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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5409_Библиотеки_им_академика_М_И_Перельмана.pdf
Implications and Future Perspectives of Nanomedicine and Plant-Based Biogenic Nanoparticles (NPs)
agents in the treatment of a variety of cancers. Ag nanoparticles have been employed to deliver medications with the potential to improve therapeutic parameters. For cancer therapy, Ag nanoparticles coupled
with phytopharmaceuticals can be used as non-toxic delivery vehicles, contrast agents, and photothermal
agents. Prostate and colon cancer can be treated using biogenic Ag nanoparticles. Ag nanoparticles made
from Indigo ferahirsuta leaf extract and pollen extract of Phoenix dactylifera, for example, demonstrated
dose-dependent cytotoxicity against various malignancies. A novel drug delivery method was created
using Ag nanoparticles coated with a camptothecin-based polymer pro drug for long-term drug release
based on pH sensitivity. Co-delivering medications with particles with varied physicochemical properties
has been proposed as another promising technique for suppressing tumor metastasis and overcoming
treatment resistance (Navya et al., 2019; Gautam et al., 2021).
Iron Oxide Nanoparticles (IONPs)
The Iron oxide nanoparticles (IONPs) aroused as the agnostic NPs given a means to image the response
of the tumors, toward the drugs delivered during the clinical trials for cancer (Manatunga et al., 2018).
Iron oxide nanoparticles (IONPs) have developed as therapeutic nanoparticles that can be used to image
drug distribution and tumor response, addressing unmet clinical problems in cancer treatment. Prostate
cancer is currently being treated with paclitaxel drug loaded on double receptor targeted iron oxide
nanoparticles. These iron oxide nanoparticles were successfully ingested by the human prostate cancer
cell line PC-3, according to the findings. When compared to normal prostate epithelial cells, in vitro
magnetic resonance imaging verified the increased binding and accumulation of ironoxide nanoparticles
in PC-3 cells. Using iron oxide nanoparticles, a theranostic nanoparticle was recently developed to
improve intra-tumoral drug delivery by overcoming drug resistance and delivering image-guided drug
delivery while minimizing systemic toxicity. The uptake and dispersion of iron oxide nanoparticles in
the PANC02 mouse pancreatic cancer cell line were studied using three different targeted nanoparticles
and one non-targeted nanoparticle. The study also showed that remaining tumors could be detected after
intraperitoneal medication, implying that drug-resistant tumors might be removed using image-guided
surgery (Navya et al., 2019).
Carbon-based Nanomaterials
Due to its attractive qualities like to cargo high amount of drugs, large surface area, and ease to adjust
surface, carbon-based nanomaterials have been widely researched in cancer imaging and diagnosis, as
well as for delivery system. Carbon nanotubes (CNTs) and graphene are the well-studied carbon nanomaterials in therapeutic applications related with the cancer. Carbon nano tubes are used as efficient system
for the delivery of drugs to target cancer cells more effectively. Recent research on multi-walled carbon
nanotubes (MWCNTs) for drug co-delivery has indicated that drug release at the cancer site, as well as
cell uptake, has the potential to cure multi-drug resistant cancer. MWCNTs have been synthesized that
have high drug loading ratio along with active targeting ability and better circulation half-life (Wang et
al., 2017). A potential multimodal nanomedicine for cancer treatment has been developed by utilizing
the heat generated by the pH-sensitive nano-platform in response to the light absorption when exposed
to near-IR (NIR) light along with the toxicity of DOX. In another study, TiO2–Au nanocomposite was
used to decorate multi-walled carbon nanotubes, and the system was found to be effective in generating
toxicity in A549 and MCF7 cancer cell lines (Navya et al., 2019).
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Implications and Future Perspectives of Nanomedicine and Plant-Based Biogenic Nanoparticles (NPs)
Mesoporous Silica Nanomaterials (MSNs)
The MSNs are among the hopeful nanocarriers for well-organized delivery of the cancer therapeutics.
The opportunity of using MSNs as probable nanocarriers has determined attention in many biomedical
claims (Manzano & Vallet-Regí, 2018). Because of the ease with which mesoporous silica nanoparticles
can be modified to have varied properties, multifunctional delivery platforms can be designed. Many
researchers have used mesoporous silica nanomaterials to load cargos and convey them to tumor tissues
because of these characteristics. Because of the medication’s solubility, stability, and bioavailability, many
anticancer therapeutic applications are limited. Li et al. (2018) created unique nanocarrier systems for
releasing the curcumin precisely at the targeted tumor site environment. Curcumin was delivered to breast
cancer cell lines loaded with hyaluronan or polyethyleneimine-folic acid using these surface changeable
mesoporous silica nanomaterials, which were tested in a mouse xenograft model (Navya et al., 2019).
Organic Nanomaterials (ONMs)
The ONMs are hopeful applicants for the progress of drug delivery systems. The low toxicity, have
allowed the nano-medicine investigation community to practice ONMs for releasing the drugs in a
controlled manner and at very precise tissue location (Daima et al., 2018).
Liposomes
Liposomes are closed spherical shaped structure made up of natural or synthetic phospholipid bilayer
adjoining an inner aqueous phase. Consistently, these vehicles compromise numerous other compensations, with self-assembly, biocompatibility, and high drug cargo loading. Liposomes are good drug-carrier
systems because of their physical similarities to biological membranes and their capacity to integrate
with a variety of compounds. In biomedical uses of liposomes, significant progress has been achieved
in enhancing the therapeutic index of encapsulated medicines over the last 20 years. Different types of
liposomes are employed as drug delivery platforms to improve the efficacy of cancer treatments. Liposomes can be attached on the exterior surface with poly(ethylene glycol) (PEG), targeting ligands and/or
antibodies, and polysaccharides to improve solubility, increase hydrophilicity, and provide passive and
active targeting functionalities, resulting in high therapeutic efficacy and minimal toxicity (Sercombe
et al., 2015; Bozzuto & Molinari, 2015).
Polymeric NPs
Beneficial molecules will be enclosed, adsorbed, or conjugated in the polymer matrix of the polymeric
nanoparticles, which are colloidal NPs. Artificial and biological polymers can be utilized to make these
NPs, and they’ve been widely used in drug-delivery systems. Because of their specific features, such as
drug solubility, stability, and preferential accumulation, these nanoparticles can be modified for a variety
of biological applications. The diverse chemical composition, charge, and physical structure, polymeric
nanoparticles serve as a varied substrate for drug delivery. Furthermore, due of their customizable drug
release kinetics, they have gained commercial importance. The cancerous cells have been targeted and
polymeric nanoparticles have been used for transfer of drugs efficiently. The tumor-specific targets have
been explored on the cell surface for destroying the tumor cells. To target specific cells, different ligands
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419
Implications and Future Perspectives of Nanomedicine and Plant-Based Biogenic Nanoparticles (NPs)
such as aptamers, peptides, proteins, antibodies, and tiny compounds have been utilized. Targeting cells
using nanoparticles resulted in extremely precise cargo delivery, resulting in high therapeutic concentrations within the cell. Several studies have been conducted. Several studies have shown that targeting
moieties improve anticancer activity. The drug docetaxel (DTX) has been successfully delivered using
the drug delivery system comprising of surface modified polylactic acid (PLA) nanoparticles for treating
the liver cancer (Masood, 2016; Navya et al., 2019).
Table 1. Classification and Functions of Nanoparticles
Nanocarriers Materials Drug Target References
Metal NPs
Carbon NPs
Mesoporous silica
NPs
Liposomes DPPC, MPPC
Polymeric NPs PLA Calcitriol Human breast cancer (in vitro) Nicolas et al.,(2018)
Apatite stacked
Gold NPs
CTAB and gold
nanoparticles
AgNPs Imatinib
PEG and AgNPs Methotrexate Human breast cancer Muhammad et al.,(2016)
PEG and single walled
carbon nanotubes
Human serum albumin,
single walled carbon
nanotubes
PEG amino-betacyclodextrin, folic
acid, mesoporous silica
nanoparticles
Aptamer, mesoporous
nanoparticles
DSPE-PEG2000-Pen,
DSPE-PEG2000-Tf
PLGA, PEG, Chitosan Curcumin
Docetaxel Human liver cancer (in vitro) Wan et al., (2018)
Fluorouracil
Cisplatin
Paclitaxel Human breast cancer (in vitro) Shao et al.,(2015)
Doxorubicin Breast cancer (in vivo) Zhnag et al.,(2013)
Doxorubicin Colon cancer (in vitro) Xie et al.,(2016)
Tamoxifen,
imatinib
5-Fluorouracil Human glioblastoma (in vitro)
Human skin cancer (in vitro/ in
vivo)
Human breast adenocarcinoma
(in vitro)
Head and neck cancer (in vitro/
in vivo)
Human breast cancer (in vitro) Jose et al.,(2018)
Human pancreatic cancer (in
vitro)
Safwat et al., (2018)
Shandiz et al.,(2017)
Bhirde et al.,(2010)
Lakkadwala and
Singh,(2018)
Arya et al.,(2018)
BIOLOGICAL SOURCES OF NANOPARTICLES SYNTHESIS
Fungal-based Nanoparticles
An efficient and environmentally acceptable method for the production of (AgNPs) utilizing aqueous
culture filtrate of Pestalotiopsis microspora has been disclosed in a study. The presence of a characteristic
absorption peak at 435 nm in ultraviolet visible examination validated the synthesis of AgNPs. In the
fungal filtrate, FT-IR spectroscopy revealed the presence of phenolic chemicals and proteins, which are
likely involved in the production and capping of AgNPs. The AgNPs were spherical in shape and 2–10
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Implications and Future Perspectives of Nanomedicine and Plant-Based Biogenic Nanoparticles (NPs)
Figure 2. Mechanism of Interaction of Bioengineered Nanoparticles and Cancerous cells (Karmous et
al., 2020).
nm in size, according to the TEM. The crystalline nature of AgNPs with a face-centered cubic (FCC)
lattice phase was determined using selected area electron diffraction and X-ray diffraction experiments.
The biosynthesized AgNPs had a high negative zeta potential of -35.7 mV, according to dynamic light
scattering studies. Strong cytotoxic effects have been reported against PC3 (human prostate carcinoma,
A549 (human lung adenocarcinoma, SKOV3 (human ovarian carcinoma, and B16F10 (mouse melanoma)
cells lings with the IC
values of 27.71, 39.83, 16.24 and 26.43 µg/mL, respectively. Normal cells (Chi-
50
nese hamster ovary cell line, IC50 =438 µg/mL) were found to be biocompatible with the biosynthesized
AgNPs. On most vulnerable SKOV3 cells, cytological observations revealed concentration-dependent
apoptotic alterations such as cell shrinkage, cell membrane blebbing, pyknotic nuclei, and karyorrhexis
followed by destructive nuclei fragmentation (Netala et al., 2016; Gautam et al., 2021).
Algal-based Nanoparticles
The shape of the NPs is kinetically regulated growth process in a solution where certain form is adopted
by the faces with low energy. Further the presence of the surfactant or templating agent results in development of the crystal by lowering the interfacial energy (Xia et al., 2003). Commercially many surfactants
are used as capping agents as well as templates for the NPs synthesis with a variety of morphologies
up to this point. However, the major concern is the complete elimination and biodegradation of these
compounds. At the present time, Green synthesis process for the nanoparticles synthesis is trending
due to its environmentally friendly and bioinspired methods. NPs of greater quality can be created by
understanding the capacity of naturally existing biomolecules to change the shape or size of a crystal.
The employment of several species of algae in the synthesis of metallic NPs has prompted scientists to
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Implications and Future Perspectives of Nanomedicine and Plant-Based Biogenic Nanoparticles (NPs)
Figure 3. Production of various extracts from fungi and production of AuNPs by various methods using: (i) extracellular extract; (ii) auto lysate; (iii) intracellular extract (Molnar et al., 2018; Gautam et
al., 2021).
develop “nature-friendly” methods. Because of their potent antibacterial properties, Ag NPs have gotten
a lot of interest.
As a result, synthesis takes place in the presence of microalgae, with the metabolites released by the
algal culture causing silver ions to be reduced. The optical characteristics of the NPs can be changed
depending on the particle size (Merin et al., 2010). Silver nitrate was shown to be reduced in the presence of the seaweed Chaetomorpha linum. The extract’s metabolites (flavonoids and terpenoids) were
shown to be excellent capping and stabilising agents, resulting in the creation of NPs with an average
size of 30 nm that might be used in medicine (Kannan et al., 2013). Biomolecules found in algae species,
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Implications and Future Perspectives of Nanomedicine and Plant-Based Biogenic Nanoparticles (NPs)
such as polysaccharides, are also crucial in influencing the size and shape of Ag NPs. The marine algae
Pterocladia capillacae, Jania rubins, Ulva faciata, and Colpmenia sinusa are effective in supporting
the production of polydispersed and spherical Ag NPs capable of immobilising on cotton fibres. As a
result, they function as antibacterial agents (El-Rafie et al., 2013). Using microalgae as a bio-template, a
composite of nano Ag-CaCO
dioxide (CO
) was mineralized using a microalga (Chlorella sp.) to generate calcium carbonate (CaCO3)
2
was created in an efficient and environmentally friendly manner. Carbon
3
microspheres (Sahoo et al., 2014).
The generation of CaCO
cells. The positively charged Ca
particles was discovered to be caused by the surface charge of microalgae
3
2+
ions agglomerated on the surface of negatively charged algal cells
due to electrostatic interactions, and so served as a driving force for the nucleation process. The size
2+
of microspheres was also affected by the concentration of Ca
ions. The larger the size of the CaCO3
microspheres, the higher the concentration, maintaining the concentration of algal cells constant and
favouring heterogeneous nucleation. The microspheres were employed as an inexpensive matrix for
the production of Ag NPs. The composite demonstrated an effective antibacterial action against model
bacteria such as E. coli, Psychrobacter alimenterius, and Staphylococcus euroum, paving the door for
its commercialization as paint additives (Sharma et al., 2019).
Plant-based Nanoparticles
In the current study, we used Heliotropium bacciferum extract and AgNO3 as starting ingredients to
make silver nanoparticles (AgNPs). Various spectroscopic and microscopic techniques were used to
confirm the size, shape, and structure of produced AgNPs. The average size of biosynthesized AgNPs
was discovered to be between 15 and 20 nanometers. In breast (MCF-7) and colorectal (HCT-116)
cancer models, the anticancer potential of these AgNPs was assessed using a battery of tests including
(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) (MTT), scratch, and comet assays.
The expression pattern of apoptotic (p53, Bax, caspase-3) and antiapoptotic (BCl-2) genes by RT-PCR
validated the toxicity of AgNPs towards cancer cells. AgNPs had IC50 values of 5.44 and 9.54 µg/mL
in MCF-7 and HCT-116 cell lines, respectively, in the cell viability assay.
ANTICANCER ACTIVITIES OF BIOGENIC NANOPARTICLES
Silver NPs (AgNPs)
The biological AgNPs can be hired against colon and prostate cancer. For example, the AgNPs manufactured by using leaves extract of Indigo ferahirsuta L. (Fabaceae) and pollen extract of Phoenix
dactylifera L. (Aracaceae)have shown anticancer activity against diverse cell lines in a dose dependent
manner (Netala et al.,2018; Banu et al.,2018). Sargassum vulgare (Phaeophyceae)-based AgNPs showed
the substantial anticancer activity against the human myeloblastic leukemic cells (HL60) and HeLa
cells (Lewis Oscar et al., 2016). At various doses of AgNPs (3 to 50 µg/mL), S. muticum-based AgNPs
showed in vitro cytotoxic characteristics against the MCF7 breast cancer cell line for approximately 48
hours, with the highest viability rate of 100.36% reported at 12.5 µg/mL concentration. These AgNPs
mainly responsible for generation of ROS intracellularly, which further leads to apoptosis and ultimately
death of cancerous cells (Supraja et al., 2016). S. myriocystum-based AgNPs has been assessed for their
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Implications and Future Perspectives of Nanomedicine and Plant-Based Biogenic Nanoparticles (NPs)
cytotoxic capabilities against the HeLa cell line at different concentrations (0, 2, 4, 8, 16, 32, 64, 128,
256, to 512 µg/mL) using MTT assay and observed that the AgNP-treated HeLa cell line showed 50%
inhibitory (Balaraman et al., 2020). Similarly, different concentration of the silver nanoparticles synthe-
sised using algae showed in vitro cytotoxicity propensity against the malignancy MCF-7 cell line when
used for24-48 h, with 20 µg/mL MIC value, indicating nuclear fragmentation, cell death, and apoptosis,
indicating AgNPs’ anticancer potential (Gopu et al., 2020).
Gold NPs (AuNPs)
It has been studied that gold NPs synthesized by use of aqueous leaves extract of Argemone mexicana
L. showed cytotoxicity in response to the breast cancer cell line (MCF-7). The activation of caspases
begins the apoptotic cell death processes (Varun & Sellappa, 2014). The aqueous extract of Corallina
officinalis L. (Corallinaceae) produced NPs, which indicated the cytotoxicity against human breast
cancer cells through necrosis and DNA damage (El-Kassas & El-Sheekh, 2014). The aqueous pollen
extract of P. dactylifera was used for AuNPs production, which showed the cytotoxicity against breast
cancer cells and by modulating the expression of pro (Bcl-2) and anti-apoptotic proteins (Banu et al.,
2018). Acanthophora spicifera-based AuNPs exhibited robust anticancer potential against the colorectal
adenocarcinoma HT-29 cell line at various concentrations (1.88, 3.75, 7.5, 15, and 30 µg/mL) using MTT
assay. The MIC value of 21.86 µg/mL was reported, which is responsible for apoptosis, and shrinkage of
cells in cancer cell lines (Babu et al., 2020). After incubation with these nanoparticles, Chaetomorpha
linum-based AuNPs showed in vitro anticancer potential towards the HCT-116 colon cancer cell line in
a dose-dependent manner. A series of apoptotic inductions has been identified, including the activation
of apoptotic caspase 3 and 9, as well as a decrease in anti-apoptotic proteins such as Bcl-xl and Bcl-2,
proving that the AuNPs generated by algae are effective anticancer agents (Acharya et al., 2020).
Copper/copper oxide NPs
Phaseolus vulgaris L. (Fabaceae) based copper oxide NPs has been showed cytotoxicity activity against
the cervical cancer. The apoptotic pathways activation was mediated by intracellular reactive oxygen
species and used for the detection of growth inhibition and death of cells as assessed by using colonyforming assay (Nagajyothi et al., 2017). The copper NPs have also attracted interest as the carcinogenic
nano-entities for their effortless availability, lower price, and metals’ close like nessin properties (Manke
et al., 2013).These nanoparticles have excellent property of transforming near infrared laser light to heat
efficiently for its use in cancer imaging(Zhou et al., 2016).Multiple malignant cell lines have been found
to be cytotoxic by a variety of naturally produced Cu/CuO NPs. Plant-based CuO NPs with a diameter
of (26.6 nm) were found to have inhibitory effects on cervical cancer cell lines HeLa by starting reactive
oxygen species (ROS) mediated apoptosis (Nagajyothi et al., 2017). CuO NPs (12 nm size), synthesised
using a green approach exhibited anticancer activity against different cancer cell line like breast cancer
(MCF-7), cervical cancer (HeLa) and lung cancer (A549) with a broader range of IC50 values (Rehana
et al., 2017). Biosynthesized spherically shaped CuO NPs of 26–30 nm diameters (with a 56.16 µg/mL
IC50 value) were used to inhibit MCF-7 breast cancer cell lines (Nisaret al., 2019). The biologically
produced CuONPs showed anticancer activity by fragmenting the nucleus to bring apoptosis of lung
cancer cell lines A549 (IC50 value of 200 µg/mL) (Sankar et al., 2014).Different sized spherical CuO
NPs showed anticancer activity against the breast cancer cell line (AMJ-13),cervical cancer cell lines
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Implications and Future Perspectives of Nanomedicine and Plant-Based Biogenic Nanoparticles (NPs)
(HeLa), lung cancer cell line(A549), ovarian cancer cell line (SKOV-3) and prostate cancer cell lines
(PC-3) with very low IC50 values (Harne et al., 2012; Prasad et al., 2016; Sulaiman et al., 2018).
Zinc and Zinc Oxide NPs (Zn/ZnO-NPs)
The biologically synthesized zinc and zinc oxide NPs has gained attention for eco-friendly nanoparticles
synthesis due to the metabolites such as alkaloids, flavonoids and phenolics present (Thema et al., 2015).
ZnONP has been biologically synthesized using numerous plant portions and their anticancer effect has
been studied in vitro by using different malignant cell lines. Different shaped biologically synthesised
ZnNPs exhibited cytotoxicity against lung cancer cell lines, A549 and Calu-6. The IC
of the nanoparticles vary greatly and affected by the plant source used for their synthesis (Firdhouse
et al., 2013). Different plant extracts were utilized for the synthesis of spherical and hexagonal ZnNPs
(ranging between 22.5–50 nm), that inhibited the WEHI-3 leukaemia cancer cell lines with varied IC50
values (Min, 2007; Park et al., 2011). The IC
value of biologically produced spherical ZnNPs varied
50
proportionally with the dose applied and was greatly affected by the plant extract used for synthesis (Zhu
et al., 2012; Saud Alarifi et al., 2013). The biologically synthesized ZnNPs (sizes 10 ± 1.5 nm) showed
inhibitory actions against the CaOV-3 ovarian cancer cell lines (IC
value of 10.8 ± 0.3 µg/mL) (Talalay
50
et al., 2003). The inhibition by biologically synthesized spherical ZnNPs (47 nm size) was observed
against colon cancer cell lines HT-29 with (9.5 µg/mL IC
value) (Yang & Xie, 2006). The epidermoid
50
cancer cell lines A43 and A44 and liver cancer cell lines Hep-G2 were shown to have putative inhibitory
effects by biologically produced ZnO-NPs (Premanathan et al., 2011; Zhao et al., 2013).
values and size
50
CONCLUSION
Several important progresses have been prepared towards the use of tailored nanomaterials (NMs) to treat
the cancer with efficiency, specificity, and high sensitivity. Tailored NMs operationalized with precise
ligands that can predictably target the cancer cells and deliver encapsulated payloads meritoriously.
Moreover, NMs can also be deliberated to increase the drug loading, controlled release, improved halflife, and selective distribution by altering their size, surface chemistry, composition, and morphology.
The conservatively existed cancer treatments have existing natural boundaries that provoked the event
and applications of nanomaterial, which compromised a hopeful and harmless dealing. The emerging
evidence suggests that nanomedicines will provide the next-generation stages for anticancer remedy.
Therefore, in this chapter, a series of biological NMs that are presently being working for the anticancer
healings and converse the central role of their biological possessions in the cancer remedy.
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