Oncolytic Viral Nanoparticles: A Combination Of Targeted And Immunotherapeutic Approach For Cancer Treatment: A Review

Abstract

Human health and survival have always been seriously threatened by cancer. Although surgery, radiation therapy, and chemotherapy could improve the survival rate of cancer patients, most patients with chronic cancer have a poor survival rate or cannot afford the high cost of treatment. The development of oncolytic viruses provides us with a new technique for treating or even curing malignant cancers. Oncolytic viruses (OVs) have gained interest as a potential approach in cancer therapy because of their potential to selectively infect and destroy tumor cells, without affecting healthy cells . They also work against cancer by releasing immunostimulatory chemicals from dead cancer cells. Oncolytic virotherapy, like other anticancer therapies, has various limitations, including viral transport to the target, tumor mass penetration, and antiviral immune responses. Nanoparticles (NPs) have gained a lot of interest in clinical studies because of their distinctive appearance characteristics. However they have encountered challenges due to the inefficiency of drug delivery to the tissue of interest and their dispersion in bloodstream. In this scenario, various chemical alterations can be employed to the nanoparticle surfaces to boost their efficacy in drug delivery. To improve the functioning of these two therapeutic methods, the sophisticated technique of OVs encapsulated with nanoparticles can be employed, which has shown significant therapeutic outcomes in the treatment of various malignancies. This review focuses on the clinical advancements of oncolytic viruses and nanoparticles in cancer therapy and their combinational effects on tumor cells. This review also provides insight into the future prospects by assessing both the advantages and disadvantages of nano-based oncolytic virotherapy.

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Available online at: https://jazindia.com 2537
Journal of Advanced Zoology
ISSN: 0253-7214
Volume 44 Issue S-5 Year 2023 Page 2537:2550
____________________________________________________________________________________________________________________________
Oncolytic Viral Nanoparticles: A Combination Of Targeted And
Immunotherapeutic Approach For Cancer Treatment: A Review
Puja Sadhu1, Suranjana Sarkar1, Aritri Laha1, Semanti Ghosh2, Bidisha Ghosh2, Subhasis
Sarkar1 *
1Department of Microbiology, School of Life Sciences, Swami Vivekananda University, Barrakpore, Kolkata-
700121
2Department of Biotechnology, School of Life Sciences, Swami Vivekananda University, Barrakpore,
Kolkata- 700121
*Corresponding Author: Subhasis Sarkar
Email: subhasiss@svu.ac.in
Article History
Received: 30/09/2023
Revised: 15/10/2023
Accepted: 30/10/2023
CC License
CC-BY-NC-SA 4.0
Abstract
Human health and survival have always been seriously threatened by
cancer. Although surgery, radiation therapy, and chemotherapy
could improve the survival rate of cancer patients, most patients with
chronic cancer have a poor survival rate or cannot afford the high cost of
treatment. The development of oncolytic viruses provides us with a new
technique for treating or even curing malignant cancers. Oncolytic
viruses (OVs) have gained interest as a potential approach in cancer
therapy because of their potential to selectively infect and destroy tumor
cells, without affecting healthy cells . They also work against cancer by
releasing immunostimulatory chemicals from dead cancer cells.
Oncolytic virotherapy, like other anticancer therapies, has various
limitations, including viral transport to the target, tumor mass
penetration, and antiviral immune responses. Nanoparticles (NPs) have
gained a lot of interest in clinical studies because of their distinctive
appearance characteristics. However they have encountered challenges
due to the inefficiency of drug delivery to the tissue of interest and their
dispersion in bloodstream. In this scenario, various chemical alterations
can be employed to the nanoparticle surfaces to boost their efficacy in
drug delivery. To improve the functioning of these two therapeutic
methods, the sophisticated technique of OVs encapsulated with
nanoparticles can be employed, which has shown significant therapeutic
outcomes in the treatment of various malignancies. This review focuses
on the clinical advancements of oncolytic viruses and nanoparticles in
cancer therapy and their combinational effects on tumor cells. This
review also provides insight into the future prospects by assessing both
the advantages and disadvantages of nano-based oncolytic virotherapy.
Keywords: Cancer, Oncolytic viruses, Virotherapy, Nanoparticles,
Drug delivery.

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INTRODUCTION
Cancer is one of the most significant health problems in the world. Cancer incidence is expected to rise by
2025, with more than 20 million new cancer cases each year, based on worldwide demographic trends (Ajam-
Hosseini et al., 2023; Zugazagoitia et al., 2016). Malignant tumors are becoming one of the top causes of
mortality worldwide. Although there are currently numerous therapies available, including surgical therapy,
radiotherapy, chemotherapy, and the most recent immunotherapy, they have certain limits. Surgical therapy is
mostly used for people with the early stages cancer, but the considerable side effects of radiotherapy and
chemotherapy make them difficult for patients to tolerate (Cao et al., 2020). Furthermore, conventional
immunotherapy has various limitations, for example, the overall success rate of patients undergoing
immunotherapy is roughly 10 to 30%, therefore enhancing immunotherapeutic functioning is necessary (Ajam-
Hosseini et al., 2023; Iwai et al., 2017).
In general, existing cancer therapy procedures are essentially inadequate, and new treatment approaches with
accurate tumor targeting, potent tumor-killing characteristics, and minimal harmful side effects must be
presented (Cao et al., 2020). As a result, the researchers focused on gene and viral therapies to treat oncotherapy
(Ajam-Hosseini et al., 2023). The very first gene therapy was conducted in 1990 (Misra, 2013), paving the way
for a new therapeutic approach, and other gene therapy products were granted approval after much work. It
should be mentioned that cancer is now the most prevalent condition treated with gene therapy, accounting for
more than 60% of clinical studies (Ajam-Hosseini et al., 2023). Viruses seem to be causing 20% of all
malignancies in humans. The Epstein-Barr virus, hepatitis B and hepatitis C, are the causes of Burkitt's
lymphoma, liver cancer and Kaposi's sarcoma, respectively (Iwai et al., 2017). Duran I Reynals had already
accepted viruses for the treatment of diseases in addition to their involvement in tumor formation (Alemany,
2013). (Alemany, 2013) Gradually, the anticancer properties of viruses were recognized in the late nineteenth
century. Dr. George Duck identified the first recorded link between a natural viral infection and a possible
anticancer impact in 1904. According to this research, following a natural influenza virus infection, a lady with
leukemia reported a decrease in leukocyte counts (Arabi et al., 2022)
Oncolytic Viruses
Oncolytic viruses (OVs) are an emerging category of cancer therapeutic agents that have attracted the interest
of researchers in recent years due to their unique features (Cao et al., 2020). OVs are viruses that specifically
target and destroy cancerous cells while ignoring healthy ones (Rahman & McFadden, 2021). OVs can elicit
an anticancer response following two different mechanisms: 1. preferential tumor cell replication , resulting in
immediate lysis, and 2. development of integrated immunity to tumors (Kaufman et al., 2015). Infection caused
by OVs, together with cancer cell death, stimulates the cell-mediated antitumor immune response, altering the
tumor micro-environment (TME) (Matos et al., 2020). The virus begins replication and makes viral proteins
after infection. Following that, it stimulates signaling pathways involved in autophagy processes by reducing
cellular function and increasing oxidative stress (Ji et al., 2022). As they depend on the human immune system's
innate capacity to destroy cancer cells, it is essential for OVs to achieve a balance between anti-tumor and
antiviral immunity to function effectively in oncotherapy (Gruijl et al., 2015). OVs are classified into two
categories based on their development: natural viruses (that is, the wild-type and native type) and genetically
engineered viral types. A few of them (notably the reovirus) have an inherent capacity to grow in cancer cells,
while others have showed promising results when genetically modified. With the use of genetic engineering,
tumor targeting ability, oncolytic activity, or creating robust antitumor immune responses of OVs can be
enhanced (Bai et al., 2019; Mondal et al., 2020). Owing to the complexity and heterogeneity of cancer tissues,
as well as the probability of tumor cell metastasis, virus selection and administration mechanism are considered
tough concerns in the field of OV therapy (Ajam-Hosseini et al., 2023; Mondal et al., 2020).
Oncolytic virotherapy is a type of cancer therapy in which a virus, capable of replicating itself, is used to kill
cancer cells. There are many different types of viral species, but not all of them can be modified to be oncolytic
viruses (OVs) (Russell et al., 2012). These OVs must be non-pathogenic, capable of targeting and destroying
cancer cells, and capable of being genetically modified to create tumor-killing proteins (Ajam-Hosseini et al.,
2023; Maroun et al., 2017). Tumor selection is often concerned with the quantity of receptor-mediated cell
entry, intracellular antiviral responses, or restriction factors affecting the sensitivity of an infected cell towards
expression and replication of viral gene (Cao et al., 2020; Kaufman et al., 2015; Seymour & Fisher, 2016).
The History and Evolution of Oncolytic Virotherapy
The idea of employing viruses to cure cancers has been around for over a century. As early as 1904, it was first
reported that the tumor of a 42-year-old leukemia patient had decreased as a result of influenza (Cao et al.,

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2020). Then, in 1912, Italian doctors found that a rabies vaccine injection may stimulate the regression of
cervical cancer, giving rise to the novel idea of OV therapy and a series of related studies (PELNER et al.,
1958). Although various clinical investigations using wild-type viruses to treat tumors were conducted
throughout the 1950s and 1970s, the OV eventually fell to second place in cancer therapy because the virus
was unable to effectively regulate its pathogenicity. Genetically modified attenuated and highly selective
viruses were first introduced in the 1980s, when genetic engineering technology made it possible to alter the
viral genome. A genetically modified human herpes simplex virus I (HSV-1) lacking thymidine kinase
(TK), was shown to have outstanding safety, increased lifespan, and the ability to inhibit the development of
glioma in mice, in preclinical animal studies in 1991 (Cao et al., 2020). Phase I clinical studies for the
genetically modified adenovirus, Onyx 015, began in 1996 (Heise et al., 1997; Xia et al., 2004). The first OV
to be licensed by regulatory authorities for the treatment of cancer was RIGVIR, a non-pathogenic enteric,
cytopathic human orphan virus, which was used to treat melanoma in Latvia in 2004 (Cao et al., 2020).
Although the modified adenovirus H101 (Oncorine, recombinant human adenovirus five injection, ankeri) was
authorized in China in 2005, its therapeutic efficacy has not been acknowledged globally (Cao et al., 2020;
Garber, 2006). In October 2015, the Food and Drug Administration (FDA) approved the commercialization
of T-VEC (talimogene laherparepvec, Imlygic). In 2016, T-VEC received approval for commercialization in
Europe and Canada, demonstrating the maturity of OV technology for cancer therapy. Three OV medications
are now on the market, with six additional OV drugs in phase III clinical trials (Coffin, 2016).
Table 1 : The characteristics of a few selected oncolytic viruses
Viruses
Characteristics
Advantages
Disadvantages
References
Adenovirus
(Ad)
Genome (Size):
dsDNA
(~35 kb)
Replication Site:
Nucleus
Vertebrate Host:
Human,
Animals
-High lytic activity -
-Genetic modification is
easily accessible
- Ability to infect a wide
range of cells (dividing as
well as non-dividing)
-Improved tumor specificity
-The physical and chemical
stability of particles
- High titre (1010 pfu/ml)
- Possessing a broad tissue
tropism
- Increasing the anticancer
effect by combining
immunomodulatory agents
-Limited tumor infection
-Limited efficacy owing
to antiviral immunity
-Attenuated viral spread
-Replication is difficult
to turn off.
(Ajam-Hosseini et al.,
2023; J. H. Kim et al.,
2006; Niemann &
Kühnel, 2017)
Herpes
simplex
virus
(HSV)
Genome (Size):
dsDNA
(~154 kb)
Replication Site:
Nucleus
Vertebrate Host:
Human
- Genetic modification is
easily accessible
- Drugs exist to turn off
undesirable viral
replication
- Only replicates in cells
lacking an anti-apoptotic
factor (E1B-19 K)
- Inhibition of host antiviral
immunity through virus
co-treatment with
cyclophosphamide
- Possibility of latent
native viral infection
- Potential inhibition of
OV-mediated antitumor
immunity
- Adverse consequences
(Ajam-Hosseini et al.,
2023; Goldufsky et al.,
2013; Kaufman et al.,
2015)

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Poxvirus:
vaccinia
virus
(VACV)
Genome (Size):
dsDNA
(160–190 kb)
Replication Site:
Nucleus
Vertebrate Host:
Human
- Large genome available for
genetic manipulation
- High insertion capacity
- Associated with relatively
minor health conditions
- Prevents the immune
system from recognizing
and clearing the virus in
circulatory system
- Does not have a cognate
receptor and can infect any
cell type
- No host genome integration
- Has an innate preference
towards tumors
- High titre (up to 1010 pfu/
ml)
- Viral-mediated
immunogenic cytotoxicity
- Clinical trial experience
- Possible fatal or serious
side effects
- Difficulty preventing
undesired viral
replication
- Potential cytopathic
consequences
- Limited intrinsic tumor
selection
- Limited intrinsic tumor
selection
- Mild viral infection
- Unknown function of
several genes
- Viral protein-induced
immune response
(Ajam-Hosseini et al.,
2023; Z. S. Guo &
Bartlett, 2004; Haddad,
2017; Thorne, 2011)
Poliovirus
(PV)
Genome (Size):
SS (+) RNA
(7.5 kb)
Replication Site:
Cytoplasm
Vertebrate Host:
Human
- Thorough understanding of
viral gene function
- Oncogenes are not
encoded.
Inability to integrate into the
host chromosome
- Penetration of the blood-
brain barrier due to the
capsid's small size
- Cannot be readily
modified genetically
- Undesirable viral
replication cannot be
easily stopped
(Ajam-Hosseini et al.,
2023; McCarthy et al.,
2019)
Newcastle
disease
virus
(NDV)
Genome (Size):
SS(− ) RNA
(15 kb)
Replication Site:
Nucleus
Vertebrate Host:
Birds
- Inherently tumor-selective
strain
- Naturally occurring
immunostimulatory virus
- Less immunogenic in
humans (avian virus)
- Ability to propagate in
tumor tissues via multicyclic
replication
- Possibility of antiviral
immunity
- Possibility of systemic
toxicity
(Ajam-Hosseini et al.,
2023; Burman et al.,
2020; Elankumaran et
al., 2006)
Reovirus
(RV)
Genome (Size):
dsRNA
(23 kb)
Replication Site:
Birds
Vertebrate Host:
Human
- Inherently tumor-selective
species
- Only replicates in cells
with an active Ras-pathway
and an impaired PKR
- Antigenicity can elicit an
immune response
- Chemotherapy can boost
antitumor response
- Associated with relatively
minor health conditions
- Thorough understanding of
viral gene function
-Problems with genetic
alteration
-Potential for antiviral
immunity
-Potential for moderate
toxicity
-No clinical trial
experience
(Ajam-Hosseini et al.,
2023; Connolly et al.,
2000; Errington et al.,
2008)
(Source: Adapted and modified from (Ajam-Hosseini et al., 2023)
Anticancer Mechanism of Oncolytic Viruses (OVs)
The unique ability of OVs to selectively grow in cancer cells, resulting in inflammation and even cell death, as
well as inducing host immune responses as a result of exposure to cancer-associated antigens, makes
them potential cancer gene therapy agents (Lichty et al., 2014). The direct oncolysis or cytotoxicity of the OV
against cancer cells, as well as indirect generation of bystander effects (such as tumor blood vessel damage)

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and immunotherapy against tumors, together make up its anticancer mechanism (Russell et al., 2012; Russell
& Peng, 2007). After infection, viruses can take control of the protein factory of tumor cells, preventing it from
producing enough protein for growth requirements, compromising the physiological processes that are
normally carried out by tumor cells. Furthermore, by eliciting an immune reaction, tumor cells can be
destroyed. Infected tumor cells have the ability to produce cytokines or chemokines, release tumor-derived
antigens following apoptosis, and then draw in a variety of immune cells, including cytotoxic T lymphocytes,
natural killer cells, dendritic cells, and phagocytic cells, leading to a tumor-specific immune response and
possibly eradicating uninfected cancer cells (Chen et al., 2012; Prestwich et al., 2009). Eventually, the immune
response is coupled with a "immune-associated" bystander effect, wherein the production of local cytokine
may cause immunological responses in nearby tumor cells even in the absence of antigen expression
(Schietinger et al., 2010). Apart from the ones stated above, OVs can also kill tumor blood vessels, decreasing
or even preventing tumor blood flow, causing oxygen and nutritional deficiency in tumor cells (Breitbach et
al., 2007, 2013). OV-induced necrosis can also result in the production of damage-associated molecular
patterns (DAMPs), which excite dendritic cells and acquired immunological responses (Jiang & Fueyo, 2014).
Despite the fact that oncolytic virotherapy can kill cancer cells directly and activate the immune system, the
tumor may prevent the anticancer immune response by interfering with nearly every stage of immune activation
thereby creating an immune-suppressive tumor microenvironment (Puré & Lo, 2016; Rabinovich et al., 2007).
Especially, in immunologically "cold" tumors, the OV can enhance overall immune responses by arming itself
with immune-modulating genes, such as those encoding immune checkpoint inhibitors, tumor antigens, and
targets for chimeric antigen receptor T cells (Achard et al., 2018). Solid tumors, on the other hand, are complex,
heterogeneous formations that impair the oncolytic action of OVs. OVs can be modified to increase their
oncolytic capacity by expressing modulatory compounds that target the composition of the tumor
microenvironment to kill tumor cells and prevent tumor growth Additionally, it has been found that OVs
combined with immunostimulatory molecules enhances the development of anticancer immune responses (Cao
et al., 2020). T-VEC was only recently granted approval by the US FDA for the treatment of melanoma by
expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) (Dolgin, 2015). In contrast to
systemic GM-CSF injection, T-VEC therapy for metastatic melanoma was risk-free and produced an overall
response rate of 10.8% (Andtbacka et al., 2015). Oncolytic virotherapy, therefore, represents a new age of
promising opportunities for cancer virotherapy (Cao et al., 2020).
Anticancer Mechanism of Nanoparticles (NPs)
The transport of therapeutic chemicals to the site of action is a significant concern in the treatment of various
illnesses (Wilczewska et al., 2012). To avoid adverse reactions on the surrounding organs , it is critical to direct
the medicine to the desired location, where the predicted therapeutic action is desired to take place (Doroudian
et al., 2023). As a result, employing a controlled system of delivering drugs is a primary technique for
increasing therapeutic molecule safety and efficacy, and it has the ability to overcome these constraints
(Farjadian et al., 2022). The drug treatment impact has been significantly increased by inventing and building
intelligent nanoplatforms for drug targeting and regulated drug release, which has the potential to
fundamentally transform the way autoimmune inflammatory illnesses are treated (Ajam-Hosseini et al., 2023;
Zhu et al., 2022).
NPs are particles with a dimension of below 100 nm and specific properties not commonly seen in bulk
specimens of the same substance (Farjadian et al., 2022). The desirable optical, chemical, and physical
characteristics of nanoparticles make them suitable for use in biomedical applications such tissue engineering,
chemical sensing, drug administration, cellular imaging, diagnostics and therapies (Mejía-Méndez et al.,
2022).Because of their significant and distinctive features, such as their significantly higher surface-to-mass
ratio than other particles, their quantum properties, and their ability to adsorb as well as transport other
compounds, these nanoparticles are appealing for clinical applications (Jong & Borm, 2008). Over the last few
decades, drug delivery techniques using NPs have advanced significantly in the treatment of a variety of solid
tumors (Pierce et al., 2021). Banham et al. proposed for the first time in 1965 that NPs, as an efficient delivery
method, could transport diverse substances through biological membranes (Ajam-Hosseini et al., 2023;
Doroudian, Azhdari, et al., 2021).
Initial cell attachment is determined by the physical and chemical surface characteristics of NPs, and this affects
further processes of cell development, proliferation, differentiation, and migration (Staehlke et al., 2019). One
of the most commonly used polymer ligands for shielding nanoparticle surfaces is polyethylene glycol (PEG),
due to it's excellent hydrophilicity, biocompatibility, and durability in high salt concentrations and pH extremes
(Guerrini et al., 2018). Polyethyleneimine (PEI) is another polymer that is available as both a branched or linear

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structure. Branching PEI, which has a molecular weight of 25 kDa, is considered as the gold standard for gene
transport due to its extremely high cationic charge, creates stronger and more compact DNA complexes than
linear PEI (Patnaik & Gupta, 2013). Another ligand is arginyl-glycyl-aspartic acid (RGD), which is the most
common peptide motif in the extracellular matrix and is in charge of regulating cell adhesion to integrin.
Because integrins are overexpressed in many cancer cells, it is assumed that RGD-coated NP penetrates the
cell readily via integrin-mediated endocytosis (Ajam-Hosseini et al., 2023; Hajipour et al., 2019).
Table 2 : The properties and therapeutic applications of a few selected nanoparticles
Nanoparticles
Characteristics
Advantages
Disadvantages
Tumors
targeted
References
Liposome
Drugs that are
lipophilic or water-
soluble can be
loaded into
liposomes, which
are closed vesicular
nanocarriers with
lipid bilayers and an
internal aqueous
cavity.
Anti-drug degradation
protection
It is less cytotoxic.
Amphiphilic and self-
assembly properties
A large payload
Extended time of activity
Drugs that are both
hydrophilic and lipophilic
can be loaded.
Non-immunogenic,
biocompatible, and
biodegradable
High manufacturing
costs
Condensed drug
molecule fusion in
vivo
Inadequate regulation
of drug release rate
Inability to overcome
biological barriers
Adequate drug
loading without the
use of pH or ionic
gradients
Phospholipids are
oxidizable and
hydrolyzable.
Breast,
Colon,
Lungs,
Ovarian
cancer
Kaposi’s
sarcoma
(Adepu &
Ramakrishna,
2021; Ajam-
Hosseini et
al., 2023;
Deng et al.,
2019; Lee,
2020;
Milewska et
al., 2021;
Souri et al.,
2022; Zheng
et al., 2022)
Polymeric
nanoparticles
Polymeric
nanoparticles are
colloidal
nanocarriers that are
solid, sphere-shaped,
and have particle
sizes less than 1000
nm which are used
to dissolve and
disseminate
therapeutic
substances in
polymer matrix.
Effect of enhanced
permeability and retention
(EPR)
Model of Controlled Drug
Release
Enhanced storage stability
as a result of chemical and
physical protection
Targeted drug delivery to
cells and tissues, with
minimal systemic
absorption.
Natural polymer
nanoparticle
biodegradability
Possibility of low toxicity
Biocompatibility
Natural polymers'
batch-to-batch
heterogeneity in
nanoparticle
manufacturing
Natural polymer
purification
challenges
Problems with
retaining active
compounds' biological
activity through the
formation of
polymeric
nanoparticles
Liver and
renal cancer
Ovarian
cancer
Advanced
solid tumors
(Ahmed et
al., 2022;
Ajam-
Hosseini et
al., 2023;
Deng et al.,
2019;
Ghasemiyeh
et al., 2022;
Rao &
Geckeler,
2011; Souri et
al., 2022;
Zheng et al.,
2022)
Polymeric
micelles
Block copolymers
self-assemble to
produce polymeric
micelles, which have
a hydrophobic
polymer core and a
hydrophilic shell.
Nano-sized
Reduce pharmacological
adverse effects by reducing
dosage frequency.
Increases cell
internalization
Non-specific targeting
Unregulated drug
release
Breast,
Skin,
Lungs
Head an
d neck
cancer
(Ajam-
Hosseini et
al., 2023;
Chaudhuri et
al., 2022;
Deng et al.,
2019; Hsu et
al., 2021;
Pham et al.,
2021; Souri et
al., 2022)
Dendrimers
Due to their multiple
peripheral functional
groups, dendrimers,
which are short,
compact molecules
with an average size
of less than 12 nm,
have a high drug
loading capacity and
Molecular weight, size,
shape, and branch length
uniformity
A high degree of branching
produces a large surface
area.
The availability of
polyvalent interior cavities
Synthesis process is
complicated.
Possible terminal
group incomplete
reactions
Production of high
generation dendrimers
is hindered by steric
hindrance of the core
Breast,
Skin,
Lungs
(Adepu &
Ramakrishna,
2021; Ajam-
Hosseini et
al., 2023; Hsu
et al., 2021)

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can deliver drugs
just to tumor cells
(Ahmed et al., 2022)
allows for increased
loading and targeting.
Water solubility is quite
high.
Biocompatibility and lack
of immunogenicity
molecule and
dendrons.
Carbon
nanotubes
Carbon nanotubes
are hydrophobic,
thin needle-like
structures whose
toxicity in biological
fluids is a major
limiting issue.
Nanotechnology-based
techniques to assisted
reproduction
Embryogenesis
Oncology of the
reproductive system
Side effects of
oxidative stress on
sexual hormones
Induction of ovarian
tissue alterations
Breast,
Skin,
Lungs
(Ahmed et
al., 2022;
Ajam-
Hosseini et
al., 2023;
Sinha &
Yeow, 2005;
Zare-Zardini
et al., 2022)
Gold NPs
(AuNPs)
Due to their
physicochemical
properties, including
size, surface
plasmon resonance,
shape, and surface
chemistry, AuNPs,
solid colloidal
particles with a size
range of 1 to 100
nm, are used in
biology.
Biocompatible excellent
optical properties
Modification potential
Capable of absorbing near-
infrared light
Enough for deep tissue
imaging
Can lead to oxidative
damage
It is not
biodegradable.
Organic polymers
must be coated to
increase solubility,
biostability, and
biodegradability.
Various
cancer
Breast
cancer
(Agabeigi et
al., 2020;
Ajam-
Hosseini et
al., 2023;
Sibuyi et al.,
2021; Singh
et al., 2018;
Younis et al.,
2022)
Solid lipid
nanoparticles
In general, solid
lipids are
disseminated in
aqueous
environments,
stabilized by
surfactants, and
form a non-polar
core by substituting
liquid lipids with
solid lipids at room
temperature.
High level of stability
Decreased toxicity
Drug entrapment protection
against sensitive
environments
Improved bioavailability of
bioactive substances that
are not readily soluble in
water
Capability of site-specific
targeting with more
payload capacity than other
carriers
Specific targeting
Long-term stability
Modified drug
administration
Both hydrophilic and
lipophilic drugs can be
used.
Increase intracellular drug
delivery.
Changes in the
polymorphism of lipid
particles
After-storage drug
elimination
Microbial activity
following storage
Active targeting can
be challenging.
Drug loading capacity
is limited.
Polymorphism,
inconvenient physical
handling
Breast,
Colon,
Lungs,
Pancreatic
(Ajam-
Hosseini et
al., 2023;
Ghasemiyeh
et al., 2022;
Khairnar et
al., 2022;
Milewska et
al., 2021)
Source: Adapted and modified from (Ajam-Hosseini et al., 2023)
Combination Therapy of OVs and NPs
As OV therapy advances, the difficulties with OV-mediated treatment becomes more obvious. For instance,
OV clearance caused by the host’s innate or adaptive immune responses and viral liver tropism, non-targeting
of tumor tissue, and passive accumulation result in inadequate virus distribution to tumor cells, disrupting the
therapeutic procedure (Goldufsky et al., 2013). With the varying clinical efficacies of OV-mediated
oncotherapy, the emphasis has turned toward various therapeutic agent shielding techniques, including
nanoparticle carriers (Ajam-Hosseini et al., 2023). In case of the shielding technique, the targeted organ or
tissue depends on the active delivery process (Yokoda et al., 2017), and that it is feasible to regulate viral

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transmission to the target tissue by modifying both the physical and chemical characteristics of nanoparticles,
which has shown mixed results (Ajam-Hosseini et al., 2023; Howard & Muthana, 2020).
Because of more effective drug delivery capabilities, increased specificity of drug release, and synergistic
benefits, many combined techniques for smart nanodrug delivery have attracted considerable attention
(Doroudian, Neill, et al., 2021). AuNP, one of the most often utilized NPs in viral treatment, can be employed
to enhance DNA permeation into tumors even when neutralizing antibodies are present (Sendra et al., 2020).
Coating Ad vectors with AuNPs having quaternary ammonium groups and an RGD peptide results in a
biocompatible compound which is extremely effective at propagating target cells while suppressing
internalized trafficking, viral infection, and deciphering (Gonzalez-Pastor et al., 2021). Biodegradable
polymers with a PEG linker targeting RGD to deliver oncolytic Ad improve effective transduction and lung
carcinoma cell death. It is also more effective at bypassing the host's innate and adaptive immune responses
than naked Ad (J. Kim et al., 2014). In vitro and in vivo, oncolytic adenovirus plasmid DNA encapsulated with
liposome (rather than Ad alone) inhibited adenovirus-neutralizing antibody production and had powerful
anticancer actions on colon cancer cells. The nano-sized liposomes are particularly stable throughout
circulation, thus aids in the activity of the complex (Aoyama et al., 2017). Tseng et al. employed recombinant
adeno-associated virus serotype 2 coated with iron oxide nanoparticles (approximately 5 nm) to facilitate
remote administration under a magnetic gradient to alleviate the constraints of intratumoral injection. They
also utilized photodynamic treatment, which resulted in a significant decrease in tumor progression via
apoptosis (S.-J. Tseng et al., 2016). The use of a PH-responsive polymeric nanoparticle complex containing
2,3-dimethylmaleic-anhydride-PEG--poly-L-lysine-doxorubicin or lapatinib as a combination therapy is
possible. This combination achieved a favourable therapeutic outcome, highlighting the tremendous potential
of synergistic therapy in the field of oncology (Z. Guo et al., 2020) . Ligands include antibodies like cetuximab
and growth factors like epidermal growth factor receptor (EGFR) (Grapa et al., 2019; S.-H. Tseng et al., 2015).
Cetuximab, a monoclonal antibody, has a greater affinity for human EGFR than natural ligands. This ligand
has been authorized by the FDA as the first therapy for EGFR-positive metastatic colorectal cancer. It is also
used as part of a combination therapy for other malignancies (S.-H. Tseng et al., 2015). EGF coupled
nanoparticles have demonstrated promising outcomes in delivering drugs, treatment of EGFR overexpression
tumors, and imaging (Grapa et al., 2019). Interestingly, OV and NP published the first clinical study in the
field of oncotherapy in 2000, which has had a considerable rising trend till now (Ajam-Hosseini et al., 2023).
Figure 1: Anticancer mechanisms of oncolytic viruses, nanoparticles and their combination therapy.
CONCLUSION

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In oncotherapy, successful approach of drug delivering techniques minimize adverse effects on the normal cells
that surround the tumor tissue. However, the oncolytic virus approach faces challenges due to diverse antiviral
responses in preclinical animal models. Careful animal studies are necessary to balance between the
immunological antiviral and antitumor responses. Advances in cancer treatment through nano-encapsulated
oncolytic viruses have reduced restrictions and controlled adverse effects, offering potential for combined
cancer therapy. Emerging technologies for nano-based oncolytic viruses also hold great promise for cancer
treatment. Plant viruses and bacteriophages are recognized nanotechnologies that have developed to transport
and deliver cargo, making them ideal drug delivery experts. VLPs are biocompatible and biodegradable,
allowing for vascular transit, cellular absorption and interactions. They are easily designed to produce novel
structures that interact with biological systems in predictable ways. In addition to carrying therapeutics or dyes
to certain cells and tissues, VLPs can exhibit functional groups that target ligands, imaging dyes, epitopes.
Since its introduction, the field of VLPs for drug delivery applications has grown significantly, with the number
of virus-based therapies in clinical trials expected to continue growing and eventually lead to advanced
therapeutics in the clinic in the near future.
FUTURE PERSPECTIVE
Advances in oncolytic virotherapy (OVs) for cancer treatment have made significant progress, with enhanced
tumor cell targeting and strategies for improving immune response. Pre-clinical studies on dosing strategy and
delivery routes are crucial for optimum therapeutic efficacy. In order to avoid latent infections, viral shedding,
and transmissions, further investigation is needed to examine the efficacy of OVs and find ways to
minimize unfavorable outcomes through genetic alterations. Identifying how OVs and the host immune system
interact dynamically in the tumor's microenvironment and enhancing those interactions should be the main
objective of oncolytic virotherapy in the future. Having a better understanding of the relationships among
patient's immunological state, malignancy, tumor mutation profiles, employed oncolytic vectors, and
their responses to virotherapy can help in the development of more dependable, personalized treatments. With
more notable outcomes anticipated in the future, combining OVs with cancer immunotherapy has become an
appealing option. As the therapeutic result depends on a dynamic balance between antiviral and antitumor
immune responses, the duration of OV administration should also be taken into account. Viral nanoparticles
(VNPs), derived from mammalian viruses, bacteriophages, and plant viruses, as well as their genome-free
counterparts, virus-like particles (VLPs), are increasingly being used in nanomedicine. The use of VLPs as
drug delivery agents is advancing, and significant research must be conducted on a regular basis in order to
deliver these therapies to the clinic.
Conflict of Interest
Authors do not have any competing interest.
Acknowledgement
Authors will remain indebted to the Department of Microbiology, Swami Vivekananda University for
providing necessary supports in completion of this project.
REFERENCES
1. Abd-Aziz, N., & Poh, C. L. (2021). Development of oncolytic viruses for cancer therapy. In Translational
Research (Vol. 237, pp. 98–123). Mosby Inc. https://doi.org/10.1016/j.trsl.2021.04.008
2. Achard, C., Surendran, A., Wedge, M.-E., Ungerechts, G., Bell, J., & Ilkow, C. S. (2018). Lighting a Fire
in the Tumor Microenvironment Using Oncolytic Immunotherapy. EBioMedicine, 31, 17–24.
https://doi.org/10.1016/j.ebiom.2018.04.020
3. Adepu, S., & Ramakrishna, S. (2021). Controlled Drug Delivery Systems: Current Status and Future
Directions. Molecules (Basel, Switzerland), 26(19). https://doi.org/10.3390/molecules26195905
4. Agabeigi, R., Rasta, S. H., Rahmati-Yamchi, M., Salehi, R., & Alizadeh, E. (2020). Novel Chemo-
Photothermal Therapy in Breast Cancer Using Methotrexate-Loaded Folic Acid Conjugated Au@SiO2
Nanoparticles. Nanoscale Research Letters, 15(1), 62. https://doi.org/10.1186/s11671-020-3295-1
5. Ahmed, S., Rehman, S. U., & Tabish, M. (2022). Cancer nanomedicine: A step towards improving the
drug delivery and enhanced efficacy of chemotherapeutic drugs. In OpenNano (Vol. 7). Elsevier Inc.
https://doi.org/10.1016/j.onano.2022.100051

Journal of Advanced Zoology
Available online at: https://jazindia.com 2546
6. Ajam-Hosseini, M., Akhoondi, F., & Doroudian, M. (2023). Nano based-oncolytic viruses for cancer
therapy. In Critical Reviews in Oncology/Hematology (Vol. 185). Elsevier Ireland Ltd.
https://doi.org/10.1016/j.critrevonc.2023.103980
7. Alemany, R. (2013). Viruses in cancer treatment. Clinical and Translational Oncology, 15(3), 182–188.
https://doi.org/10.1007/s12094-012-0951-7
8. Andtbacka, R. H. I., Kaufman, H. L., Collichio, F., Amatruda, T., Senzer, N., Chesney, J., Delman, K. A.,
Spitler, L. E., Puzanov, I., Agarwala, S. S., Milhem, M., Cranmer, L., Curti, B., Lewis, K., Ross, M.,
Guthrie, T., Linette, G. P., Daniels, G. A., Harrington, K., … Coffin, R. S. (2015). Talimogene
Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. Journal of
Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 33(25), 2780–2788.
https://doi.org/10.1200/JCO.2014.58.3377
9. Aoyama, K., Kuroda, S., Morihiro, T., Kanaya, N., Kubota, T., Kakiuchi, Y., Kikuchi, S., Nishizaki, M.,
Kagawa, S., Tazawa, H., & Fujiwara, T. (2017). Liposome-encapsulated plasmid DNA of telomerase-
specific oncolytic adenovirus with stealth effect on the immune system. Scientific Reports, 7(1), 14177.
https://doi.org/10.1038/s41598-017-14717-x
10. Arabi, F., Mansouri, V., & Ahmadbeigi, N. (2022). Gene therapy clinical trials, where do we go? An
overview. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 153, 113324.
https://doi.org/10.1016/j.biopha.2022.113324
11. Bai, Y., Hui, P., Du, X., & Su, X. (2019). Updates to the antitumor mechanism of oncolytic virus. Thoracic
Cancer, 10(5), 1031–1035. https://doi.org/10.1111/1759-7714.13043
12. Breitbach, C. J., Arulanandam, R., Silva, N. D., Thorne, S. H., Patt, R., Daneshmand, M., Moon, A., Ilkow,
C., Burke, J., Hwang, T.-H., Heo, J., Cho, M., Chen, H., Angarita, F. A., Addison, C., McCart, J. A., Bell,
J. C., & Kirn, D. H. (2013). Oncolytic vaccinia virus disrupts tumor-associated vasculature in humans.
Cancer Research, 73(4), 1265–1275. https://doi.org/10.1158/0008-5472.CAN-12-2687
13. Breitbach, C. J., Paterson, J. M., Lemay, C. G., Falls, T. J., McGuire, A., Parato, K. A., Stojdl, D. F.,
Daneshmand, M., Speth, K., Kirn, D., McCart, J. A., Atkins, H., & Bell, J. C. (2007). Targeted
inflammation during oncolytic virus therapy severely compromises tumor blood flow. Molecular
Therapy : The Journal of the American Society of Gene Therapy, 15(9), 1686–1693.
https://doi.org/10.1038/sj.mt.6300215
14. Burman, B., Pesci, G., & Zamarin, D. (2020). Newcastle disease virus at the forefront of cancer
immunotherapy. In Cancers (Vol. 12, Issue 12, pp. 1–15). MDPI AG.
https://doi.org/10.3390/cancers12123552
15. Cao, G. D., He, X. B., Sun, Q., Chen, S., Wan, K., Xu, X., Feng, X., Li, P. P., Chen, B., & Xiong, M. M.
(2020). The Oncolytic Virus in Cancer Diagnosis and Treatment. In Frontiers in Oncology (Vol. 10).
Frontiers Media S.A. https://doi.org/10.3389/fonc.2020.01786
16. Chaudhuri, A., Ramesh, K., Kumar, D. N., Dehari, D., Singh, S., Kumar, D., & Agrawal, A. K. (2022).
Polymeric micelles: A novel drug delivery system for the treatment of breast cancer. Journal of Drug
Delivery Science and Technology, 77, 103886. https://doi.org/10.1016/j.jddst.2022.103886
17. Chen, N. G., Szalay, A. A., Buller, R. M. L., & Lauer, U. M. (2012). Oncolytic Viruses. Advances in
Virology, 2012, 1–2. https://doi.org/10.1155/2012/320206
18. Chung, Y. H., Cai, H., & Steinmetz, N. F. (2020). Viral nanoparticles for drug delivery, imaging,
immunotherapy, and theranostic applications. In Advanced Drug Delivery Reviews (Vol. 156, pp. 214–
235). Elsevier B.V. https://doi.org/10.1016/j.addr.2020.06.024
19. Coffin, R. (2016). Interview with Robert Coffin, inventor of T-VEC: the first oncolytic immunotherapy
approved for the treatment of cancer. Immunotherapy, 8(2), 103–106. https://doi.org/10.2217/imt.15.116
20. Connolly, J. L., Rodgers, S. E., Clarke, P., Ballard, D. W., Kerr, L. D., Tyler, K. L., & Dermody, T. S.
(2000). Reovirus-induced apoptosis requires activation of transcription factor NF-kappaB. Journal of
Virology, 74(7), 2981–2989. https://doi.org/10.1128/jvi.74.7.2981-2989.2000
21. Deng, Y., Zhang, X., Shen, H., He, Q., Wu, Z., Liao, W., & Yuan, M. (2019). Application of the Nano-
Drug Delivery System in Treatment of Cardiovascular Diseases. Frontiers in Bioengineering and
Biotechnology, 7, 489. https://doi.org/10.3389/fbioe.2019.00489
22. Dolgin, E. (2015). Oncolytic viruses get a boost with first FDA-approval recommendation. Nature
Reviews. Drug Discovery, 14(6), 369–371. https://doi.org/10.1038/nrd4643
23. Doroudian, M., Armstrong, M. E., & Donnelly, S. C. (2023). Nano-Based Therapies for Acute and
Chronic Lung Diseases (pp. 271–286). https://doi.org/10.1007/978-981-19-8342-9_12

Journal of Advanced Zoology
Available online at: https://jazindia.com 2547
24. Doroudian, M., Azhdari, M. H., Goodarzi, N., O’Sullivan, D., & Donnelly, S. C. (2021). Smart
Nanotherapeutics and Lung Cancer. Pharmaceutics, 13(11).
https://doi.org/10.3390/pharmaceutics13111972
25. Doroudian, M., Neill, A. O., Loughlin, R. M., Prina-Mello, A., Volkov, Y., & Donnelly, S. C. (2021).
Nanotechnology in pulmonary medicine. Current Opinion in Pharmacology, 56, 85–92.
https://doi.org/10.1016/j.coph.2020.11.002
26. Elankumaran, S., Rockemann, D., & Samal, S. K. (2006). Newcastle disease virus exerts oncolysis by
both intrinsic and extrinsic caspase-dependent pathways of cell death. Journal of Virology, 80(15), 7522–
7534. https://doi.org/10.1128/JVI.00241-06
27. Errington, F., Steele, L., Prestwich, R., Harrington, K. J., Pandha, H. S., Vidal, L., Bono, J. de, Selby, P.,
Coffey, M., Vile, R., & Melcher, A. (2008). Reovirus activates human dendritic cells to promote innate
antitumor immunity. Journal of Immunology (Baltimore, Md. : 1950), 180(9), 6018–6026.
https://doi.org/10.4049/jimmunol.180.9.6018
28. Farjadian, F., Ghasemi, S., Akbarian, M., Hoseini-Ghahfarokhi, M., Moghoofei, M., & Doroudian, M.
(2022). Physically stimulus-responsive nanoparticles for therapy and diagnosis. Frontiers in Chemistry,
10, 952675. https://doi.org/10.3389/fchem.2022.952675
29. Garber, K. (2006). China approves world’s first oncolytic virus therapy for cancer treatment. Journal of
the National Cancer Institute, 98(5), 298–300. https://doi.org/10.1093/jnci/djj111
30. Ghasemiyeh, P., Mohammadi-Samani, S., Noorizadeh, K., Zadmehr, O., Rasekh, S., Mohammadi-
Samani, S., & Dehghan, D. (2022). Novel topical drug delivery systems in acne management: Molecular
mechanisms and role of targeted delivery systems for better therapeutic outcomes. Journal of Drug
Delivery Science and Technology, 74, 103595. https://doi.org/10.1016/j.jddst.2022.103595
31. Goldufsky, J., Sivendran, S., Harcharik, S., Pan, M., Bernardo, S., Stern, R. H., Friedlander, P., Ruby, C.
E., Saenger, Y., & Kaufman, H. L. (2013). Oncolytic virus therapy for cancer. Oncolytic Virotherapy, 2,
31–46. https://doi.org/10.2147/OV.S38901
32. Gonzalez-Pastor, R., Hernandez, Y., Gimeno, M., Martino, A. de, Man, Y. K. S., Hallden, G., Quintanilla,
M., Fuente, J. M. de la, & Martin-Duque, P. (2021). Coating an adenovirus with functionalized gold
nanoparticles favors uptake, intracellular trafficking and anti-cancer therapeutic efficacy. Acta
Biomaterialia, 134, 593–604. https://doi.org/10.1016/j.actbio.2021.07.047
33. Grapa, C. M., Mocan, T., Gonciar, D., Zdrehus, C., Mosteanu, O., Pop, T., & Mocan, L. (2019). Epidermal
Growth Factor Receptor and Its Role in Pancreatic Cancer Treatment Mediated by Nanoparticles.
International Journal of Nanomedicine, 14, 9693–9706. https://doi.org/10.2147/IJN.S226628
34. Gruijl, T. D. de, Janssen, A. B., & Beusechem, V. W. van. (2015). Arming oncolytic viruses to leverage
antitumor immunity. Expert Opinion on Biological Therapy, 15(7), 959–971.
https://doi.org/10.1517/14712598.2015.1044433
35. Guerrini, L., Alvarez-Puebla, R. A., & Pazos-Perez, N. (2018). Surface Modifications of Nanoparticles
for Stability in Biological Fluids. Materials (Basel, Switzerland), 11(7).
https://doi.org/10.3390/ma11071154
36. Guo, Z. S., & Bartlett, D. L. (2004). Vaccinia as a vector for gene delivery. Expert Opinion on Biological
Therapy, 4(6), 901–917. https://doi.org/10.1517/14712598.4.6.901
37. Guo, Z., Sui, J., Ma, M., Hu, J., Sun, Y., Yang, L., Fan, Y., & Zhang, X. (2020). pH-Responsive charge
switchable PEGylated ε-poly-l-lysine polymeric nanoparticles-assisted combination therapy for
improving breast cancer treatment. Journal of Controlled Release : Official Journal of the Controlled
Release Society, 326, 350–364. https://doi.org/10.1016/j.jconrel.2020.07.030
38. Haddad, D. (2017). Genetically Engineered Vaccinia Viruses As Agents for Cancer Treatment, Imaging,
and Transgene Delivery. Frontiers in Oncology, 7, 96. https://doi.org/10.3389/fonc.2017.00096
39. Hajipour, H., Ghorbani, M., Kahroba, H., Mahmoodzadeh, F., Emameh, R. Z., & Taheri, R. A. (2019).
Arginyl-glycyl-aspartic acid (RGD) containing nanostructured lipid carrier co-loaded with doxorubicin
and sildenafil citrate enhanced anti-cancer effects and overcomes drug resistance. Process Biochemistry,
84, 172–179. https://doi.org/10.1016/j.procbio.2019.06.013
40. Heise, C., Sampson-Johannes, A., Williams, A., McCormick, F., Hoff, D. D. V., & Kirn, D. H. (1997).
ONYX-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficacy
that can be augmented by standard chemotherapeutic agents. Nature Medicine, 3(6), 639–645.
https://doi.org/10.1038/nm0697-639
41. Howard, F., & Muthana, M. (2020). Designer nanocarriers for navigating the systemic delivery of
oncolytic viruses. Nanomedicine (London, England), 15(1), 93–110. https://doi.org/10.2217/nnm-2019-
0323

Journal of Advanced Zoology
Available online at: https://jazindia.com 2548
42. Hsu, J.-F., Chu, S.-M., Liao, C.-C., Wang, C.-J., Wang, Y.-S., Lai, M.-Y., Wang, H.-C., Huang, H.-R., &
Tsai, M.-H. (2021). Nanotechnology and Nanocarrier-Based Drug Delivery as the Potential Therapeutic
Strategy for Glioblastoma Multiforme: An Update. Cancers, 13(2).
https://doi.org/10.3390/cancers13020195
43. Iwai, Y., Hamanishi, J., Chamoto, K., & Honjo, T. (2017). Cancer immunotherapies targeting the PD-1
signaling pathway. Journal of Biomedical Science, 24(1), 26. https://doi.org/10.1186/s12929-017-0329-9
44. Ji, Q., Wu, Y., Albers, A., Fang, M., & Qian, X. (2022). Strategies for Advanced Oncolytic Virotherapy:
Current Technology Innovations and Clinical Approaches. Pharmaceutics, 14(9).
https://doi.org/10.3390/pharmaceutics14091811
45. Jiang, H., & Fueyo, J. (2014). Healing after death: Antitumor immunity induced by oncolytic adenoviral
therapy. Oncoimmunology, 3(7), e947872. https://doi.org/10.4161/21624011.2014.947872
46. Jong, W. H. D., & Borm, P. J. A. (2008). Drug delivery and nanoparticles:applications and hazards.
International Journal of Nanomedicine, 3(2), 133–149. https://doi.org/10.2147/ijn.s596
47. Kaufman, H. L., Kohlhapp, F. J., & Zloza, A. (2015). Oncolytic viruses: A new class of immunotherapy
drugs. Nature Reviews. Drug Discovery, 14(9), 642–662. https://doi.org/10.1038/nrd4663
48. Khairnar, S. V., Pagare, P., Thakre, A., Nambiar, A. R., Junnuthula, V., Abraham, M. C., Kolimi, P.,
Nyavanandi, D., & Dyawanapelly, S. (2022). Review on the Scale-Up Methods for the Preparation of
Solid Lipid Nanoparticles. Pharmaceutics, 14(9). https://doi.org/10.3390/pharmaceutics14091886
49. Kim, J. H., Oh, J. Y., Park, B. H., Lee, D. E., Kim, J. S., Park, H. E., Roh, M. S., Je, J. E., Yoon, J. H.,
Thorne, S. H., Kirn, D., & Hwang, T. H. (2006). Systemic armed oncolytic and immunologic therapy for
cancer with JX-594, a targeted poxvirus expressing GM-CSF. Molecular Therapy : The Journal of the
American Society of Gene Therapy, 14(3), 361–370. https://doi.org/10.1016/j.ymthe.2006.05.008
50. Kim, J., Nam, H. Y., Choi, J. W., Yun, C.-O., & Kim, S. W. (2014). Efficient lung orthotopic tumor-
growth suppression of oncolytic adenovirus complexed with RGD-targeted bioreducible polymer. Gene
Therapy, 21(5), 476–483. https://doi.org/10.1038/gt.2014.18
51. Lee, M.-K. (2020). Liposomes for Enhanced Bioavailability of Water-Insoluble Drugs: In Vivo Evidence
and Recent Approaches. Pharmaceutics, 12(3). https://doi.org/10.3390/pharmaceutics12030264
52. Lichty, B. D., Breitbach, C. J., Stojdl, D. F., & Bell, J. C. (2014). Going viral with cancer immunotherapy.
Nature Reviews. Cancer, 14(8), 559–567. https://doi.org/10.1038/nrc3770
53. Maroun, J., Muñoz-Alía, M., Ammayappan, A., Schulze, A., Peng, K.-W., & Russell, S. (2017). Designing
and building oncolytic viruses. Future Virology, 12(4), 193–213. https://doi.org/10.2217/fvl-2016-0129
54. Matos, A. L. de, Franco, L. S., & McFadden, G. (2020). Oncolytic Viruses and the Immune System: The
Dynamic Duo. In Molecular Therapy—Methods and Clinical Development (Vol. 17, pp. 349–358). Cell
Press. https://doi.org/10.1016/j.omtm.2020.01.001
55. McCarthy, C., Jayawardena, N., Burga, L. N., & Bostina, M. (2019). Developing Picornaviruses for
Cancer Therapy. Cancers, 11(5). https://doi.org/10.3390/cancers11050685
56. Mejía-Méndez, J. L., Vazquez-Duhalt, R., Hernández, L. R., Sánchez-Arreola, E., & Bach, H. (2022).
Virus-like Particles: Fundamentals and Biomedical Applications. International Journal of Molecular
Sciences, 23(15), 8579. https://doi.org/10.3390/ijms23158579
57. Milewska, S., Niemirowicz-Laskowska, K., Siemiaszko, G., Nowicki, P., Wilczewska, A. Z., & Car, H.
(2021). Current Trends and Challenges in Pharmacoeconomic Aspects of Nanocarriers as Drug Delivery
Systems for Cancer Treatment. International Journal of Nanomedicine, 16, 6593–6644.
https://doi.org/10.2147/IJN.S323831
58. Misra, S. (2013). Human gene therapy: A brief overview of the genetic revolution. The Journal of the
Association of Physicians of India, 61(2), 127–133.
59. Mondal, M., Guo, J., He, P., & Zhou, D. (2020). Recent advances of oncolytic virus in cancer therapy. In
Human Vaccines and Immunotherapeutics (Vol. 16, Issue 10, pp. 2389–2402). Bellwether Publishing,
Ltd. https://doi.org/10.1080/21645515.2020.1723363
60. Niemann, J., & Kühnel, F. (2017). Oncolytic viruses: Adenoviruses. Virus Genes, 53(5), 700–706.
https://doi.org/10.1007/s11262-017-1488-1
61. Patnaik, S., & Gupta, K. C. (2013). Novel polyethylenimine-derived nanoparticles for in vivo gene
delivery. Expert Opinion on Drug Delivery, 10(2), 215–228.
https://doi.org/10.1517/17425247.2013.744964
62. PELNER, L., FOWLER, G. A., & NAUTS, H. C. (1958). Effects of concurrent infections and their toxins
on the course of leukemia. Acta Medica Scandinavica. Supplementum, 338, 1–47.

Journal of Advanced Zoology
Available online at: https://jazindia.com 2549
63. Pham, D. T., Chokamonsirikun, A., Phattaravorakarn, V., & Tiyaboonchai, W. (2021). Polymeric micelles
for pulmonary drug delivery: A comprehensive review. Journal of Materials Science, 56(3), 2016–2036.
https://doi.org/10.1007/s10853-020-05361-4
64. Pierce, K. M., Miklavcic, W. R., Cook, K. P., Hennen, M. S., Bayles, K. W., Hollingsworth, M. A.,
Brooks, A. E., Pullan, J. E., & Dailey, K. M. (2021). The evolution and future of targeted cancer therapy:
From nanoparticles, oncolytic viruses, and oncolytic bacteria to the treatment of solid tumors. In
Nanomaterials (Vol. 11, Issue 11). MDPI. https://doi.org/10.3390/nano11113018
65. Prestwich, R. J., Errington, F., Diaz, R. M., Pandha, H. S., Harrington, K. J., Melcher, A. A., & Vile, R.
G. (2009). The case of oncolytic viruses versus the immune system: Waiting on the judgment of Solomon.
Human Gene Therapy, 20(10), 1119–1132. https://doi.org/10.1089/hum.2009.135
66. Puré, E., & Lo, A. (2016). Can Targeting Stroma Pave the Way to Enhanced Antitumor Immunity and
Immunotherapy of Solid Tumors? Cancer Immunology Research, 4(4), 269–278.
https://doi.org/10.1158/2326-6066.CIR-16-0011
67. Rabinovich, G. A., Gabrilovich, D., & Sotomayor, E. M. (2007). Immunosuppressive strategies that are
mediated by tumor cells. Annual Review of Immunology, 25, 267–296.
https://doi.org/10.1146/annurev.immunol.25.022106.141609
68. Rahman, M. M., & McFadden, G. (2021). Oncolytic viruses: Newest frontier for cancer immunotherapy.
In Cancers (Vol. 13, Issue 21). MDPI. https://doi.org/10.3390/cancers13215452
69. Rao, J. P., & Geckeler, K. E. (2011). Polymer nanoparticles: Preparation techniques and size-control
parameters. Progress in Polymer Science, 36(7), 887–913.
https://doi.org/10.1016/j.progpolymsci.2011.01.001
70. Russell, S. J., & Peng, K.-W. (2007). Viruses as anticancer drugs. Trends in Pharmacological Sciences,
28(7), 326–333. https://doi.org/10.1016/j.tips.2007.05.005
71. Russell, S. J., Peng, K.-W., & Bell, J. C. (2012). Oncolytic virotherapy. Nature Biotechnology, 30(7),
658–670. https://doi.org/10.1038/nbt.2287
72. Schietinger, A., Philip, M., Liu, R. B., Schreiber, K., & Schreiber, H. (2010). Bystander killing of cancer
requires the cooperation of CD4(+) and CD8(+) T cells during the effector phase. The Journal of
Experimental Medicine, 207(11), 2469–2477. https://doi.org/10.1084/jem.20092450
73. Sendra, L., Miguel, A., Navarro-Plaza, M. C., Herrero, M. J., Higuera, J. de la, Cháfer-Pericás, C., Aznar,
E., Marcos, M. D., Martínez-Máñez, R., Rojas, L. A., Alemany, R., & Aliño, S. F. (2020). Gold
Nanoparticle-Assisted Virus Formation by Means of the Delivery of an Oncolytic Adenovirus Genome.
Nanomaterials (Basel, Switzerland), 10(6). https://doi.org/10.3390/nano10061183
74. Seymour, L. W., & Fisher, K. D. (2016). Oncolytic viruses: Finally delivering. British Journal of Cancer,
114(4), 357–361. https://doi.org/10.1038/bjc.2015.481
75. Sibuyi, N. R. S., Moabelo, K. L., Fadaka, A. O., Meyer, S., Onani, M. O., Madiehe, A. M., & Meyer, M.
(2021). Multifunctional Gold Nanoparticles for Improved Diagnostic and Therapeutic Applications: A
Review. Nanoscale Research Letters, 16(1), 174. https://doi.org/10.1186/s11671-021-03632-w
76. Singh, P., Pandit, S., Mokkapati, V. R. S. S., Garg, A., Ravikumar, V., & Mijakovic, I. (2018). Gold
Nanoparticles in Diagnostics and Therapeutics for Human Cancer. International Journal of Molecular
Sciences, 19(7). https://doi.org/10.3390/ijms19071979
77. Sinha, N., & Yeow, J. T. W. (2005). Carbon nanotubes for biomedical applications. IEEE Transactions
on Nanobioscience, 4(2), 180–195. https://doi.org/10.1109/tnb.2005.850478
78. Souri, M., Soltani, M., Kashkooli, F. M., Shahvandi, M. K., Chiani, M., Shariati, F. S., Mehrabi, M. R.,
& Munn, L. L. (2022). Towards principled design of cancer nanomedicine to accelerate clinical
translation. Materials Today. Bio, 13, 100208. https://doi.org/10.1016/j.mtbio.2022.100208
79. Staehlke, S., Lehnfeld, J., Schneider, A., Nebe, J. B., & Müller, R. (2019). Terminal chemical functions
of polyamidoamine dendrimer surfaces and its impact on bone cell growth. Materials Science &
Engineering. C, Materials for Biological Applications, 101, 190–203.
https://doi.org/10.1016/j.msec.2019.03.073
80. Thorne, S. H. (2011). Immunotherapeutic potential of oncolytic vaccinia virus. Immunologic Research,
50(2–3), 286–293. https://doi.org/10.1007/s12026-011-8211-4
81. Tseng, S.-H., Chou, M.-Y., & Chu, I.-M. (2015). Cetuximab-conjugated iron oxide nanoparticles for
cancer imaging and therapy. International Journal of Nanomedicine, 10, 3663–3685.
https://doi.org/10.2147/IJN.S80134
82. Tseng, S.-J., Huang, K.-Y., Kempson, I. M., Kao, S.-H., Liu, M.-C., Yang, S.-C., Liao, Z.-X., & Yang,
P.-C. (2016). Remote Control of Light-Triggered Virotherapy. ACS Nano, 10(11), 10339–10346.
https://doi.org/10.1021/acsnano.6b06051

Journal of Advanced Zoology
Available online at: https://jazindia.com 2550
83. Wilczewska, A. Z., Niemirowicz, K., Markiewicz, K. H., & Car, H. (2012). Nanoparticles as drug delivery
systems. Pharmacological Reports : PR, 64(5), 1020–1037. https://doi.org/10.1016/s1734-
1140(12)70901-5
84. Xia, Z.-J., Chang, J.-H., Zhang, L., Jiang, W.-Q., Guan, Z.-Z., Liu, J.-W., Zhang, Y., Hu, X.-H., Wu, G.-
H., Wang, H.-Q., Chen, Z.-C., Chen, J.-C., Zhou, Q.-H., Lu, J.-W., Fan, Q.-X., Huang, J.-J., & Zheng, X.
(2004). [Phase III randomized clinical trial of intratumoral injection of E1B gene-deleted adenovirus
(H101) combined with cisplatin-based chemotherapy in treating squamous cell cancer of head and neck
or esophagus]. Ai Zheng = Aizheng = Chinese Journal of Cancer, 23(12), 1666–1670.
85. Yokoda, R., Nagalo, B. M., Vernon, B., Oklu, R., Albadawi, H., DeLeon, T. T., Zhou, Y., Egan, J. B.,
Duda, D. G., & Borad, M. J. (2017). Oncolytic virus delivery: From nano-pharmacodynamics to enhanced
oncolytic effect. Oncolytic Virotherapy, 6, 39–49. https://doi.org/10.2147/OV.S145262
86. Younis, N. K., Roumieh, R., Bassil, E. P., Ghoubaira, J. A., Kobeissy, F., & Eid, A. H. (2022).
Nanoparticles: Attractive tools to treat colorectal cancer. Seminars in Cancer Biology, 86(Pt 2), 1–13.
https://doi.org/10.1016/j.semcancer.2022.08.006
87. Zare-Zardini, H., Hatamizadeh, N., Haddadzadegan, N., Soltaninejad, H., & Karimi-Zarchi, M. (2022).
Advantages and disadvantages of using Carbon Nanostructures in Reproductive Medicine: Two sides of
the same coin. JBRA Assisted Reproduction, 26(1), 142–144. https://doi.org/10.5935/1518-
0557.20210070
88. Zheng, Y., Wang, Y., Xia, M., Gao, Y., Zhang, L., Song, Y., & Zhang, C. (2022). The combination of
nanotechnology and traditional Chinese medicine (TCM) inspires the modernization of TCM: review on
nanotechnology in TCM-based drug delivery systems. Drug Delivery and Translational Research, 12(6),
1306–1325. https://doi.org/10.1007/s13346-021-01029-x
89. Zhu, J., Chen, W., Sun, Y., Huang, X., Chu, R., Wang, R., Zhou, D., & Ye, S. (2022). Recent advances
on drug delivery nanoplatforms for the treatment of autoimmune inflammatory diseases. Materials
Advances, 3(21), 7687–7708. https://doi.org/10.1039/D2MA00814A
90. Zugazagoitia, J., Guedes, C., Ponce, S., Ferrer, I., Molina-Pinelo, S., & Paz-Ares, L. (2016). Current
Challenges in Cancer Treatment. Clinical Therapeutics, 38(7), 1551–1566.
https://doi.org/10.1016/j.clinthera.2016.03.026