Journal of Molecular Liquids 334 (2021) 116040

Contents lists available at ScienceDirect

Journal of Molecular Liquids

journal homepage: www.elsevier.com/locate/molliq

Nanoparticles: Mechanism of biosynthesis using plant extracts, bacteria,

fungi, and their applications
Safi Ur Rehman Qamar a,b,⇑, Jam Nazeer Ahmad a
a
Integrated Genomics, Cellular, Developmental, and Biotechnology Laboratory (IGCDBL), University of Agriculture, Faisalabad 38000, Punjab, Pakistan
b
Applied Biological Sciences Program, Chulabhorn Graduate Institute, 54 Kamphaeng Phet 6 Road, Lak Si, Bangkok 10210, Thailand

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

Article history: The synthesis of eco-friendly nanoparticles (NPs) is a crucial step in nanotechnology. In recent years, to
Received 5 February 2021 avoid environmental contamination, many efforts have been made many efforts are made to develop
Revised 25 March 2021 green methods for this purpose. For this reason, natural resources including plant extract, fungi and bac-
Accepted 30 March 2021
teria have been used to synthesize NPs. Plant extract contains active compounds of terpenoids, alkaloids,
Available online 6 April 2021
phenols, tannins, and vitamins that act as capping and reducing agents. The size, shape and applications
of NPs are determined by the source from which they are manufactured. While active compounds of bac-
Keywords:
teria and fungi are intracellular enzymes, sugar molecules, canonical membrane proteins, Nicotinamide
Green synthesis
Nanoparticles
Adenine Dinucleotide (NADH) and Nicotinamide Adenine Dinucleotide Phosphate (NADPH) dependent
Chemical composition enzymes play a crucial part as reducing agents. The characterization of NPs can be done by Fourier-
Medical applications Transform Infrared Spectroscopy (FTIR), X-ray Crystallography (XRD), Energy-dispersive X-ray
Antimicrobial application Spectroscopy (EDX), Scanning Electron Microscope (SEM), Transmission Electron microscopy (TEM)
and UV–Visible spectroscopy. This review paper elaborates major natural resources with detailed mech-
anisms involved in NPs synthesis and their few applications in biomedical science, life science and
electronics.
Ó 2021 Elsevier B.V. All rights reserved.

1. Introduction reduction [9], microemulsion [10], electrochemical [11], micro-

Nanotechnology refers to the depiction, assembly and structure
used to control the size of nanoparticles (NPs) and nanomaterials
[1]. Nanotechnology was introduced by a Japanese scientist named
Taniguchi [2]. Since then, it has become part of several fields such
as electronics, biotechnology, material science, and engineering
[3]. Nanotechnology and green chemistry are now considered as
an interdisciplinary approach that has extended the range of bio-
logically and cytogenetically compatible metal NPs [4]. NPs of size
from 1 nm to 100 nm are referred to as bridges between bulk mate-
rials and atomic-scale material [5]. Nanoscale material has extraor-
dinary distinct properties compared to bulk material. These
peculiarities are due to their physical, chemical properties and
the surface to volume proportion of nano molecules [6].
Broadly, there are two main methods of NPs synthesis. Firstly,
chemical synthesis of NPs which involves photochemical (use of
photons of light) [7], physiochemical (c-radiation) [8], chemical
⇑ Corresponding author at: Integrated Genomics, Cellular, Developmental, and
Biotechnology Laboratory (IGCDBL), University of Agriculture, Faisalabad 38000,
Punjab, Pakistan.
E-mail address: ranasafi73@gmail.com (S.U.R. Qamar).
wave irradiation [12], and laser ablation [13]. All these methods
yield a high number of NPs with limitations due to their toxic
ingredients, costly and labour-intensive equipment. Among these
methods, the chemical reduction method is commonly used for
NPs synthesis. Various chemicals such as tollens, polyethylene gly-
col, sodium borohydride, sodium citrate and elemental hydrogen
act as reducing agents in an aqueous medium. These reducing
compounds reduce metal ion (M+) into their metallic form (M0),
which forms clusters of NPs [14].
Secondly, green or biosynthesis is an efficient process that uses
natural compounds as capping, stabilizing, and reducing agents
instead of expensive toxic chemicals. Due to this fact, researchers
adapt biosynthetic methods [15,16]. There are several reasons for
this preference. Firstly, biologically synthesized NPs possess
unique physicochemical properties than that of chemically synthe-
sized NPs [17]. Secondly, this method is comparatively cheaper and
human friendlier than the chemical method that utilizes expensive
chemicals [18]. These chemicals are toxic to humans, animals and
particularly to the environment. Therefore, most experts call green
synthesis the bottom-up approach, which replaced chemicals with
plant extract (roots, leaves, fruit, and fruit peel) [19–21]. Thirdly,

https://doi.org/10.1016/j.molliq.2021.116040
0167-7322/Ó 2021 Elsevier B.V. All rights reserved.
Safi Ur Rehman Qamar and Jam Nazeer Ahmad
Nomenclature
NPs Nanoparticles
XRD X-ray Crystallography
AuNPs Gold Nanoparticles
AgNPs Silver Nanoparticles
FTIR Fourier-Transform Infrared Spectroscopy
HILIC Hydrophilic Interaction Chromatography
EDX/EDAX Energy-Dispersive / X-ray Spectroscopy
the biogenic approach allows us to recycle metallic salts that con-
taminate water supplies [22,23].
Regardless of the number of research publications that use the
top-down approach, the synthesis of gold nanoparticles (AuNPs)
and silver nanoparticles (AgNPs) are extensively studied in terms
of applications and biosynthesis compared to other metallic NPs.
NPs have a broad application spectrum due to their unique attri-
butes, i.e., size and shape. NPs are actively used in the field of
biomedical science (i.e., imaging, drug delivery, quick diagnosis,
medical equipment, and tissue regeneration) [24–26], textile
industry [27], packing food product [28], catalysis [29], cosmetic
industry [30], sensor [31], biological sciences [32], antimicrobial
[33], optoelectronics [34], plasmonics [35], DNA sequencing [36],
bioremediation [37] and electronic devices [37].
We chose bacterial, plant and fungi-based biosynthesis for this
review because it is cheaper and safer than chemical synthesis.
Furthermore, due to environmental concerns, many scientists are
shifting towards a greener approach for NPs synthesis. The reason
for this shift is that the by-products of plants, bacterial and fungal
secretions, if released in the environment they degrade easily.
While on the contrary, various chemical or by-products of chemi-
cal synthesis, if released by chance in the environment, results in
bioaccumulation and biomagnification. This review presents an
up-to-date overview of several semiconductors and metallic NPs,
including Fe, Ag, Au, CuO, ZnO, and TiO2, with a focus on their
biosynthesis and application. This review provides comprehensive
information of all three biological methods in one combination,
unlike other review articles that provide a single set of
information.
2. Mechanism of NPs synthesis
Broadly, NPs are synthesized by following two dominant
approaches; the first one is the bottom-up approach (BUA) and
the second one is the top-down approach (TDA) [38]. In the
bottom-up approach, NPs synthesis is carried out using biopoly-
mers and smaller active compounds present in plant extract and
microorganism’s secretions [39]. Conversely, in the top-down
approach, the bulk of NPs are size-reducing products of various
photochemical reactions during the bottom-down approach, which
further breaks into nano-sized particles. For understanding the
synthesis approaches, a graphical view is represented here in Fig. 1.
Both reaction mechanisms follow the same chemistry of reduc-
tion and oxidation (Fig. 2). In general, the perfection of homogene-
ity and fewer defects are observed in many biogenic reactions, i.e.,
BUA [40]. Further, plant extract’s active compounds serve as a cap-
ping agent that stabilizes NPs for a long time [41].
3. Plant-based synthesis
The plant-based green synthesis technique is widely adopted as
compared to the others. The plants are easy to find and biologically
2
Journal of Molecular Liquids 334 (2021) 116040
TEM Transmission Electron Microscopy
SEM Scanning Electron Microscope
DLS Dynamic Light Scattering Microscopy
NMR Nuclear Magnetic Resonance Spectroscopy
safer than the microorganism and fungi-mediated synthesis. Both
involve a lengthy process of cell culture [42,43]. Plant extract con-
tains active compounds of terpenoids, alkaloids, phenols, tannins,
and vitamins known for their use in therapeutic and environmen-
tal values [44]. These compound’s basic building blocks are simple
hydrocarbon, monoterpenoids, isoprenoids, carotenoids, sesquiter-
penoids, turpentine, and sterol. Metabolites of these small molecu-
lar blocks form complex metabolites such as phytol tail in
chlorophyll [45]. Due to the presence of these valuable compounds,
NPs synthesized from plants are more stable. These compounds
can cap NPs, crucial for aggregation, inhibition and growth termi-
nation [41]. In addition, they are determinants of the size and
shape of NPs due to difference in reducing ability.
AgNPs were first synthesized using Alfalfa sprout as a living sys-
tem. The roots possess the ability to absorb Ag from agar growth
media and to transport it to shoot without changing its oxidation
state. In stem, atoms of Ag are arranged in a manner to form AgNPs
[46]. Velmurugan et al. (2015) synthesized AgNPs from the extract
of a peanut shell [47]. These AgNPs acted as an antifungal agent
when compared with commercial AgNPs. The characterization
was done via FTIR, UV–Vis, XRD, and TEM. It was observed that
the shape looks like an oval in size range from 10 nm to 50 nm.
Benelli et al. synthesized AuNPs using lemongrass extract [48].
Their study provided evidence that these NPs help control early-
stage dengue and malarial mosquito larvae at a 1 ppm dose. Simi-
larly, another study was carried out by researchers in which AgNPs
were synthesized from Artemisia annua extract. Their research pro-
vided evidence that AgNPs at a low dose have larvicidal activity
against Aedes aegypti [49].
Punica granatum peel extract synthesized AgNPs was tested
against cotton pest Spodoptera litura [50]. They observed the low
activation energy of gut enzymes, including amylases, lipases, pro-
teases, and invertase. Microflora on gut and enzyme synthesis was
decreased at LC50 of 19.21 mg per larva. Alagesan and Venugopal
(2019) synthesized selenium nanoparticles using Withania som-
nifera extract and tested their antibacterial activity against Staphy-
lococcus aureus, Bacillus subtilis, and Klebsiella pneumoniae. They
also tested them against A549 cells and observed the anti-
proliferative ability of SeNPs. The LC50 for bacteria and A549 cells
was 14.81 lg/mg and 25 lg/ml, respectively [51].
Cu, Ag, ZnO, TiO2, and Fe3O4 nanoparticles were synthesized by
Alavi et al. (2019) [52]. All these NPs acted as antibacterial, antiox-
idant Antiquorum sensing, and antibiofilm agents against Staphylo-
coccus aureus (ATCC 43300), Escherichia coli (ATCC 25922) and
Pseudomonas aeruginosa (ATCC 27853). They characterized NPs
using XRD, FESEM, UV–vis spectroscopy, and FT-IR techniques.
Sabouri et al. synthesized NiO NPs using Okra plant extract [53].
They characterized these NPs via TIR, XRD, UV–Vis, FESEM, EDX,
TGA/DTA, and VSM. The size was between 15 and 52 nm. NiO
NPs acted as an antibacterial against S. aureus, E. coli, and P. aerug-
inosa. Moreover, they observed that these NPs also acted as neuro-
toxic agents when applied to neuro2A cells. They concluded that
plant-based synthesis produces pure and small-sized particles
Safi Ur Rehman Qamar and Jam Nazeer Ahmad Journal of Molecular Liquids 334 (2021) 116040

Fig. 1. Graphical Representation of Techniques used in NP synthesis.

Fig. 2. Summary for the biosynthesis of nanoparticles (1) Biomolecules are found in plant extract or secreted by bacteria or fungi act as capping and reducing agents. These
molecules are sugar, carbohydrate, enzymes, and proteins, which reduce metallic ions from (M+) to (M0) via oxidation/reduction mechanism. (2) Reduced metallic form
aggregates and creates clusters of NPs that can be confirmed through the reaction mixture by changing color.

favorable in various environmental and antibacterial applications. 4. Bacterial based synthesis

Further studies are listed in Table 1 with their synthesis method,
characterization, application, and target organism.
Most of the studies supported the synthesis of NPs using plant
extracts. However, based on our literature analysis, we came across
several issues and limitations which hinder the plant-based syn-
thesis. These limitations include flaws in technicality and engi-
neering approach. The ratio of plant extract and chemical
solution was the primary factor that affects the size of NPs and sta-
bility. Additionally, economic constraints were associated with
plant extract’s purity, chemical solutions, reliable product achieve-
ment with good yield, stoichiometric regent’s ratio, and most
importantly, characterization and applications. Moreover, lack of
life cycle assessment, limitations in process engineering, and oper-
ation stability are considered significant issues.
There are two methods reported for the synthesis of NPs; the
Intracellular method and the extracellular method [85]. However,
the exact mechanistic process is still not fully known. Studies sug-
gest that the formation of NPs occurs in the following manner;
firstly, the metal ion is trap either on the surface or inside the bac-
terial cell. Secondly, this ion undergoes a reduction reaction when
it is catalyzed by bacterial enzymes [86]. The extracellular method
is given more preference due to the easy harvest and purification
process of NPs as compared to the intracellular method. Bacteria
synthesize extracellular and intracellular material, which acts as
a reducing agent mixed with Ag or Au solution to form NPs
[32,87]. These reducing agents are intracellular enzymes, sugar
molecules, canonical membrane proteins and biochemical path-

3
Safi Ur Rehman Qamar and Jam Nazeer Ahmad Journal of Molecular Liquids 334 (2021) 116040

Table 1
List of plant-based synthesized NPs and their application.

Source Plant Species NPs Preparation Mixture Characterization Size Application Target Organism/Cell Reference
Type
Tropaeolum majus L Ag 1 mM AgNO+3 Extract (1:9) UV–Vis, XRD, 38– Antibacterial Pseudomonas aeroginosa [54]
FTIR, SEM, TEM 82 nm
Camellia Sinensis 0.1 mol/L AgNO+3
Extract 4–50 nm Antibacterial S. aureus [55]
(1:1)
Ferula gumosa, Ferula 1 mM AgNO+3 Extract (3:1) 20– Antibacterial E. Coli, S. aureus [56]
latisecta, Teucrium 80 nm
polium, Trachomitum
venetum
Juniperus procera 1 mM 30– Antibacterial B. subtilis, Candida albicans, Proteus [57]
AgNO3(98.5 mL) + Extract 90 nm mirabilis, Micrococcus luteus,
(0.5 mL) K. pneumoniae
Holoptelea integrifolia 2 mM 32– Anti-diabetic, E. Coli, S. typhimurium [58]
AgNO3(50 mL) + Extract 38 nm Antibacterial,
(100 mL) Anti-
inflammatory
Prosopis farcta fruit 0.001 M AgNO3 + Extract 11– Antioxidant, S. aureus (Britol A9596), S. typhi (PTCC [59]
(1:3) 15 nm antibacterial 1609), S. pneumoniae (NCTC 7465),
E. Coli (ATCC 25922)
Piper longum L. 1 mM 28.8 nm Antioxidant, HeLa cells, [60]
AgNO3(45 mL) + Extract Anti-cancer, Anopheles stephensi, Aedes aegypti,
(5 mL) Anti-larvicidal Culex quinquefasciatus
Artocarpus heterophyllus TiO2 0.5 M TTIP 15– Anticancer, HeLa cells, [61]
solution + Extract (4:1) 20 nm Cytotoxic, E. Coli (ATCC 25922), S. aureus (ATCC
Antibacterial 12228), S. typhimurium (ATCC 14028),
B. subtilis (ATCC 14579)
Lippia citriodora 5 mM TiCl4 solution 20– Treatment of Wistar [62]
(80 mL) + Extract (20 mL) 40 nm brain injury Han (Gravid rats), uterus embryos
(E18- E19)
Citrus sinensis (Orange 1 M TiCl4 solution 20– Anti-cancer, A549 cell lines, S. aureus, E. Coli, P. [63]
peel) (100 mL) + Extract (10 mL) 50 nm Cytotoxic, aeruginosa
Antibacterial
Musa alinsanaya TiO2 bulk particles 31.5 nm Larvicidal, Musca domistica, Bacillus sp., S. aureus, [64]
(Banana Peel) solution (5 mL) + Extract () antibacterial Streptococcus sp., Staphylococcus
epidermidis
Ricinus communis Au 1 mM HAuCl4

3H2O 40– Antimicrobial, Splenic Cells, Hela and HepG2 cell [65]
(1 mL) + Extract (99 mL) 80 nm Anti-cancer lines
Solidago canadensis Ag, 1 mM HAuCl4
xH2O and 100– Cytotoxicity H4IIE-luc and HuTu-80 cells [66]
Au, AgNO3 (500 mL 300 nm
Ag- separately) + Extract
Au (50 mL)
Anacardium occidentale Au 0.01 M HAuCl4 10– Antibacterial, MCF-7 cells, PBMC cells, E. Coli, B. [67]
(20 mL) + Extract (1 mL) 60 nm Anti-cancer subtilis
Dracocephalum kotschyi 1 mM HAuCl4 5–21 nm Anti-cancer H1229 and MCF-7 cancer cell lines [68]
(90 mL) + Extract (10 mL)
Euphorbia peplus 1 mM HAuCl4

3H2O 50 nm Anti-cancer, Hela and HepG2 cell lines, E. Coli, P. [69]
(1 mL) + Extract (99 mL) Antibacterial, mirabilis, S. aureus, S. flexneri, Candida
Insecticidal albican, Culex pipiens
Trianthema ZnO 3  10-2 M ZnSO4 solution UV–Vis, XRD, 25– Cytotoxic, MC3T3-E1 cell line, S. aureus, E. Coli, [70]
portulacastrum (25 mL) + Extract (10 mL) FTIR, SEM, TEM, 90 nm Antibacterial, Aspergillus niger, Aspergillus fumigatus,
XPS Antifungal, Aspergillus flavus
Antioxidant
Matricaria chamomilla 1 M ZnO solution + Extract UV–Vis, XRD, 40.5– Antibacterial Xanthomonas oryzae pv. (GZ 0003) [71]
L., Lycopersicon (1:1) FTIR, SEM, TEM, 124 nm
esculentum M., Olea EDS
europaea
Punica granatum Zn(NO3)2
6H2O UV–Vis, XRD, 32.98– Cytotoxic, E. Coli, Enterococcus faecalis [72]
solution + Extract (10:1) FTIR, SEM, TEM 81.84 nm Antibacterial
Rheum turketanicum 8 mM zinc (II) nitrate 17– Cytotoxic WEHI 164 murine fibrosarcoma cells [73]
hexahydrate solution 20 nm
(60 mL) + Extract (40 mL)
Tecoma castanifolia 1 mM ZnSO4 70– Antibacterial, A549 cell lines, E. Coli, [74]
(90 mL) + Extract (10 mL) 75 nm Antioxidant, P. aeruginosa
Anti-cancer
Silybum marianum 1 M ZnSO4 (2 mL) + Extract 31.2 nm Antifungal, Artemia salina, S. epidermidis, B. subtilis, [75]
(100 mL) Antibacterial, Klebsiella pneumonia, E. Coli, P.
Cytotoxic aeruginosa, S. marianum
Cucurbita seeds 0.1 M Zn(CH3COO)2
2H2O 45– Larvicidal, Culex tritaeniorhynchus, E. coli, Bacillus [76]
(90 mL) + Extract (10 mL) 65 nm Antibacterial, pumilus, Salmonella typhi, Aspergillus
Antifungal flavus, Aspergillus niger
Ruellia tuberosa CuO CuSO4 solution + Extract UV–Vis, XRD, 83.23 nm Antibacterial, S. aureus, K. pneumoniae, E. Coli [77]
(1:1) FTIR, SEM, TEM, Protection for
EDX textile fabric

4
Safi Ur Rehman Qamar and Jam Nazeer Ahmad Journal of Molecular Liquids 334 (2021) 116040

Table 1 (continued)

Source Plant Species NPs Preparation Mixture Characterization Size Application Target Organism/Cell Reference
Type
Tilia Platyphyllos 5 mM CuCl2
2H2O UV–Vis, XRD, 30 nm Reusable Water molecules [78]
(20 mL) + Extract (80 mL) FTIR, SEM, TEM Catalyst, Water
purification
Ocimum tenuiflorum 0.2 M Cu(CH3COO)2 20– Antibacterial S. mutans, E. coli, P. vulgaris. S. aureus [79]
solution 30 nm
(100 mL) + Extract (20 mL)
Moringa oleifera 0.01 M Cu(CHO) HO 35– Antifungal Aspergillus niger, C. albicans, [80]
solution + Extract (1:1) 95 nm Trichophyton mentographytes,
Aspergillus clavatus, Epidermophyton
floccosum.
Platanus orientalis Fe2O3 Fe(NO3)3
9H2O power 38 nm Antifungal Aspergillus niger, Mucor piriformis [81]
(1 g) + Extract (10 mL)
Rhus punjabensis FeCl3 solution + Extract 41– Disease control, S. aureus, Bacillus subitilis, P. [82]
(1:1) 46 nm Anti-cancer aeruginosa, E. coli, HL-60 leukemic
cancer cell lines, DU-145 prostate
cancer cell lines
Moringa oleifera FeO 0.5 M FeCl3 solution 15– Antibacterial E. coli, Shigella, P. aeruginosa, [83]
(80 mL) + Extract (20 mL) 21 nm Pasteurella, Salmonella typhi, S. aureus
Ruellia tuberosa 1 M FeSO4 solution 20– Antibacterial, K. pneumoniae, E. coli, S. aureus [84]
(50 mL) + Extract (50 mL) 80 nm Water
purification

ways. For instance, it was reported that cofactors, Nicotinamide
Adenine Dinucleotide (NADH) and NAD-phosphate (NADPH)
dependent enzymes, play a crucial part in reducing agents. NADH
transfers enzyme under the influence of NADH dependent
enzymes and becomes an electron carrier.
Researchers carried out the synthesis of AuNPs following the
extracellular pathway in Rhodopseudomonas capsulate bacterium
[88]. Bacteria secreted NADH and NADPH enzymes which carried
out the electron transfer process. We created schematic illustra-
tions of both intracellular and extracellular mechanisms of bacte-
rial medicated NPs synthesis and presented them in Figs. 3 and
4, respectively. It was observed that bacteria aggregated on Ag
and created biomass [89]. Bacterial use was recommended by Poo-
ley in 1982 in an industry where Ag leaching occurs because it
accumulates Ag in their cell wall very efficiently. In 1999, for the
first-time, Pseudomonas stutzeri (AG259) were used to synthesize
AgNPs. The amount of AgNPs which were accumulated in the bac-
terial cell was 200 nm [90]. According to Klaus et al. work, Ag accu-
mulates in the cell membrane because of its association with H2S
gas conversion. Through this conversion, bacteria make H2S gas
nontoxic to itself. Further, nitrate reductase and cofactor perform
the central role in the bioreduction of AgNPs in Bacillus licheni-
formis. A recent study confirmed that the reductase enzyme and
catalytic proteins are involved in the synthesis and reduction of
AgNPs [91].
Bacterial growth was reported good even after AgNPs synthesis
while comparing with chemical methods [92]. In a conventional
chemical method, bacterial growth and the reduction process were
slower. Extracellular AgNPs synthesis was carried out using the
extract of Pantoeaananatis sp., an endophytic bacterium [93]. Abi-
naya et al. (2018) used exopolysaccharide (EPS) of Bacillus licheni-
formis to synthesize ZnO [94]. These bacterial based NPs have
shown antifungal and antibiofilm activity. Furthermore, it also
has demonstrated larvicidal activity against Zika and Malaria virus
vectors. Few recent studies in which bacteria species were used as
a source to synthesize NPs are listed in Table 2.
Although bacterial-based NPs synthesis provides a significantly
good product, there are several drawbacks associated with the pro-
duction we want to highlight here. Firstly, the purification of NPs
from bacteria involves tiresome steps with poor understating of
some mechanistic aspect. Secondly, the major challenge among
all the above-reported studies was controlling the size and shape
5
of the NPs for achieving the suspension solution phase. Our analy-
sis found that some technical challenges must be surmounted
before carrying out NPs synthesis using bacteria. Lastly, the most
critical challenge is the industrial-scale production and processing
of NPs. More reliable information is needed in this regard for the
rational and economic development of NPs.
5. Fungi based synthesis
The synthesis of NPs using a fungus can occur via two processes,
i.e., Extracellular, and intracellular methods. Metallic precursors in
fungal culture filtrate in extracellular method, which contain
metabolites and enzymes secreted by fungal cells [115]. These
metabolites include griseofulvin, mevastatin, cyclosporine, and
lovastatin [116]. The redox enzymes found in fungi are ACCases,
NADH, NADPH and peroxidases [117]. These agents reduce metal-
lic ion to the reduced metallic form resulting in the production of
NPs. While in the intracellular method, the metallic precursor is
added to fungal mycelia culture. In both cases, NPs need to be puri-
fied to eliminate any remaining fungal by-products via simple fil-
tration, chemical washing or centrifuge [118]. A general scheme
of NPs synthesis in fungal cells is presented in Fig. 5.
The extracellular process of AgNPs formation was reported in
Macrophomina phaseolina [119]. Ag ion, which was reduced by
extracellular redox proteins, was present on the cell wall’s surface.
Another study of Verticillium species medicated NPs synthesis
reported that cell wall proteins and sugars reduced Au+3 ions. Fur-
ther, they suggested that the cell wall enzymes absorbed AuCl-4
via electrostatic interaction with the help of positively charged
lysine [120]. While in the intracellular synthesis of NPs, it was
reported that Au3+ ions crossed the cell membrane via ion channels
and then reduced by cytosolic redox enzymes [121]. Nevertheless,
it is not evident that either this path utilized energy or not.
Biomass of Epicoccum nigrum fungus was used to synthesize
AgNPs [122]. These NPs acted as antifungal agents when applied
to pathogenic fungus, Cryptococcus neoformans and Sporothrix
schenckii. The characterization was done using XRD, SEM, and
UV–vis spectroscopy. The size of the AgNPs was 1–22 nm. El-
Sayyed et al. (2018) used Penicillium chrysogenum as a biomass
source for MgO NPs synthesis. Their study provided insight into
the antibacterial properties of these NPs against multidrug-
resistant bacteria [123]. Castro-Longoria et al. (2011) synthesized
Safi Ur Rehman Qamar and Jam Nazeer Ahmad
Fig. 3. Intracellular mechanism of AgNPs synthesis in bacterial cell. Bacteria uptake M+ ion via the outer membrane, reduced to its M0 stage by nitrate reductase enzyme
under NADH’s influence.
AuNPs and AgNPs using filaments of Neurospora crassa. The size of
AuNPs and AgNPs was 11 nm and 32 nm, respectively. They
reposted that this fungus can synthesize NPs via both extracellular
and intracellular mechanisms [124]. Recently, reported fungal spe-
cies which are capable of synthesizing NPs are listed in Table 3.
Even though these NPs are efficient in their applications, several
problems need to be solved before practical application in various
science fields. One important thing is to have a stable shape and
size of NPs for desired applications. However, controlling the
shape, size and surface properties has not yet been solved. Further-
more, the downstream processing of NPs is quite tricky as these
fungal species are challenging to handle. The studies mention in
Table 3 provided an insight that some of these problems can be
solved. For example, specific parts of fungal culture have the ability
from which we can obtain specific shape and size of NPs. Fungal
biomass culture yielded spherical shaped NPs that were stable
trough out the experiment. In addition to that, culture condition
optimization such as incubation time, medium, biomass activity,
reaction time and concentration of chemical was used to control
the shape and size of NPs.
6. Application of NPs
NPs can be used in different ways because of the peculiar prop-
erties. Some of the vital applications of biosynthesized NPs are dis-
cussed in this section.
6
Journal of Molecular Liquids 334 (2021) 116040
6.1. Application in the biomedical and pharmaceutical industry
NPs, either complex or simple, have distinct physicochemical
properties, which is why nanodevices are now used in the
biomedical and pharmaceutical industries [138]. Their capability
to deliver drugs in an optimum range increased therapeutic’s
efficiency and enhanced patient compliance. Iron oxide NPs
are most commonly used for pharmacological applications
[139]. In addition to that, iron oxide NPs can be employed in
MRI, tissue repair, hyperthermia, immunoassay, cell suspension,
and drug delivery due to their super magnetic ability. For these
applications, mainly 80–100 nm-sized NPs with super magneti-
zation is required [140].
Cell imaging and photo-thermal therapeutics depend on the
optical properties of NPs. For calculating the optical resonance
and scattering ability of NPs, the discrete dipole approximation
method and Mie theory are used for Si-AuNPs and AuNPs [141].
Over the last several years, hydrophilic NPs were employed as drug
carriers. The most efficient NPs are polyethylene oxide NPs [142].
NPs, which are synthesized from metal, can diagnose, and kill can-
cer cells. Surface plasmon resonance of NPs traps energy, which
can be exploited using photo-laser thermal therapy for cancer
[143]. Also, NPs can restrict the growth of bacterial infection and
tumor cells. Fe, Ag, Au, CuO, ZnO, and TiO2 NPs are used as antimi-
crobial/antifungal agents to restrict the growth of pathogenic fun-
gus and bacteria with mortality [144,145].
Safi Ur Rehman Qamar and Jam Nazeer Ahmad
Fig. 4. Extracellular mechanism of NPs synthesis in bacteria. The outer membrane of bacteria trapped the metal ion (M+) and reduced it to its M0 form by using multiple
enzymes, including reductase and NADPH. (Modified with permission from [162]).
6.2. Application of NPs in environment, energy production and
electronic industry
The most common problem the world facing is water contami-
nation due to heavy metals and precipitates. Because of the
surface-to-mass ratio, NPs play a vital role in water purification
by binding with debris, precipitates, and heavy metal [146]. This
binding depends on the morphology, composition, and absorbency
of NPs. The environmental application of NPs comes under three
categories. Firstly, making environmentally safe products via green
chemistry to prevent pollution [147]. Secondly, the bioremediation
of environmental contaminants [148]. Thirdly, NPs as sensors to
identify the change in environmental stages [149].
TiO2 NPs are an effective photocatalytic agent used in water
treatment. These NPs are explored to filter out the organic contain-
ments from various water reservoirs [150]. Iron oxide (FeO) NPs
have gained attention due to their ability to bioremediate heavy
metals such as lead, mercury, arsenic, cadmium, and thallium from
water [151]. In addition to bioremediation, photodegradation by
NiO and ZnO NPs have also been practiced [152,153]. The efficient
photodegradation was due to nano-sized NPs (10–50 nm) [154].
This research group also reported the synthesis of various NPs
7
Journal of Molecular Liquids 334 (2021) 116040
(i.e., ZnO, Au, SiO2, and NiO) with their degradation, optical and flu-
orescence application [155].
Solar energy is very environmentally friendly because it helps in
reducing CO2 emission alongside producing electric energy. Practi-
cally solar energy is harvested using solar power plants and solar
cells to fulfil energy demand [156]. Previously, the absorption
capacity of fluid present in solar devices was low and was a critical
issue. However, now with the help of nanotechnology, it is
resolved because NPs replaced the fluid. These NPs provide an
enormous surface area to trap and store solar energy efficiently
[157]. Soon, it is predicted that NPs incorporated solar devices to
trap solar energy would be more efficient than today.
In electronics, due to high demand, electronic metallic NPs have
become an essential part now. In these devices, NPs work as elec-
tronic molecules that provide a bright display. Ceramics based NPs
are primarily used in this industry due to their rapid flow rate
[158]. Peculiar shape, electrical and optical properties of NPs lead
them to create semiconductors, sensors, and photonic material
from them [159]. The ability of reversible assembly and facile
manipulation of NPs allows them to incorporate into electronic
devices. The benchmark in nanotechnology is the bottom-up
approach of NPs synthesis.
Safi Ur Rehman Qamar and Jam Nazeer Ahmad Journal of Molecular Liquids 334 (2021) 116040

Table 2
List of bacterial-based synthesized NPs and their application.

Source Bacterial NPs Source Component Characterization Size Application Target Organism/Cell Reference
Species Type for Preparation
Lactobacillus casei Au Glycolipids of the SEM, HILIC chromatography, 14–20 nm Industrial mass N/A [95]
cell membrane Mass spectroscopy, NMR, TEM production
Lactobacillus casei Membrane SEM, Mass spectroscopy, NMR, 7–56 nm metal recycling, Contaminated water [96]
diglycosyl TEM phytoremediation
diacylglycerols
Streptomyces spp. Supernatant SEM, TEM, UV–Vis- 50–100 nm Antifungal Microphyton gypseumI, [97]
spectroscopy, EDX, XRD, FTIR, Trichophyton rubrum
Spirulina maxima Polysaccharide EDAX 16–23 nm C. albicans [98]
Lactobacillus casei Se mitochondrial Nrf2 SEM, TEM, FTIR, XPS, EDX 50–80 nm Cytotoxicity, NCM460 cells, HepG2 cells [99,100]
(ATCC 393) signaling pathway Antioxidant,
Anticancer
Pseudomonas Supernatant SEM, TEM, EDS 100–500 nm Catalyse reduction N/A [101]
putida
(KT2440)
Lactobacillus Ag SEM, TEM, UV–Vis- 8–26 nm Antibacterial Multidrug-resistant [102]
paracasei spectroscopy, EDX, XRD, FTIR, bacteria
Serratia spp EDAX 1–100 nm NPs Synthesis N/A [103]
Serratia 10–31 nm Antibacterial B. subtilis, P. aeruginosa, K. [104]
nematodiphila planticola
Actinobacteria 4–45 nm B. subtilis, S. aureus, E. Coli, [105]
(CGG11n) K. pneumoniae, P.
aeruginosa, Proteus
mirabilis, Salmonella infanti
Streptomyces 9–20 nm P. aeruginosa [106]
parvus (Al-
Dhabi-91)
Streptomyces 12–20 nm Antibacterial, S. pneumoniae [107]
olivaceus Biomedical (ATCC49619), Streptococcus
(MSU3) application mutant (NCIM2063), E. Coli
(ATCC25922), K.
pneumoniae (ATCC10273),
Enterobactor faecalis
(ATCC29212)
Oscillatoria 3–18 nm Anticancer, human breast (MCF-7) cell, [108]
limnetica Antibacterial human colon cancer cell
(HCT-116), E. Coli, Bacillus
cereus
Endophytic Bacterial biomass 83–176 nm Antibacterial E. Coli, Klebsiella [109]
bacteria pnuemoniae
Bacillus Co Bacterial 80–170 nm Antimalarial, anti- Anopheles subpictus, Aedes [110]
thuringiensis suspension culture dengue, larvicidal aegypti
Pseudomonas ZnO Supernatant 20–46 nm Antibacterial, Bacillus cereus [111]
putida Antibiofilm (MCC 2039), Pseudomonas
oleovorans
(MCC 2566), Pseudomonas
otitidis (MCC 2509),
Enterococcus
faecalis (MCC 2041),
Acinetobacter baumannii
(MCC 2366)
Bacillus haynesii 20–100 nm Antibacterial E. Coli (ATCC35218), S. [112]
aureus (ATCC29213)
Aeromonas 20–57 nm Antibacterial, P. aeruginosa, Aspergillus [113]
hydrophila Antifungal flavus
Streptomyces spp. Fe 65–86 nm Antibacterial, B. subtilis, E. Coli, S. aureus, [114]
Biomedical Shigella flexneri, K.
application pneumoniae

Recently, several studies warned about the energy crisis due to
the overuse of fossil fuels. For this reason, researchers are now
focusing on the production of renewable, cheap energy sources.
They started to take an interest in NPs as it is the most reliable
source for this purpose due to their vast surface area, optical and
catalytic properties. Several studies found that NPs generate
energy via photo-electrochemical and electrochemical water
splinting mechanism [160 161]. Several other applications of NPs
based on data presented in the table are illustrated in Fig. 6.
7. Conclusion and future considerations
In conclusion, due to environmental concerns, the biosynthesis
of NPs is preferred. The utilization of waste material, plant extract,
biopolymers, bacteria, and fungus are an efficient and eco-friendly
way to synthesize NPs. Active compounds in plant extract, includ-
ing terpene, alkaloids, phenols, and tannins, act as reducing agent.
In bacteria and fungus, NADH and NADPH dependent enzymes play
a crucial part as reducing agents. NADH transfers enzyme under

8
Safi Ur Rehman Qamar and Jam Nazeer Ahmad Journal of Molecular Liquids 334 (2021) 116040

Fig. 5. Schematic mechanism of NPs synthesis in the typical fungal cell. Fungal cells are capable of synthesizing NPs in both ways intracellular and extracellular pathways. (a)
In the extracellular pathway, metallic ions are (M+) reduced to their neutral state M0 using membrane redox proteins (ACCases). (b) On the other hand, in the intracellular
pathway, metallic ion first enters cell using membrane ion channels and then reduced to its neutral state by activating intracellular redox proteins (NADPH). (Modified with
permission from [163])

Table 3
List of fungal-based synthesized NPs and their application.

Source Fungi Species Type Source Component Characterization Size Application Target organism/cell Reference
of NP for Preparation
Piriformospora indica Ag Fungal biomass UV–Vis 1–30 nm Anticancer MCF-7 cell line, HeLa [125]
spectroscopy, TEM, cell line, HepG2 cell
SEM, FTIR, XRD, line
Penicillium duclauxii EDAX, XRD, EDS, 3–32 nm Antifungal B. sorghicola [126]
Tritirachium oryzae W5H DLS 12–22 nm Antibacterial S.Epidermidis, S. aureus, [127]
E. coli, E. aerogenes
Aspergillus fumigatus Fungal protein 10–34 nm Antibacterial, E. coli, B. mycoides, C. [128]
(DSM819) Anticancer albicans, HCT116 cells,
A549 cells, MCF7 cells,
PC3 cells
Ganoderma lucidum Fungus extract 15–22 nm Antibacterial E. Coli, P. aeruginosa, S. [129]
aureus, B. cereus L.
pneumophila subsp.
Pneumophila, E. hirae
Penicillium oxalicum Supernatant 25–67 nm S. dysenteriae, S. aureus, [130]
Salmonella typhi
Fusarium keratoplasticum, ZnO 8–38 nm Antibacterial, B. subtilis, S. aureus, P. [131]
Aspergillus niger Anticancer aeruginosa, E. Coli,
colorectal
adenocarcinoma cell
line
Thermophilic fungus Au 11–17 nm NPs synthesis N/A [132]
Fusarium solani Fungal biomass 40–45 nm Anticancer, cervical cancer cells (He [133]
Biomedical La), human breast
application cancer cells (MCF-7)
Aspergillus flavus TiO2 fungal ball of mycelia 12–15 nm Growth control in Vigna radiata L. [134]
plants
Aspergillus flavus Mycelium 62–74 nm Antibacterial E. Coli [135]
Trichoderma spp. CuO Mycelial extract 10–190 nm Anticancer, human lung carcinoma [136]
A549 cancer cells
Aspergillus oryzae Se Fungal biomass 45–70 nm Antibacterial, A. calcoaceticus, S. aurus, [137]
Antifungal C albicans, A. flavus

9
Safi Ur Rehman Qamar and Jam Nazeer Ahmad
Fig. 6. Other Applications of NPs.
the influence of NADH dependent enzymes and becomes an elec-
tron carrier. All these active compounds provide capping NPs,
which are responsible for stability. Biosynthesis is a simple and
easy method of using biological resources. This method seems
promising as compared to the chemical method. This review pro-
vides a multidisciplinary spectrum of NPs synthesis using biologi-
cal resources and a few applications.
However, several aspects might be considered for the future
production of NPs from their reported biological methods.
(1) Selection of plant, bacterial and fungal species: To achieve
the specific size and maximum purity of NPs, researchers
should focus on intrinsic properties of plant extract, growth
rate and enzymatic activity of bacteria and fungi. Most
importantly, the mechanism by which specific species of
fungi and bacteria synthesize NPs and the application point
of view for these NPs.
(2) Selection of fungal and bacterial catalysis state: From the
literature, we found that bacteria and fungi have biocata-
lysts that act as a capping agent in NPs synthesis. There-
fore, cell supernatant could be used to enhance the
reaction rate and production yield. Most of the studies
reported that reduction reactions are responsible for NPs
synthesis, which use coenzymes. These enzymes can be
recycled in cells; therefore, using the whole cells might
be preferable.
(3) Extracting and purifying NPs from fungi and bacteria:
Methods for purification and extraction of synthesized NPs
are not well investigated. There is a need to focus on detailed
methodological extraction and purification process. Several
steps involving extraction and purification can utilize ultra-
sound waves or add detergent to eliminate the bacterial and
10
Journal of Molecular Liquids 334 (2021) 116040
fungal biomass to acquire pure NPs. Additionally, physico-
chemical methods that include heating, freezing, thawing,
and osmotic shock can help extract synthesized NPs from
cells. However, it may interfere with the NPs structure, i.e.,
precipitation and aggregation.
(4) Upscale production: Industrial scale production can be
achieved by optimizing laboratory reaction conditions to
enhance NPs yield. Biological methods can produce NPs
while considering the type of organisms, their genetic and
inheritable properties, and optimal conditions for enzymatic
activities. Morphological characteristics can be controlled by
changing the reaction conditions.
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.
Acknowledgement
We want to thank two anonymous reviewers, Mayer L. Calma
from the University of Philippines, and Nisanart Charoenlap from
Chulabhorn Research Institute, for valuable suggestions that
helped us in improving the quality of the manuscript.
Appendix A. Supplementary material
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.molliq.2021.116040.
Safi Ur Rehman Qamar and Jam Nazeer Ahmad Journal of Molecular Liquids 334 (2021) 116040

References [48] K. Murugan, G. Benelli, C. Panneerselvam, J. Subramaniam, T. Jeyalalitha, D.

Dinesh, M. Nicoletti, J.-S. Hwang, U. Suresh, P. Madhiyazhagan, Exp. Parasitol.
153 (2015) 129.
[1] M. Rafique, I. Sadaf, M.S. Rafique, M.B. Tahir, Artificial cells, Nanomed.
[49] K. Murugan, V. Priyanka, D. Dinesh, P. Madhiyazhagan, C. Panneerselvam, J.
Biotechnol. 45 (2017) 1272.
Subramaniam, U. Suresh, B. Chandramohan, M. Roni, M. Nicoletti, Parasitol.
[2] N. Taniguchi, Proceeding of the ICPE, Tokyo, Japan, 1974, pp. 18–23.
Res. 114 (2015) 3601.
[3] S. Parveen, R. Misra, S.K. Sahoo, Nanomedicine 8 (2012) 147.
[50] R.A. Bharani, S.K.R. Namasivayam, J. Environ. Chem. Eng. 5 (2017) 453.
[4] R. Abdelaziz, D. Disci-Zayed, M.K. Hedayati, J.-H. Pöhls, A.U. Zillohu, B.
[51] V. Alagesan, S. Venugopal, BioNanoScience 9 (2019) 105.
Erkartal, V.S.K. Chakravadhanula, V. Duppel, L. Kienle, M. Elbahri, Nat.
[52] M. Alavi, N. Karimi, T. Valadbeigi, ACS Biomater. Sci. Eng. 5 (2019) 4228.
Commun. 4 (2013) 2400.
[53] Z. Sabouri, A. Akbari, H.A. Hosseini, A. Hashemzadeh, M. Darroudi, J. Cluster
[5] K.N. Thakkar, S.S. Mhatre, R.Y. Parikh, Nanomed.: Nanotechnol. Biol. Med. 6
Sci. 30 (2019) 1425.
(2010) 257.
[54] S. Valsalam, P. Agastian, M.V. Arasu, N.A. Al-Dhabi, A.-K.M. Ghilan, K.
[6] S.K. Srikar, D.D. Giri, D.B. Pal, P.K. Mishra, S.N. Upadhyay, Green Sustainable
Kaviyarasu, B. Ravindran, S.W. Chang, S. Arokiyaraj, J. Photochem.
Chem. 6 (2016) 34.
Photobiol., B 191 (2019) 65.
[7] M.A. dos Santos, L.G. Paterno, S.G.C. Moreira, M.J.A. Sales, SN Appl. Sci. 1
[55] W.R. Rolim, M.T. Pelegrino, B. de Araújo Lima, L.S. Ferraz, F.N. Costa, J.S.
(2019) 554.
Bernardes, T. Rodigues, M. Brocchi, A.B. Seabra, Appl. Surf. Sci. 463 (2019) 66.
[8] A.K. Sharma, B.S. Kaith, U. Shanker, B. Gupta, J. Drug Delivery Sci. Technol. 56
[56] F. Mohammadi, M. Yousefi, R. Ghahremanzadeh, Adv. J. Chem.-Sect. A 2
(2020) 101550.
(2019) 266.
[9] M.G. Guzmán, J. Dille, S. Godet, Int. J. Mater. Metall. Eng. 2 (2008) 91.
[57] E.H. Ibrahim, M. Kilany, H.A. Ghramh, K.A. Khan, S. ul Islam, Saudi J. Biol. Sci.
[10] X. Sun, Q. Qiang, Z. Yin, Z. Wang, Y. Ma, C. Zhao, J. Colloid Interface Sci. 557
26 (2019) 1689.
(2019) 450.
[58] V. Kumar, S. Singh, B. Srivastava, R. Bhadouria, R. Singh, J. Environ. Chem. Eng.
[11] E.E. Elemike, D.C. Onwudiwe, O.E. Fayemi, T.L. Botha, Appl. Phys. A 125 (2019)
7 (2019) 103094.
42.
[59] S. Salari, S. Esmaeilzadeh Bahabadi, A. Samzadeh-Kermani, F. Yosefzaei, J.
[12] N. Pauzi, N.M. Zain, N.A.A. Yusof, Bullet. Chem. React. Eng. Catal. 14 (2019)
Iran, Pharm. Res. 18 (2019) 430.
182.
[60] R. Yadav, H. Saini, D. Kumar, S. Pasi, V. Agrawal, Mater. Sci. Eng., C 104 (2019)
[13] M. Rafique, M.S. Rafique, U. Kalsoom, A. Afzal, S.H. Butt, A. Usman, Opt. Quant.
109984.
Electron. 51 (2019) 179.
[61] A.K.M. Atique Ullah, A.N. Tamanna, A. Hossain, M. Akter, M.F. Kabir, A.R.M.
[14] C.D. De Souza, B.R. Nogueira, M.E.C. Rostelato, J. Alloys Compd. 798 (2019)
Tareq, A.K.M. Fazle Kibria, M. Kurasaki, M.M. Rahman, M.N.I. Khan, RSC Adv. 9
714.
(2019) 13254.
[15] G.S. Dhillon, S.K. Brar, S. Kaur, M. Verma, Crit. Rev. Biotechnol. 32 (2012) 49.
[62] Y. Sun, S. Wang, J. Zheng, J. Photochem. Photobiol., B 194 (2019) 1.
[16] A. Arumugam, C. Karthikeyan, A.S.H. Hameed, K. Gopinath, S. Gowri, V.
[63] A. Mobeen Amanulla, R. Sundaram, Mater. Today:. Proc. 8 (2019) 323.
Karthika, Mater. Sci. Eng., C 49 (2015) 408.
[64] R.S. Hameed, R.J. Fayyad, R.S. Nuaman, N.T. Hamdan, S.A. Maliki, J. Pure Appl.
[17] A. Singh, N. Singh, I. Hussain, H. Singh, S. Singh, Int. J. Pharm. Sci. Invent. 4
Microbiol. 13 (2019) 2241.
(2015) 25.
[65] H.A. Ghramh, K.A. Khan, E.H. Ibrahim, W.N. Setzer, Nanomaterials 9 (2019)
[18] P. Singh, Y.-J. Kim, D. Zhang, D.-C. Yang, Trends Biotechnol. 34 (2016) 588.
18.
[19] L.H. Madkour, Global Drugs Therapeutics 3 (2018).
[66] T.L. Botha, E.E. Elemike, S. Horn, D.C. Onwudiwe, J.P. Giesy, V. Wepener, Sci.
[20] P. Kaur, Biotechnol. Res. Innovat. 2 (2018) 63.
Rep. 9 (2019) 4169.
[21] M.A. Nasseri, M. Shahabi, A. Allahresani, M. Kazemnejadi, Asian J. Green
[67] V. Sunderam, D. Thiyagarajan, A.V. Lawrence, S.S.S. Mohammed, A. Selvaraj,
Chem. 3 (2019) 382.
Saudi J. Biol. Sci. 26 (2019) 455.
[22] P.K. Gautam, A. Singh, K. Misra, A.K. Sahoo, S.K. Samanta, J. Environ. Manage.
[68] A. Chahardoli, N. Karimi, A. Fattahi, I. Salimikia, J. Biomed. Mater. Res. Part A
231 (2019) 734.
107 (2019) 621.
[23] S.K. Sanyal, J. Shuster, F. Reith, Earth Sci. Rev. 190 (2019) 131.
[69] H.A. Ghramh, K.A. Khan, E.H. Ibrahim, Molecules 24 (2019) 1431.
[24] Y. Su, I. Cockerill, Y. Wang, Y.-X. Qin, L. Chang, Y. Zheng, D. Zhu, Trends
[70] Z.U.H. Khan, H.M. Sadiq, N.S. Shah, A.U. Khan, N. Muhammad, S.U. Hassan, K.
Biotechnol. 37 (2019) 428.
Tahir, S.Z. Safi, F.U. Khan, M. Imran, N. Ahmad, F. Ullah, A. Ahmad, M. Sayed,
[25] C. Vissers, G.-L. Ming, H. Song, Adv. Drug Deliv. Rev. 148 (2019) 239.
M.S. Khalid, S.A. Qaisrani, M. Ali, A. Zakir, J. Photochem. Photobiol. B: Biol. 192
[26] K.Y. Choi, H.S. Han, E.S. Lee, J.M. Shin, B.D. Almquist, D.S. Lee, J.H. Park, Adv.
(2019) 147.
Mater. 31 (2019) 1803549.
[71] S.O. Ogunyemi, Y. Abdallah, M. Zhang, H. Fouad, X. Hong, E. Ibrahim, M.M.I.
[27] A. Wahab, M. Imran, M. Ikram, M. Naz, M. Aqeel, A. Rafiq, H. Majeed, S. Ali,
Masum, A. Hossain, J. Mo, B. Li, Artificial Cells Nanomed. Biotechnol. 47
Appl. Nanosci. 9 (2019) 1823.
(2019) 341.
[28] R. Apjok, A.M. Cozmuta, A. Peter, L.M. Cozmuta, C. Nicula, M. Baia, A. Vulpoi,
[72] S.N.A. Mohamad Sukri, K. Shameli, M. Mei-Theng Wong, S.-Y. Teow, J. Chew,
Cellulose 26 (2019) 1923.
N.A. Ismail, J. Mol. Struct. 1189 (2019) 57.
[29] T. Rasheed, F. Nabeel, M. Bilal, H.M. Iqbal, Biocatal. Agric. Biotechnol. 19
[73] S. Nemati, H.A. Hosseini, A. Hashemzadeh, M. Mohajeri, Z. Sabouri, M.
(2019) 101154.
Darroudi, R.K. Oskuee, Mater. Res. Express 6 (2019) 125016.
[30] A.C. Santos, F. Morais, A. Simões, I. Pereira, J.A. Sequeira, M. Pereira-Silva, F.
[74] G. Sharmila, M. Thirumarimurugan, C. Muthukumaran, Microchem. J. 145
Veiga, A. Ribeiro, Expert Opin. Drug Deliv. 16 (2019) 313.
(2019) 578.
[31] N. Wu, A. Yu, L. Zhang, W. Liu, J. Gao, C. Zhang, Y. Zheng, Adv. Mater.
[75] S. Hameed, A.T. Khalil, M. Ali, M. Numan, S. Khamlich, Z.K. Shinwari, M.
Interfaces 6 (2019) 1900732.
Maaza, Nanomedicine 14 (2019) 655.
[32] N. Abdel-Raouf, N.M. Al-Enazi, I.B.M. Ibraheem, R.M. Alharbi, M.M. Alkhulaifi,
[76] K. Velsankar, S. Sudhahar, G. Maheshwaran, M. Krishna Kumar, J Photochem.
Saudi J. Biol. Sci. 26 (2019) 1207.
Photobiol. B: Biol. 200 (2019) 111650.
[33] R. Varghese, M.A. Almalki, S. Ilavenil, J. Rebecca, K.C. Choi, Saudi J. Boil. Sci. 26
[77] S. Vasantharaj, S. Sathiyavimal, M. Saravanan, P. Senthilkumar, K.
(2019) 148.
Gnanasekaran, M. Shanmugavel, E. Manikandan, A. Pugazhendhi, J.
[34] M. Shkir, M.T. Khan, I. Ashraf, S. AlFaify, A.M. El-Toni, A. Aldalbahi, H.
Photochem. Photobiol., B 191 (2019) 143.
Ghaithan, A. Khan, Ceram. Int. 45 (2019) 21975.
[78] B. Khodadadi, A. Yeganeh Faal, A. Shahvarughi, J. Appl. Chem. Res. 13 (2019)
[35] A. Campos, N. Troc, E. Cottancin, M. Pellarin, H.-C. Weissker, J. Lermé, M.
51.
Kociak, M. Hillenkamp, Nat. Phys. 15 (2019) 275.
[79] N.C. Joshi, Y. Prakash, Asian J. Pharm. Clin. Res. 12 (2019) 288.
[36] A.R. Gliga, S. Di Bucchianico, J. Lindvall, B. Fadeel, H.L. Karlsson, Sci. Rep. 8
[80] K. Pagar, S. Ghotekar, T. Pagar, A. Nikam, S. Pansambal, R. Oza, D. Sanap, H.
(2018) 1.
Dabhane, Asian J. Nanosci. Mater. 3 (2020) 15.
[37] O.M. Darwesh, I.A. Matter, M.F. Eida, J. Environ. Chem. Eng. 7 (2019) 102805.
[81] H.S. Devi, M.A. Boda, M.A. Shah, S. Parveen, A.H. Wani, Green Process. Synth. 8
[38] M.-S. Yang, C. Song, J. Choi, J.-S. Jo, J.-H. Choi, B.K. Moon, H. Noh, J.-W. Jang,
(2019) 38.
Nanoscale 11 (2019) 2326.
[82] S. Naz, M. Islam, S. Tabassum, N.F. Fernandes, E.J. Carcache de Blanco, M. Zia, J.
[39] E. Calzoni, A. Cesaretti, A. Polchi, A. Di Michele, B. Tancini, C. Emiliani, J. Func.
Mol. Struct. 1185 (2019) 1.
Biomater. 10 (2019) 15.
[83] S.O. Aisida, N. Madubuonu, M.H. Alnasir, I. Ahmad, S. Botha, M. Maaza, F.I.
[40] C. Yan, T. Yu, C. Ji, D.J. Kang, N. Wang, R. Sun, C.-P. Wong, Adv. Electron. Mater.
Ezema, Appl. Nanosci. 10 (2020) 305.
5 (2019) 1800548.
[84] S. Vasantharaj, S. Sathiyavimal, P. Senthilkumar, F. LewisOscar, A.
[41] H. Veisi, R. Ghorbani-Vaghei, S. Hemmati, M.H. Aliani, T. Ozturk, Appl.
Pugazhendhi, J. Photochem. Photobiol., B 192 (2019) 74.
Organomet. Chem. 29 (2015) 26.
[85] R. Singh, U.U. Shedbalkar, S.A. Wadhwani, B.A. Chopade, Appl. Microbiol.
[42] T. Khan, N. Ullah, M.A. Khan, Z.-U.-R. Mashwani, A. Nadhman, Adv. Colloid
Biotechnol. 99 (2015) 4579.
Interface Sci. 272 (2019).
[86] A. Ramesh, M. Thiripura Sundari, P.E. Thirugnanam, Bio-Nanoparticles, 2015,
[43] R.H. Ahmed, D.E. Mustafa, Int. Nano Lett. 10 (2020) 1.
pp. 53–81.
[44] D. Savoia, Future Microbiol. 7 (2012) 979.
[87] J. Ali, N. Ali, L. Wang, H. Waseem, G. Pan, J. Microbiol. Methods 159 (2019) 18.
[45] Z.-U.-R. Mashwani, M.A. Khan, T. Khan, A. Nadhman, Adv. Colloid Interface
[88] S. He, Z. Guo, Y. Zhang, S. Zhang, J. Wang, N. Gu, Mater. Lett. 61 (2007) 3984.
Sci. 234 (2016) 132.
[89] R.M. Slawson, J.T. Trevors, H. Lee, Arch. Microbiol. 158 (1992) 398.
[46] J.L. Gardea-Torresdey, E. Gomez, J.R. Peralta-Videa, J.G. Parsons, H. Troiani, M.
[90] T. Klaus, R. Joerger, E. Olsson, C.-G. Granqvist, Proc. Natl. Acad. Sci. 96 (1999)
Jose-Yacaman, Langmuir 19 (2003) 1357.
13611.
[47] P. Velmurugan, S. Sivakumar, S. Young-Chae, J. Seong-Ho, Y. Pyoung-In, S.
[91] P. Venkatachalam, M. Jayaraj, R. Manikandan, N. Geetha, E.R. Rene, N.C.
Jeong-Min, H. Sung-Chul, J. Ind. Eng. Chem. 31 (2015) 51.
Sharma, S.V. Sahi, Plant Physiol. Biochem. 110 (2017) 59.

11
Safi Ur Rehman Qamar and Jam Nazeer Ahmad
[92] O.V. Kharissova, H.V.R. Dias, B.I. Kharisov, B.O. Pérez, V.M.J. Pérez, Trends
Biotechnol. 31 (2013) 240.
[93] T. Monowar, M.S. Rahman, S.J. Bhore, G. Raju, K.V. Sathasivam, Molecules 23
(2018) 17.
[94] M. Abinaya, B. Vaseeharan, M. Divya, A. Sharmili, M. Govindarajan, N.S.
Alharbi, S. Kadaikunnan, J.M. Khaled, G. Benelli, J. Trace Elem. Med Biol. 45
(2018) 93.
[95] Y. Kato, E. Yoshimura, M. Suzuki, ChemistrySelect 4 (2019) 7331.
[96] F. Kikuchi, Y. Kato, K. Furihata, T. Kogure, Y. Imura, E. Yoshimura, M. Suzuki,
Sci. Rep. 6 (2016) 34626.
[97] J. Vinay Gopal, M. Thenmozhi, K. Kannabiran, G. Rajakumar, K. Velayutham, A.
A. Rahuman, Mater. Lett. 93 (2013) 360.
[98] S.H.S. Dananjaya, N.T. Thu Thao, H.M.S.M. Wijerathna, J. Lee, M. Edussuriya, D.
Choi, R. Saravana Kumar, Process Biochem. 92 (2020) 138.
[99] C. Xu, L. Qiao, L. Ma, Y. Guo, X. Dou, S. Yan, B. Zhang, A. Roman, Int. J.
Nanomed. 14 (2019) 4491.
[100] C. Xu, L. Qiao, Y. Guo, L. Ma, Y. Cheng, Carbohydr. Polym. 195 (2018) 576.
[101] R. Avendaño, N. Chaves, P. Fuentes, E. Sánchez, J.I. Jiménez, M. Chavarría, Sci.
Rep. 6 (2016) 37155.
[102] E.Z. Gomaa, Int. J. Pept. Res. Ther. 25 (2019) 1113.
[103] C. De Silva, A.A. Mohd Noor, M.M. Abd Karim, B. Gunasekaran, S. Abd Gani, M.
A. Cabrera, S.A. Ahmad, Revista Mexicana De Ingeniería Química 19 (2020)
1327.
[104] C. Malarkodi, S. Rajeshkumar, K. Paulkumar, M. Vanaja, G.D.G. Jobitha, G.
Annadurai, Drug Invent. Today 5 (2013) 119.
[105] V. Railean-Plugaru, P. Pomastowski, M. Wypij, M. Szultka-Mlynska, K.
Rafinska, P. Golinska, H. Dahm, B. Buszewski, J. Appl. Microbiol. 120 (2016)
1250.
[106] N.A. Al-Dhabi, A.-K.M. Ghilan, G.A. Esmail, M.V. Arasu, V. Duraipandiyan, K.
Ponmurugan, J. Photochem. Photobiol., B 197 (2019) 111529.
[107] M. Sanjivkumar, R. Vaishnavi, M. Neelakannan, D. Kannan, T. Silambarasan, G.
Immanuel, Biocatal. Agric. Biotechnol. 17 (2019) 151.
[108] R.A. Hamouda, M.H. Hussein, R.A. Abo-elmagd, S.S. Bawazir, Sci. Rep. 9 (2019)
13071.
[109] M. Shariq Ahmed, R. Soundhararajan, T. Akther, M. Kashif, J. Khan, M.
Waseem, H. Srinivasan, Environ. Sci. Pollut. Res. 26 (2019) 26939.
[110] S. Marimuthu, A.A. Rahuman, A.V. Kirthi, T. Santhoshkumar, C. Jayaseelan, G.
Rajakumar, Parasitol. Res. 112 (2013) 4105.
[111] J. Jayabalan, G. Mani, N. Krishnan, J. Pernabas, J.M. Devadoss, H.T. Jang,
Biocatal. Agric. Biotechnol. 21 (2019) 101327.
[112] S. Rehman, B.R. Jermy, S. Akhtar, J.F. Borgio, S. Abdul Azeez, V. Ravinayagam,
R. Al Jindan, Z.H. Alsalem, A. Buhameid, A. Gani, Artif. Cells Nanomed.
Biotechnol. 47 (2019) 2072.
[113] C. Jayaseelan, A.A. Rahuman, A.V. Kirthi, S. Marimuthu, T. Santhoshkumar, A.
Bagavan, K. Gaurav, L. Karthik, K.V.B. Rao, Spectrochim. Acta Part A Mol.
Biomol. Spectrosc. 90 (2012) 78.
[114] S. Rajeswaran, S. Somasundaram Thirugnanasambandan, N.K. Dewangan, R.K.
Moorthy, S. Kandasamy, R. Vilwanathan, Biol. Trace Elem. Res. 194 (2020)
273.
[115] K. Gudikandula, P. Vadapally, M.S. Charya, OpenNano 2 (2017) 64.
[116] J. Hoeksma, T. Misset, C. Wever, J. Kemmink, J. Kruijtzer, K. Versluis, R.M.J.
Liskamp, G.J. Boons, A.J.R. Heck, T. Boekhout, J. den Hertog, Sci. Rep. 9 (2019)
17546.
[117] L.B. Brenelli, G.F. Persinoti, J.P.L.F. Cairo, M.V. Liberato, T.A. Gonçalves, I.V.R.
Otero, P.H. Mainardi, C. Felby, L.D. Sette, F.M. Squina, Sci. Rep. 9 (2019) 17564.
[118] B. Yahyaei, P. Pourali, Sci. Rep. 9 (2019) 1.
[119] F.N. Spagnoletti, C. Spedalieri, F. Kronberg, R. Giacometti, J. Environ. Manage.
231 (2019) 457.
[120] N. Durán, P.D. Marcato, M. Durán, A. Yadav, A. Gade, M. Rai, Appl. Microbiol.
Biotechnol. 90 (2011) 1609.
[121] S.K. Das, J. Liang, M. Schmidt, F. Laffir, E. Marsili, ACS Nano 6 (2012) 6165.
[122] Y. Qian, H. Yu, D. He, H. Yang, W. Wang, X. Wan, L. Wang, Bioprocess Biosyst.
Eng. 36 (2013) 1613.
[123] G.S. El-Sayyad, F.M. Mosallam, A.I. El-Batal, Adv. Powder Technol. 29 (2018)
2616.
[124] E. Castro-Longoria, A.R. Vilchis-Nestor, M. Avalos-Borja, Colloids Surf., B 83
(2011) 42.
[125] N. Aziz, M. Faraz, M.A. Sherwani, T. Fatma, R. Prasad, Front. Chem. 7 (2019).
[126] K.S. Almaary, S.R.M. Sayed, O.H. Abd-Elkader, T.M. Dawoud, N.F. El Orabi, A.M.
Elgorban, Saudi J. Biol. Sci. 27 (2020) 1333.
[127] H. Qaralleh, K.M. Khleifat, M.O. Al-Limoun, F.Y. Alzedaneen, N. Al-Tawarah,
Adv. Nat. Sci.: Nanosci. Nanotechnol. 10 (2019) 025016.
12
Journal of Molecular Liquids 334 (2021) 116040
[128] A.M. Othman, M.A. Elsayed, N.G. Al-Balakocy, M.M. Hassan, A.M. Elshafei, J.
Genet. Eng. Biotechnol. 17 (2019) 8.
[129] A. Aygün, S. Özdemir, M. Gülcan, K. Cellat, F. S ß en, J. Pharm. Biomed. Anal. 178
(2020) 112970.
[130] N. Feroze, B. Arshad, M. Younas, M.I. Afridi, S. Saqib, A. Ayaz, Microsc. Res.
Tech. 83 (2020) 72.
[131] A.A. Mohamed, A. Fouda, M.A. Abdel-Rahman, S.E.-D. Hassan, M.S. El-Gamal,
S.S. Salem, T.I. Shaheen, Biocatal. Agric. Biotechnol. 19 (2019) 101103.
[132] Z. Molnár, V. Bódai, G. Szakacs, B. Erdélyi, Z. Fogarassy, G. Sáfrán, T. Varga, Z.
Kónya, E. Tóth-Szeles, R. Szu } cs, I. Lagzi, Sci. Rep. 8 (2018) 3943.
[133] P. Clarance, B. Luvankar, J. Sales, A. Khusro, P. Agastian, J.C. Tack, M.M. Al
Khulaifi, H.A. Al-Shwaiman, A.M. Elgorban, A. Syed, H.J. Kim, Saudi J. Biol. Sci.
27 (2020) 706.
[134] R. Raliya, P. Biswas, J.C. Tarafdar, Biotechnol. Rep, 5 (2015) 22.
[135] G. Rajakumar, A.A. Rahuman, S.M. Roopan, V.G. Khanna, G. Elango, C.
Kamaraj, A.A. Zahir, K. Velayutham, Spectrochim. Acta Part A Mol. Biomol.
Spectrosc. 91 (2012) 23.
[136] K. Saravanakumar, S. Shanmugam, N.B. Varukattu, D. MubarakAli, K.
Kathiresan, M.-H. Wang, J. Photochem. Photobiol., B 190 (2019) 103.
[137] F.M. Mosallam, G.S. El-Sayyad, R.M. Fathy, A.I. El-Batal, Microb. Pathog. 122
(2018) 108.
[138] A. Loureiro, N.G. Azoia, A.C. Gomes, A. Cavaco-Paulo, Curr. Pharm. Des. 22
(2016) 1371.
[139] A. Ali, M.Z. Hira Zafar, I. ul Haq, A.R. Phull, J.S. Ali, A. Hussain, Nanotechnol.
Sci. Appl. 9 (2016) 49.
[140] T. Vangijzegem, D. Stanicki, S. Laurent, Expert Opin. Drug Deliv. 16 (2019) 69.
[141] O. Bibikova, A.P. Popov, A.V. Bykov, A. Prilepskii, M.T. Kinnunen, K. Kordas, V.
Bogatyrev, N. Khlebtsov, S. Vainio, V.V. Tuchin, J. Biomed. Opt. 20 (2015)
076017.
[142] L. Wang, J. Yao, X. Zhang, Y. Zhang, C. Xu, R.J. Lee, G. Yu, B. Yu, L. Teng, Colloids
Surf., B 161 (2018) 464.
[143] G. Darabdhara, M.R. Das, S.P. Singh, A.K. Rengan, S. Szunerits, R. Boukherroub,
Adv. Colloid Interface Sci. 271 (2019) 101991.
[144] D. Ahirwar, M. Bano, I. Khan, S.S. Gound, M.U.D. Sheikh, R. Mondal, F. Khan, J.
Solid State Chem. 273 (2019) 233.
[145] M. Zare, K. Namratha, S. Alghamdi, Y.H.E. Mohammad, A. Hezam, M. Zare, Q.A.
Drmosh, K. Byrappa, B.N. Chandrashekar, S. Ramakrishna, Sci. Rep. 9 (2019) 1.
[146] S.T. Khan, A. Malik, J. Hazard. Mater. 363 (2019) 295.
[147] M.P. Wilson, M.R. Schwarzman, Environ. Health Perspect. 117 (2009) 1202.
[148] S.R. Benjamin, F.D. Lima, E.O.P.T. Florean, M.I.F. Guedes, Int. J. Environ. Pollut.
66 (2019) 19.
[149] J. Chen, A. Zheng, A. Chen, Y. Gao, C. He, X. Kai, G. Wu, Y. Chen, Anal. Chim.
Acta 599 (2007) 134.
[150] W. Wu, X. Xiao, S. Zhang, F. Ren, C. Jiang, Nanoscale Res. Lett. 6 (2011) 533.
[151] P. Thomas, N.P. Rumjit, P.J. George, C.W. Lai, P. Tyagi, M.R.B. Johan, M.P.
Saravanakumar, Nanotechnol. Food Agric. Environ. (2020) 255–296.
[152] A. Bashir, L. Razanamahandry, A. Nwanya, K. Kaviyarasu, W. Saban, H.
Mohamed, S. Ntwampe, F. Ezema, M. Maaza, J. Phys. Chem. Solids 134 (2019)
133.
[153] T. Varadavenkatesan, E. Lyubchik, S. Pai, A. Pugazhendhi, R. Vinayagam, R.
Selvaraj, J. Photochem. Photobiol., B 199 (2019) 111621.
[154] E.A. Rogozea, A.R. Petcu, N.L. Olteanu, C.A. Lazar, D. Cadar, M. Mihaly, Mater.
Sci. Semicond. Process. 57 (2017) 1.
[155] E.A. Rogozea, N.L. Olteanu, A.R. Petcu, C.A. Lazar, A. Meghea, M. Mihaly, Opt.
Mater. 56 (2016) 45.
[156] A.K. Hussein, Renew. Sustain. Energy Rev. 42 (2015) 460.
[157] Z. Abdin, M.A. Alim, R. Saidur, M.R. Islam, W. Rashmi, S. Mekhilef, A. Wadi,
Renew. Sustain. Energy Rev. 26 (2013) 837.
[158] X. Chen, H. Zhang, Y. Zhang, X. Guan, Z. Zhang, D. Chen, Nanomaterials 10
(2020) 518.
[159] M. Holzinger, A. Le Goff, S. Cosnier, Front. Chem. 2 (2014) 63.
[160] V. Avasare, Z. Zhang, D. Avasare, I. Khan, A. Qurashi, Int. J. Energy Res. 39
(2015) 1714.
[161] F. Ning, M. Shao, S. Xu, Y. Fu, R. Zhang, M. Wei, D.G. Evans, X. Duan, Energy
Environ. Sci. 9 (2016) 2633.
[162] Jafar Ali, Naeem Ali, Wanga Lei, Hassan Waseem, Gang Panad, Revisiting the
mechanistic pathways for bacterial mediated synthesis of noble metal
nanoparticles, Journal of Microbiological Methods 159 (2019) 18–25,
https://doi.org/10.1016/j.mimet.2019.02.010.
[163] Michael Kitching, Meghana Ramani, Enrico Marsili, Fungal biosynthesis of
gold nanoparticles: mechanism and scale up, Microbial Biotechnology 8 (6)
(2015) 904–917, https://doi.org/10.1111/1751-7915.12151.