NAME KAHDIJA

ROLL NO. MSBT 15

ASSIGNMENT NANOBIOTECHNOLOGY

TOPICS INCLUDED
COVID 19 VIRUS
INFLUENZA VIRUS
CANCER IMMUNOTHERAPY
COVID 19 VIRUS

INTRODUCTION
In 1965, Tyrrell and Bynoe made the initial diagnosis of the human coronavirus using a
sample of the respiratory tract from an adult who had a common cold and grew it on
human embryonic trachea. The virus's surface resembles a crown, which led to its
naming. A βcoronavirus was identified in Wuhan, China, in December 2019. The new illness has been identified as SARS-
CoV-2 by the International Committee's Coronavirus Study Group (CSG) and as Coronavirus disease 2019 (COVID-19) by
the World Health Organization (WHO). The initial outbreak of an unidentified acute respiratory tract infection on
December 29, 2019, in Wuhan, China, was most likely connected to a seafood market. According to numerous research,
bats might be the main disease reservoirs. Sadeghi dousari, A., Taati Moghadam, M., & Satarzadeh, N. (2020). COVID-19
(Coronavirus Disease 2019): A New Coronavirus Disease. Infection and Drug Resistance, 13, 2819 - 2828.

DEATH RATE
As of March 25, 2020, the overall rate of deaths per number of diagnosed cases is 4.5 percent; ranging from 0.2 percent
to 15 percent according to age group and other health problems. Kader, S.M., & Rob, S.A. (2021). COVID-19:
Epidemiology, Management and Environmental Innovations.

As per the World Health Organization (WHO) novel Coronavirus (COVID-19) Situation Board, there are about 16.2 million
confirmed cases of COVID-19 recorded in 216 countries, and 0.65 million deaths occurred among them, as of 26th July
2020. Maideen, N.M. (2021). Adjuvant Therapies of COVID-19 – A Literature Review. Coronaviruses.

Currently, COVID-19 is a pandemic that according to the latest WHO report, until July 08, 2020, a total of 11,635,939
cases were infected in more than 216 countries around the world, and 539,026 cases died. Sadeghi dousari, A., Taati
Moghadam, M., & Satarzadeh, N. (2020). COVID-19 (Coronavirus Disease 2019): A New Coronavirus Disease. Infection
and Drug Resistance, 13, 2819 - 2828.

As of December 7th, 2020, the virus has led to 67 million cases and more than 1.5 million deaths reported globally. Yang,
K., Lin, J., Tsai, H., Hsu, C., Shih, V., & Hu, C.J. (2021). Nanotechnology advances in pathogen- and host-targeted antiviral
delivery: multipronged therapeutic intervention for pandemic control. Drug Delivery and Translational Research, 11,
1420 - 1437.

Up to April 2021 more than 2.91 million deaths have been reported. Ali, J., Elahi, S.N., Ali, A., Waseem, H., Abid, R., &
Mohamed, M.M. (2021). Unveiling the Potential Role of Nanozymes in Combating the COVID-19
Outbreak. Nanomaterials, 11.

Globally, as of 14 July 2021, there have been more than 4 million deaths and almost 190 million confirmed cases of
infection. Chałupnik, A., Borkowska, A., Chilimoniuk, Z., Dobosz, M., Wieteska, M., & Mizerski, G. (2022). Wpływ
pandemii COVID-19 na zdrowie psychiczne wybranych grup społecznych. Journal of Education, Health and Sport.

This new virus spread far more quickly. Since the virus was discovered, it has spread over the globe causing hundreds of
millions of infected cases and millions of mortalities as of October 2022. The overall mortality rate from this pandemic
was estimated to be 4.7%, but in older patients. with aged 60 or over, it can increase to approximately 14.8%, This
pandemic has caused healthcare systems and economies of many affected nations to collapse. Ying, Z. (2023). Antiviral
Treatments for COVID-19 and Evaluation of Their Clinical Benefits. Highlights in Science, Engineering and Technology.
VIRUS SPREAD
Coronaviruses are a common cause of acute respiratory illnesses in humans, other mammals, and birds. The primary
means of transmission for this disease is by respiratory droplets, which can be spread by direct means (cough, sneeze,
and droplet inhalation) as well as indirect means (contact with mucous membranes in the mouth, nose, and eyes).
Sadeghi dousari, A., Taati Moghadam, M., & Satarzadeh, N. (2020). COVID-19 (Coronavirus Disease 2019): A New
Coronavirus Disease. Infection and Drug Resistance, 13, 2819 - 2828.

Respiratory droplets produced during coughing or sneezing. Respiratory droplets may be produced during breathing, but
the virus is not considered airborne. Kader, S.M., & Rob, S.A. (2021). COVID-19: Epidemiology, Management and
Environmental Innovations.

There is growing evidence that droplets and airborne particles can remain suspended in the air and be breathed in by
others and travel distances beyond 6 feet. Tanne, J.H. (2020). Covid-19: CDC publishes then withdraws information on
aerosol transmission. BMJ, 370.

Recent data suggested that SARS-CoV-2 might potentially be an intestinal virus that spreads orally through feces. Dental
practitioners and patients are particularly vulnerable to catching COVID-19 because of the handling of sharp instruments,
direct contact with patients, and exposure to blood and saliva. According to Verdavas et al., smokers are nearly 2.4 times
more likely than non-smokers to be admitted to an intensive care unit, need mechanical ventilation, or pass away. They
are also 1.4 times more likely to have severe COVID-19 symptoms. Breast milk can carry the COVID-19 virus, but an
infected woman can also pass the virus to her kid through respiratory droplets. Sadeghi dousari, A., Taati Moghadam, M.,
& Satarzadeh, N. (2020). COVID-19 (Coronavirus Disease 2019): A New Coronavirus Disease. Infection and Drug
Resistance, 13, 2819 - 2828.

ANTIVIRAL TREATMENT
Sadeghi dousari, A., Taati Moghadam, M., & Satarzadeh, N. (2020). COVID-19 (Coronavirus Disease 2019): A New
Coronavirus Disease. Infection and Drug Resistance, 13, 2819 - 2828.

This section mainly focuses on the popular and efficient antiviral treatments for COVID-19 over the world.

Antiviral Oral Drugs: There are several different small-molecule antiviral drugs which are recommended COVID-19
treatments, including paxlovid (ritonavir-boosted nirmatrelvir), remdesivir, bebtelovimab, and molnupiravir. Ying, Z.
(2023). Antiviral Treatments for COVID-19 and Evaluation of Their Clinical Benefits. Highlights in Science, Engineering and
Technology.

Remdesivir: Remdesivir is a novel nucleotide analogue antiviral initially developed for the management of the Ebola and
Marburg viruses. Remdesivir is a mono phosphoramidate Prodrug of remdesivir triphosphate, an adenosine analog that
acts as an inhibitor of RNA-dependent RNA polymerases. Remdesivir-TP competes with adenosine-triphosphate for
incorporation into nascent viral RNA chain. However, it has efficacy against a broad range of pathogenic viruses, including
both SARS-CoV and MERS-CoV in in vitro and in vivo models. There has been much interest in this molecule, following
treatment of the first COVID-19 case and subsequent recovery in the United States of America. Sharma, A. (2022).
COVID-19: Accident or plan. Pharmaspire.

Favipiravir: It is a broad-spectrum antiviral with in vitro activity against RNA viruses. Favipiravir is an RNA-dependent RNA
polymerase inhibitor that inhibits viral RNA synthesis. Sharma, A. (2022). COVID-19: Accident or plan. Pharmaspire.

Paxlovid: Paxlovid is recommended over remdesivir for treating non-hospitalized COVID-19 patients. In a 2021 trial,
those getting paxlovid early had significantly lower hospital admission and mortality rates compared to a placebo, with
strong statistical significance. Ying, Z. (2023). Antiviral Treatments for COVID-19 and Evaluation of Their Clinical
Benefits. Highlights in Science, Engineering and Technology.
Monoclonal Antibodies: Another major antiviral treatment is intravenous (IV) therapy of monoclonal antibodies that
specifically targets SARS-CoV-2 virus. Bebtelovimab, sotrovimab, casirivimab plus imdevimab, tixagevimab plus
cilgavimab, and bamlanivimab plus etesevimab and are monoclonal antibodies therapies that are available to treat or
prevent COVID-infection. Ying, Z. (2023). Antiviral Treatments for COVID-19 and Evaluation of Their Clinical
Benefits. Highlights in Science, Engineering and Technology.

An international clinical study on the utility of the monoclonal baricitinib (currently used for rheumatoid arthritis)
showed a 71% mortality benefit in elderly patients (median 81 years age) with moderate–severe covid-19. Baricitinib
reduces viral infectivity by inhibiting kinases associated with viral endocytosis and also has anti-inflammatory activities,
thus reducing lung damage and mortality. Ismail, A.A. (2021). SARS-CoV-2 (Covid-19): A short update on molecular
biochemistry, pathology, diagnosis and therapeutic strategies. Annals of Clinical Biochemistry, 59, 59 - 64.

Some non-pharmacological interventions are also being proposed in the world, mainly to prevent the contamination
and spread of COVID-19. These measures include social distance, washing hands with soap and water, using masks,
cleaning with 70% alcohol, closing schools and banning crowds, among others. In addition, non-pharmacological
treatments, related to supportive therapies, such as oxygenation, have been used. Pereira, A.A., de Oliveira Andrade, A.,
de Andrade Palis, A., Cabral, A.M., Barreto, C.G., de Souza, D.B., de Paula Silva, F., Santos, F.P., Silva, G.L., Guimarães, J.F.,
de Araújo, L.A., Nóbrega, L.R., Mendes, L.C., Brandão, M.R., Milagre, S.T., de Lima Gonçalves, V., de Freitas Morales, V.H.,
& da Conceição Lima, V. (2021). Non-pharmacological treatments for COVID-19: current status and consensus. Research
on Biomedical Engineering, 38, 193 - 208.

Various studies have been identified for the use of corticosteroids, interferons, monoclonal antibodies, etoposide,
ruxolitinib, anticoagulants, convalescent plasma, immunoglobulins, mesenchymal stem cells, natural killer (NK) cells, and
inhaled nitric oxide (NO) as adjuvant therapy to manage the patients with COVID-19 along with the repurposed drugs
targeting SARS-CoV-2. Maideen, N. M. (2021). Adjuvant Therapies of COVID-19-A Literature Review. Coronaviruses, 2(10),
7-16.

NANOBIOTECHNOLOGY ROLE
FORMULATION VIRUS PAY LOAD FEATURES REFERENCE
TYPE
- Inhibit ROS generation Yang, K., Lin, J., Tsai, H.,
Liposome COVID-19 Lactoferrin Hsu, C., Shih, V., & Hu, C.J.
- Pulmonary targeted (2021). Nanotechnology
advances in pathogen- and
- Decrease viral replication host-targeted antiviral
delivery: multipronged
therapeutic intervention
for pandemic
control. Drug Delivery and
Translational Research,
11, 1420 - 1437.
- Pulmonary targeted
Inhaled COVID-19 Remdesivir
nanoparticle - Accessible administration

- Lower systemic toxicity

 SENSOR BASED DETECTION:
Researchers developed a lateral flow assay for detecting
anti-SARS-CoV-2 IgG antibodies using lanthanide-doped
nanoparticles. The virus RNA was extracted, and RT-PCR
produced the full-length nucleocapsid protein, which was
then cloned and expressed in E. coli. Lanthanide-doped
nanoparticles were conjugated with mouse anti-human
IgG and rabbit anti-human IgG antibodies for use in the
assay strips. The test involved loading serum samples into
a strip with various components, enclosed in a plastic shell. Fluorescence detected the presence of antibodies after 10
minutes. Another assay using gold nanoparticles (AuNPs) was designed to detect IgM antibodies against SARS-CoV-2. The
AuNPs were synthesized and combined with the virus nucleoprotein to capture samples. This test provided results in 15
minutes with a small sample size and required no sophisticated equipment. Bisht, A., Mishra, A., Bisht, H.S., & Tripathi,
R.M. (2021). Nanomaterial Based Biosensors for Detection of Viruses Including SARS-CoV-2: A Review. Journal of Analysis
and Testing, 5, 327 - 340.

Roh et al. utilized quantum dots containing fluorescent nanoparticles for rapid and sensitive viral detection. Conjugated
RNA aptamers were employed to the fluorescent quantum dots. In the presence of the virus, interaction with the RNA
aptamer caused a change in the optical signal of the quantum dots. This method proved effective in detecting virus
particles at a concentration as low as 0.1 pg/ml. Tharayil, A., Rajakumari, R., Chirayil, C.J., Thomas, S., & Kalarikkal, N.
(2021). A short review on nanotechnology interventions against COVID-19. Emergent Materials, 4, 131 - 141.

Electrochemical biosensors, featuring gold nanoparticles, are highly efficient for detecting the COVID-19 virus. Layqah
et al. developed an immunosensor using carbon electrodes coated with gold nanoparticles, immobilizing COVID-19 spike
S1 protein. This sensor can detect various coronaviruses, including MERS-CoV, with a detection limit of about 0.4 to 1.0
pg ml−1. Another genosensor utilized gold nanoparticles and thiolated oligonucleotides on carbon electrodes for SARS
and COVID-19 detection, achieving a detection limit of about 2.5 pmol l−1. Ishikawa et al. employed In2O3 nanowires for
sensing nucleocapsid proteins, demonstrating high sensitivity with sub-nanomolar detection limits. Tharayil, A.,
Rajakumari, R., Chirayil, C.J., Thomas, S., & Kalarikkal, N. (2021). A short review on nanotechnology interventions against
COVID-19. Emergent Materials, 4, 131 - 141.

Chiral biosensors, such as chiral zirconium quantum dots and self-assembled layers of quantum dots and
chiroplasmonic gold nanoparticles, prove effective for detecting SARS and COVID-19 viruses. The chiral zirconium
quantum dots, combined with magnetic nanoparticles and coronavirus-specific antibodies, exhibit a magneto-plasmonic
fluorescence, allowing the detection of virus presence with a limit of 79.15 EID/50 μl. Chiral immunosensors, utilizing
self-assembled layers of quantum dots and chiroplasmonic gold nanoparticles, achieve a low detection limit of 47.91
EID/50 μl in blood samples for coronavirus. However, the application of nanotechnology in the fight against COVID-19
poses challenges, including nanoparticle toxicity, lack of standardized protocols, and the need for reliable in vivo models
to assess long-term exposure effects. Tharayil, A., Rajakumari, R., Chirayil, C.J., Thomas, S., & Kalarikkal, N. (2021). A
short review on nanotechnology interventions against COVID-19. Emergent Materials, 4, 131 - 141.

Nanozymes:
Nanozymes, known for their stability and catalytic efficiency, have been utilized in colorimetric strip tests and
chemiluminescence paper tests for rapid and sensitive detection of SARS-CoV-2 spike antigen. For instance,

Co-Fe@hemin nanozyme showed potential in point-of-care testing (POCT) with a detection limit of 0.1 ng/mL in 16
minutes. Additionally, magnetic nanozyme-linked immunosorbent assay (MagLISA) demonstrated ultrasensitive
colorimetric detection of Influenza A (H1N1) virus, suggesting a potential enhancement for serological tests (ELISA) for
SARS-CoV-2. Nanozyme-mediated paper-based lateral flow assays (LFAs) have been proposed as efficient point-of-care
strategies, offering improved performance and sensitivity compared to conventional LFAs. Furthermore, nanozyme-
mediated aptamers show promise in ultrasensitive detection of SARS-CoV-2-related antigens, contributing to the
development of effective therapeutics and vaccines. Overall, nanozymes exhibit potential in various detection strategies
for SARS-CoV-2, including POCT, LFAs, and ELISA, enhancing sensitivity and specificity in diagnosis. Ali, J., Elahi, S.N., Ali,
A., Waseem, H., Abid, R., & Mohamed, M.M. (2021). Unveiling the Potential Role of Nanozymes in Combating the COVID-
19 Outbreak. Nanomaterials, 11.

Possible mechanism of nanozyme-mediated sandwich enzyme-linked immunosorbent assay (ELISA) for SARS-CoV-2
detection Ali, J., Elahi, S.N., Ali, A., Waseem, H., Abid, R., & Mohamed, M.M. (2021). Unveiling the Potential Role of
Nanozymes in Combating the COVID-19 Outbreak. Nanomaterials, 11.

Metallic nanoparticles, including silver, copper, and titanium dioxide, are proposed alternatives due to their broad
antiviral activities. Silver nanocluster/silica coatings on masks and photocatalytic coatings based on titanium dioxide
nanoparticles show viricidal effects. Nanomaterials can enhance face masks' inhibitory effects, with options like
graphene being used for adsorption and elimination of viruses. Talebian, S., Wallace, G.G., Schroeder, A., Stellacci, F., &
Conde, J. (2020). Nanotechnology-based disinfectants and sensors for SARS-CoV-2. Nature Nanotechnology, 15, 618 -
621.

INFLUENZA VIRUS

[Link] [Link]/flu/professionals/laboratory/[Link].
INTRODUCTION
The RNA genome of influenza viruses is single-stranded, negative-sense, segmented, and they are members of the
Orthomyxoviridae family. Playford, G., & Dwyer, D.E. (2002). LABORATORY DIAGNOSIS OF INFLUENZA VIRUS
INFECTION. Pathology, 34, 115–125. The influenza virus was first isolated in 1933. Baxter, D.N. (2016). Evaluating the
case for trivalent or quadrivalent influenza vaccines. Human Vaccines & Immunotherapeutics, 12, 2712 - 2717.

Based on antigenic variations in the nucleoprotein and matrix proteins, three different types of influenza viruses—the
influenza A virus, influenza B virus, and influenza C virus—are identified. A segmented genome and a viral envelope
containing glycoproteins essential for viral entry and exit from cells are two traits that all three viruses have in common.
The influenza strain identification, year of isolation, place of initial isolation, and influenza type are all included in the
standard nomenclature for influenza viruses. Hemagglutinin (HA) is the protein that the influenza virus uses to attach
itself to cells that are receptive to it and to fuse its envelope with the cell membrane. The primary defense mechanism
brought on by infection or immunization is the antibody to the HA, which neutralizes viral infectivity. Another envelope
glycoprotein that is crucial to the virus's escape from cells is neuraminidase (NA). Viral replication is also inhibited by
antibodies to the NA, making the NA a crucial target for antiviral treatment. Amantadine and rimantadine block the M2,
a third membrane protein that is found in trace amounts on virions. Lastly, nucleoprotein (NP) and matrix (M), two viral
structural proteins, are significant targets for cytotoxic T lymphocytes (CTL). Treanor, J.J., & Fleming, D. (2002).
Respiratory Viruses. Practical Guidelines in Antiviral Therapy, 223 - 256.

DEATH RATE
With the use of viral sequences found in preserved or buried tissues belonging to 1918 influenza pandemic victims,
researchers may now investigate the reasons for the virus's high pathogenicity—more than 200,000 people died from it,
most of them being young adults in their prime. Yewdell, J., & García-Sastre, A. (2002). Influenza virus still
surprises. Current opinion in microbiology, 5(4), 414–418. [Link]

Seasonal influenza in temperate climates is estimated to impact 5–15% of the population annually with a case fatality
rate of less than 0.01%; this can lead to 3–5 million instances of severe illness and 250,000–500,000 fatalities. An
estimated 201,200 people lost their lives to respiratory illnesses during the most recent H1N1 2009 pandemic. Over 50
million people are thought to have died because of the 1918–19 H1N1 pandemic worldwide. Baxter, D.N. (2016).
Evaluating the case for trivalent or quadrivalent influenza vaccines. Human Vaccines & Immunotherapeutics, 12, 2712 -
2717.

Seasonal influenza is thought to afflict 5–10% of the global population each year, resulting in 3–5 million severe cases
and 250–500,000 fatalities. Seasonal influenza in North America results in an increase of hospital admissions (230–1670
per 100,000 individuals over 65), 32,000 fatalities from respiratory and cardiovascular diseases, and 43,000 deaths from
all causes per year. A new A/H1N1 influenza virus appeared in 2009 and spread quickly, resulting in a pandemic.10 /11
The WHO received reports by November of 8768 deaths and 622 482 laboratory-confirmed pandemic influenza A/H1N1
illnesses. Lee, N., Choi, K.W., Chan, P.K., Hui, D.S., Lui, G., Wong, B.C., Wong, R.Y., Sin, W.Y., Hui, W.M., Ngai, K.L., Cockram,
C.S., Lai, R., & Sung, J.J. (2010). Outcomes of adults hospitalised with severe influenza. Thorax, 65, 510 - 515.

With 141.15 deaths per 100,000 people, adults over 75 had the highest average yearly rate of influenza-associated
mortality; by contrast, children under 18 had the lowest average mortality rate, at 0.41 deaths per 100,000 people.
Quandelacy, T.M., Viboud, C.G., Charu, V., Lipsitch, M., & Goldstein, E. (2014). Age- and sex-related risk factors for
influenza-associated mortality in the United States between 1997-2007. American journal of epidemiology, 179 2, 156-
67.
VIRUS SPREAD
Respiratory droplets are how influenza viruses are spread from person to person. under droplets and on non-porous
surfaces, environmental survival can last longer than 24 hours under low humidity. Due to the short incubation period
(one to five days) and high virus concentrations in respiratory secretions during the early stages of the illness, influenza
spreads quickly across human populations. Playford, G., & Dwyer, D.E. (2002). LABORATORY DIAGNOSIS OF INFLUENZA
VIRUS INFECTION. Pathology, 34, 115–125.

Influenza mostly spreads through the respiratory system. Viral-laden mucus particles of various sizes are released during
coughing, sneezing, and even talking. Smaller particles, less than 5 microns in diameter, can be inhaled into the terminal
bronchioles and alveoli, while larger particles may strike the oropharynx directly, causing illness. The biggest particles
may gravitationally descend and land on nearby surfaces, where they could infect hands by transferring to their mucosal
surfaces. Baxter, D.N. (2016). Evaluating the case for trivalent or quadrivalent influenza vaccines. Human Vaccines &
Immunotherapeutics, 12, 2712 - 2717.

TREATMENT
Zanamivir and oseltamivir, two approved inhibitors, work well against different influenza strains. Oseltamivir is given
orally, whereas zanamivir is inhaled; both drugs suppress neuraminidase in different ways. The inhibitory concentrations
of these drugs in clinical isolates vary from 2 to 20 nmol/L in cell culture. Even individuals with a higher risk of influenza-
related problems benefited with zanamivir, which decreased respiratory difficulties from 46% to 14%. Treanor, J.J., &
Fleming, D. (2002). Respiratory Viruses. Practical Guidelines in Antiviral Therapy, 223 - 256.

CLASS/AGENT TRADE NAME ROUTE OF REFERENCE

ADMINISTRATION
Playford, G., & Dwyer,
M2 inhibitors D.E. (2002). LABORATORY
Amantidine Symmetrel Oral DIAGNOSIS OF
Rimantidine Flumadine Oral INFLUENZA VIRUS
INFECTION. Pathology,
34, 115–125.
Playford, G., & Dwyer,
NI inhibitors D.E. (2002). LABORATORY
Zanamivir Relenza Inhaled (by Diskhaler) DIAGNOSIS OF
Oseltamivir Tamiflu Oral INFLUENZA VIRUS
INFECTION. Pathology,
34, 115–125.

VACCINATION

Influenza can be effectively controlled and prevented with vaccination. Now, the most widely used influenza vaccinations
are injectable trivalent inactivated virus (TIV) flu shots against seasonal influenza viruses. Three influenza virus strains—
two A subtypes, H3N2, H1N1, and one B type—make up TIV vaccinations. These strains were principally chosen based on
their expected predominance during the intended influenza season. The second B lineage is included in QIV vaccinations.
There are three distinct formulations of TIV vaccines: whole virus, split virus, and submit. Both these vaccinations were
used for treatment of different seasonal influenza viruses there are three Method of production of influenza vaccine
approve by US food medication and administration (FDA).

 Egg-Based Flu vaccine

 Cell Based Flu Vaccine
 Recombinant Flu Influenza
Varsha, S., & Vandita, B. (2019). A Review: Influenza and its Therapeutic Approaches. International Journal of Scientific
Research and Reviews.

As of right now, ribavirin, neuraminidase inhibitors, and adamantanes are the available antivirals. The most recent
medication to join the group of anti-influenza medications is baloxavir marboxil, the prodrug of baloxavir, which was
approved by the US FDA on October 24, 2018. By blocking Cap-dependent endonuclease (CEN), an essential stage in the
transcription of viral RNA, baloxavir works through a unique mechanism to stop the virus from spreading further. Tejus,
A., Mathur, A.G., Pradhan, S., Malik, S., & Salmani, M.F. (2021). Drug update - Baloxavir marboxil: Latest entrant into the
arena of pharmacotherapy of influenza. Medical journal, Armed Forces India, 78 2, 125-130.

NANOBIOTECHNOLOGY ROLE
An innate immune activator can be delivered by gold nanorods (GNRs), resulting in a targeted therapeutic response. This
study demonstrates the effectiveness of GNR-5′PPP-ssRNA nanoplex, a biocompatible gold nanorod, as an antiviral tactic
against the type A influenza virus. This nanoplex triggered the retinoic acid-inducible gene I (RIG-I) pathogen recognition
pathway in human pulmonary bronchial epithelial cells, leading to an upregulation of IFN-β and other IFN-stimulated
genes (ISGs), such as PKR, MDA5, IRF1, IRF7, and MX1. This increase in type I IFN and ISGs resulted in a decrease in the
replication of H1N1 influenza viruses.

Chakravarthy, K.V., Bonoiu, A.C., Davis, W.G., Ranjan, P., Ding, H., Hu, R., Bowzard, J.B., Bergey, E.J., Katz, J., Knight, P.R.,
Sambhara, S., & Prasad, P.N. (2010). Gold nanorod delivery of an ssRNA immune activator inhibits pandemic H1N1
influenza viral replication. Proceedings of the National Academy of Sciences, 107, 10172 - 10177.

Use of Nanoparticles in Vaccines:

Schematic representation of different nanotechnology applications in vaccination strategies.

The main goals are the stimulation of antibody (Ab) production and lymphocyte (T cell) activation.
For this purpose, different vaccination strategies were used: viral antigens immobilized on nanoparticles’
(NPs) surfaces (A); viral self-amplifying mRNA encapsulated in NPs, which replicate inside cells,
leading to antigen expression (B); or inactivated virus encapsulated in NPs (C).

Researchers are looking into using nanoparticles to make HA-containing vaccinations. In this application, nanoparticles
refer to extremely small particles that can be composed of gold (Au NPs), calcium phosphate (CaP NPs), chitosan (CS
NPs), or polyanhydride (NPs). The purpose of these nanoparticles is to deliver HA as a component of a vaccination.
 Sr# Nanoparticle Design Application Results
1 Wang et al.: As an adjuvant, they created gold In mice, this nanovaccine dramatically raised the levels
nanoparticles (Au NPs) with a dual linker that carried of antibodies specific to the virus. Additionally, it
influenza HA as well as the bacterial flagella protein activated T cell-mediated immunity and immunological
flagellin (FliC). pathways.
2 Knuschke et al.: They produced immune-activating These nanoconjugates elicited potent T cell-mediated
molecules (TLR9 ligand CpG) and HA in immunological responses in mice.
biodegradable calcium phosphate nanoparticles
(CaP NPs).
3 To distribute encapsulated HA, chitosan This nanovaccine reduced influenza morbidity and
nanoparticles (NPs) were coupled with sodium offered total protection against a lethal dose in mice by
tripolyphosphate (CS/TPP). inducing a high number of IFN-γ-secreting cells.
4 Kanekiyo et al.: They created nanoparticles by fusing Immunization against a wide range of influenza viruses
the HA protein with ferritin. protected mice and ferrets against HA antibodies by
lowering their levels and generating neutralizing
antibodies against HA structures.
5 Ross et al.: They looked at H53 that was This combination resulted in decreased weight loss,
encapsulated in hydrogel and polyanhydride NPs. lower virus loads in the lungs, and high neutralizing
antibody levels that were maintained for at least 70 days
in the mice.

Wieczorek, K., Szutkowska, B., & Kierzek, E. (2020). Anti-Influenza Strategies Based on Nanoparticle
Applications. Pathogens, 9.

Preclinical research is presently being conducted on Sirnaomics' polymer-based nanotherapeutic STP702 (FluquitTM).
For efficient antiviral action against H5N1 (avian flu), H1N1 (swine flu), and the recently emerging H7N9, this includes
siRNA that targets the conserved areas of influenza.

Liposomes were employed by Hendricks et al. to carry glycosyl sialylneolacto-N-tetraose c (LSTc)-sialoside, a synthetic
decoy receptor that binds influenza. The outcomes demonstrated that these liposomes could prevent influenza A virus
infection of target cells in a dose-dependent manner and are very efficient in competitively binding and capturing
influenza A viruses.

Oseltamivir-modified silver nanoparticles have been demonstrated in a study by Li et al. 166 to effectively reduce H1N1
infection by blocking both HA and NA activity in vitro. It was demonstrated that these nano-constructs' antiviral qualities
were also influenced by their ability to prevent DNA breakage, chromatin condensation, and caspase-3 activity. When
compared to oseltamivir controls, the toxicity profiles of these oseltamivir-modified silver nanoparticles were also shown
to be improved in MDCK cells, as assessed by the cytopathic effect, transmission electron microscopy, and cell viability
assays.

Using a polylysine linker, titanium dioxide (TiO2) nanoparticles functionalized with DNA fragments targeting the 3′ non-
coding region of the influenza A virus were created. These nanocomposites were shown to be effective influenza A virus
inhibitors in vitro and were able to penetrate cells without the need for transfection agents.

Singh, L., Kruger, H.G., Maguire, G.E., Govender, T., & Parboosing, R. (2017). The role of nanotechnology in the treatment
of viral infections. Therapeutic Advances in Infectious Disease, 4, 105 - 131.
Compared to bark extracts, the green generated silver nanoparticles made from Cinnamomum cassia exhibited greater
anti-influenza action against the H7N3 strain. Gansukh, E., Anthonydhason, V., Jung, S., Kim, D.H., Muthu, M., Gopal, J., &
Chun, S. (2018). Nanotherapeutic Anti-influenza Solutions: Current Knowledge and Future Challenges. Journal of Cluster
Science, 29, 933-941.

CANCER
INTRODUCTION
A class of diseases known as cancer arises from the body's cells proliferating uncontrollably. Uncontrollably dividing and
proliferating, these cells have the potential to spread throughout the body and harm vital organs. Metastasis is the term
for the spread of cancer to other body parts. Cancer cells can spread when they reach the lymphatic or circulatory
systems. The body's circulatory systems facilitate cell movement throughout the body. Malignant tumors, another name
for cancer, are a class of disorders characterized by abnormal cell proliferation that can infiltrate or spread to other parts
of the body. Benign tumors do not metastasize to other areas of the body; not all tumors are cancerous. Sravan, M.V.,
Shankar, M., Kumar, R.C., & Babu, M.N. (2015). A Current View on New Cancer Drugs (2014-USFDA Approved) Over Old
Drugs.

Most malignancies are called for the organ or cell type that they first appear in. There are three main groups into which
cancer kinds can be divided. Sarcoma (cancer that starts in bone, cartilage, muscle, blood vessels, or other connective or
supportive tissue), Carcinoma (cancer that starts in the skin or in tissues that line or cover internal organs), and Leukemia
(cancer that starts in bloodforming tissue such as the bone marrow and causes production of large numbers of abnormal
blood cells and enter the blood) are the main categories of cancer. Champanery, R., & Patel, K. (2020). Rajashri et al.
Himalayan Journal of Health Sciences ISSN: 2582-0737.

DEATH RATE
Roughly 13% of fatalities in humans are related to cancer. The American Cancer Society reports that 7.6 million
individuals worldwide lost their lives to cancer in 2007. Over 4.5 million people worldwide lose their lives to cancer, with
an estimated 9 million new cases of the disease being diagnosed each year. In India, there are 7 lakh cancer diagnoses
annually, over 3.5 lakh cancer-related deaths, and 2.3 lakh new cases linked to tobacco use. Kumari, S., & Jesudas, L.L.
(2014). 1699-1707 Prema Kumari 452.

The World Health Organization estimates that there will be 10 million cancer deaths and 20 million new cases of cancer
in 2020, making cancer the second greatest cause of death worldwide. Roughly 70% of cancer fatalities worldwide occur
in low- and middle-income nations, which have been disproportionately impacted by the growth in cancer incidence.
Aljurf, M., Majhail, N.S., Koh, M.B., Kharfan-Dabaja, M.A., & Chao, N.J. (2021). Introduction. The Comprehensive Cancer
Center.

Breast cancer accounts for over 25% of all cancer cases; in 2012, 1.67 million new cases were anticipated to have been
diagnosed. Breast cancer is responsible for around 500000 deaths annually. In high-risk women, the reported incidence
of breast cancer is 43.4 cases per 1,000 years. Takalkar, U.V., Takalkar, M.U., & Advani, S.H. (2018). Recent Studies &
Advances in Breast Cancer.

With 440,000 new cases of esophageal cancer diagnosed globally and 442,000 new deaths from the disease, esophageal
cancer is the ninth most common cancer and the sixth most common cause of cancer-related death worldwide,
respectively. Delliturri, A., Chiba, S., & Brichkov, I. (2019). Malignant: Esophageal Cancers. Clinical Gastroenterology.

VIRUS SPREAD
However, estimates place the frequency of virus-induced cancer at 15% to 20% of all malignancies worldwide. In human
immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) (HIV/AIDS), viruses are expected
to cause a much larger fraction of cancer.

Human papillomaviruses (HPVs) are the primary causative agents of most cervical and anogenital carcinomas, many
laryngeal carcinomas, and a tiny percentage of cutaneous carcinomas in non-HIV-positive populations. Hepatocellular
carcinomas (HCC), a common disease in the world, are mostly caused by the hepatitis B and C viruses (HBV and HCV).

Epstein-Barr virus (EBV) has been linked to the etiology of several cancers, including lymphomas, Hodgkin's disease (HD),
B-cell proliferative disease in immunocompromised people, and nasopharyngeal carcinoma (NPC), a malignancy that
affects groups.

Adult T-cell leukemia (ATL), a rare malignancy, is linked to the human T-cell leukemia virus (HTLV-1).

Human herpesvirus 8 (HHV8, commonly known as KSHV) is implicated in Kaposi’s sarcoma (KS), a rare malignancy in
most human cultures, but more common among some Mediterranean and African groups, in multicentric Castleman’s
disease, and in body cavity B-cell lymphomas (BCBLs). While EBV is highly ubiquitous in all populations, HPV, HBV, HCV,
HHV8, and possibly, to a minor extent, HTLV-1, are more common in those exposed to blood, blood products, or sexually
transmitted diseases and are consequently more prevalent in HIV/AIDS. Kieff, E. (1998). Current perspectives on the
molecular pathogenesis of virus-induced cancers in human immunodeficiency virus infection and acquired
immunodeficiency syndrome. Journal of the National Cancer Institute. Monographs, 23, 7-14.

TREATMENT
CANCER IMMUNOTHERAPY
Cancer immunotherapy aims to stimulate the immune system and cause the disease to stabilize. Unlike the other
methods of administration, immunotherapy's main goal is to stop the disease from spreading metastatically. Melanoma
can be treated with cancer immunotherapy by taking advantage of the immune system's specificity. Both active and
passive immunotherapy are methods of treating cancer. Cancer vaccines that co-administer tumor antigen(s) with an
adjuvant to elicit a particular T cell or B cell response are considered forms of active immunotherapy. Monoclonal
antibodies that block immunological checkpoints like CTLA-4 and PD-1 are a part of passive immunotherapy. Mitra, A.K.,
Agrahari, V., Mandal, A., Cholkar, K., Natarajan, C., Shah, S.J., Joseph, M., Trinh, H.M., Vaishya, R., Yang, X., Hao, Y.,
Khurana, V., & Pal, D. (2015). Novel delivery approaches for cancer therapeutics. Journal of controlled release : official
journal of the Controlled Release Society, 219, 248-268 .
 a) Check Point Inhibitors
Immune checkpoints work to stop autoimmunity from developing because of unchecked T cell activation. This method
can be used by tumor cells to their advantage by turning off tumor-infiltrating lymphocytes (TILs) and stopping them
from attacking tumor cells. One important immune checkpoint ligand, for instance, is called programmed death ligand -1
or 2 (PD-L1 or PD-L2), and programmed death-1 (PD-1) is the receptor for it. Active T cells have the PD1 receptor
expressed on their surface. When this receptor binds to its ligand, which is overexpressed on the surface of malignant
cells, the activated T cells undergo a conformational shift that results in an inactive phenotype and become ineffective.

Mechanism of Immune Checkpoint Inhibition. MHC presents

antigens to the T-cell receptor to active T cells (1). Through
interactions with the CD80 on tumor cells and the CD28 on T cells,
T cells can be deactivated (2). Additionally, CTLA4 competes with
CD80 to deactivate T cells as well (3). Lastly, PD-L1 binds to the PD-
1 receptor on T cells to deactivate T cells (4). Tumor cells employ
the use of these mechanisms to prevent T cells from clearing
malignant cells. By using inhibitors that prevent this interaction
from occurring, T-cells remain active after identifying tumor cells
and can clear them from the host. Abbreviations: CD; cluster of
differentiation, CTLA-4; cytotoxic T lymphocyte associated antigen-
4, MHC; major histocompatibility complex, PD-1; programmed
death-1, PD-L1; programmed death ligand-1, TCR; T-cell receptor.

A type of monoclonal antibody immunotherapy known as immune

checkpoint inhibitors works by blocking immune checkpoint
receptors, enabling T cells to become activated and eliminate tumor cells. Anti-cytotoxic T-lymphocyte associated
antigen-4 (CTLA-4) and anti-PD-L1 are the two checkpoint inhibitors that are now authorized. Immune checkpoint
blockade drugs, specifically these two types, have demonstrated efficacy in treating many malignancies, including
metastatic melanoma. To attach to CD28 and disable T cells, CTLA-4 normally competes with the ligands CD80 and CD86
for binding. The suggested mechanism of action is that T cell activity is increased and Treg activity is decreased
simultaneously by blocking CTLA-4 from

inactivating T cells.

Similarly, deactivating Tregs and activating antitumor T-cells are the results of inhibiting PD-1. In contrast to CTLA-4, PD-1
is expressed on tumor cells as well as other healthy cells found all over the body, most of which are myeloid cells in the
TME. This method works much better in triggering an immunological response. Response rates to this immunotherapy,
however, can differ between various tumors as well as within tumor groups that belong to the same cancer category.

Manpreet Sambi, Leila Bagheri, Myron R. Szewczuk, "Current Challenges in Cancer Immunotherapy: Multimodal
Approaches to Improve Efficacy and Patient Response Rates", Journal of Oncology, vol. 2019, Article ID 4508794, 12
pages, 2019. [Link]

b) Cytokines
To boost the immune response, systemically introducing certain cytokines is another method of immunotherapy. IFN-
alpha and IL-2 are currently given to patients undergoing cancer treatment. To be more precise, IFN-alpha has been
described as an immune stimulator that increases T1 response, CTL activity, and the cytotoxic effects of NK cells by
stimulating DC and promoting antigen presentation to elicit an immune response. To improve treatment efficacy, IFN-
alpha is also given in addition to cancer vaccinations. Comparably, it has been shown that IL-2 broadens the immune
system's anticancer effects by boosting NK cell activity and T cell activity, particularly tumor infiltrating cells. Manpreet
Sambi, Leila Bagheri, Myron R. Szewczuk, "Current Challenges in Cancer Immunotherapy: Multimodal Approaches to
Improve Efficacy and Patient Response Rates", Journal of Oncology, vol. 2019, Article ID 4508794, 12 pages, 2019.
[Link]

c) Cancer Vaccines

Mechanism of Action of Cancer Vaccines. As illustrated, cancer vaccines are administered through an intradermal
injection (1) with adjuvants that activate dendritic cells (2). Immature dendritic cells take up the antigen; typically, this
antigen is uniquely expressed on tumor cells (3) and presents the antigen to CD4 cells (4) and CD8 cells (5). CD8 cells
are then activated to seek out the antigen on the surface of tumor cells (6). Abbreviations. CD: a cluster of
differentiation and MHC: major histocompatibility complex

The purpose of cancer vaccines containing whole or fragmented cancer cells or antigens is to elicit an immune response.
Peptide-based vaccines, for instance, must only be given to a small proportion of patients who exhibit the tumor antigen
since they are made to react to a single tumor antigen in combination with its HLA. Immune or dendritic cell-based
vaccines are an additional strategy that has showed potential in treating castration-resistant prostate cancer. To
specifically target prostate cancer cells expressing the PA2024 prostate tumor antigen, this strategy entails removing
antigen-presenting cells (APCs), such as DCs, activating them, and then restoring the activated cells into the patient.
Prostatic acid phosphatase (PAP), which is expressed in 95% of prostate tumors, is the component of this vaccination.
PA2024 is administered with granulocyte macrophage-colony-stimulating factor (GM-CSF) to be taken up by APCs to
activate the host’s T cells and, additionally, direct them to target exposed PAP on prostate cancer cells. Ovarian tumors
that express TAA CA-125 are treated with a similar strategy to that used in prostate cancer research to activate DCs.

Manpreet Sambi, Leila Bagheri, Myron R. Szewczuk, "Current Challenges in Cancer Immunotherapy: Multimodal
Approaches to Improve Efficacy and Patient Response Rates", Journal of Oncology, vol. 2019, Article ID 4508794, 12
pages, 2019. [Link]

d) Cell-Based Immunotherapy
Chimeric antigen receptor T therapy (CAR-T) is one of the most promising cell-based immunotherapies available today.
By genetically modifying T cells ex vivo, this immunotherapy strategy improves the specificity and anticancer mode of
action of the immune system. To specifically target cancer cells without relying on the patient's HLA, CAR-T cells are
generated ex vivo and reintroduced into the body. This treatment can prevent cancer cells that preferentially lose their
HLA molecules from evading the immune system. According to the theory behind this immunological treatment, a tumor
must express an antigen that is "chimeric-like" to trigger a cytotoxic reaction. Manpreet Sambi, Leila Bagheri, Myron R.
Szewczuk, "Current Challenges in Cancer Immunotherapy: Multimodal Approaches to Improve Efficacy and Patient
Response Rates", Journal of Oncology, vol. 2019, Article ID 4508794, 12 pages, 2019.
[Link]

NANOBIOTECHNOLOGY ROLE
Chinese research teams exploited gold (Au) nanorod-loaded human cytokine-induced killer (CIK) cells for improved
immunotherapy, photothermal therapy, and photoacoustic imaging for the treatment of gastric cancer. They created
human CIK cells loaded with Au nanorods by first preparing silica-modified Au nanorods and then incubating them with
human CIK cells. The immunotherapy, photothermal therapy efficacy, cytotoxicity, and targeting ability of gastric cancer
in vitro and in vivo were assessed further for those human CIK cells loaded with Au nanorods.

Similarly, another study found that human CIK cells labeled with PEGylated gold nanoprisms (Au NPRs) had improved
immunotherapy and photothermal therapy efficacy in vivo. Cancer therapies have benefited greatly from
nanotechnology, and some nanostructures have apparently been employed in drug delivery systems. Additional research
indicates that a variety of nanocarriers, including liposomes, metal nanoparticles, biodegradable nanoparticles, solid
lipid nanoparticles, and polymer–drug conjugates, can be employed in both active and passive nanoimmunotherapies
to transfer immune effectors into cells. Using nanodiscs, a different group of researchers has effectively treated colon
cancer and melanoma tumors in mice. Wahid, B., Ali, A., Rafique, S., Waqar, M., Wasim, M.H., Wahid, K., & Idrees, M.
(2018). An overview of cancer immunotherapeutic strategies. Immunotherapy, 10 11, 999-1010.

Nanotechnology Solutions: By enhancing the bioavailability, stability, and safety of immunomodulatory chemicals,
nanotechnology provides answers to problems. Target-specific payload release, in vivo stability, and circulation times are
all improved by nano formulations. Tumors are the preferred location for nanoparticle accumulation due to the increased
permeability and retention (EPR) effect.
Applications for Nanoparticles Examples, IFN-g, IFN-a, IL-2, and TNF-a-carrying liposomes lengthen plasma residence
times and boost therapeutic outcomes. Lipid-coated calcium phosphate nanoparticles are one type of nanoparticle that
targets TGF- in the tumor microenvironment to reduce immunosuppression. Nanoparticles delivering PD-L1 siRNA show
promise in modifying immunosuppressive characteristics in cancer-associated dendritic cells. Shukla, S., & Steinmetz, N.F.
(2016). Emerging nanotechnologies for cancer immunotherapy. Experimental Biology and Medicine, 241, 1116 - 1126.

Applications of Nanoparticles:

Wu P, Han J, Gong Y, Liu C, Yu H, Xie N. Nanoparticle-Based Drug Delivery Systems Targeting Tumor Microenvironment for
Cancer Immunotherapy Resistance: Current Advances and Applications. Pharmaceutics. 2022; 14(10):1990.
[Link]
 The purpose of pH-sensitive liposomes is to release their payload inside of cells, hence enhancing cellular
immunity. For example, in tumor-bearing mice, liposomes containing peptides derived from the protein OVA
were able to efficiently trigger immunological responses.
 The utilization of Poly(propylene) sulfide (PPS) nanoparticles for the targeted delivery of immunomodulatory
drugs to dendritic cells (DCs) in tumor-draining lymph nodes (TDLNs). The objective is to overcome the
immunosuppressive microenvironment in melanoma patients and improve DC activation.
 Because of their special qualities, gold nanoparticles (AuNPs) have potential use in immunotherapy. Researchers
discovered that OVA peptides and CpG ODN were best delivered by 60 and 80 nm AuNPs, respectively, and that a
combination (NanoAu-cocktail) improved antigen presentation and strongly stimulated CD8+ T cell response.
Furthermore, rod-shaped AuNPs generated cytokines that were dependent on the inflammasome, but spherical
40 nm AuNPs were successful in generating WNV-specific antibodies. These results demonstrate the
efficaciousness of AuNPs as adjuvants for boosting immune responses in immunotherapy applications, regardless
of their size and shape.
 Because of their enormous surface area, carbon nanotubes (CNTs) are useful nanoscale transporters for
bioactive compounds like antibodies. NT bundles with absorbed anti-CD3 antibodies revealed improved T cell
activation compared to standard surfaces. The creation of clusters by aCD3 and aCD28 on NT is responsible for
the increased T cell activation on CNTs, even with normalized antibody presentation, as demonstrated by the
FRET-AP approach. This emphasizes how unique CNTs are for effective T cell stimulation.

European Journal of Pharmaceutics and Biopharmaceutics

Volume 115, June 2017, Pages 243-256