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Recent advcances on plant-based bioengineered nanoparticles using secondary

Recent advcances on plant-based bioengineered nanoparticles using secondary
metabolites and their potential in lung cancer management
metabolites and their potential in lung cancer management
Atiqul Islamaa, Iqra Rahatbb, Anuragbb, Chandrababu Rejeethcc, Devkant Sharmadd, Alok Sharmab,b,**
Atiqul Islam , Iqra Rahat , Anurag , Chandrababu Rejeeth , Devkant Sharma , Alok Sharma
a
Department of Pharmacognosy, College of Pharmacy, JSS Academy of Technical Education, Sector-62, Noida 201301, India
a
b
Department of Pharmacognosy, College of Pharmacy,
Pharmaceutical Technology, JSS Academy
Meerut Institute of Technical
of Engineering Education, (MIET),
and Technology Sector-62, Noida250005,
Meerut 201301,India
India
cb
Pharmaceutical
Department of Biochemistry, Technology,
Periyar Meerut
University, Institute
Salem of Engineering
636011, India and Technology (MIET), Meerut 250005, India
cd
Department
Ch. Devi LalofCollege
Biochemistry, PeriyarYamuna
of Pharmacy, University,
NagarSalem 636011,
135003, IndiaIndia
d
Ch. Devi Lal College of Pharmacy, Yamuna Nagar 135003, India

ARTICLE INFO ABSTRACT

ARTICLE INFO ABSTRACT
Article history: As modern technology evolves, researchers are attempting to discover novel strategies for controlling deadly
Article
Receivedhistory:
22 November 2022 As
lungmodern
cancer.technology
The use ofevolves,
secondaryresearchers
metabolites are from
attempting
plantstoasdiscover novelinstrategies
a precursor the greenfor controlling
synthesis deadly
of metallic
Received 22 November
in revised form2022
3 January 2023 lung cancer. The
nanoparticles has use of secondary
several advantagesmetabolites from plants
over the more common as aphysiochemical
precursor in thesynthesis
green synthesis of metallic
as it includes, low
Received in
Accepted 28revised form 3 January 2023
May 2023 nanoparticles has severalbiocompatibility,
cost, energy efficiency, advantages overand thetherapeutic
more common value.physiochemical
This review aims synthesis as it includes,
to investigate low
the effects
Accepted 28
Available May31
Online 2023
January 2024 cost, energy efficiency, biocompatibility, and therapeutic value. This review
Available Online 31 January 2024 of employing materials made from plant-based synthesis that contain metallicaims to investigate
nanoparticles (Ag, the
Au,effects
CuO,
of employing
Se, ZnO, Pt, andmaterials
SnO2) made from plant-based
highlighting the advantagessynthesis thatwidespread
of their contain metallic nanoparticles
application (Ag, Au,
in lung cancer CuO,
treatment
Keywords: Se,the
of ZnO, Pt, and SnO2) Despite
next-generation. highlighting the advantages
a persisting prejudiceof their
aboutwidespread application
the application in lung cancer treatment
of nanotechnological products
Keywords:
Green synthesis of the next-generation. Despite a persisting prejudice about the application of nanotechnological
and medicine. The phytochemicals found in plants that are responsible for nanoparticle bio-reductionproducts
include
Green synthesis
Metallic nanoparticles and medicine. The phytochemicals found in plants that are responsible for nanoparticle bio-reduction
flavones, terpenoids, sugars, ketones, aldehydes, carboxylic acids, and amides. These molecules rangeinclude
in size
Metallic nanoparticles
Bioactive flavones, terpenoids,
from small moleculessugars,
to lowketones,
molecular aldehydes,
weight (MWcarboxylic acids,
> 5 000) and amides.
compounds. These molecules
Additionally, these range in size
plant extract
Bioactive
Lung cancer from small molecules
biomolecules serve as to low molecular
a reducing weight (MW
and stabilizing agent,> 5resulting
000) compounds. Additionally,
in nanoparticles that are these
stableplant
and extract
have a
Lung cancer
Nanotechnology biomolecules serve
regulated form. Theasfocus
a reducing and stabilizing
of this review is on theagent, resultinggreen
biomolecule in nanoparticles
nanoparticlesthat areinstable
used and haveofa
the treatment
Nanotechnology
Molecular weight regulated form. The focus of this review is on the biomolecule greengeneration
nanoparticles used inmaterials.
the treatment of
lung cancer found in the plant extract, which is thought to be the next of futuristic
Molecular weight lung cancer©found
2025 in the plant
Beijing extract,ofwhich
Academy Food is thought Publishing
Sciences. to be the next generation
services of futuristic
by Elsevier B.V. onmaterials.
behalf of KeAi
© 2025
© 2025 Beijing
Beijing Academy of
Academy
Communications of Food
Food
Co., Ltd.Sciences.
Sciences.
This is anPublishing
Publishing
open access services
services byunder
articleby Elsevier
Elsevier
the CCB.V.BY-NC-ND
B.V. on behalf oflicense
KeAi
Communications Co.,
Communications Co., Ltd.
Ltd. This
This is
is an
an open
open access article
access article under
under the
the CC
CC BY-NC-ND
BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/). license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
(http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction biological and medical applications, e.g., antibacterial, antifungal,

1. Introduction biological
and antiviral and medical
products applications,
considered moree.g., antibacterial,
attention [3] antifungal,
. Green synthesis of
[3]
Nanoparticles are attracting much attention in the fields of and antiviral products considered more attention . Green
nanoparticles, with minimal toxicity, has been a popular research area synthesis of
Nanoparticles
research are attracting
and medicine. Because ofmuch attention
its unique in the fields
characteristics, of
such nanoparticles, with minimal toxicity, has been a popular research area
for increasing biomedical applications, including the preparation of
research and medicine. Because of its unique characteristics, such for increasing biomedical applications, including
as nanoscale size (> 100 nm diameter), customized delivery, and implantable biomaterial, molecular imaging, woundthe preparation
healing, of
and drug
as nanoscale
high efficacy,size (> 100 nm
researchers havediameter),
begun to customized delivery, and
examine nanomedicine [1]
. implantable
[4] biomaterial, molecular imaging, wound healing, and drug
[1] delivery[4]. Green nanoparticles can be synthesized using a variety of
For the synthesis of nanoparticles, noble metals including silver,.
high efficacy, researchers have begun to examine nanomedicine . Green
delivery such
methods nanoparticles
as ultraviolet (UV)canirradiation,
be synthesized using airradiation,
microwave variety of
For the
gold, synthesis
copper, zinc,ofand
nanoparticles,
platinum are noble metalspreferred
typically including
[2] silver,
. Silver methods such as ultraviolet (UV) irradiation, microwave irradiation,
[2] chemical reduction, photochemical reduction, c-irradiation, and
gold, copper, zinc, and platinum are typically preferred . Silver chemical reduction,methods. photochemical
nanoparticles (AgNPs) with an annual usage of 500 tones mostly for sonoelectrochemical Despite reduction,
being efficient c-irradiation, and
at synthesizing
nanoparticles (AgNPs) with an annual usage of 500 tones mostly for sonoelectrochemical methods. Despite being efficient at synthesizing
nanoparticles with a high level of purity and specificity, these
nanoparticles
methods with a high
were extremely level ofand
expensive purity
mightandhave specificity,
been harmful theseto
*
Corresponding author at: Department of Pharmaceutical Technology, Meerut Institute of methods
*
Corresponding author at: Department
Engineering of
andPharmaceutical Technology,
Technology (MIET), MeerutMeerut
250005,Institute
India. of the environment[5]. Cancer ranks as a leading cause of death andtoa
were extremely
[5] expensive and might have been harmful
Engineering and the environment
significant hindrance . Cancer ranks as
to extending lifea expectancy
leading cause of death
in every and[6]a.
country
E-mail address: alokalok22@gmail.com (A.Technology
Sharma) (MIET), Meerut 250005, India. [6]
E-mail
Peer address:
review alokalok22@gmail.com
under responsibility of KeAi(A. Sharma)
Communications Co., Ltd. By 2027, the death rate from cancer is projected to increase by 70%,.
significant hindrance to extending life expectancy in every country
Peer review under responsibility of KeAi Communications Co., Ltd. By 2027,
with the deathofrate
the majority from
cases cancer
being lung,is breast,
projected to increase
prostate, by 70%,
and colorectal
with the majority of cases being lung, breast, prostate, and colorectal

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2772-5669/©license
BY-NC-ND 2025 Beijing Academy of Food Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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2772-5669 © 2025 Beijing Academy of Food Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the
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2 Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1–20

2 Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1-20

cancers[7]. In 2020, lung cancer, also known as lung carcinoma, is
expected to be the second-most common cancer to be diagnosed
and the leading cause of cancer mortality, accounting for nearly one
in ten (11.4%) cancer diagnoses and one in five (18.0%) fatalities.
There are expected to be 2.2 million new cancer cases and 1.8 million
cancer-related deaths[8]. Lung cancer is the major cause of cancer
death in men in 93 countries, owing in part to its high fatality rate[9].
The majority of lung cancer cases are caused by cigarette smoking
and tobacco smoke exposure (85%) surgery, chemotherapy, radiation
therapy, and hormone therapy are the most common approaches for
cancer treatment and management[10]. In addition to being expensive
and ineffective, the current lung cancer therapeutic agents have
severe side effects and toxicity on non-cancerous tissue. Green
nanoparticles have ushered in a new era of interdisciplinary research
covering chemistry, medicine, engineering, and biology, with a focus
on lung cancer detection, diagnosis, therapy, and prevention[11]. To
the best of our knowledge, no comprehensive review concerning
green nanoparticles from different metals for the study of lung cancer
has been reported to far. This review highlights the biosynthesis of
various nanoparticles and includes current examples of applying
nanoparticles for lung cancer treatment along with a detailed
mechanism of action and toxicity of green synthesized nanoparticles.
A literature survey was conducted via an electronic search using
PubMed, Web of Science, Google Scholar, Scopus, and ACS. Based
on the literature search, we reviewed the achievements of research on
green nanoparticles, plants extract, and anticancer activity for further
research on, and development of, green synthesis nanoparticles.
2. Nanomaterials (NMs) in plant science and/or in food science
NMs have unique physicochemical properties and can be
employed in a variety of ways to functionalize biomolecules [12].

Table 1
Green synthesis from various metals and their potential in lung cancer therapy. Secondary metabolites from different plants sources along their molecular weight.
Name of plants Plant bioactives and molecular weight
Silver nanoparticles
Herniarin(176.16), Umbelliferone (162.14), Apigenin(270.24), Apigenin-7-O-glucoside(432.4), Luteolin(286.24), Quercetin(302.23),
Matricaria chamomilla
Rutin(610.5), Naringenin(272.25)
Dodonaea viscosa Kaempferol(286.23), Sakuranetin(286.28), Hautriwaic acid(332.4),
Gallic acid(170.12), Ellagic acid(302.19), Punicalin(782.52), Punicalagin(1 084.7), Caffeic acid(180.16), Ellagitannins(992.7),
Punica granatum
Luteolin(286.24), Kaempferol(286.23), Quercetin(302.23)
Derris trifoliate Rotenone(394.41), Tephrosin(410.41), 12a-Hydroxyrotenone(410.4), Deguelin(394.42).
Camphene(136.23), Limonene(136.23), Myrcene(136.23), Ocimene(136.23), α-pinene(136.23), β-pinene(136.23), Chlorogenic acid
Gossypium hirsutum
(354.31), Ferrulic acid (194.18), Gallic acid(170.12), Benzoic acid (122.12).
Gallic acid(170.12), Catechol(11.11), p-Comuaric acid(164.16), Ferulic acid, O-Coumaric acid(164.16), Cinnamic acid(148.16),
Beta vulgaris
Myricetin(318.23), Neringenin, Kaempferol(286.23), Apigenin(270.24).
Zanthoxylum rhetsa Lupeol(426.7), Kobusin(370.4), Sesamin(354.35), β-Amyrin(426.7), Hesperetin(302.28)
Caffeic acid(180.16), Vanillic acid(168.15), Chlorogenic acid (354.31), Ferrulic acid (194.18), Gallic acid(170.12), Aucubin(346.33),
Euphrasia officinalis
Catapol(362.33), Euphroside(376.36), Apigenin(270.24), Luteolin(286.24), Kaempferol(286.23), Quercetin(302.23)
Bauhinia purpurea beta-Sitosterol, Stigmasterol(412.7), Lupenone, Lupeol, Kaempferol(286.23), Quercetin(302.23), Vanillic acid, Isotachiostde
Gold nanoparticles
Caffeic acid(180.16), Chlorogenic acid (354.31), Ferrulic acid (194.18),Gallic acid(170.12), p-Comuaric acid, o-Coumaric acid, Myricetin,
Moringa oleifera
Kaempferol(286.23), Apigenin(270.24), Ellagic acid(302.19), Stigmasterol(412.7), β-Amyrin
Vasicine(188.23), Vasicinol(204.22), Vasicinone(202.21), Apigenin(270.24), Astragalin(448.4), Kaempferol(286.23), Quercetin(302.23),
Justicia adhatoda
Vitexin(432.38).
Campene(136.32), Eugenol(164.2), alpha-pinene(136.23), 1,8-Cineol(154.25), Caryophyllene(204.35), Chavibetol(164.20),
Piper betle
Safrole(162.19), p-cymene(134.21), 4-terpineol(154.25).
Sitoindoside-IV(977.4), Sitosterol(414.7), Gentiobioside(342.3), Leucocyanidin(306.26), Caffeic acid(180.16), Cinnamic acid, p-coumaric,
Musa paradisiaca
Ferulic acid, Gallic acid(170.12).
Zinc oxide nanoparticles
Gallic acid(170.12), Vanillic acid, Syringic(198.17), Protocatechuic(154.12), and p-hydroxybenzoic acids(138.12), p-coumaric,
Mangifera indica Chlorogenic, Ferulic acid, and Caffeic acid(180.16), Catechin(290.27), Quercetin(302.23), Kaempferol(286.23), Rhamnetin(316.26),
Tannic acid(1071.2), Mangiferin(422.33)
Gallic acid(170.12), Chlorogenic acid, Caffeine, Coffeic acid, Syringic acid, Rutin(610.5), Ellagic acid(302.19), Coumaric acid, Vanillic
Deverra tortuosa
acid, Ferulic acid, Naringenin(272.25) , Propyl Gallate(212.20), Quercetin(302.23), and Cinnamic acid.
Laurus nobilis Apinene, β-pinene, Myrcene, Limonene, Linalool, Methyl chavicol(148.20)
Raphanus sativus var. Longipinnatus Sinapine(310.36), Quercetin(302.23), Kaempferol(286.23), Myricetin, Apigenin(270.24), and Luteolin(286.24)(286.24)
Iron oxide nanoparticles
Phyllanthus emblica Gallic acid(170.12), Ellagic acid(302.19), Quercetin(302.23), β-sitosterol, Chebulinic acid(956.67), Kaempferol(286.23), Ascorbic acid(176.12)
Copper nanoparticles (CuONPs)
Linalool(154.25), Methyl chavicol, Eugenol, Methyl cinnamate(162.18), Caffeic acid(180.16), Vanillic acid, Rosmarinic acids(360.31),
Ocimum americanum
Quercetin(302.23), Rutin(610.52), Apigenin(270.24), Chlorogenic and p-hydroxybenzoic
Platinum and Palladium nanoparticles
β-Sitosterol(414.7), Campesterol(400.68), Stigmasterol(412.7), Stigmastan-3,5-dien(396.7), Carvone(150.22), Menthol(156.27),
Ononidis radix
Menthone(154.25), Linalool(154.25), Estragole(148.20), Borneol(125.25), and cis-anethole(148.20)
Peganum harmala Harmine(212.25), Harmol(198.23), Harmaline(214.26), Harmalol(200.24), and Peganine(188.23), Eugenol
Selenium nanoparticles
Enicostema axillare Swertiamarin(374.34), Apigenin(270.24), Swertisin(446.4)
 Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1–20 3

Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1-20 3

Furthermore, certain NMs have been discovered to respond to external agrochemicals or biomolecules in plants, as well as the potential to
AtiqulasIslam
stimuli, such as gold and magnetic nanoparticles, welletasal.polymeric
/ Journal of Future
boostFoods
crop 5-1 (2025)
yield [15]
. 1-20 3
or hybrid NMs, allowing macromolecules to be released in a time-
Furthermore, certain NMs have been discovered to respond to external agrochemicals or biomolecules in plants, as well as the potential to
controlled way. Engineered nanomaterials have been successfully 3. Micro, and [15] macromolecules (bio-active substances) of
stimuli, such as gold and magnetic nanoparticles, as well as polymeric boost crop yield .
assessed and used in medicine and pharmacology for the past two plant-based matrices
or hybrid NMs, allowing macromolecules to be released in a time-
decades for these reasons, especially for diagnostic and therapeutic
controlled way. Engineered nanomaterials have been successfully 3. Plant
Micro, and macromolecules (bio-active substances)
applications[13-14]. Nanotechnology has lately piqued attention in bioactive compounds have emerged as key components ofin
assessed and used in medicine and pharmacology for the past two plant-based matrices
plant science, particularly for the application of NMs as vehicles for maintaining and preventing diverse diseases. The metabolites found in
decades for these reasons, especially for diagnostic and therapeutic
applications[13-14]. Nanotechnology has lately piqued attention in Plant bioactive compounds have emerged as key components in
plant science, particularly for the application of NMs as vehicles for maintaining and preventing diverse diseases. The metabolites found in

Fig. 1 Different methods of production nanoparticles owing to their unique electrical, optical, thermal, physical and chemical properties.

Table 2
List of research
Fig.that
1 used plantmethods
Different extracts in
of the synthesisnanoparticles
production of NPs to inhibit
owinglung cancer
to their cell lines
unique and some
electrical, practical
optical, information
thermal, about
physical and synthesized
chemical nanoparticles.
properties.
Absorbance maxima
Plant Part used NP size/Shape Metal salt solution Reference
Table 2 (λmax)
List of research
Silver that used
nanoparticles plant extracts in the synthesis of NPs to inhibit lung cancer cell lines and some practical information about synthesized nanoparticles.
(AgNPs)
Abelmoschus Absorbance maxima
Plantesculentus Flower
Part used 5.52−31.96 nm/spherical
NP size/Shape 1 mmol/L silver
Metalnitrate (AgNO3) solution
salt solution 430 nm [134]
Reference
(λ )
Acorous calamus Rhizome 31.83 nm/spherical AgNO3 solution (1 mmol/L) 421maxnm [135]
Silver nanoparticles (AgNPs)
Allium sativum L. Bulb 8.18 nm/spherical 2mL of 0.025 mol AgNO3 449 nm [136]
Abelmoschus esculentus Flower 5.52−31.96 nm/spherical 1 mmol/L silver nitrate (AgNO3) solution 430 nm [134]
Albizia adianthifolia Leaf 4−35 nm 49 mL of 1 × 10−3 mol/L AgNO 3 448 nm [137]
Acorous calamus Rhizome 31.83 nm/spherical AgNO3 solution (1 mmol/L) 421 nm [135]
Artemisia princeps Leaf 20 nm/spherical 100 mL of 1 mmol/L aqueous AgNO3 solution 410 nm [138]
Allium sativum L. Bulb 8.18 nm/spherical 2mL of 0.025 mol AgNO3 449 nm [136]
Avicennia marina Leaf 10−20 nm/spherical 90 mL of 1 mmol/L AgNO3 solution 420 nm [139]
Albizia adianthifolia Leaf 4−35 nm 49 mL of 1 × 10−3 mol/L AgNO3 448 nm [137]
Beta vulgaris Taproot 5−20 nm/spherical, Circular 90 mL of 1mmol/L AgNO3 solution 450 nm [49]
Artemisia princeps Leaf 20 nm/spherical 100 mL of 1 mmol/L aqueous AgNO3 solution 410 nm [138]
30 to 80 nm/spherical, hexagonal, and
Borago officinalis
Avicennia marina Leaf
Leaf 10−20irregular
nm/spherical AgNO
90 mL of 13 mmol/L (1 mmol/L)
solution AgNO 422 nm
nm [140]
3 solution 420 [139]
Beta vulgaris
Camellia sinensis L. Taproot
Leaf 5−208.29nm/spherical, Circular
nm/spherical 90 mL of 1mmol/L
2 mL AgNO
of 0.025 mol 3 solution
AgNO 3
450 nm
451 nm [49]
[136]
Carpesium cernuum Whole 30 to 8013.0
nm/spherical, hexagonal, and
± 0.2 nm/spherical
Borago officinalis Leafplant AgNOAgNO 3 solution
3 solution (1 mmol/L)
430
422 nm
nm [141]
[140]
irregular
Chrysanthemum morifolium longan peel 27.2 nm 50 mL of AgNO3 (2 mmol/L) 430 nm [113,142]
Camellia sinensis L. Leaf 8.29 nm/spherical 2 mL of 0.025 mol AgNO3 451 nm [136]
Coptis chinensis Leaf 6−45 nm/spherical 0.75 mmol/L AgNO3 450 nm [143]
Carpesium cernuum Whole plant 13.0 ± 0.2 nm/spherical AgNO3 solution 430 nm [141]
Croton bonplandianum Leaf 32 nm/spherical 90 mL of 1mmol/L aqueous AgNO3 solution 425 nm [144]
Chrysanthemum morifolium longan peel 27.2 nm 50 mL of AgNO3 (2 mmol/L) 430 nm [113,142]
Cucumis prophetarum Leaf 30−50 nm/spherical AgNO3 solution 420 nm [145]
Coptis chinensis Leaf 6−45 nm/spherical 0.75 mmol/L AgNO3 450 nm [143]
Curcuma longa L. Rhizome 6.06 nm/spherical 2 mL of 0.025 mol AgNO 3 447 nm [136]
Croton bonplandianum Leaf 32 nm/spherical 90 mL of 1mmol/L aqueous AgNO3 solution 425 nm [144]
Cymbopogon citratus Leaves 17−25.8 nm/spherical 1 mmol/L AgNO3 in 1:4 435 nm [146]
Cucumis prophetarum Leaf 30−50 nm/spherical AgNO3 solution 420 nm [145]
Cymodocea serrulata Leaf 29.28 nm/spherical 95 mL of aqueous solution of 1 mmol/L AgNO3 420 nm [147]
Curcuma longa L. Rhizome 6.06 nm/spherical 2 mL of 0.025 mol AgNO3 447 nm [136]
Dendropanax morbifera Leaf 100−150 nm/Polygon AgNO3 solution (1 mmol/L) 548 nm [148-149]
Cymbopogon citratus Leaves 17−25.8 nm/spherical 1 mmol/L AgNO3 in 1:4 435 nm [146]
Derris trifoliate Seed 16.05 ± 5.0 nm 20 mL of 1 mmol/L solution of AgNO3 419 nm [46]
Cymodocea serrulata Leaf 29.28 nm/spherical 95 mL of aqueous solution of 1 mmol/L AgNO3 420 nm [147]
Dodonaea viscosa Leaf 70−100 nm/spherical 25 mL of 1 mmol/L AgNO3 Solution 441-654 nm [42]
Dendropanax morbifera Leaf 100−150 nm/Polygon AgNO3 solution (1 mmol/L) 548 nm [148-149]
Gloriosa superba Tuber 7−14 nm/spherical 45 mL of 1 mmol/L AgNO3 400-500 nm [150]
Derris trifoliate Seed 16.05 ± 5.0 nm 20 mL of 1 mmol/L solution of AgNO3 419 nm [46]
Gossypium hirsutum Leaf 13−40 nm/spherical 100 mL of 1 mmol/L AgNO3 410 nm [47,120]
Dodonaea viscosa Leaf 70−100 nm/spherical 25 mL of 1 mmol/L AgNO3 Solution 441-654 nm [42]
Juniperus chinensis Leaf 12.96 nm/spherical 40 mL of 1 mmol/L AgNO3 438 nm [151]
Gloriosa superba Tuber 7−14 nm/spherical 45 mL of 1 mmol/L AgNO 400-500 nm [150]
Matricaria chamomilla leaf 45.12 nm/spherical 50 mL of 1 mmol/L aqueous solution3of AgNO3 430 nm [40]
Gossypium hirsutum Leaf 13−40 nm/spherical 100 mL of 1 mmol/L AgNO3 410 nm [47,120]
Momordica charantia Fruit 1−13.85 nm/spherical 100 mL of 1 mmol/L AgNO3 solution 432 nm [152]
Juniperus chinensis Leaf 12.96 nm/spherical 40 mL of 1 mmol/L AgNO3 438 nm [151]
Musa paradisiaca Leaf 10−80 nm/bead, crystalline 40 mL of 0.000 1 mol/L AgNO 3 476 nm [153]
Matricaria chamomilla leaf 45.12 nm/spherical 50 mL of 1 mmol/L aqueous solution of AgNO3 430 nm [40]
Ocimum americanum Leaf 48.25 nm/spherical 100 mL of 1 mmol/L AgNO3 435 nm [154]
Momordica charantia Fruit 1−13.85 nm/spherical 100 mL of 1 mmol/L AgNO3 solution 432 nm [152]
Origanum vulgare Leaf 136 ± 10.09 nm/spherical 90 mL of 1 mmol/L AgNO3 solution 440 nm [154]
Musa paradisiaca Leaf 10−80 nm/bead, crystalline 40 mL of 0.000 1 mol/L AgNO3 476 nm [153]
Panax ginseng Leaf 5−15 nm/spherical 1 mmol/L of AgNO3 solution 420 nm [155-156]
Ocimum americanum Leaf 48.25 nm/spherical 100 mL of 1 mmol/L AgNO3 435 nm [154]
Origanum vulgare Leaf 136 ± 10.09 nm/spherical 90 mL of 1 mmol/L AgNO3 solution 440 nm [154]
Panax ginseng Leaf 5−15 nm/spherical 1 mmol/L of AgNO3 solution 420 nm [155-156]
 4 Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1–20

4 Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1-20

Table 2 (Continued)
Absorbance maxima
Plant Part used NP size/Shape Metal salt solution Reference
(λmax)
Pinus roxburghii Fruit needles 80 nm AgNO3 solution (1 mmol/L) 459 nm [157]
Pleuropterus multiflorus Root 274.8 nm/spherical 1 mmol/L AgNO3 460 nm [158]
Punica granatum Peel 6–45 nm/spherical 10 mL of 4 mmol/L AgNO3 450 nm [45]
Rosa damascena Petal 15–27 nm/spherical 10 mmol/L silver AgNO3 at 2:3 ratio 420 nm [159]
Rhynchosia suaveolens Leaf 10–30 nm/spherical 95 mL of 1 mmol/L AgNO3 426 nm [160]
Syzygium aromaticum Fruit 5–20 nm/spherical 90 mL of 1 mmol/L silver nitrate solution 470 nm [161]
Zanthoxylum rhetsa Seed 10–68 nm/spherical 95% of 0.1 mmol/L AgNO3 solution 426 nm [50]
Gold nanoparticles (AuNPs)
Alternanthera bettzickiana Leaf 80–100 nm/spherical 20 mL of 1 mmol/L gold chloride (HAuCl4) 520 nm [110]
Bauhinia purpurea Leaf Spherical 10 mL of 1 mmol/L HAuCl4 560 nm [52]
30–90 nm/spherical, irregularly and 480 to 670 nm for
Dodonaea viscosa Leaf 25 mL of 0.01 mmol/L HAuCl4 [162]
distorted different solvents extracts
Euphrasia officinalis Leaf 49.72 ± 1.2 nm/quasi-spherical 1 mmol/L chloroauric acid (HAuCl4) 558 nm [163]
Indigofera tinctoria Leaf 19.73 nm/spherical 90 mL of 1 mmol/L HAuCl4·3H2O solution 545 nm [164]
Justicia adhatoda Leaf 40.1 nm/spherical 7 mL of HAuCl4·3H2O solution 547 nm [66]
Marsdenia tenacissima Whole plant 50 nm/spherical HAuCl4 solution (4 mmol/L) 527–537 nm [165]
37 nm/spherical with face-centred cubic 1 mmol/L auric
Millettia pinnata Leaf 520 nm [166]
arrangement Chloride solution
Moringa oleifera Leaf 203 nm/spherical -3
49 mL of 1 × 10 mol/L HAuCl4 solution 540 nm [63]
Musa paradisiaca Peel 50 nm/spherical 25 mL of 1 mmol/L HAuCl4 541 nm [75]
Nigella arvensis Leaf 3–37 nm/spherical 90 mL of HAuCl4 solution (1 mmol/L) 546 nm [167]
Nigella sativa Essential oil 15.6–28.4 nm/spherical 30 mL of 2.5 × 10-4 mol/L HAuCl4 solution 540 nm [168]
10 mL of aqueous Gold (III) chloride salt
Piper betle Leaf 10 nm/spherical 540 nm [74]
solution (0.025 mol/L)
190 mL 1 mmol/L Gold (III) chloride trihydrate
Rabdosia rubescens Leaf 130 nm/ring like 550 nm [59]
solution
Sesuvium portulacastrum L. Leaf ~37 nm/spherical 95 mL of 1 mmol/L HAuCl4 solution 530 nm [169]
Zinc oxide nanoparticles (ZnONPs)
2.5 g of zinc nitrate hexahydrate
Deverra tortuosa Aerial parts 9.26–31.18 nm/crystalline 374 nm [81]
(Zn(NO3)2·6H2O)
47.27 nm/spherical and hexagonal 50 mL of zinc acetate (2 mol/L) followed by
Laurus nobilis Leaf 338 nm [84]
wurtzite addition of 50 mL of NaOH
45–60 nm/spherical and hexagonal
Mangifera indica Leaf 80 mL of 0.1 mol/L zinc nitrate 355 nm [80]
quartzite
Raphanus sativus var.
Leaf 66.43 nm/spherical and hexagonal 80 mL of 0.1 mol/L zinc acetate 369 nm [87]
Longipinnatus
177–249 nm/Nanorod, hexagonal
Cycas pschannae Leaf Zinc acetate (1 mol/L) 382 nm [170]
crystalline
Iron oxide nanoparticles (IONPs)
Phyllanthus emblica Fruit 4.1 nm/Spherical Fe3+ and Fe2+ salt solution (2:3 molar ratio) Unknown [90]
Copper oxide nanoparticles (CuONPs)
Ocimum americanum Leaf ~ 68 nm/irregularly spherical 100 mL of 1 mmol/L CuSO4·5H2O 360.74 nm [93]
Tin oxide nanoparticles (SnO2 NPs)
8.85 ± 3.5, 12.76 ± 3.9 and S1-270 nm, S2-289 nm
Piper nigrum Seed 30 mL of 0.1 mol/L SnCl2·2H2O [171]
29.29 ± 10.9 nm/crystalline and S3-293 nm

small quantities in various plants are known as bioactive chemicals[16].
Primary and secondary metabolites are plant phytochemical
substances that play different functions in basic metabolic processes.
Primary plant metabolites are more or less comparable in all live
cells because they are involved in vital life functions. On the other
hand, secondary plant metabolites are byproducts of secondary routes
like the shikimic acid pathway[17]. Alkaloids, phenolics, flavonoids,
saponins, terpenes, lipids, and carbohydrates are examples of
secondary plant metabolites[18]. Secondary plant metabolites have long
been utilized to treat several diseases in traditional and folk medicine.
In modern medicine, they offered lead chemicals for the production
of drugs to treat many disorders ranging from migraine to cancer[17].
A micro molecule is a small, light-weight molecule that is frequently
referred to as a monomer. Micro molecules control various biological
processes. Nucleotides, amino acids, monosaccharides, fatty acids,
and glycerol are the most significant micromolecules in cells. In
contrast to micromolecules, macromolecules are larger molecules
with a high molecular weight. Monomers, or small micromolecules,
are linked together to produce macromolecules [19] . Plant
macromolecules have a high molecular weight, which distinguishes
them from the rest of the ecosystem. Although the molecular weight
of other plant metabolites rarely surpasses 1 000, this can range from
10 000 to above 1 000 000 Da[20]. Plants have three major groups of
macromolecules proteins, polysaccharides, and nucleic acids. Table 1
illustrate the secondary metabolites from plants sources along with
molecular weight (g/mol). Anticancer drugs such as vinca alkaloids,
 Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1–20 5

Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1-20 5

taxanes and their derivatives, camptothecin and its derivatives, lung parenchyma or the bronchi. The pathophysiology of lung cancer
anthracyclines, and others have been produced by nature
Atiqul Islam in the of Future
et al. / Journal is very Foodscomplex
5-1 (2025)and 1-20
incompletely understood. It is hypothesized that 5
past[21]. In contrast, half of all anti-cancer drugs approved worldwide repeated exposure to carcinogens, such as cigarette smoke, causes
taxanes
are either and their derivatives,
natural products or camptothecin
their derivatives, and itsandderivatives,
they were lung parenchyma
dysplasia of the lung or the bronchi. The
epithelium. pathophysiology
Continued exposure causes of lunggenetic
cancer
anthracyclines,
developed using and others gathered
knowledge have been produced
from natural by nature
small in the
molecules is very complex
alterations and incompletely
and interferes with protein understood.
production It is
[28]hypothesized that
. As a result, the
[21]
or . In contrast, half
pastmacromolecules. Plantof bio
all anti-cancer
actives have drugs
beenapproved
reportedworldwide
to inhibit repeated
cell cycle exposure
is disrupted, to carcinogens,
inducing carcinogenesis. such as cigarette The most smoke, causes
significant
are either
tumor natural providing
progression, products aornovel theirweapon
derivatives, and they
for fighting cancer wereby dysplasia of the lung epithelium. Continued
genetic mutations responsible for lung cancer development are MYC, exposure causes genetic
developeditsusing
targeting knowledge
characteristic gathered
hallmarks [19]
. from natural
The ability of small molecules
Cell Penetrating alterations
BCL2, and andp53 interferes
for small cell withlung proteincancer production [28]
and EGFR,. KRAS, As a result,
and p16 the
or macromolecules.
Peptides (CPP) to deliver Planta biowideactives
range have been reported including
of macromolecules, to inhibit cell cycle is disrupted,
for non-small cell lung cancer inducing [29-30]carcinogenesis.
. The most significant
tumor progression,therapeutic
oligonucleotides, providing adrugs, novelproteins,
weapon for andfighting
medicalcancer
imaging by genetic
Lung mutations
cancers responsible
can be broadly for classified
lung cancer intodevelopment are MYC,
two forms, non-small
targetingbyitsforming
agents, characteristic hallmarks[19]
nanoparticulate . The ability
carriers of Cellof
in a variety Penetrating
cells has BCL2, and p53 for small cell lung cancer and EGFR, KRAS, and p16
cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC
Peptides
made them(CPP) to delivertool
a promising a widefor range of macromolecules,
both macromolecule including
delivery and for non-small cell lung cancer [29-30]
.
is further classified into squamous cell carcinoma, adenocarcinoma,
oligonucleotides,
understanding the therapeutic
fundamentalsdrugs, proteins,
of cellular andacross
uptake medical theimaging
plasma and Lunglargecancers can be broadly
cell carcinoma [31]
. NSCLC classified into two 80%
represents forms,ofnon-small
all lung
agents, by[22]
membrane forming
. nanoparticulate carriers in a variety of cells has
cancers, with adenocarcinoma accounting for 40%(SCLC).
cell lung cancer (NSCLC) and small cell lung cancer NSCLC
of all cases of
made them a promising tool for both macromolecule delivery and is further classified into squamous cell tumors
carcinoma,
lung cancer. Adenocarcinoma are lung withadenocarcinoma,
more than 10%
understanding
4. Green production the fundamentals of cellular uptake across the plasma
of nanoparticles [31]
. NSCLC which represents
and large and
glandular cell squamous
carcinomacomponents tend 80% to grow of all lung
toward
membrane[22]. cancers, with of adenocarcinoma accounting forevery
40% of
the periphery the lung and double in size 161alldays
cases of.
[32-33]

To synthesize NPs, both “top-down” and “bottom-up” approaches lung cancer. Adenocarcinoma are lung tumors with more than 10%
[23] Squamous-cell carcinomas account for approximately 30% of all lung
4. Green
can be employed production (Fig.of1).nanoparticles
Ball milling, chemical etching, laser glandular andis squamous components whichtypestend of totumors
grow toward
cancers. This one of the two most prevalent related
ablation, and sputtering are examples of “top-down” strategies [32-33]

“top-down” to smoking, the other being small-cell carcinoma. Squamous-cell.

the periphery of the lung and double in size every 161 days
that To
cansynthesize
be implemented NPs, both using a varietyand of “bottom-up”
physical andapproaches
chemical Squamous-cell carcinomas
can be employed
[24] [23]
(Fig. 1). Ball milling, chemical etching, islaser tumors are typically seen inaccount
the center for approximately
of the chest and 30%growof all lung
slowly,
processes . The incidence of surface detection on nanoparticles the cancers. This is one of the two most
[32] prevalent types of tumors related
ablation,problemand sputtering are examples of The“top-down” doubling in size every 88 days . Large-cell carcinomas (LCC) are
primary with the top-down strategy. bottom-upstrategies
approach to smoking, the other
that can the least prominent typebeing
of lung small-cell carcinoma.for
cancer, accounting Squamous-cell
10%–15% of
refers to be
the implemented
construction of using a variety
material fromofthephysical
bottom and chemical
up: atom-by-
[24] tumors
all cases. areLCCtypically
is a seen
type of in the
malignant center of the
epithelial chest
tumour and growlacks
that slowly,
the
processes
atom, . The incidence of surface
molecule-by-molecule, detection on nanoparticles
or cluster-by-cluster, with reduction/is the [32]
doubling
cytologic in size every
characteristics 88 of days
glandular, . Large-cell
squamous, carcinomas
or (LCC)
neuroendocrine are
primary problem
oxidation with the top-down
as the dominant strategy. The
reaction. Bottom-up bottom-up
processes are approach
chemical
the least prominent type of lung cancer,
cancers. LCC is often composed of circular to polygonal cells with accounting for 10%–15% of
refers
or to the
biologic in construction of material
nature with minimum fromand
defects the homogenous
bottom up: atom-by-
chemical
all cases. LCC is a type of malignant epithelial
prominent nucleoli. These tumors grow at a rate similar to squamous- tumour that lacks the
atom, molecule-by-molecule,
composition (e.g., revere-micelle cluster-by-cluster,
or method, with reduction/
sol-gel synthesis, colloidal
oxidation as the dominant reaction. cytologic
cell cancers characteristics
in a peripheral of glandular,
location, doubling squamous,every or neuroendocrine
86 days[32,34].
precipitation, hydrothermal synthesis)Bottom-up
[25]
. Table 2processes
mentioned arethechemical
list of
or biologic in nature cancers. LCC
Whereas, SCLCisisoften mainly composed
composed of ofcircular
round,to oval,polygonal
or angulatedcells cells
with
plants and their partswith minimum
exhibiting defects and metallic
biosynthesized homogenous chemical
nanoparticles
composition (e.g., revere-micelle method, sol-gelandsynthesis, colloidal prominent
with little nucleoli.
cytoplasm These
and a tumors
size grow
roughly at a
that rate
of a similar
resting to squamous-
lymphocyte.
along with their method of preparation, size, shape, absorbance. [32,34]
precipitation, hydrothermal synthesis)[25]. Table 2 mentioned the list of cell cancers
They typicallyinoriginate
a peripheral location,
in a central doubling
position andevery 86 days
proliferate rapidly;.
plants and their parts exhibiting biosynthesized metallic nanoparticles Whereas,
the doubling SCLC timeisismainly
about composed
29 days of round,
[32,35]
(Fig. 2). oval, or angulated
Significant cells
advances
5. Pathophysiology of lung cancer
along with their method of preparation, size, shape, and absorbance. with little cytoplasm and a size roughly
in lung cancer biology may lead to customized therapy based on that of a resting lymphocyte.
Lung cancer is one of the most prevalent and lethal cancers (18.0% They typically
targeting specific originate
genes and in apathways.
central position The main and signaling
proliferatepathways
rapidly;
[32,35]
5. the
of Pathophysiology
total cancer deaths) of lung
in thecancer [8]
world . It is the leading cause of the doubling time is about 29 days
that could provide roadmaps for therapy include the following: (Fig. 2). Significant advances
cancer death among men and the second leading cause of cancer in lung cancer biology
growth-promoting pathways may(Epidermal
lead to customized Growth Factor therapy based on
Receptor/Ras/
deathLung
among cancer is oneworldwide,
women of the mostwithprevalent and lethal2.2
approximately cancers
million (18.0%
new PhosphatidylInositol 3-Kinase), growth inhibitory pathways pathways
targeting specific genes and pathways. The main signaling (p53/Rb/
of theand
cases total1.8 cancer
milliondeaths) [8]
the world .. Lung
deathsinannually [12,27] It is the leading
cancer, alsocause
known of that couldSTK11),
P14ARF, provideapoptotic
roadmaps for therapy
pathways include the following:
(Bcl-2/Bax/Fas/FasL), DNA
cancer
as death among
bronchogenic men and
carcinoma, is athe second
type of cancer leading
that cause of cancer
develops in the growth-promoting
repair and immortalization pathways (Epidermal
genes [36]
. Growth Factor Receptor/Ras/
death among women worldwide, with approximately 2.2 million new PhosphatidylInositol 3-Kinase), growth inhibitory pathways (p53/Rb/
[12,27]
cases and 1.8 million deaths annually . Lung cancer, also known P14ARF, STK11), apoptotic pathways (Bcl-2/Bax/Fas/FasL), DNA
as bronchogenic carcinoma, is a type of cancer that develops in the repair and immortalization genes[36].

Fig. 2 The pathogenesis of lung carcinomas along with site of lung cancer.

Fig. 2 The pathogenesis of lung carcinomas along with site of lung cancer.
6 Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1–20
6 Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1-20
6. Need of advance research nanotechnology applications in
plants
In the last years, nanotechnology has made significant progress in
the synthesis of NMs and their application in medicine for diagnosis
and therapy. On the other hand, the application of NMs for plants is
still insufficient. More studies are needed in this direction to enhance
the synthesis and bio-functionalizations of NMs, based on recent
findings and present uses. It is reasonable to suggest that the potential
and the benefits of the application of NMs in plant sciences and
agriculture are still being underutilized, owing to several obstacles
that can be characterized as follows: (i) the requirement for safe
NMs to be designed and synthesized; (ii) the role of bio-actives;
(iii) the lack of knowledge about the extract processes (iv) the lack
of multidisciplinary approaches, required for the designing and
implementing of nanotechnology applications in plants.
7. Biological application of green synthesis and metals in
lung cancer
The conventional methods for producing nanoparticles are
expensive, hazardous, and harmful to the environment. To address
these challenges, several researchers have discovered the precise
green routes, or naturally occurring sources and their products that
can be used to synthesis NPs. Noble metal nanoparticles have sparked
considerable interest due to their ultra-small sizes, which allow them
to exhibit a wide range of unique and improved physical, chemical,
and biological properties and functions. The list of studies exhibiting
biosynthesized nanoparticles and the significance of nanoparticle
biosynthesis employing plant extract to suppress lung cancer cells are
summarized in Table 3.
7.1 AgNPs
Due to their attractive qualities, including as high electrical and
thermal conductivity, chemical stability, high catalytic activity,
surface enhancement, and antibacterial properties, AgNPs have
drawn the attention of several researchers [36]. In response to the
growing threat posed by bacteria that are resistant to antibiotics,
the synthesis of AgNPs, among other noble metals, has become
more popular as an antibacterial agent[37-38]. Since they improved
chemotherapeutic potency while reducing systemic toxicity, AgNPs
special features are mostly advantageous for cancer therapy. Instead
of using chemical reducing agents, plant extracts have typically been
used as reducing agents in the green method. Many different parts of
plants, including roots, fruits, bark, seeds, stems, and leaves, contain
plant biochemicals that are involved in decreasing, capping, and
stabilizing the AgNPs. Several studies have effectively synthesized
and stabilized AgNPs for their anti-lung cancer efficacy using
wholly different preparation methods. Aqueous leaf extract from
Matricaria chamomilla was used as a bioreducing agent in a study by
Dadashpour et al.[40], and extracellular synthesis of AgNPs (45.12 nm,
spherical) was completed by combining the aqueous leaf extract with
an aqueous solution of silver nitrate (AgNO3) for Ag+ ion reduction.
The appearance of brownish color in the reaction mixture indicated
the formation of AgNPs which was caused by the excitation of
surface plasmon vibrations in the NPs showing the highest absorption
at 430 nm in the UV–visible spectrum [39]. Previous research on
M. chamomilla extracts revealed the presence of phytochemicals
like sesquiterpenes, flavonoids, coumarins, and polyacetylenes.
Among all phytochemicals, the OH (phenolic compound) functional
group on the surface of AgNPs was seen to be useful in reducing
Ag ions. The spherical NP assemblies demonstrated notable anti-
cancer activities against A549 lung cancer cells by Bax, caspase-3,
and caspase-7 were upregulated whereas Bcl-2, an anti-apoptotic
gene, was downregulated. This resulted in half-maximal inhibitory
concentrations (IC 50 ) against A549 cells of 62.82 μg/mL and
42.44 μg/mL for 24 h and 48 h, respectively[40].
The biosynthesis of pure metallic silver nanoparticles from
Dodonaea viscosa leaf extract using several polar and non-polar
solvents has been reported by Anandan et al.[42]. The formation
of AgNPs was accomplished by adding leaf extract (reductant) to
a solution of AgNO3 (1 mmol/L, 25 mL) with 2.5 mL of freshly
prepared buffer, followed by 2 h of magnetic stirring, resulting in the
formation of a dark brown color from a colorless solution of AgNO3,
which was eventually turned to black to confirm the production of
AgNPs. The leaf extract contains phytochemicals such as kaempferol,
sakuranetin, hautriwaic acid, and flavonoids which act as a reductant
and capping agent in the synthesis of AgNPs. The surface plasmon
resonance (max at 441–564 nm) in ultraviolet–vis spectra confirm
the synthesis of silver nanoparticles from Ag+ to Ag0 and HR-SEM
study reveals that the particle size for nano worms is in the 20–50 nm
range, 50–100 nm for flowers, 70–100 nm for spherical particles, and
micro-sized dendrites with a diameter of 0.7–2.5 nm and a length of
3.3–30 nm. Authors also reported that the cytotoxicity of synthesized
silver nanoparticles in A549 NSCLC cells using the MTT assay was
found to be 14, 3, 80, and 4 μg/mL for AgNPs synthesized using leaf
extracts obtained from methanol, acetone, acetonitrile, and water,
respectively. Nanoparticles of various sizes and surface properties
had a significant impact on cell membranes and it was observed that
enhancing the surface roughness of nanoparticles enhances the lipid
membrane’s phase transition temperature. Therefore, the findings
reveal that the fabricated AgNPs limit the proliferation of A549
NSCLC cancer cells synergistically[41-42].
Aceituno et al. [43] investigated how to synthesize AgNPs
nanoparticles from Pleuropterus multiflorus in an environmentally
sustainable way (root). With a z-average hydrodynamic diameter of
274.8 nm a large part of the AgNPs were spherical and crystalline.
After 3 h of incubation at 80 °C with 1 mmol/L AgNO3, the reaction
mixture changed color from pale yellow to dark brown, indicating the
formation of Pm-AgNPs. Proteins and phenols were found to be the
most important components in their synthesis and stability. Further,
Pm-AgNPs at a concentration of 25 mg/mL were noticeably cytotoxic
to A549 lung cancer cells[43]. Apoptosis, which seems to have distinct
morphological characteristics, has always been assumed to be an
indispensable component of various processes such as normal cell
turnover, embryonic development, and chemically induced cell
death[44]. In another work, Annu et al.[45] worked on the green synthesis
of AgNPs using an aqueous extract of Punica granatum peel as a
precursor, as well as both stabilizing and reducing agents. For the
synthesis of AgNPs, a 4 mmol/L solution of silver nitrate was
prepared in an Erlenmeyer flask, and 1 mL of plant extract was added
to 10 mL of silver nitrate solution separately. To prevent
photoactivation of silver nitrate at room temperature, this setup was
Table 3
List of studies exploiting plant-mediated nanoparticles anti-lung cancer activity.
Plant Nanoparticles Chemical constituents Mechanism of action IC50 Cell line activity Methods/ assays Reference
Induce oxidative stress, leading to apoptosis via caspase-mediated and
Abelmoschus esculentus AgNPs Polyphenolic compounds, catechins, flavanols, tannins 1.74 μg/mL A549 MTT [134]
mitochondria-dependent pathways
Carbohydrates, flavonoids, glycosides, phenolic
Synthesized agnps exhibits significant activity in killing the cells by
Allium sativum AgNPs compounds, proteins and amino acids, saponins, 13.26 ± 1.01 μg/mL A549 MTT [136]
apoptosis
tannins and terpenoids
Artemisia princeps AgNPs Phenolic compounds and volatile compound Induced mitochondrial-mediated apoptosis 30 μg/mL A549 MTT [138]
Avicennia marina AgNPs Ros/mitochondrial damages 50 μg/mL A549 MTT [139]
Activation of caspases, phosphatidylserine, externaliza- tion, plasma
Phenolic and flavonoids content such as gallic acid,
membrane blebbing, bi-nucleation, cytoplasmic vacuolation, cell
Azadirachta indica CuONPs quercetin, catechins, epigallocatechine gallate, ferulic 26.03± 1.84 μg/mL A549 MTT [94]
shrinkage, nuclear sfragmentation, chromatin condensation, and
acid, proanthocyanidins
chromosomal apoptotic bodies and dna fragmentation
Borago officinalis AgNPs Linolenic acid Reactive oxygen species (ros) 5 μg/mL A549 MTT [140]
Carbohydrates, flavonoids, glycosides, phenolic
Synthesized agnps exhibits significant activity in killing the cells by
Camellia sinensis AgNPs compounds, proteins and amino acids, saponins, 17.25 ± 0.43 μg/mL A549 MTT [136]
apoptosis
tannins and terpenoids
Ros generation leads to an impairment of proteins and nucleic acids and WST formazan
Carpesium cernuum AgNPs Glycosides, sterols and sesquiterpenoid lactones dose-dependent A549 [141]
results in cytotoxicity dye
CC-agnps regulated apoptosis using the intrinsic pathway to inhibit a549-
Coptis chinensis AgNPs Carboxyl (-c=o) and hydroxyl (-oh) groups 10 μg/mL A549 MTT [143]
cell proliferation
Synthesized agnps exhibits significant activity in killing the cells by
Curcuma longa AgNPs Cineol, borneol and curcumin 11.11 ± 0.59 μg/mL A549 MTT [136]
apoptosis
Enhanced cellular uptake and retention of nps, the cp-agnps showed a
Cucumis prophetarum AgNPs Tannins, alkaloids, triterpenoids, phenol, saponins 105.8 μg/mL A549 MTT [145]
difference in cytotoxicity
3-Feroylquinic acid, neochlorogenic acid, chlorogenic
acid, p-coumaric acid, carlinoside, isoschaftoside,
Cymbopogon citratus AgNPs isoorientin, cynaroside, veronicastroside, Increasing the apoptotic gene expression 25 μg/mL A549 MTT [146]
luteolin 7-oneohesperidoside, kurilensin a and
cassiaoccidentalin b
Inhibition of nf-κb activity, a decrease in bcl-2, and an increase in
Dimocarpus longan AgNPs Phenolic acids, flavonoids 5.33±0.37 μg/mL H1299 MTT [113]
caspase-3 and survivin expression
14, 3, 80 and 4 μg/mL for
Kaempferol, sakuranetin, hautriwaic acid for methanol, acetone,
Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1–20

Dodonaea viscosa AgNPs Apoptosis or necrosis A549 MTT [42]

Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1-20

And flavonoids acetonitrile and water

extracts, respectively
4, 60, 8, and 100 μg/mL
of leaf extracts obtained
Flavonoids and other phenolic
Dodonaea viscosa AuNPs Inducing apoptosis from methanol, acetone, A549 MTT [162]
Compounds
acetonitrile and water,
respectively
Enicostema axillare SeNPs Flavanoids and lignin Apoptotic activity 80 μg/mL A549 MTT [100]
Omega-3 fatty acids, essential oil, phenolic and water-soluble
Cell growth inhibition, cell damage, cell clump, cell burst, a higher level
Hibiscus cannabinus AgNPs flavonoid compounds, phenylpropanoid compounds, 849.33 μg/mL A549 tetrazolium [123]
of ros generation, and apoptotic cells
and ascorbic acid, kaempferol (WST)
Activation of caspases, phosphatidylserine, externaliza- tion, plasma
Phenolic and flavonoids content such as gallic acid and membrane blebbing, bi-nucleation, cytoplasmic vacuolation, cell
Hibiscus rosa-sinensis CuONPs 20.15 ± 1.22 μg/mL A549 MTT [94]
quercetin shrinkage, nuclear fragmentation, chromatin condensation, and
chromosomal apoptotic bodies and dna fragmentation
Up-regulation of caspase 3,9 and p53, Annexin V-FITC/PI, DAPI
7

Juniperus chinensis AgNPs Flavones, lignins, and terpenes 9.87 μg/mL A549 MTT [151]
7

staining, and ROS production indicated the remarkable apoptotic effect

 8
8

Table 3 (Continued)
Plant Nanoparticles Chemical constituents Mechanism of action IC50 Cell line activity Methods/ assays Reference
Α-pinene, β-pinene, myrcene, limonene, linalool,
Generation of intracellular ros, leakage of plasma membrane, dysfunction
Laurus nobilis ZnONPs methyl chavicol, neral, α-terpineol, geranyl acetate, 80 mg/ mL A549 MTT [84]
of mitochondria and cell death
eugenol, and chavicol
Elevated ros directs to the fragmentation of nucleus and depolarization of
Magnolia officinalis AuNPs Phenolic compounds and terpenoids 20 μg/mL A549 MTT [112]
mitochondria, which results in oxidative stress interceded apoptosis
Flavonoid Ptnps enter the cell and arresting cellular growth by damaging the double
Maytenus royleanus PtNPs Dose dependent A549 MTT [128]
Derivatives, phenolic acids stranded dna molecules
Millettia pinnata AuNPs Ascorbic acid and ascorbic oxidasec Apoptotic 14.76 μg/mL A549 MTT [166]
Flavonoids, saponins, lectins, protein, steroid, Induced cytotoxicity is often mediated through generation of intracellular Sulforhodamine
Momordica charantia AgNPs 51.93 mg/mL A549 [152]
triterpene, phenolic compound and alkaloid oxidative stress B (SRB)

Activation of caspases, phosphatidylserine, externaliza- tion, plasma

Phenolic and flavonoids content such as membrane blebbing, bi-nucleation, cytoplasmic vacuolation, cell
Moringa oleifera CuONPs 34.37 ± 1.81 μg/mL A549 MTT [94]
Catechol, quercetin, shrinkage, nuclear fragmentation, chromatin condensation, and
chromosomal apoptotic bodies and dna fragmentation

Activation of caspases, phosphatidylserine, externaliza- tion, plasma

Phenolic and flavonoids content such as gallic acid, membrane blebbing, bi-nucleation, cytoplasmic vacuolation, cell
Murraya koenigii CuONPs 25.05 ± 1.31 μg/mL A549 MTT [94]
catechol, quercetin shrinkage, nuclear fragmentation, chromatin condensation, and
chromosomal apoptotic bodies and dna fragmentation

Induction of apoptosis
Protein, amino acids, tannins, saponins, flavonoids,
Ocimum americanum CuONPs And arrested the inhibition of a549 lung cancer cells in g0/g1 18.43 μg/mL A549 MTT [93]
terpenoids and/or steroids, alkaloids
Phase
Inhibit cell viability, induced oxidative stress, inhibited the epidermal
Ginsenosides, polysaccharides, triterpenoids and
Panax ginseng AgNPs growth factor (egf)-enhanced migration, as well as decreased the mrna 20 μg/mL A549 MTT [155-156]
flavonoids
levels and phosphorylation of egf receptors in a549 cells.
Induce apoptosis via reactive oxygen species generation, mitochondrial
Pinus roxburghii AgNPs Flavonoids and phenolics depolarization, cell cycle perturbation, stimulation of caspase-3 and 11.28 ± 1.28 μg/mL A549 MTT [157]
Parp-1
Alkaloids (such as piperine, wisanine, dipiperamides, 135, 157 and 187 μg/L for
Piper nigrum SnO2NPs and piperidines), Induce the production of ros samples S1 (300 °C), S2 A549 MTT [171]
Glycosides, tannins, and flavonoids (500 °C) and S3 (900 °C)
Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1-20
Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1–20

Induced the apoptosis of skov3 cells by up regulating the caspase-3,

Rhynchosia suaveolens AgNPs Flavonoids and proteins caspase -8, caspase -9, p53 and bax and down regulating the antiapoptotic 24.7 μg/mL A549 MTT [160]
protein bcl-2
Flavonoids, terpenes, antocyanins, glycosides,
Physiochemical interaction of silver nanoparticles with the intracellular
Rosa damascene AgNPs carboxylic acid, vitamin c, myrcene, kaempferol 80 μg/mL A549 MTT [159]
proteins and dna.
And quercetin
Stimulate reactive oxygen species and effect in damage cellular
Syzygium aromaticum AgNPs Carvacrol, thymol, eugenol and cinnamaldehyde 50 μg/mL A549 MTT [161]
components which lead to cell death
Activation of caspases, phosphatidylserine, externaliza- tion, plasma
Phenolic and flavonoids content such as gallic acid, membrane blebbing, bi-nucleation, cytoplasmic vacuolation, cell
Tamarindus indica CuONPs 18.11± 0.93 μg/mL A549 MTT [94]
resveratrol shrinkage, nuclear fragmentation, chromatin condensation, and
chromosomal apoptotic bodies and dna fragmentation
 Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1–20
Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1-20
incubated in a dark chamber. The color change of the solution from
colorless to brown confirmed the reduction of Ag to Ag 0. The
inhibited cell growth of lung cancer A549 cells and non-cytotoxicity
of biologically synthesized silver nanoparticles revealed anti-
cancerous activity, which may be due to its ability to arrest the cell
cycle at the G1 phase[45]. Derris trifoliate seed extract, when introduce
to aqueous silver nitrate solution, resulted in the extracellular synthesis
of stable crystalline silver nanoparticles. The metal ions were bio-reduced
relatively quickly in solution, resulting in a high density of stable silver
nanoparticles with average sizes (16.05 ± 5) nm. The produced
nanoparticles appeared to be almost spherical in shape and polydisperse.
Cyril et al.[46] reported that the presence of secondary metabolites with
hydroxyl, amine, and carbonyl groups in D. trifoliate seed participated
in the bio-reduction of silver ions and stabilization of the nanoparticles. In
addition, the reduction of Ag+ to its corresponding silver atoms of
nanoscale dimensions could be induced and catalyzed by sunlight. It was
believed that the anticancer activity of D. trifoliate was due to its relative
stability, which facilitated their penetration and survival in A549
tumor cells. Furthermore, non-aggregated, small AgNP-DTa (using an
aqueous seed extract of D. trifoliata) are capable of producing
reactive oxygen species (ROS) in cells (Figs. 3 and 4). Accumulation
of ROS can result in oxidative stress, which can cause DNA damage,
significant morphological changes in A549, and eventually apoptotic
cell death[46]. In an elegant study, Kanipandian et al.[47] reported the
rapid biological production of silver nanoparticles (13–40 nm,
spherical) using commercially useful crop Gossypium hirsutum
(cotton) leaves extract as phyto-reducer and capping agent. For silver
ion reduction in the photo-synthesis protocol, 20 mL of aqueous leaf
extract was added dropwise into 100 mL of 1 mmol/L silver nitrate
with constant stirring. The presence of proteins, phenolic compounds,
and silicon (Si-O-Si) in leaf extract may act as a reducing agent to
form Ag ions. The formation of AgNPs is indicated by the appearance
of a dark brown color in the reaction mixtures which seems to be an
effective effect against human lung cancer cells (A549). The
researchers reported that when A549 cells were treated with AgNPs,
they went into G2/M arrest, which eventually leads to apoptosis cell
death. Moreover, gene analysis showed decreased expression of
anti-apoptotic (Bcl-2) and increased expression of pro-apoptotic (Bax)
mitochondrial genes[47-48]. The reaction of aqueous silver ions with
Beta vulgaris concentrate resulted in the extracellular production of
silver nanoparticles at different temperatures. The reduction of Ag+
ions was accomplished by adding 10 mL of B. vulgaris concentrate to
90 mL of 1 mmol/L silver nitrate solution. The solution turned greyish
red, confirming the reduction of silver nitrate into silver nanoparticles.
The AgNPs formed were predominantly spherical and poly-disperse
with sizes in the range of 10 to 20 nm. Nayaka et al.[50] revealed that
resulting NPs have a good cytotoxic impact against A549 cells
compared to normal cell lines. The IC50 values for B. vulgaris aqueous
extract and produced AgNPs against the A549 cell line were around
70 μg/mL and 42.8 μg/mL after 48 h of incubation, respectively.
However, when compared to B. vulgaris extract, cell viability
decreased with increasing concentrations of test AgNPs. This could
be due to silver nanoparticles production of reactive oxygen species
(ROS) and their effect on cellular components, which leads to cell
death[49]. Spherical AgNPs were synthesized via a facile one-step
green method using Zanthoxylum rhetsa (Roxb) DC seed coat extract.
AgNPs were synthesized by interacting 5% of seed coat extract with
9
9
95% of 0.1 mmol/L AgNO 3 solution. The aqueous extract of
Z. rhetsa, which contains protein residues and flavonoids, has a high
affinity for silver ions, resulting in the creation of a capping that
protects AgNPs from agglomeration and provides stability. The
nanoparticles are poly-dispersed and size in the range of 10–68 nm.
The produced AgNPs displayed anticancer activity and showed a
direct dose dependent response on A549 cell lines. AgNPs
significantly inhibited the proliferation of A549 cells, with an IC50
value of 65.17 μg/mL. The authors of this study mentioned that the
action of AgNPs on cancer cell lines is not yet understood properly. It
was assumed that the Ag+ ions released by AgNPs have a strong
interaction with cell membrane proteins and nucleic acids such as
DNA and RNA. It has also been noted that AgNPs have the ability to
either break lysosomal membrane integrity or disrupt cell membrane
integrity by causing leakage. By capturing free electrons inside the
cell membrane, nanoparticles cause the production and accumulation
of ROS, which causes oxidative stress and cell deformation. In
addition, ATP production decreases. These reactive oxygen species
can attack DNA-dependent protein kinase and impair its enzymatic
activity, which is considered necessary for DNA damage repair via
non-homologous end joining. As a consequence, cancer cells lose
their ability to repair damaged nucleic acid content, which results in
cell death [50] . Nanoparticles of silver were prepared by using
Euphrasia officinalis leaf aqueous extract. Singh et al.[51] illustrate the
stable synthesis of AgNPs was achieved by mixing aqueous solutions
of AgNO3 with E. officinalis leaf extract for 19 min and incubating at
65 °C. The color was switched from yellow to light brown to reflect
the synthesis of AgNPs, as the particles trigger surface plasmon
resonance (SPR), which results in a light brown color. The presence
of functional groups in plant extract is involved in the reduction of
silver ions to metal nanoparticles. The size of the synthesized
crystalline AgNPs was determined to be 40.37 ± 1.8 nm. The particles
showed anticancer activity against A549 (human lung cancer) cell
line. The MTT technique evaluates the activity of succinate
dehydrogenase, thus the observed result could be owing to the
cytostatic or cytotoxic action of nanoparticles, though the activity
highlighted the substantial anticancer activity of AgNPs[51]. Bauhinia
purpurea (Fabaceae) leaf extracts have produced noble silver
nanoparticles (100–150 nm) within 1 min. For the biosynthesis of
AgNPs, 5 mL of leaf extract was mixed with 45 mL of deionized
water, and AgNO3 solution was added to a final concentration of
1 mmol/L in the reaction mixture. The emergence of silver nanoparticles
prompted the color of the silver nitrate leaf extract reaction mixture to
change from colorless to yellowish brown. It was suggested that leaf
extract performed as both a reducing and stabilizing agent for the
development of nanoparticles [52] . Phytochemical analysis of
B. purpurea leaf extract reveals that it contains glycosides, flavonoids,
phenolic compounds, saponins, tannins, fats, fixed oils, and
phytosterols[53-54]. These nanoparticles had an excellent anticancer
effect against lung carcinoma cell line A549 in a dose-dependent
manner with IC 50 values of 27.97 μg/mL. Nanoparticles have a
significant cytotoxic effect due to their high affinity for biological
macromolecules and easy penetration to cellular barriers[55]. According
to several research, nanoparticles cause cytotoxicity by releasing
reactive oxygen species (Fig. 3). It generates intracellular oxidative
stress, which damages cellular components and eventually
leads to death[56-57].
10 Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1–20

10 Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1-20

Fig. 3 The roles of physicochemical and biological features of green synthesis nanoparticles and their interactions with malignant cell properties.

Fig. 4 Schematic interpretation of green synthesized nanoparticle (NP) cellular effects.

7.2 Gold nanoparticles (AuNPs)
Plant extracts have been widely used in the production of AuNPs.
Proteins, enzymes, vitamins, terpenoids, flavonoids, polyphenols, and
polysaccharides are examples of plant biomolecules that can serve
as reducing, stabilizing, or capping agents[58]. Plant extracts contain
a variety of plant biomolecules in various forms and dosages, which
might also affect the biological activity of produced nanoparticles.
Zhang et al.[59] found that AuNPs (130 nm) were prepared using leaf
extracts of Rabdosia rubescen. AuNPs were produced by mixing
10 mL of R. rubescens aqueous extract with 190 mL of 1 mmol/L
Gold (III) chloride trihydrate solution and incubating for 15 min
at room temperature. The structure of AuNPs exhibits a ring-like
structure which signifies the AuNP synthesized is of crystalline
nature nanoparticles. The authors also found that produced
nanoparticles have an IC50 dosage of 25 μg/mL against the A549 lung
cancer cell line[59]. The active components ponicidin and oridonin,
two diterpenoids with substantial anti-angiogenic activity, were
accountable for the cytotoxic action of RR-AuNP[60]. Moreover, gold
atoms provide an interface that prevents intracellular proteins and
phosphate from binding to nitrogen groups in DNA[61]. The ability of
gold nanoparticles to inhibit the expression of signaling proteins such
as Ras, Akt, and tumor markers (Fig. 4), among others, is responsible
for their anticancer properties[62]. Researchers investigated the effect
of RR-AuNP on apoptotic signaling proteins, which constitute a
critical pathway disrupted in most cancer[59]. Stable AuNPs were
synthesized from flower aqueous extract of Moringa oleifera. For the
production of nanoparticles, 1 mL of the supernatant flower extract
was added to 49 mL of 1 × 10-3 mol/L HAuCl4 solution at room
temperature and stirred. The development of the pink color validated
the existence of a redox reaction in which Au+ ions are reduced to
Au0 by plant components, which confirm the successful formation
 Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1–20
Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1-20
of nanoparticles. Components such as phenolics, polyols, amines,
flavonoids, water-soluble heterocyclic components, tannins, saponins,
gallic acids, proteins, reducing sugars, and other oxido-reductively
labile metabolites can act as reducing agents[63]. Previous research on
the phytochemistry of M. oleifera revealed a large number of organic
chemicals, implying that water-soluble hydroxy functional group-
containing molecules are responsible for the reduction of Au+ ions[64-65].
The particles are spherical or nearly spherically shaped and poly-
dispersed in the colloidal solution, with a size distribution of 3–5 nm.
The MTT tests were utilized to assess cytotoxicity in transformed
A549 (human lung epithelial adenocarcinoma cells) and healthy
peripheral lymphocytes (PLs). At dilutions of 1:100, 1:50, 1:25, 1:10,
and 1:3, the AuNPs were considerably cytotoxic to A549 cells, with
viabilities of 140%, 139%, 71%, 49%, and 12%, respectively [63].
Latha et al.[66] have used leaf extract of Justicia adhatoda to produce
gold nanoparticles in an aqueous solution. AuNPs (40.1 nm) were
synthesized by adding 1 mL of leaf extract to 7 mL of HAuCl4·3H2O
solution. The reduction of Au3+ ions to Au0 caused a pink-ruby red
color to occur within 20‒30 min which confirm the formation of
AuNP[66]. Previous studies reported that the leaf contains phenols,
tannins, alkaloids (vasicine, vasicinol, vasicinone, adhavasinone,
adhatonine and peganine), anthraquinones, saponins, flavonoids
(apigenin, astragalin, kaempferol, quercetin, vitexin), reducing
sugars and vitamin C [67]. These phytocompounds help to reduce
metal levels while also acting as a capping and stabilizing agent. The
fabricated spherical nanoparticles showed remarkable cytotoxicity
activity against the A549 cancer cell line. The produced AuNPs
caused 50% cell death at a concentration of 80 μg/mL, which is
termed the IC50 value[66]. Biosynthesized AuNPs can pass through
cell membranes into ion channels and bind with DNA molecules,
preventing replication and other nuclear functions and therefore
reducing metabolic activity [68-69]. In another study, Jha et al. [74]
used the leaf extract of Piper betle to make gold nanoparticles (10 nm)
by mixing it with an aqueous Gold (III) chloride salt solution
(0.025 mol/L). The leaf extracts of medicinal P. betle are high in
phytochemicals and contain a lot of alkaloids, steroids, terpenoids,
and flavonoids, all of which help with nano-transformation. These
phytochemicals also have the added benefit of acting as capping
agents, which helps to stabilize the nanoparticles[70-72]. The cytotoxic
effect of biogenic gold nanoparticles against the lung cancer cell line
(A549) was tested by incubating them with different doses of AuNPs
for 24 h. AuNPs effectively inhibited cancer cell proliferation, with
a reduction of 49.46% at a concentration of 200 μg/mL compared
to the control. The toxicity of AuNPs is caused by physiochemical
interactions of gold atoms with intracellular proteins and DNA,
resulting in cell death[73-74]. Nanoparticles of gold were prepared by
using the aqueous peel extract of Musa paradisiaca (MPPE-AuNPs).
The formation of gold nanoparticles was confirmed when 2 mL of
peel extract was combined with 25 mL of 1 mmol/L HAuCl4 and the
color changed from pale yellow to dark wine red[74]. The presence of
tannins, flavonoids, quinones, phenols, steroids, and phytosteroids
was discovered in a qualitative phytochemical examination of
M. paradisiaca peel aqueous extract which acts as a reducing and
stabilizing agent. The synthesized MPPE-AuNPs were crystalline in
form, spherical to triangular, and particle size ranged within 50 nm.
The authors investigated the in vitro cytotoxic effect of MPPE-AuNPs
against a human lung cancer cell line (A549) at various dosages
11
11
(25‒100 μg/mL) and discovered that the inhibitory concentration
(IC50) of MPPE-AuNPs against A549 lung cancer cells was 58 μg/mL.
Moreover, as compared to peel extract, A549 cells treated with
MPPE-AuNPs revealed nuclear morphological alterations such as cell
clumping and loss of membrane integrity at 100 μg/mL after 24 h[75].
7.3 Zinc oxide (ZnO) nanoparticles
ZnO nanoparticles have attracted attention in recent years due
to their broad variety of applications in electronics, optical, and
biological systems[76-77]. ZnO nanoparticles are the most appealing
metal oxides because they are cheap to manufacture, safe, and simple
to prepare[78]. ZnO has been classified as a GRAS (generally regarded
as safe) metal oxide by the US Food and Drug Administration[79].
It has numerous medicinal applications, including medication
delivery, anti-diabetic, anti-cancer, antifungal, antibacterial, and
agronomic qualities. ZnO nanoparticles have a very strong anti-
cancerous effect at a very low concentration on lung cancer confirmed
by the studies, they have shown a strong cytotoxicity effect than
the ZnO nanoparticles synthesized chemically. For example,
Rajeshkumar et al.[68] reported the biosynthesis of zinc oxide nanoparticles
(45‒60 nm) using Mangifera indica leaves by interacting 80 mL of
0.1 mol/L zinc nitrate with 20 mL of plant extract. The white
precipitate generated after the reaction mixture served as an early
indicator of successful ZnO nanoparticle synthesis. The chemical
mangiferin is abundant in M. indica leaf extracts. Pharmacologically,
mangiferin has been demonstrated to have antioxidative, antibacterial,
antifungal, antiviral, anti-inflammatory, anticancer, and anti-allergic
properties. In vitro, cytotoxicity experiments utilizing the MTT test
revealed dose-dependent activity changes in ZnO NPs’ cytotoxic
activity. At a concentration of 25 μg/mL, the percentage of viable cells
was inversely proportional to the concentration of ZnO nanoparticles.
However, the effectiveness of M. indica leaves in the production of
ZnO nanoparticles as well as their pharmacological effects have yet
to be investigated. The authors hypothesized that the nanoparticle
may pass past cell membrane ion channels and interact with DNA’s
nitrogen bases and intracellular proteins[80].
In another study, Selim et al.[81] used an environmentally friendly
extract of the aerial portions of Deverra tortuosa as a reducing and
capping agent to produce ZnO nanoparticles (15.22 nm). The addition
of crude plant extract to zinc nitrate hexahydrate (Zn(NO3)2·6H2O)
for synthesis resulted in a change in the color of the solution and
the production of a yellowish-white precipitate, indicating that the
zinc nitrate concentration had been reduced. Using the MTT test, the
potential anticancer activity was studied in vitro against human lung
adenocarcinoma (A549) and compared to the activities on the human
lung fibroblast cell line (WI38). The extract and Zn ONPs had IC50 of
193.12 and 83.47 μg/mL in A549 cells, respectively. The intracellular
release of dissolved zinc ions, coupled with ROS induction, is the
primary mechanism behind ZnO nanoparticle cytotoxicity. HPLC
examination reveals the presence of Gallic acid, Chlorogenic acid,
Caffeine, Coffeic acid, Syringic acid, Rutin, Ellagic acid, Coumaric
acid, Vanillin, Ferulic acid, Naringenin, Propyl Gallate, Quercetin,
Cinnamic acid, which could account for their therapeutic potential[81].
ZnO nanoparticles were synthesized by using the aqueous leaf
extract of Laurus nobilis (Ln-ZnO NPs) by the co-precipitation
method. The method of synthesis is that biomolecules found in the
12 Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1–20
12 Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1-20
leaf extract, such as apinene, β-pinene, myrcene, limonene, linalool,
methyl chavicol, neral, a-terpineol, geranyl acetate, eugenol, and
chavicol, form complexing agents with the precursors (zinc acetate),
which initially starts the process of nucleation forming reverse
micelle and then further causing reduction and shaping of NPs[82-83].
The formed nanoparticles were predominantly crystalline, flower-like,
and have a hexagonal wurtzite structure with a mean particle size of
47.27 nm. Vijaykumar et al.[84] investigated their anticancer activity in
human A549 lung cancer cells using an MTT[3-(4,5-dimethylthiazol-
2-yl)-2,5-diphenyltetrazolium bromide] assay. The results showed
that increasing the concentration of Ln-ZnO nanoparticles to
80 μg/mL reduced the viability of A549 cells[84]. ZnO nanoparticles
have generated an increase in intracellular ZnO concentration due to
their tiny size and large specific surface area, increasing intracellular
ROS production, plasma membrane leakage, mitochondrial
malfunction, and cell death[85-86].
Umamaheswari et al. [87] discovered the green manufacture of
zinc oxide nanoparticles (209 nm) from the leaves of Raphanus
sativus var. Longipinnatus and their anticancer efficacy in A549 lung
cancer cells. The synthesis of ZnO nanoparticles is demonstrated by
the white precipitate formed after the addition of zinc acetate to the
ethanolic extract of leaves. The presence of flavonoids and terpenoids
in the extract plays an important role in the reduction of metal ions
into nanoparticles via active chelation. The SEM magnification
images revealed that the ZnO nanoparticles are spherical, hexagonal-
shaped, and aggregated nanoparticles with irregular morphology. The
cytotoxicity of biosynthesized ZnO nanoparticles was investigated
in vitro using A549 lung cancer cell lines, and the IC50 was found to be
40 μg/mL[87]. The authors suggested that probable mechanisms include
DNA damage pathways, paraptosis, autophagy, radio-sensitization,
overcoming chemoresistance, inhibition of carcinogen-activation of P450
enzymes (phase I metabolism), or induction of carcinogen-detoxifying
enzymes (phase II metabolism) or oxidative stress regulation or induction
of apoptosis or interrupting of the cancer cell cycle[88-89].
7.4 Iron oxide nanoparticles (IONPs)
Thoidingjam and Tiku (2019) investigated the synthesis of two
types of IONPs, one without any coating (IONPUC, 12.8 nm) and the
other coated with Phyllanthus emblica (Amla) fruit extract (IONPA,
4.1 nm). The co-precipitation technique was used to coat NP with
plant extract by adding amla extract to iron salts and heating the
solution at 60 °C for 15 min with gentle stirring. The formation of
IONPs was confirmed by obtaining a black-colored solution, which
was then agitated for 90 min at 80 °C[90]. The fruit extract has a
high concentration of phytochemicals such as polyphenols, tannins,
flavonoids, terpenoids, alkaloids, saponins, proteins, carboxylic
acids, and others, as previously reported [91-92]. However, when
P. emblica extract was added to the IONPs precipitation process, the
components might act as reducing and stabilizing agents by adhering
to the surfaces, resulting in the creation of more stable and smaller
NPs. The therapeutic efficacy of both NPs was examined against lung
cancer cell lines, and the IC50 for A549 cancer cells was 359.8 μg/mL
(IONPUC) and 104.7 μg/mL (IONPUC) (IONPA). The researchers
noted that produced NPs increased reactive oxygen species
generation, DNA damage, and apoptosis, all of which increased
cancer cell toxicity[90].
7.5 Copper nanoparticles (CuONPs)
Manikandan et al.[93] investigated CuONPs (67.7 nm) synthesized
from Ocimum americanum aqueous leaf extract, which was employed
as a potential stabilizing and reducing agent for CuONP production.
Copper nanoparticles were formed by adding 2 mL of aqueous
leaf extract with 100 mL of 1 mmol/L CuSO4·5H2O solution in a
beaker. FT-IR analysis was used to confirm that the key functional
biomolecules (O–H, C=C, C–H, C–O) are responsible for CuONP
reduction and stabilization. The capping agent for stable CuONP
synthesis is phytochemicals from the leaf extract, which convert
copper sulfate II into Cu2+ and SO4. Furthermore, Cu2+ dissociates
from Cu0 by decreasing the phytochemicals present in the extract,
which then combine to create nanoparticles from copper nuclei, with
reaction time[93]. The manufactured CuONPs were assessed for dose-
dependent cytotoxicity against A549 human lung adenocarcinoma,
and the results revealed that 50% of cell death occurred at
18.43 μg/mL. The cytotoxicity of spherical CuONPs may be attributed
to the role of reactive oxygen species (ROS) in the formation of
programmed cell death at the end of the reaction[93].
In another study, Rehana et al. [94] revealed that copper oxide
(CuO) nanoparticles were manufactured via green chemistry using
several plant extracts taken from the leaves of Azadirachta indica,
Hibiscus rosa-sinensis, Murraya koenigii, Moringa oleifera, and
Tamarindus indica. In the green synthesis, 2 μg of copper acetate
tetrahydrate was dissolved in 20 mL of the aqueous extract while
being continuously stirred with a magnetic stirrer. Leaf extracts of
A. indica, H. rosa-sinensis, M. koenigii, M. oleifera, and T. indica
included carbohydrates, flavonoids, glycosides, phenolics, proteins
and amino acids, saponins, and tannins, where phenols and flavonoids
acted as a reducing and capping agent for the creation of copper oxide
nanoparticles. By using the MTT assay with cisplatin as a standard,
the anticancer activity of the synthesized copper oxide nanoparticles
was evaluated in vitro against a panel of human cancer cell lines lung
(A549). The potent efficacy of CuO-S6 may be due to the strong
influence of additional phytochemicals present in the extract used to
synthesize these nanoparticles. The CuO nanoparticles synthesized
from various plant leaf extracts have significant activity in killing
cells mostly through apoptosis[94].
7.6 Platinum (Pt) and palladium nanoparticles
To find new ways to make nanomaterials, Dobrucka et al. [95]
propose the biological synthesis of platinum nanoparticles using
Ononidis radix extract. For the nanoparticle synthesis, 0.02 μg
K2PtCl6 was added to a cooled 30 mL extract of O. radix and stirred
continuously for 5 h at 80 °C. During mixing the color change from
yellow to yellowish brown indicated the formation of platinum
nanoparticles as a result of the reduction of Pt4+ to Pt0 nanoparticles[95].
Phytochemical studies on O. radix revealed the presence of flavonoid
derivatives, sterols (-sitosterol, campesterol, stigmasterol, stigmastan-
3,5-dien), terpenic compounds, phenolic acids, and essential oils
(carvone, menthol, menthone, isomenthone, linalool, estragole,
borneol, and cisanethole which served as reducing and capping agents
for Pt nanoparticles[96]. The authors also examined the influence of
platinum nanoparticles on human non-small cell lung carcinoma
cells A549[95].
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Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1-20
Platinum and palladium nanoparticles (Pt NPs and Pd NPs) were
biologically synthesized from alkaloidal seed fraction of Peganum
harmala. When the seed fraction of P. harmala was introduced
to an aqueous solution containing 1 mmol/L Pt (IV) chloride or
1 mmol/L Pd (II) acetate, the color changed from yellow to dark
brown, indicating the production of Pt and Pd NPs[97]. The seed of
P. harmala is high in potent bioactive alkaloids, such as -carboline
and quinazoline alkaloids (such as harmine, harmane, harmol,
harmaline, harmalol, and peganine), which are collectively referred to
as harmala alkaloids[98]. In addition, oxygenated monoterpenes (such
as eugenol), anthraquinones, flavonoids, and polysaccharides found in
the seed of P. harmala are responsible for the bio-reduction of various
metal ions[98-99]. Using the SRB assay, the cytotoxic activities of generated
Pt NPs, Pd NPs, and Pt-Pd NPs were compared to the individual metal
ions on lung cancer cells (A549). The IC50 value of Pt NPs, Pd NPs, and
Pt-Pd NPs was found to be 10.9 ± 0.31, 31 ± 0.28, and 8.8 ± 0.11 μg/mL,
respectively. The anticancer effect of biogenic metals may be
mediated by inhibition of a key proteolytic enzyme, according to
docking results, which are validated by in vitro assay information[97].
7.7 Selenium nanoparticles
A simple biological technique utilizing the reducing power of
Enicostema axillare leaf extract was used to accomplish the green
synthesis of selenium nanoparticles (SeNPs) under an ambient
condition. When E. axillare leaf extract was added to the selenious
acid solution, it turned ruby red [100]. The formation of selenium
nanoparticles is induced by the reduction of selenious acid by
flavonoids and lignin found in E. axillare[101]. The cytotoxicity of
biogenic SeNPs was investigated using the MTT assay, with the
concentration of SeNPs necessary for 50% cell death (IC50) in A549
cell lines being 80 μg/mL in 24 h and ~ 40 μg/mL[102-103]. The results
showed that the synthesized SeNPs exhibit effective apoptotic action
in a lung cancer cell line, indicating that they have a bright future in
cancer therapy.
Fig. 5 Mechanisms of bioengineered nanoparticle interactions with biological components of a human lung cancer cell.
13
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8. Possible mechanism of synthesized nanoparticles
Although a lot of research has looked at the anticancer action of
biosynthesized nanoparticles, the detailed mechanisms underlying this
process are still unknown. Plant-based NPs typically elicit reactive
oxygen species (ROS), which leads to cellular death. ROS alters
signal transduction pathways, resulting in cellular apoptosis[104]. The
molecular and cellular alterations generated by phytoconstituents
can be either inhibitory (primarily of anticancer qualities like cell
viability, tumor invasion, expansion, proliferation, and development)
or promoting (mainly of apoptotic pathway and cell death). In human
cells, NPs can interfere with processes like pinocytosis, endocytosis,
and phagocytosis[105]. NPs might release ions that enter the nucleus
and cause DNA fragmentation/hypermethylation and/or cell cycle
arrest in cancer cells (Fig. 5). Furthermore, NPs’ inhibitory effect
on cellular viability is due to the downregulation of antiapoptotic
genes, e.g. Bcl2, generation of reactive oxygen species (ROS),
mitochondria fission and autophagy and events that finally induce
cell death through apoptosis[106]. For example, AgNPs have been
shown to cause cytotoxicity in mammalian cells through a variety of
mechanisms[107], including (a) disruption of energy-dependent cellular
functions and impaired DNA replication caused by free silver ion
uptake (b) production of reactive oxygen species (ROS) and free
radicals (c) cell membrane damage caused by direct interaction with
AgNPs[108-109]. Nagalingam and co-workers, in their study observed
in vitro anticancer potential of A. bettzickiana mediated AuNPs against
lung cancer cell lines A549. In the in-vitro study, AuNP showed
potent antiproliferative activity against lung cancer cell line with
IC50 ranging from 10–50 μg/mL. AuNP induced A549 cell apoptosis
with downregulation of BCL-2 and upregulation of Bax, caspase 3,
caspase 9, and cytochrome C. Survivin, dc25C, CDK2, CDK4,
CDK6, COX-1, COX-2, PGE2 expression levels, and reduction
of the proteins cyclin A-B in A549 human lung cancer cell lines
were drastically reduced after treatment with plant-based silver
nanoparticles. Moreover, a significant up-regulation of the pro-
inflammatory genes like IL0, IL1β, IL-6, NF-KB, and TNF-α (Fig. 5)
in AuNP exposed A549 cells[110].
14 Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1–20
14 Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1-20
Nanomaterials can induce apoptotic signaling via both intrinsic
and extrinsic mechanisms. ROS generation causes mitochondrial
membrane depolarization, which leads to cytochrome c release into
the cytosol in the event of apoptosis caused by the intrinsic pathway.
This cytochrome c then activates the caspase-9/3 apoptotic cascade by
activating pro-apoptotic proteases in extrinsic pathway apoptosis[111].
According to Zheng et al.[112], AuNP treatment caused ROS generation
in A549 cells, which could lead to oxidative stress-induced apoptosis,
as well as down regulation of Bcl2 and Bid and overexpression of Bax,
caspase 3, and Beclin 1 with IC50 ranging from 20–25 μg/mL[112]. In
another lung cancer in vitro experiment, with IC50 of 5.33 ± 0.37 μg/mL
AgNPs show a powerful inhibitory effect on H1299 cells[113], which
had a greater rate of metabolism, rapid cell division, and so had
more AgNPs internalization, resulting in a higher cell death rate. The
sequence of steps includes inhibition of NF-κB activity, a decrease
in bcl-2, and an increase in caspase-3 and surviving expression[114-115].
Fig. 5 depicts the key theories proposed in the literature about the
many ways in which green biosynthesized NPs may operate or
interact with malignant cells.
On the other side, the anticancer potential of some green-
produced NPs may be related to the attributes of the biomolecules
or phytochemical constituents inherent in the plant extract.
Sharma et al. [116] produced TiO 2NPs from Rheum emodi roots,
recognized for their therapeutic effects due to the presence of
chrysophanol, emodin, and aloe-emodin anthraquinones. The
cytotoxic potential of these NPs was investigated using a good
diffusion technique and the results revealed that biosynthesized
TiO2NPs had a very effective role as a nano drug to treat cancer cells
while also protecting other healthy cells[116].
9. Toxicity and biofate of green synthesized nanoparticles
Despite the promising potential of green synthesis nanoparticles in
the biomedical area, there are certain adverse health effects associated
with their use. As toxicity is considered a major concern regarding
the limitations of using nanoparticles in biomedical applications.
Consequently, the effects of increased nanoparticle exposure in
animals, humans, and the environment, as well as the potential hazards
in terms of acute and chronic toxicity, must be investigated [117].
Different properties of green synthesized NPs, including shape, size,
surface chemistry, targeting ligand, elasticity, and composition,
influence their toxicity to biological systems. In addition, when metal-
containing nanoparticles were exposed to human lung epithelial cells,
reactive oxygen species were produced, which can cause oxidative
stress and cellular damage[118-119]. In vivo and in vitro potential hazards
of green synthesized nanoparticles to cells and their possible risks are
reviewed here.
A recent study on the toxicity of plant-mediated AgNPs has found
that they have a significant anti-lung cancer potential while posing
little risk to normal cells. For instance, Kanipandian et al.[120] study the
toxicity effect of AgNPs synthesized from G. hirsutum to the living
system is carefully investigated by in vivo analysis. Remarkably, no
pathological evidence was found in the AgNPs-treated mice group,
indicating that AgNPs do not cause toxicity to major organs [120].
Kummara et al. [121] investigated the cytotoxicity of Azadirachta
indica-mediated AgNPs against the NCI-H460 non-small cell lung
cancer (NSCLC) cell line. At a concentration of 120 × 10-6, it was
found that half of the malignant cells were destroyed. In the case of
chemical AgNPs, toxicity was shown in normal cells at concentrations
of 120 ×10-6[121]. Biosynthesized AgNPs are more compatible with
normal cell lines as acidic pH in not provided around normal cells.
These findings were confirmed when AgNPs made from Olax
scandens leaf extract were found to have significantly higher killing
activity in cancer cells (A549: human lung cancer cell lines) than in
122]
normal cell lines (rat cardio-myoblast normal cell line H9C2) . In
another study in vitro cytotoxicity and cell viability of the synthesized
AgNPs employing seed extract of H. cannabinus were investigated
against mouse embryonic fibroblast cells (NIH3T3) and human
lung cancer cells line (A549). The results showed that in the case of
normal cells (NIH3T3), AgNPs exhibited mild toxicity in a dose-
dependent manner, with 32.77% suppression of cell growth found
at the optimum dose (1 000 μg/mL)[123]. AgNPs synthesized from
P. daemia and P. rubrasis latex had no discernible harmful impact
on P. reticulata upon 24‒48 h exposure to manufactured AgNPs
containing up to 14.08 mg/L[124].
Similarly, Green synthesized AuNPs can induce toxicity in cancer
cell lines through oxidative stress and inflammation by generating
ROS[125] which favors DNA damage and hence leads to apoptosis and
cell death[126-127]. Anand et al.[63] performed MTT assays to investigate
the cytotoxicity of AuNP synthesized from M. oleifera in transformed
A549 (human lung epithelial adenocarcinoma cells) and normal
healthy peripheral lymphocytes (PLs). The results showed that AuNPs
cause considerable cytotoxicity to A549 cells but not to normal
healthy PLs[63]. Another study studied zebra fish embryos to evaluate
the toxicity profile of ZnO NPs biosynthesized from Cycas pschannae
leaf extract, and found that Daniorerio had the lowest embryo
mortality, implying higher biocompatibility at 20 μg/mL. Treatment
of normal human lung cell lines (L132) and lung cancer cell lines
(A549) with IONPs showed dose-dependent toxicity. However,
IONPs synthesized from Phyllanthus emblica fruit extract were more
toxic to cancer cell lines (A549) compared with normal cell lines
(L132)[90]. PtNPs produced employing leaf extract of M. royleanus,
were reported to exhibit anticancer activity against A549 cancer cells
and low cytotoxicity against normal cells[128].
Phyto biochemical coatings of the plant-mediated NPs are
released easily with the aid of acidic tumor environments and thus
boost the anticancer activities of nanoparticles. To reduce toxicity,
the biological synthesis of NPs is preferred due to the occurrence of
biocompatible phytoconstituents[129-130]. Thus, plant-synthesized NPs
can be produced much safer than chemical-synthesized NPs[104]. All
such studies confirm that plant-mediated NPs represent high anti-
lung cancer activity along with low toxicity toward normal cells.
These findings from the latest studies could provide a new way for
NPs utilization in clinical trials for lung cancer treatment shortly.
Considering the cost, environmentally friendly green synthesized
NPs could be advocated as potent futuristic candidates for potential
biomedical applications owing to their significant specificity and
lesser toxicity.
10. Future outlook
Despite recent improvements in cancer treatment, lung cancer
continues to be the main cause of mortality globally. Since plants
are a natural source of bioactive phytochemicals with the unique
 Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1–20
Atiqul Islam et al. / Journal of Future Foods 5-1 (2025) 1-20
property of reducing metals and can produce NPs of various sizes
and applications, they have drawn a lot of interest in the field of
nanoscience over the past 10–12 years. These NPs demonstrated
exceptional efficacy as anti-lung cancer agents in vitro. To
determine the future path of their application, clinical trials of
green-produced NPs-based nanomedicines are necessary. The most
important problems now being addressed in clinical trials are NPs’
biodegradability, dose, administration method, and side effects[131-132].
Additionally, 1) methods for synthesizing NPs with the best possible
qualities that make them effective anticancer agents and minimize
potential toxicity on human or animal cell lines, and 2) identification
of prospective targets among the numerous cancer cells that can be
successfully targeted, 3) Thorough evaluation should be done before
producing universally recognized clinical forms of NPs for anticancer
purposes [133]. Because of its physicochemical characteristics and
biological benefits, plant-based NPs will therefore turn into a really
useful tool for researchers to combat life-threatening diseases.
Additionally, industry analysts believe that the future of the global
nanotechnology sector is promising.
11. Conclusion
The macromolecular and micromolecular phytochemicals found
in plants are responsible for nanoparticle bio-reduction. Plants have
sophisticated chelation processes to detoxify metals to counteract
metal toxicity. Metal ions can be removed from the body via vacuolar
squassation by oligopeptides, photoheating, and a low molecular
weight > 5 000 compounds called metallothioneins. The use of these
plant-based micromolecules and macromolecules for the production
of metallic nanoparticles is simple, convenient, economical, easily
scaled up, less energy-intensive, eco-friendly, and reduces the
use of hazardous ingredients while increasing process efficiency.
Furthermore, green synthesize NPs are more stable and effective than
those produced by physicochemical approaches. It is particularly
well suited to the production of NPs that need to be free of toxic
contaminants for biomedical and therapeutic applications.
Researchers have focused their efforts on comprehending the
biological pathways and enzymatic activities involved in nanoparticle
biosynthesis, as well as the detection and characterization of
biomolecules involved in metallic nanoparticle formation. Metal
nanoparticle bio-reduction, synthesis, and stability may be aided
by plant biomolecules such as proteins/enzymes, amino acids,
polysaccharides, alkaloids, alcoholic compounds, and vitamins.
Future studies could concentrate on improving reaction conditions
and creating recombinant organisms for the high-volume production
of proteins, enzymes, and biomolecules involved in nanoparticle
manufacturing and stabilization.
Nanoparticles derived from several plant extracts have shown
promise in the treatment of lung malignant cells. As a result, of
their decreased cytotoxicity towards cancer cell lines, normal cells
may be a possible future cancer treatment candidate. In vitro tests
have been conducted to investigate the anti-lung cancer activity of
biosynthesized NPs, however, very few studies have been done in vivo
experiments to confirm the anti-lung cancer activity of biosynthesized
NPs. To further investigate the anti-lung cancer advantages of
biosynthesized NPs, in vivo, studies should be conducted. The future
approach to increasing the productivity and anti-lung cancer activity
15
15
of these bioactives in nanoparticle manufacturing is to genetically
modify plants with enhanced metal tolerance and accumulation
capacity.
Competing interests
The authors declare no conflicts of interest.
Acknowledgments
We thank the Department of Pharmacognosy, ISF College of
Pharmacy, Moga, Punjab and NMPB, New Delhi for providing the
necessary facilities. We thank Editage Ltd. for editing the English text
of a draft of this manuscript.
Author contributions
Dr. Alok perceived the idea of the review manuscript. Mr. Atiqul
has done extensive literature search sing various searching tools and
prepare the first draft of the manuscript. Dr. Iqra Rahat contribute
in the revision of the manuscript. Dr. Devkant prepare figures in
this manuscript. Dr. Chandrababu Rejeeth and Prof. Xianting Ding
provided critical feedback and guided in the compilation and data
analysis of this manuscript.
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