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INTERNATIONAL JOURNAL OF AGRICULTURE & BIOLOGY
ISSN Print: 1560–8530; ISSN Online: 1814–9596
23–0232/2023/30–3–189–199
DOI: 10.17957/IJAB/15.2075
http://www.fspublishers.org
Review Article
To cite this paper: Shnawa BH, PJ Jalil, SO Swar (2023). Greener nanoparticles: potential alternative approach to fight protozoal diseases. Intl J Agric Biol
30:189‒199
Greener Nanoparticles: Potential Alternative Approach to Fight
Protozoal Diseases
Bushra Hussain Shnawa1*, Parwin Jalal Jalil1,2 and Sara Omar Swar3
1Department of Biology, Faculty of Science, Soran University, Soran 30802, Iraq
2Scientific Research Centre, Soran University, Soran 30802, Iraq
3College of Agricultural Engineering Sciences, Salahaddin University, Kurdistan, Iraq
*For correspondence: bushra.shnawa@soran.edu.iq
Received 23 June 2023; Accepted 15 July 2023; Published 28 August 2023
Abstract
Protozoa are unicellular eukaryotes parasitic organisms that are the primary causes of global morbidities and mortalities, in
particular in developing nations. Several of them cause zoonotic protozoal diseases, such as toxoplasmosis, Chagas' disease,
babesiosis, giardiasis and leishmaniasis, which can produce dangerous infections, with asymptomatic animals being able of
spreading sickness. At present, protozoa are cured with chemotherapeutic antiparasitic medicines, although resistance to these
treatments has developed over time due to misuse. Recently, Nanoparticles (NPs) are confirmed to be a significant innovation
in the therapy and manipulation of parasitic infections in this scenario. In the last years, there has been tremendous progress in
the discipline of parasite control using nanomedicine. Furthermore, NPs synthesized in green methods have a significant effect
against most of the protozoan parasites. Recent research showed that green-based synthesized silver and gold NPs have
demonstrated promising outcomes in the treatment and management of several parasitic illnesses. Additionally, other
nanoparticles including zinc and copper and their oxides nanoparticles also exhibited anti-protozoan effects in recent studies.
However, there are no sufficient studies explaining the mechanism of nanoparticles against protozoa. These nanoparticles
function in a variety of methods, including organism plasma membrane damage, DNA interruption and protein production
suppression, besides free radical fabrication. These substances are also efficient against intracellular parasites. The objective of
this review is to summarize the technologies utilized to create nanoparticles as well as their potential modes of action against
protozoal parasites. Additionally, it focuses on all the recent updates about biosynthesized nanoparticles against protozoan.
This pilot review was designed to cover the updated nano medication against protozoal diseases which hopes to develop a
modern effective drug and vaccine. © 2023 Friends Science Publishers
Keywords: Nanoparticles; Antiprotozoal; Green fabrication; Plant extract; Drug resistance
Introduction
The parasites are eukaryotic organisms that live inside or
on their hosts and rely on them for resources like nutrition,
accommodation and safety (Pritt 2020). Parasites are
categorized into three divisions including protozoa, beside
helminths as well as ectoparasites based on the parasites’
morphology, genetic variation, evolution and adaptations
(Rokkas et al. 2021). Parasitic infections are a major cause
of death in these illnesses, and the majority of these
illnesses are regarded as neglected tropical diseases.
Chemotherapeutic drugs and ethnobotanicals remedies
have been used traditionally by people to treat certain
parasite illnesses, particularly malaria and gastrointestinal
parasitic infections as well as echinococcosis (Shnawa et
al. 2017; Ebiloma et al. 2019; Belete 2020; Imarhiagbe
2021; Aslam et al. 2022; Nawaz et al. 2022). Furthermore,
the secondary metabolites that give these therapeutic plants
their anthelmintic potential include tannins, flavonoids and
essential oils (Degla et al. 2022).
Parasite transmission happens via vectors, faecal-oral
contamination, or direct connection (Imarhiagbe 2021).
Both humans and animals are susceptible to parasite attacks,
which constitute a serious threat to both of their lives.
Because parasitic illnesses may not present any observable
symptoms, they are more difficult to diagnose and cure than
bacterial diseases (Shnawa 1995; Zaheer et al. 2021).
Protozoa include several pathogenic parasites that
impact human and animal health like Entamoeba
histolytica, Toxoplasma gondii, Sarcosystis spp. and others
(Shani et al. 2012; Shnawa 2017; Swar and Shnawa 2020).
Among these protozoan parasites, the most harmful and
fatal parasite infecting humans is Plasmodium falciparum
(White et al. 2014; Tabassum et al. 2022). Some
antiprotozoal medications that are available and used to treat
various protozoal illnesses are including antimalarials, anti-
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190
amoebic, anti-giardial, trypanocidal, anti-leishmanial and
anti-toxoplasmic medicines (Shibeshi et al. 2020; Syed et
al. 2020; Sobhy et al. 2021; Stevens et al. 2022). The
parasite DNA is disrupted, protein synthesis is inhibited, the
parasite membrane is damaged and the protozoa are killed
by these chemicals (Bahuguna and Rawat 2020). However,
several of the available treatments against these protozoans
are no longer effective owing to the progress of resistance
by these pathogenic protozoa (Raj et al. 2020). In this
aspect, antimalarial drug resistance refers to a parasite
strain's capacity to persist and/or proliferate despite the
administration and absorption of medication at doses that
are equal to or higher than those typically advised. The
parasite mutation rate, total parasite load, chosen drug
strength and other factors are among those that encourage
the development of resistance to currently available
antimalarial drugs (Shibeshi et al. 2020).
In recent times, nanotechnology is emerged as a
promising arena of multidisciplinary research because of
its extensive use in various fields of science. Metal NPs
such as silver and gold nanoparticles (NPs) are
recommended for various illnesses as drugs (Patra et al.
2015; Xu et al. 2020). The production of NPs through
green biosynthesis, which relies on plant extracts, is
advised today. Aside from being simple, clean, efficient,
safe, and affordable, the green production of metal NPs
has many other benefits as well. According to recent
results, using plants as an immune stimulant in
Oreochromis niloticus culture systems represents a more
affordable option than fish meal (Kiran et al. 2022).
As a result of NPs' exceptional characteristics, such as
their large surface-to-mass ratio, quantum structures, and
capacities to adsorb and transport other compounds (drugs,
probes and proteins), nanoparticles are crucial for medical
applications. Due to their ease of use, environmental
friendliness, accessibility, and nontoxicity, the greener
fabrication of metal oxide nanoparticles has garnered a lot
of attention over the past few years. Also, nanoparticles are
tested as anti-microbial substances to enhance the shelf life
of food products (Shnawa et al. 2021; Azam et al. 2022;
Shnawa et al. 2022a). The green process of NPs fabrication
is depicted in Fig. 1.
Numerous studies on the development of
nanotechnologies using a variety of plant extracts from
various plant parts have been published (Kumar and
Rajeshkumar 2018; Hano and Abbasi 2021).
Exosomes, liposomes, and solid lipid NPs, besides
nano-vaccines, are examples of nano-sized particles used in
the formulation of novel treatments and drugs carriers that
have the potential to overcome problems with little
bioavailability, reduced toxicity, sub-therapeutic drug
accumulation in microbial reservoirs, in addition to, low
patient adherence because of drug-correlated side effects
and lengthy therapeutic schedules. Therapeutic methods
based on nanotechnology provide a crucial tool in the battle
against contagious protozoan diseases (Raghav et al. 2023).
The use of nanoparticle technology in the diagnosis,
prognosis and treatment of diseases in people is known as
nanomedicine. This field of study has the potential to
revolutionize medical research. Nanomedicine applications
include chemotherapeutic aspects, insulin pumps, diagnostic
tests and a variety of medical sensors. They also include
drug delivery systems for use in body tissues (Shnawa et al.
2022b).
Different diseases are caused by parasitic protozoan
organisms. They are extremely complicated to control. The
utilization of AuNPs and AgNPs against these protozoal
diseases has been successful (Fig. 2). Below is a description
of a few of these protozoans (Bajwa et al. 2022).
Globally, parasitic protozoan diseases are a major
cause of mortality and morbidity. Tropical or non-endemic
diseases spread because of numerous factors like climate
change, extreme poverty, migration, and a lack of
opportunities in life. Although there are many medications
available to treat parasitic diseases, it has been noted that
some strains are resistant to common medications (Gaona-
López et al. 2023). Additionally, a lot of first-line
medications have negative side effects that can range from
mild to severe, including possible carcinogenic effects. To
combat these parasites, new lead compounds are therefore
required. Several studies were achieved regarding the
antiparasitic potency, it is believed that nanoparticles play
an essential role in vital aspects against these organisms
within in vitro and in vivo models Therefore, it is anticipated
that there will be significant growth in the field of using
nanotechnology to combat these parasites. This review
provides a concise summary of the main fabricated
nanostructures, specifically biosynthesized ones and their
potential as treatments for a group of medically significant
protozoal diseases.
Updated nanoparticles research for controlling
protozoal diseases
Plasmodium (malarial disease): Malaria is a member of
the greatest frequent tropical infections, which is brought on
by parasite protozoa of the species Plasmodium spp. It is a
significant public health issue with a value of 228 million
patients with a great number of morbidity and mortality on a
global scale (Ezzi et al. 2017). The rise of parasites that are
resistant to medication, insufficient vector control methods,
and a lack of malaria vaccines offer severe obstacles to the
eradication of malaria. The drugs are frequently used in the
medication and limitation of malaria, resulting in a variety
of tissue damages, such as harmful toxic effects and the
establishment of medication resistance (Al-Salahy et al.
2016; Gujjari et al. 2022).
Due to the various antimicrobial capabilities that have
been assessed, research on silver nanoparticles (AgNPs) has
lately intensified (Galatage et al. 2021). In an investigation
into the antimalarial potential of gold (AuNPs) and silver
(AgNPs) nanoparticles generated by Syzygium jambos (L.),
Alston (Myrtaceae) leaf and bark extract. Both preparations
Effect of Nanoparticles against Protozoa / Intl J Agric Biol Vol 30, No. 3, 2023
191
derived from AgNPs exhibited stronger antiplasmodial
activity (Dutta et al. 2017).
Additionally, NPs created by S. jambos extracts
showed minimal cytotoxicity towards rat skeletal muscle
cell line (L6) and human cervical cancer cell line (HeLa),
indicating their biocompatibility (Dutta et al. 2017). In a
similar investigation, two Artemisia species, A.
abrotanum and A. arborescens, were used to fabricate
green-based silver nanoparticles (Ag NPs), which
displayed hemocompatibility and antimalarial activity in
vitro experiments on Plasmodium falciparum cells have
been investigated. However, it was observed that A.
abrotanum-AgNPs had stronger activity on pRBCs than
A. arborescens-AgNPs. Additionally, the parasite growth
was stopped in the ring stage after 24 and 48 h of A.
abrotanum-AgNPs treatment, demonstrating the ability of
these nanoparticles to prevent P. falciparum from
maturing (Avitabile et al. 2020).
Also, AuNPs created by using the leaf extract from
Cymbopogon citrus have demonstrated significant efficacy
against a variety of mosquito species, including Anopheles
(A. stephensi) (Mohammadi et al. 2021a). This evidenced
that plasmodim spp. may be controlled by utilizing
nanoparticles against mosquitos.
In another investigation, the effectiveness of neem-
silver nitrate NPs utilizing watery extracts against two
laboratory-adapted strains of P. falciparum— the 3D7 which
is classified as (chloroquine-sensitive) and W2 known as
Fig. 1: Green fabrication of Nanoparticles
Fig. 2: Silver and gold nanoparticles' antiparasitic effects (Bajwa et al. 2022)
Shnawa et al. / Intl J Agric Biol Vol 30, No. 3, 2023
192
chloroquine-resistant was assessed. They verified that
synthetic neem-AgNPs have a significant capability for
usage in the medication of malaria. also, According to the
hemolysis assay, both the aqueous extract and the
synthesized neem-AgNPs do not have hemolysis action
against healthy and parasitized erythrocytes (Ghazali et al.
2022).
Along the same line, adequate knowledge of the
mechanisms of NPs that contribute to antiplasmodial
activities is absent until now. Studies describing the
biological mechanisms underlying Ag NPs' antiprotozoal
activity are relatively rare (Sjöholm and Sandler 2019).
Meanwhile, the study of AgNPs' antibacterial properties
revealed important features of their action, which are mainly
related to the production of reactive oxygen species, which
promotes cell death mechanisms, particularly via
mitochondrial apoptotic ways, along with significant cell
membrane impairment and enzyme deactivation via silver
binding (Huq et al. 2022). Moreover, Avitabile et al. (2020)
explained that the main effects of nanoparticles include
extensive cell membrane damage, enzyme deactivation via
AgNPs binding, and the production of ROS (reactive
oxygen species), which is a catalyst for cell death
mechanisms, particularly via mitochondrial apoptotic
pathways. All of these occurrences, singly or collectively,
may be able to impair plasmodium cell functionality,
producing effective results. According to their findings, the
same authors concluded that the antiplasmodial activity of
Artemisia-derived AgNPs in vitro tests against P.
falciparum is promising (Avitabile et al. 2020).
In conclusion, malaria treatment and management
depend mainly on chemical substances, which come with
many drawbacks like serious toxic side effects, the
emergence of drug resistance, and high medication costs.
The development of new drugs is urgently required to
overcome the clinical shortcomings of anti-malarial drugs.
Nevertheless, the process of finding and developing new
drugs is costly and time-consuming. Nanotechnological
approaches could present promising alternatives, with
increased efficacy and safety, for the treatment and control
of malarial disease. Existing anti-malarial chemotherapeutic
agents can be improved with nanotechnology-based
preparations to achieve greater therapeutic benefits, safety,
and cost-effectiveness, which improves patient agreement
with treatment.
Leishmania (Leishmaniasis)
More than 20 different Leishmania species cause the
zoonotic disease leishmaniasis, which is spread by more
than 90 different phlebotomine sandflies, especially in low-
income tropical nations. According to the World Health
Organization, leishmaniasis causes 700,000 to 1 million
new cases worldwide each year and up to 30,000 fatalities.
The three main clinical manifestations of leishmania
infection are cutaneous leishmaniasis, mucocutaneous
leishmaniasis, and visceral leishmaniasis (WHO 2022a).
Nanotechnology has also been investigated as a
potential innovation to treat these diseases because of the
toxicity of the few therapeutic options available to treat
neglected tropical diseases like leishmaniasis and Chagas
disease. Green nanotechnology has recently enabled the
development of various green nanoparticle treatment
methods for leishmaniasis. In a study, the promastigote, as
well as the amastigote form of Leishmania major, were
treated in vitro with manufactured silver nanoparticles using
ginger extract. Anti-amastigote assay results showed NPs'
IC50 value was calculated to be 2.35mg.kg-1 after 72 h.
Additionally, AgNPs significantly increased apoptosis and
produced programmed cell death in promastigotes of L.
major (Mohammadi et al. 2021b). They concluded that
these nanoparticles may effectively reduce infected
macrophages and that they caused the reduction of the
proliferation rate of intramacrophage amastigotes. Based on
these outcomes mentioned to treat Leishmania infections,
these nanoparticles could be used as promising anti-
leishmanial drugs. Similarly, another study utilizing a
watery extract of Eucalyptus camaldulensis leaves was
done, and the antileishmanial consequence of green
synthesized AgNPs revealed a strong cytotoxic effect
against Leishmania tropica at minimal doses (Zein et al.
2022).
The majority of reports suggest that the slow release of
Ag ions, which damage the cell's surface while penetrating
the cytoplasm and binding with the target locations, is what
gives silver nanoparticles their antileishmanial capabilities.
Additionally, reactive oxygen species can be created by
silver nanoparticles. Leishmania is well recognized to be
extremely sensitive to these oxygen species, making the
medication, which may produce reactive oxygen species, an
effective agent against Leishmania (Zein et al. 2022).
Awad et al. (2021) employed Commiphora molmol
(myrrh) to synthesize Ag and Au NPs. Myrrh silver
nanoparticles (MSNPs) were employed for subcutaneous
lesions on mice infected by L. major in vivo and also in
cultures (in vitro). MSNPs exhibited a concentration-
dependent and when compared to chemical NPs and
pentostam at the same doses, the MSNPs were considerably
more efficient at the higher doses. Lesions healed
completely in vivo after 21 days, but topical medications
like pentostam and CNPs had little to no healing impact.
Due to NPs' spherical shape, they can enter cells
(Kalangi et al. 2016) through phagocytosis, leading to the
production of phagolysosomes in an acidified condition.
AgNPs are subjected to oxidation, which releases free Ag+
ions that kill intracellular amastigotes. The oxidation of NPs
is stimulated by the intracellular ROS that release by
macrophages, which increases ROS production even more.
AgNPs were able to activate macrophages to produce ROS,
which significantly suppressed amastigote proliferation
without killing the macrophages. In addition to the ROS,
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193
phytochemicals (capping agents) generated from AgNPs
may have favourable differential effects in infected and
uninfected macrophages. These effects may improve the
antileishmanial activity through their immunomodulatory
effects by protecting the host cells (Lodge and Descoteaux
2006; Alti et al. 2020).
According to other recent research findings, silver
nanoparticles with a curcumin coating may be a new,
safe, and effective antileishmanial agent for the healing of
cutaneous leishmaniasis (CL) infection. Increasing
curcumin solubility and bioavailability is facilitated by
the conjugate fabrication of curcumin and Ag NPs. The
promastigotes and amastigotes of the protozoan parasite
L. major were dramatically reduced by Curcumin AgNPs,
confirming in vitro cell cytotoxicity and leishmanicidal
action against parasites. During 48 h after infection, the
NPs revealed strong antileishmanial action with IC50
values of 58.99 g/mL for promastigotes and EC50 values
of 58.99 g/mL for amastigotes, without detrimental
harmful toxicity on the murine macrophages. The CL
lesion size was dramatically reduced in BALB/c mice that
had been infected and were being treated with AgNPs
(Badirzadeh et al. 2022).
Even though recently developed composite drugs
based on the nanoparticles be successful, to combat the
NPs' toxicity, bimetallic NPs made by reduction through
greener plant extracts are suggested. Three different kinds
of AU-Ag bimetallic nanoparticles were created in the
study using fenugreek, coriander and soybean leaf
extracts in a single reduction step. The antileishmanial
effects of all three types of w bimetallic nanoparticles
were very strong against promastigotes. The
promastigotes experienced an apoptosis-like death
brought on by the synthesized, bimetallic nanoparticles
and the macrophages' antileishmanial activity was
amplified. In macrophages, the number of intracellular
amastigotes decreased by 31–46% (Alti et al. 2020).
It is crucial to look for new and effective medications
that can treat this parasitic infection with few or no side
effects given the rising number of leishmaniasis cases
around the world, particularly cutaneous leishmaniasis.
Recent research on green nanosynthesis has shown promise
as a therapeutic strategy.
Toxoplasma gondii (Toxoplasmosis)
Toxoplasma gondii is a worldwide distributed food-borne
zoonotic protozoan parasite through frequent infection
sources, that infects up to one-third of the population of
humans (Shani et al. 2010). It causes noteworthy clinical
signs, particularly in immunocompromised people,
pregnant females, and cattle. Moreover, there is currently
no reliable human vaccine available to combat this illness.
Prophylaxis can therefore be recommended as the primary
method of preventing toxoplasmosis (Chu and Quan 2021).
Till now, chemotherapy using the drugs pyrimethamine and
sulfadiazine is regarded as the "gold standard" therapy for
toxoplasmosis owing to the absence of an efficient
vaccination to avoid toxoplasmosis (Dunay et al. 2018). In
recent years, different types of NPs have been used against
T. gondii (Costa et al. 2020). More recently, nano vaccines
have shown promise in preventing experimental
toxoplasmosis in many experimental studies that have
tested them (Brito et al. 2023).
In a study against chronic toxoplasmosis caused by T.
gondii in mice, the anti-toxoplasmosis properties of green
copper nanoparticles (CuNPs) alone and in combination
with atovaquone were documented. The experimental
groups had significantly fewer T. gondii tissue lesions than
the control group, according to the results. CuNPs alone and
in combination with atovaquone were found to be effective
in preventing toxoplasmosis in mice (Albalawi et al. 2021).
According to another study, AgNPs prevent bacterial
growth and the development of biofilms while also reducing
the viability of some parasitic species' cells (Vergara-Duque
et al. 2020).
In addition, Mahmoodi et al. (2018) revealed that Cu
NPs through the interaction with sulfhydryl groups(-SH)
might lead to the denaturation of protein in bacteria. The
findings of the other study by Chatterjee et al. (2014)
showed that CuNPs may damage cell membranes as well as
have numerous harmful consequences, including the
oxidation of proteins, peroxidation of lipids, and the
generation of ROS. To be linked in an in vivo research
showed that cytokines enhance anti-Toxoplasma action in
microglia via a NO-mediated mechanism (Halonen et al.
1998).
Furthermore, Albalawi et al. (2021) achieved
quantitative real-time PCR to assess the mRNA levels of
several cellular immunity mediators in mice infected with
toxoplasmosis and treated with CuNPs, including IFN-γ,
IL-12 and iNOs. In comparison to the control group, all
mice in the experimental groups had higher levels of IFN-
γ, IL-12, and iNO mRNA. Their outcomes showed that
CuNPs alone and in combination with atovaquone had
high efficacy in preventing mouse toxoplasmosis. CuNPs
also have other benefits like enhanced cellular immunity
and low toxicity, in addition to their preventative effects
(Albalawi et al. 2021).
In addition, the Pretreatment of Toxoplasma-infected
Balb/c mice with Toxoplasma with green fabricated
AgNPs from Phoenix dactylifera and Ziziphus spina-
christi through in vivo research led to reduced liver
damage and improved histological characteristics.
However, liver homogenate's antioxidant enzyme activity
was markedly increased after nanoparticle treatment,
which considerably reduced hepatic lipid peroxidation
(LPO) and hepatic nitric oxide (NO) concentrations and
proinflammatory cytokines. Additionally, the nanoparticle
treatment decreased the immunoreactivity of hepatic
tissues by regulating cytokines production like TGF-β and
NF-B in the Balb/c mice (Alajmi et al. 2019).
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194
According to previous research, these nanoparticles
likely exert their antimicrobial properties via dual chief
ways either through direct action via decreased cell
permeability, inhibition of cell growth, and initiation of
apoptosis and/or indirect impacts through the orientation of
oxidative stress through the creation of H2O2 and the release
of Zn ions, which allows them to penetrate cell walls and
represent their toxic impacts (Khashan et al. 2020). Potential
antiparasitic responses, particularly against toxoplasmosis,
may result from increased synthesis of inflammatory
cytokine in a variety of ways, containing higher expression
levels of iNOs, ROS and NO synthesis and suppression of
tryptophan within the cells, IFN-γ for instance, modifies cell
metabolism, which can result in tryptophan deficiency in
fibroblasts and iron starvation in enterocytes (Hunter and
Sibley 2012; Chandrasekar et al. 2015).
The results of an experiment conducted recently by
Saadatmand et al. (2021), showed that ZnNPs synthesized
using Lavandula angustifolia extract have considerable
therapeutic benefits against mice infected with chronic
toxoplasmosis. Their conclusions showed that the number
and the diameter of the tissue cysts in the brain of the
infected mice significantly decreased after 14 days of oral
treatment of Zn NPs. In the larger dose of Zn NPs taken
orally, no T. gondii tissue cysts were seen. Compared to
control groups, mice given 32.5, 75 and 150 mg/kg of
ZnNPs for two weeks showed significantly higher
expression levels of IFN-γ and iNOs. As it suggested that
ZnONPs enhanced the innate immune system, which may
account for its potent preventive benefits (Saadatmand et al.
2021).
As a result, the recent studies finding offer fresh
insights into several natural plants that have historically been
used to treat toxoplasmosis and other parasitic infections and
may be helpful as a different mode of therapy for T. gondii
infections as well as their greener-derived nanoparticles.
Trypanosoma (Trypanosomiasis)
Trypanosoma cruzi, the parasite that causes Chagas disease,
is thought to infect 6 to 7 million people worldwide (WHO
2022b). Patients who are infected might show signs like
hepatosplenomegaly, lymphadenopathy and facial edema.
Nifurtimox and benznidazole which are nitro heterocyclic
drugs with the mechanism of action of causing the
formation of reactive oxygen species like superoxide
radicals and hydrogen peroxide are used to treat Chagas
disease. These reactive oxygen species subsequently result
in oxidative damage to the parasite, which ultimately leads
to its death. However, patients taking these medications run
the risk of suffering from many serious side effects,
including skin irritation, liver and pancreatic damage
(Thakare et al. 2021; Fernandes et al. 2022).
In the aspect of targeting T, cruzi, Souza et al. (2022)
extracted bioactive fucoidan from Spatoglossum schröederi,
a brown seaweed. Then an environmentally friendly
synthesis technique was used to create AgNPs that included
fucan A (AgFuc). Regardless of the length of the treatment,
AgFuc was found to be more effective than fucan A or
silver at preventing parasites. AgFuc also caused 17% of
parasites to die via apoptosis and 60% of parasites to die by
necrosis. AgFuc, therefore, causes mitochondrial damage in
the parasites, indicating that it has anti-Trypanosoma cruzi
properties.
Moreover, by reducing the particle size, antibacterial
AgNPs activity can be more effective. The particles are quite
polydisperse, as can be seen from the AgFuc characterization,
notably the UV-vis analysis and the size-dispersion
histogram. As a result, the larger Ag fucan nanoparticles
might not reach the parasites' cytoplasm, which could
compromise AgFuc's ability to kill Trypanosomes. They
recommended future research to focus on the perfect way for
producing AgFuc NPs of a smaller size and assessing the
impact of this on T. cruzi survival (Souza et al. 2022).
It is claimed that silver nanoparticles, which are
produced from the bioactive polysaccharide xylan taken
from corn cobs, have anti-Trypanosoma properties.
Regardless of the length of the trial, the silver-xylan
nanoparticles NX were more successful than benznidazole
in reducing the ability of parasites (Brito et al. 2020).
Based on the IC50 value against Trypanosoma evansi
in a study conducted by Rani et al. (2022), three
naphthoquinone (NTQ) derivatives were chosen and gum
damar was used to encapsulate them. All three NNTQs had
a strong antitrypanosomal action and morphological
alterations at 2–3 times lower drug concentrations, these
nanopreparations produced more reactive oxygen species in
the axenic culture of T. evansi. According to the findings,
NNTQs increased ROS, apoptosis, and necrosis, which had
a greater negative effect on T. evansi's growth.
Furthermore, researchers integrated dual ideas: green
chemistry and agro-waste valorization in a whole zero-
waste procedure to solve pollution and neglected tropical
disease topics. FM2-free Ag/Cu NPs were investigated for
anti-kinetoplastid activity against two flagellates,
Leishmania spp. and T. cruzi. The strongest leishmanicidal
and trypanocidal effects were demonstrated by free Ag/Cu
nanoparticles (Snoussi et al. 2022).
The gap in the mechanism of nanoparticles against
protozoan has been investigated by Wang et al. (2021).
African trypanosomiasis is caused by Trypanosoma brucei.
Endocytosis of dual noble metal nanoclusters (NM-NCs),
Ag2S-NC@MPA and AuNC@GSH, was studied in T.
brucei. Both forms of NC can be efficiently taken up by T.
brucei through a clathrin-dependent endocytosis route and
demonstrated anti-parasitic activity by inducing pathological
changes in apoptosis-related organelles. The Ag2S-
NC@MPA primarily related to the proteins of the
mitochondrion as well as the endoplasmic reticulum,
whereas the AuNC@GSH primarily disrupted the biological
action of cytoplasmic enzymes shared in mRNA maturation
and signal transmission.
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195
Table 1: The efficiency of different nanoparticles against the protozoal parasites
Nanoparticle
Source
Model
Parasite
Effect
Reference
AgFuc
nanoparticles
Bioactive fucoidan
from Spatoglossum
schröederi
in vitro
Trypanosoma
cruzi
-Regardless of the length of the treatment, AgFuc was more
effective than fucan A or silver at preventing parasites from
reducing MTT.
-AgFuc also caused 17% of parasites to die via apoptosis and
60% of parasites to die by necrosis.
-AgFuc causes mitochondrial damage in the parasites.
Souza et al.
(2022)
AgNPs
Neem leaves
Azadirachta indica
in vitro
P. falciparum
-Neem-AgNPs prevent P. falciparum from growing in infected
human red blood cells. T
-The hemolysis outcome demonstrates that AgNPs are non-toxic
because their mean blood hemolysis rate (%) was 13%.
(Ghazali et al.
2022)
Gum damar-
loaded
naphthoquinone
nanocapsules
(NNTQ)
Gum damar
in vitro
Trypanosoma
evansi
-Each of the three NNTQs shows a sizable antitrypanosomal
impact as well as morphological alterations.
-Compared to pure NTQs, the nanoformulations showed
increased (ROS) generation in the axenic culture of T. evansi
- Low cytotoxicity on horse peripheral blood mononuclear cells.
(Rani et al.
2022)
Ag/Cu NPs
sugarcane bagasse
in vitro
L. donovani & L.
amazonensis and
T. cruzi
-The Ag/Cu nanoparticles had strong leishmanicidal and
trypanocidal effects, with IC50 values of 2.909 ± 0.051 for L.
donovani, 3.580 ± 0.016 for L. amazonensis, and 3.020 ± 0.372
mg.kg-1 for T. cruzi.
(Snoussi et al.
2022)
AgNPs
Eucalyptus
camaldulensis
in vitro
L. tropica
-The highest inhibitory effect on parasites was at the highest
concentration of AgNPs (3.75 g/mL), which resulted in a 90%
reduction in parasite growth.
(Zein et al.
2022).
Curcumin-
coated silver
nanoparticle
(Cur@AgNPs)
curcumin derived from
turmeric
in vitro &
in vivo
L. major
-An IC50 of 58.99 g/ml for promastigotes and an EC50 of 58.99
g/ml for amastigotes, the nanoparticle demonstrated strong
antileishmanial activity.
-The size of the (CL) lesion was dramatically reduced in the
BALB/c mice that were being treated for infection with
Cur@AgNPs.
(Badirzadeh et
al. 2022)
CuNPs
Capparis spinosa fruit
alone & combined with
atovaquone
in vivo
Tehran strain T.
gondii
- All experimental group mice showed higher mRNA for IFN-γ,
IL-12, and iNO compared to the control group.
(Albalawi et al.
2021)
AgNPs
Commiphora myrrha
(oelo-gum resins)
in vitro &
in vivo
L. major
- At the higher concentrations 100, 150 l/100 l/100 ul showed a
significant inhibitory effect for the MSNPS.
- After receiving MSNP treatment in vivo, lesions were fully
cured in 21 days.
Awad et al.
(2021)
ZnNPs
Lavandula
angustifolia Vera
in vivo
T. gondii
-Mice who had 32.5, 75, and 150 mg/kg of ZnNPs for two weeks
showed significantly higher expression levels of IFN-γ and iNOs.
-The average count of brain tissue cysts in the studied animals
was significantly decreased using Zn NPs at 32.5 and 75 mg/kg
for three weeks.
-At 150 mg/kg for 14 days, no tissue cysts of T. gondii were seen
in mice.
(Saadatmand et
al. 2021)
AgNPs
Ginger rhizome extract
in vitro
L. major
-After one, two, and three days, the proliferation of L. major
promastigotes was suppressed by Ag NPs at (40, 20, 10 and 5
mg.kg-1).
-There were reports of 7.3% and 32.2% viability % for
macrophages and L. major promastigotes treated with the highest
NPs amount (40 mg.kg-1).
-After 72 hours of incubation, the mean number of amastigotes in
each macrophage was reduced by 1.25 and 2.5 mg.kg-1 of Ag-
NPs in comparison to control groups.
-Additionally, after 72 hours of exposure, the IC50 value for this
parasite strain of L. major was 2.35 mg.kg-1.
(Mohammadi et
al. 2021b)
silver-xylan
nanoparticles
(NX)
xylan, extracted from
corn cob
in vitro
Trypanosoma
cruzi
-The NX at 100 μg/mL cause 95% mortality of parasites through
necrosis.
-Although it displayed negligible cytotoxicity at 2000 μg/mL.
-In 100 μg/mL the NX exhibit more effectiveness in affecting the
parasites.
(Brito et al.
2020)
AgNPs
Two Artemisia species,
A. abrotanum and A.
arborescens
in vitro
P. falciparum
-Compared to A. arborescens- AgNPs, A. abrotanum-AgNPs
exhibit higher antimalarial activity.
-The smaller AgNPs have a more strong dose-dependent
hemolytic impact. The small size of the NPs showed a distinctive
impact on the parasite of A. abrotanum-AgNPs.
-A. abrotanum-AgNPs were able to prevent the parasite from
reaching its mature stage, keeping it in the ring stage.
(Avitabile et al.
2020)
Table 1: Continued
Shnawa et al. / Intl J Agric Biol Vol 30, No. 3, 2023
196
Despite the promising findings of nanoparticle effects
against trypanosomiasis, however, additional research will
be needed to verify this expectation.
The general mechanism that has been suggested and
explained to be responsible for protozoan death after
treatment with nanoparticles has been illustrated in Fig. 3
and the recent updates against protozoan parasites using
green nanoparticles were summarized in Table 1.
Conclusion
With the growing number of parasitic disease cases
worldwide, it is critical to seek out novel and effective
medications capable of curing these parasitic infections
with little or no adverse effects. The usage of nanoparticles
for the treatment of numerous parasite illnesses has recently
expanded due to their unique structural properties. Recent
research on green nano synthesis has revealed that it is a
viable medicinal method. Testing these nanoparticles can
cause DNA disruption, protein synthesis inhibition,
membrane damage, damage to the ribosomes, ROS free
radical generation and protozoal death. However, the
mechanisms of NP antiplasmodial activity are not entirely
understood or elucidated. Our understanding of protozoa
parasites has significantly increased over the last few years.
However, drug development to combat protozoan diseases
is still urgently needed. This gap must be addressed more
rigorously in future studies. However, the research suggests
Table 1: Continued
Ag–Au BNPs
fenugreek, coriander,
and soybean leaf
extracts
in vitro
Leishmania
-Three different Au-Ag BNP types had IC50 values that ranged
from 0.03 to 0.035 g/mL and demonstrated strong antileishmanial
effects against promastigotes.
-IC50 values for BNPs are significantly lower than those for
miltefosine (IC50 = 10 g/mL).
-The promastigotes experienced an apoptosis-like death brought
on by the synthesized BNPs, and macrophages' antileishmanial
activity was amplified.
-In macrophages, the number of intracellular amastigotes was
decreased by 31-46%.
(Alti et al. 2020)
AuNPs and
AgNPs
Bark and leaf extract of
Syzygium jambos (L.)
Alston (Myrtaceae)
in vitro
P. falciparum
-AgNPs and AuNPs produced by both extracts exhibit great
antiplasmodial activity against both chloroquine-sensitive (3D7)
and resistant (Dd2) strains of P. falciparum.
-NPs produced by S. jambos extracts were determined to be
harmless to HeLa and L6 cell lines.
(Dutta et al.
2017)
Fig. 3: Schematic illustration of the possible mechanisms of antiprotozoal activity of green-derived nanoparticles
Effect of Nanoparticles against Protozoa / Intl J Agric Biol Vol 30, No. 3, 2023
197
additional in vivo and clinical studies are warranted to
validate these findings as well as further work should be
done for the identification of antiprotozoal activities of
these nanoparticles under in vivo and in vitro models. Fig. 3
depicts the possible mechanisms of antiprotozoal activity of
green-derived nanoparticles.
Author Contributions
All authors contributed to the design and the writing of the
manuscript.
Conflicts of Interest
The authors declare no competing interests.
Data Availability
Not applicable.
Ethics Approvals
Not applicable.
Funding Source
The authors received no funding for this work.
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