparticle-
sand macrophage[30]. Size 10 to 100 nm and conc. Range 5 to 10
mgmL 1 of silver nanoparticles is very much toxic to the mitochon-
drial functions accourding to in vivo experiments[31,32].
in vitrostudies also tells us that silver nanoparticles affect the
reproduction,morphological deformities and non mammalian ani-
mals[33]. There are many paper which assumed thatAgNPs cross
the cell membrane and also mitochondria but there is no evidence
weather AgNPs enter to the organelle To oxidative damage or
AgNPs directly interact with mitochondria. Silver nanoparticles
can affect the respiratory chain of mitchondria ,producing ROS
and affecting the ATP, DNA damage. silver nanoparticles are toxic
to human also . Factor that effect the cyotoxicity of silver nanopar-
ticles are surface chemistry crystallinity, shape, size, capping agent.
Ionic strength, ph, presence of complexing agents all these envi-
ronmental factor also effect the toxicity of AgNPs[34].The nanopar-
ticles of silver also effects the proliferation. Not human but
naonosilver are also toxic to animals some studies shows that sil-
ver nanoparticles has 50% high toxicity than chrysolite asbestos.
Nanoparticles of silver accumulate in the testes by crossing blood
barrier and affect the sperm cells[35].In a research silver nanopar-
ticles are appeared in different organ of mice like kidney liver lungs
heart and brain the appearance of nanoparticles of silver shows
that brain blood barrier are penetrated bye nanoparticles (AgNPs)
(SCG. [36]. In a research of the harmful effects of silver nanoparti-
cles to the photosynthesis action of algae is studied the result of
this study is that the coating of protein did not stimulate toxicity
but the consumption of silver naoparticles and release of Ag + ion
cause photosynthes reduction[37].
3.1. Damage to cell membrane
Silver nanoparticles cause damage and toxicity by interacting
with cell membranes although silver has antimicrobial properties
because they can interact with bacterial membrane or surface.
Intraction with bacterial membrane depends upon the pH and Nacl
concentration .for this interaction surface charge is very important
but in vitro studies it is found that silver nanoparticles cause dam-
ages in cell membranes of mammalian cells [38].It is found that
cell membrane is disrupts and through oxidative damages apopto-
sis caused .Calcium influx is allows due to the damage of fibroblast
membranes this damages also caused potential variation in mito-
chondrial membranes overproduction of Reactive Oxygen Species
[33]
T. Jaswal and J. Gupta
Fig. 2. Green or biological process for synthesis of silver nanoparticles [28]. (For interpretation of the references to colour in this figure legend, the reader is referred to the
web version of this article.)
3.2. Silver nanoparticles’s uptake
Silver nanoparticles consumed different cells (Joel N. [39,40]and
also by human body by different path ways like oral, dermal, res-
piratory ways [17] Consumption of silver nanoparticles is done
by diffusion, endocytosis and phagocytosis method . uptaking pro-
cess may be differ for different cell. AgNPs can uptake by phago-
cytic and non phagocytic ways in macrophages cell, uptake
depends upon the cell types and size of silver nanoparticles[5].
Human skin uptake the AgNPs is depends upon their shape, size
and incubation time . cell membrane is penetrate by the spherical
and cylindrical or rod formed silver nanoparticles and uptake
depends upon the incubation time[41]. HepG2 cell line was exam-
ined under different concentration of both silver nanoparticles and
silver ion (Ag±) after experimental period of 24 h the uptake
amount of silver nanoparticles examined by measuring silver con-
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tent in digested cell . it is found that at 1 mg/L concentration of
AgNPs the content of intracellular silver is low as compare to the
content silver at 10 mg/L concentration of silver nanoparticles. It
is also found that cellular uptake of both AgNPs and Ag±are simi-
lar[14].
4. Production of ROS (Reactive oxygen species)
Silver nanoparticles toxicity is connected to the over production
of ROS. ROS is requisite for the normal physiological activities but
extreme production of ROS can damages the DNA [42,43]lipids and
proteins and also extreme productionof ROS can crash the antiox-
idant defense system[44].In the study of harmfull effect of silver
nanoparticles in liver cells and primary fibroblast it is found that
the silver nanoparticles activate the antioxidant mechanisms in
mitochondria[31].there is many publication which shows the cor-
T. Jaswal and J. Gupta
Fig. 3. Possible consumption and cytotoxicity of silver nanoparticles in cell [5].
relation between ROS level and mitochondrial damage. In a study
small nanopartciles of silver produce ROS and cause apoptosis in
stem cell of mouse [45]. Mitochondria release ROS this ROS leads
the oxidative stress, disturbance in synthesis of ATP, damage the
DNA and apoptosis [46].Due to the ROS level increase the level of
GSH decrease and at the same time LDH increase which leads
Apoptosis[47].In intracellular level redox homeostasis is affected
by the generation of ROS as a result there is caused of protein car-
bonylation and lipids peroxidation and gulatathione level decrease
and also antioxidant enzymes activity are decreased which leads
the apoptosis hence the cytotoxicity of silver nanoparticles is apop-
tosis mediated and cell death[5]. In a study of HepG2 Cell line it is
found that the HepG2 cell has adverse effect of silver nanopartciles
. silver nanoparticles affect the cell viability and LDH membrane
leakage it is also found that both silver nanoparticle and ionic sil-
ver decrease the viability of HepG2 cells. At higher concentration
the AgNPs is very toxic to the cell[14].
5. Interaction between silver nanoparticles and proteins
Interaction between proteins and nanoparticles of silver is
major phenomena of toxicity of silver nanoparticles this interac-
tion studied by many researcher [48]Interaction between silver
nanoparticles and human blood protein hemoglobin was also stud-
ied and by using spectroscopic methods cytoskeletal proteins has
been also studied hemoglobin has been examined with silver nano
particles which are ime and con. Dependent silver nanoparticles
interact or bind to heme amide and tryptopham.afterbinding the
hemoglobin b-sheet structure increases and hb start unfolding
charge complex is formed by AgNPs –Hb in this complex formation
of Hb –AgNPs assembled structure and Hb – AgNPs along with sil-
ver nanoparticles involved in mechanism of electron transfer. The
probable binding residues in hemoglobinwithsilvernanoparticles
like amide group and was revealed by Raman spectroscopy and
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by FTIR[49]. In a study some researcher investigate that serum pro-
teins ,albumin and Keratins react with nanoparticles of silver
(AgNPs), PVP and Citrate coated nanoparticles shows higher bind-
ing Quality than small nanoparticles of silver (JH [50] .
6. Conclusion and future perspectives
The application of silver nanoparticles are increasing day by day
in consumer products due to there antibacterial properties there-
fore number of research paper and review articles on the uses
and synthesis of silver nanoparticles but there is very few publica-
tions on the toxicity of silver nanoparticles. There are many ques-
tion that is remain to be answered like, which form of silver
contribute more toxicity silver nanoparticles or ionic silver in this
paper we discussed about the size of particles toxicity and mecha-
nism of toxicity. Small size of silver nanoparticles contribute mare
toxicity than larger AgNPs. In this review paqper it is clear that sil-
ver nanoparticle penetrate the cell membrane. They target the cell
membrane and harm the DNA by ROS. Silver nanoparticles also
react with the proteins. So it is necessary to be examined how sil-
vernanoprticles produce toxicity. Only when we are able to find the
method for reducing the toxicity of silver nanoparticles . but
another fact is that silver nanoparticles have antibacterial proper-
ties because of that it is the first choice for antibacterial application
in future. The aim of this review paper is to inspire more research
in the field of toxicity of silver nanoparticles.
CRediT authorship contribution statement
Tamanna Jaswal: Conceptualization, Methodology, Software,
Writing - review & editing. Jasmine Gupta: Data curation, Writing
- original draft.
T. Jaswal and J. Gupta
Declaration of Competing Interest
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
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