NANOSPONGES: AN UNDERUTILIZED, EFFECTIVE METHOD TO PREVENT SARS-COV-2

INDEX

Sr. Content Page

No No.

1. MAINTEXT 3

2. TYPES OF NANOSPONGES AND THEIR APPLICATION 5

3. SYNTHESIS OF NANOSPONGES 7

4. CHEMISTRY AND STRUCTURE OF NANOSPONGES 9

5. NANOSPONGES AGAINST SARS-COV-2 10

6. APPLICATION OF NANOSPONGES IN HEALTHCARE AND ENVIRONMENT 16

7. CURRENT DEVELOPMENT IN SARS-COV-2 MANAGEMENT 19

8. CONCLUSION 23

9. REFERENCE 24

ABSTRACT

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An Effective medicinal treatment for the SARS-CoV-2 virus using cellular nanosponges. Plasma
membranes from human lung epithelial type II cells or human macrophages are used to create
two different forms of cellular nanosponges. These nanosponges exhibit the same protein
receptors both known and unknown that SARS-CoV-2 uses for cellular entrance. SARS-CoV-2
is found to be neutralized and unable to infect cells after being incubated with the nanosponges.
Importantly, the nanosponge platform is unaffected by viral alterations and potentially infectious
viral species. The nanosponges will be able to kill the virus as long as it continues to target the
identified host cell.

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NANOSPONGES: AN UNDERUTILISED, EFFECTIVE METHOD TO

PREVENT SARS-COV-2
1. INTRODUCTION
The severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) is responsible for the recent
pandemic of coronavirus disorder 2019 (COVID-19), a disaster with an exceptional chance to
global public health.1–3 so far, the antiviral drugs which includes remdesivir, 4 monoclonal
antibodies including bamlanivimab and etesevimab, 5 and vaccines manufactured through
PfizerBioNTech, Moderna, and Janssen6 have been approved as emergency-use authorization
inside the u.s for COVID-19 treatment and prevention. But, SARS-CoV-2 can go through
genetic mutations through the years, ensuing in the unpredictable evolutions of recent viral
strains proof against the current therapeutics or vaccines. 7–9 therefore, progressive techniques that
may inhibit the infectivity of SARS-CoV-2 and its ability mutated strains are incredibly
demanded.
Nano medicine platforms have proven excessive potential inside the diagnosis, remedy, and
prevention of viral infections.10–13 amongst them, cell-membrane-covered nanoparticles,
specifically, “cellular nanosponges”, have attracted an awful lot interest. Cellular nanosponges
are made through cloaking plasma membranes of the host cells onto artificial cores. They inherit
natural protein and glycan receptors from the host cells, both known or unknown, to bind with
viral proteins and divert the viruses far from the intended cellular targets. 12,14 this kind of
operating mechanism shifts the point of interest from the causative viruses to the hosts and hence
overcomes virus variety, restricting the traditional antiviral method. Cellular nanosponges
successfully capture and inactivate pathogenic viruses including human immunodeficiency virus
(HIV),15 influenza virus,16 Zika virus,17 and currently SARS-CoV-2,14,18,19 unlocking a broad-
spectrum antiviral method.
Throughout the infection, SARS-CoV-2 viruses use their spike like proteins (S proteins) on the
surface to connect to the cellular angiotensin-converting enzyme 2 (ACE2) for getting into the
host cells. Latest researches recommend that, earlier than the ACE2 binding, the receptor-
binding area (RBD) of the viral S protein first interacts with the glycocalyx additives of the
membranes including heparin or heparan sulfate (HS). 20 Such interactions cause an open
conformation of the S protein that enhances its next binding to the ACE2. 21This observation is
similarly supported by means of SARS-CoV-2 inhibition in vitro the usage of heparin or heparan

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sulfate.22,23 therefore, alteration of heparan sulfate at the host cell surface gives ability therapeutic
opportunities in opposition to SARS-CoV-2 contamination. On the premise of this medical
premise, we hypothesize that a higher stage of heparin on the cellular nanosponges will cause a
higher binding capability with the viral S protein and therefore a better inhibition efficacy in
opposition to SARSCoV-2 for host safety. (Figure 1)

2. TYPES OF NANOSPONGES AND THEIR APPLICATION

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Cyclodextrin-Based Nanosponges
Cyclodextrin-based Nanosponges are sponge-like lyophilized structures which have the
functionality to react by way of small molecules in its matrix. The NSs have been developed
through cross-linking different classes of cyclodextrin with the cross-linkers like di-phenyl
carbonate, carbonyl-di-imidazole dimethyl carbonate, and many others. Cyclodextrins are
acquired from a certain quantity of certainly taking place α-, β-, and γ-cyclodextrin cross-
hyperlinks. They may be usually prepared from β-cyclodextrins as they have the best complexity
and stability attributable to their appropriate cavity size with cross-linkable polymers
Application
Cyclodextrin-based totally NS is specifically used as drug transport agent in biomedical
application. Further, it acts as effective agents in eliminating pollutants from contaminated water,
is utilized in cosmetics, and is used even in agriculture24,25
Titanium-Based Nanosponges
Titanium-based nanosponges are the coating of polystyrene microspheres which have been
organized from copolymerizing polymerizable surfactants with styrene
Application
Fabrication of TiO2/ZnO hybrid NSs are used as photo-anodes for photo-electrochemical
applications. Metal NS like TiO2 NS, carbon coated metallic NS and silicon NS debris have
been suggested in a plethora of programs including recyclable oil absorbents, photo-catalytic
properties, electrodes, pollutant elimination, super capacitors, antimicrobial application,
biosensors, and drug transport26,27
Silicon-Based Nanosponges
Silicon Nanosponges particles are prepared from a metallurgical grade silicon powder and nearly
1–4 micron particles were scratched to yield silicon nanosponge particles
Application
The highly porous silicon nanosponges acts a carrier material in the field of sensors, drugs and
catalysts, photosensitizers, explosives, adsorbents, and electrode in fuel cells. It is also turned as
precursors for ceramic materials which have high surface area like SiNa and SiC 28

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Hyper-Linked Polystyrene-Based Nanosponges

The individual polystyrene coils have been suspended in dilute solvents, and rigid intramolecular
bridges have been introduced in massive quantities ensuing in sturdy contraction of those coils to
form spherical NSs. The NS solutions confirmed excessive diffusion, low viscosity, and
excessive quotes of sedimentation. Those NSs exhibited improved internal surface area and the
swelling became very sturdy in the presence of linear polystyrene non solvent
Application
The hyper-cross-related NS have been utilized in suitable separation of inorganic electrolytes by
way of applying the standards of size exclusion chromatography. Hyper-cross-linked polystyrene
NS and cyclodextrin-based totally NS were used in tissue scaffolds29

3. SYNTHESIS OF NANOSPONGES
Solvent Technique
Solvent technique may be used to put together NSs, through the combination of polymer and
suitable solvent just like polar aprotic solvent including dimethyl form amide (DMF) and

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dimethyl sulfoxide (DMSO). The extra quantities of the cross-linker have been delivered with
molar ratio of cross-linker and polymer as 1:4, accompanied by means of reflux up to 1 to 48 h.
in addition, the combination must be set apart for cooling at room temperature, and extra of
distilled water became added to the product. For getting the final product, the solution became
filtrated under vacuum, and next purification became also done for extended Soxhlet extraction
with ethanol. It became set to dry under vacuum for final touch of the technique30
Ultrasound assisted Synthesis
In ultrasound-assisted synthesis technique, uniform sized NSs are produced in spherical form.
The procedure of NS synthesis consists of sonication the usage of ultrasound water bath in the
course of the response with polymers and cross-linkers within the absence of solvent. The set
became allowed to heat at 90 °C and sonicated for 5 h. Then, the product became allowed to cool
observed via crushing the product and washing it for the elimination of the non-reacted polymer
and became purified via elongated Soxhlet extraction with ethanol. In the final step, the product
became dried under vacuum and saved at 25 °C to be used within the future31
Emulsion Solvent Diffusion Technique
In emulsion solvent diffusion technique, the NSs have been synthesized with the addition of
ethyl cellulose and polyvinyl alcohol in numerous proportions. The dispersed segment
comprising ethyl cellulose and drug become made to combine with 20 ml of dichloromethane,
and within the aqueous segment, 150 ml of polyvinyl alcohol became added slowly. This
composite became stirred at 1000 rpm for 2 h, and the prepared NS became collected via
filtration observed by using oven-drying at 400°C for 24 h. To ensure the elimination of residual
solvent, the dried NSs have been saved in vacuum32,33
Hyper crosslinking Technique Of β-Cyclodextrin Synthesis
Hyper-cross-linked β-cyclodextrins (β-CD) act as carrier for drug transport as it is a nonporous
material. NSs are synthesized by using reacting cyclodextrin and cross-linkers which can be in
acidic or impartial form. Generally, nanosponges have a diameter within 1 μm, and that they can
also be taken into consideration if it levels less than 500 nm. Numerous techniques have been
used for loading the drug into NS. In a proceeding observe, the NS have been suspended in water
accompanied by using sonication to avoid aggregation. In addition, the samples have been
centrifuged, and the supernatant became separated and dried via freeze-drying technique to
acquire the NS. For drug loading, aqueous suspensions of NS have been prepared, and drug

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became brought and become maintained below steady stirring for required time to acquire the
complexation. Centrifugation became carried out to separate the un-dissolved drug, and solid
crystals have been acquired through freeze-drying yielding drug-loaded NS. 34,35 There is
additionally a technique known as the quasi-emulsion solvent diffusion technique wherein the
NSs are also synthesized with different polymer quantities. The internal segment became
organized the usage of Eudragit RS 100 and dissolved with a appropriate solvent. Subsequent,
the drug became dissolved with the aggregate under ultra-sonication at 35 °C. This internal
segment became added into the external segment containing PVA solution in water, and the
combination became stirred for 60 min. They have been filtered to isolate NS and dried the usage
of air-heated oven at 40 °C for 12 h to get the final product 36 In preparation of this kind of NSs,
there had been few cross-linkers used like dimethyl carbonate, di-isocyanate, di-phenyl
carbonate, di-aryl carbonate, carbonyl-di-imidazole, and carboxylic acid dianhydrides which
assist to deliver the instant release of a drug. 37 Every synthesis technique has each execs and
cons. In solvent technique, we will isolate the appropriate segment the use of the Soxhlet
apparatus; however we need a massive volume of solvent for the extraction on this technique. In
ultrasound assisted synthesis, although the initial combination became made by the assistance of
ultrasound, for minimizing the aggregation, and we could avoid the Soxhlet solvents, for final
purification, Soxhlet become most effective used. In emulsion solvent diffusion technique, it is
convenient to contain the medicine in the course of the synthesis procedure to make sure proper
loading of the drug, however on the other hand, we need to heat the sample at excessive
temperatures to dispose of any impurity. The heat-labile drugs, consequently loaded, may also
get disintegrated throughout this step.

4. CHEMISTRY AND STRUCTURE OF NANOSPONGES

Cyclodextrin NSs generally have an average diameter inside 1 μm, with a totally low
polydispersity index, displaying mono-dispersed particles. The NSs are very solid with
excessive, generally negative, zeta potential values and own swelling properties that are
depending on the cross-linker used for the duration of synthesis and the ratio among cyclodextrin

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and the cross-linker. The branching of cross-linker, attachment of primary and acidic
organizations, additionally influences the swelling characteristics of the NSs. the quantity of
cross-linker can influence the surface area and porosity. The NSs made up of cyclodextrin are
thermally solid as much as 300 °C and show different peaks in FTIR spectroscopy. 38 In some
other observe to find out the β-Cyclodextrin NSs applications, minute mesh-like structures
composed Nano catalysts of porous 3-dimensional structure have been synthesized. One-pot
condensation response with 3 components became hired with different aromatic aldehydes that
had activated methylene compounds, like thiobarbituric acid, four-hydroxy-6-methyl-2-pyrone,
dimedone, 4-hydroxycoumarin, and nucleophiles that covered amines and indole. While the β-
cyclodextrin monomer reacted with 1,1′-carbonyldiimidazole, the cross-linked NSs have been
obtained, and to which the three-substituted indole moieties were introduced. The Yonemitsu-
kind condensation reaction became employed for the 3-substituted indole moieties synthesis with
the response aggregate of indole (0.117gr, 1 mmol), 2-chloro benzaldehyde (0.14 gr, 1 mmol),
and dimedone (0.14 gr, 1 mmol) as shown in Fig. 239

5. NANOSPONGES AGAINST SARS-COV-2

Nanosponges exist in each crystalline and Para crystalline forms, that are decided primarily
based particularly at the reaction/synthesis and processing situations; crystallization of
nanosponges can assist in controlling and determining their drug-loading ability. 40 distinctive
strategies were explored for synthesizing nanosponge-based systems, along with interfacial
phenomena, hot melting methods, hyper-cross-linked cyclodextrin, ultrasound-assisted synthesis,

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solvent condensation, microwave-assisted synthesis, interfacial condensation, mechano-chemical

synthesis, chain-growth polycondensation, and emulsion solvent evaporation. 41 A complete
description of every technique may be determined somewhere else. 29,38 In assessment to great
studies at the biological neutralization capability of cellular nanosponges, there are only confined
investigations bearing on their applicability as Nano platforms for antiviral transport (Fig. 2). 42,43
Cyclodextrin-based nanosponges (~400 nm) bearing carboxylic groups within their structures
had been evaluated for the transport of acyclovir and proven excessive loading capability for this
antiviral drug (70 % w/w) with prolonged-release performance; similarly in vivo evaluation is
needed in phrases of complete efficacy and bio-distribution tests of those nanosponges. Notably,
the cytotoxicity and biosafety parameters are crucial for future scientific and biomedical makes
use of nanosponge based systems. Rao et al. 44 evaluated the cytotoxicity of β-cyclodextrin
nanosponges built for encapsulation of a phytotherapeutic agent (Babchi oil) towards HaCaT
cellular lines. The organized nanosponge-based totally transport system exhibited excessive
biosafety, stability, and therapeutic results with targeting properties, decreasing the specified
dose/intake of the drug/therapeutic agents and minimizing systemic destructive results, with
improved drug localization on the targeted sites. Babchi oil has been explored for its
antibacterial, antifungal, antioxidant, immune modulatory and antitumor effects; but, its antiviral
effects must be in addition explored.44
Numerous innovatively designed Nano materials were broadly explored as antivirals due to their
ability to imitate the cellular attachment of pathogenic viruses. For the reason that those viruses
bind to molecules on host cells using glycoproteins on their surfaces, nanosponges will be
designed based totally in this premise after removing the cellular contents even as retaining only

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the membranes. Ultimately, those membranes may be broken into hundreds of tiny vesicles 100-
nm huge. Biocompatible and biodegradable nanostructures built from polymers, including poly
(lactic-co-glycolic acid), can be covered with cellular membranes to form core–shell structures
with excessive stability, functioning as a decoy of a human cell. The designed nanosponges with
their binding points at the membranes can surround viruses, stopping them from getting into host
cells.18,45 Rao et al.46 suggested an effective two-step neutralization method based on a decoy
nanoparticle against COVID-19, which includes SARS-CoV-2 neutralization, observed by way
of cytokine neutralization. Those nanosponges can efficaciously defend host cells from infection
by way of SARS-CoV-2 by competing with them for virus binding. Through introducing those
nanosponges, interactions among the complex of the SARS-CoV-2 S protein and human ACE2
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reduced and, rather, viral receptors of the nanosponges confirmed excessive affinity for binding
to ACE2.
Standard, cellular binding and the access of SARS-CoV-2 may be mediated by way of its S
protein via attachment to the ACE2 receptor and glycosaminoglycan’s (e.g., heparin) 45
consequently; cellular nanosponges mimic host cells for attracting and neutralizing SARS-CoV-2
through natural cellular receptors, hence supplying a broad-spectrum antiviral approach.
Increasing the heparin density at the cellular nanosponge surface additionally advanced the
inhibitory results of heparin towards the virus. Therefore, azido become expressed on host
cellular membranes to put together cellular nanosponges with heparin adhered to their surfaces.
Those cellular nanosponges established considerable binding capability with viral S
glycoproteins, offering useful inhibition against SARS-CoV-2 infectivity. accordingly, the
surface engineering of host mimicking cellular nanosponges with glycosaminoglycan's is a
promising method for reinforcing inhibition of SARS-CoV-2, and will prolonged to different
glycan-dependent viruses (Fig.1).45 further, plasma membrane-derived nanosponges were
evaluated for in vitro neutralization of SARS-CoV-2; those plasma membranes originated from
human lung epithelial type II cells or human macrophage-covered poly(lactic-co-glycolic acid)
nanoparticles.18 The designed nanosponges contained protein receptors crucial for the cellular
access of SARS-CoV-2. Therefore, SARS-CoV-2 becomes neutralized, and its infectivity
becomes decreased in a attention-based way; virus became not able to contaminate cells after the
incubation with those engineered nanosponges. Such nanosponge-based totally structures with
promising inhibitory results ought to be similarly evaluated against SARS-CoV-2 mutants and
different viral species. considerably, nanosponges shrouded with the cellular membranes of
macrophages offer the more benefit of absorbing circulating anti-inflammatory cytokine proteins
generated due to the immune system reaction to viral contamination.18
Hybrid membrane-lined biomimetic nanomaterial's with appealing and specific biological
properties have attracted growing studies interest for biological and biomedical applications,
mainly for drug transport,47 with an emphasis on immune remedy, tumor vaccines, phototherapy,
and detoxing.48 as an example, membrane nanoparticles derived from ACE2-rich cells displayed
green blocking off outcomes towards SARS-CoV-2 infectivity (Fig. 3) due to the fact they
successfully suppressed the entrance of SARS-CoV-2 S pseudo-vision's into host cells via
obstructing viral infectivity each in vitro and in vivo. 19 Biomimetic Nano carriers were built for

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antiviral drug transport programs towards COVID-19 and simultaneously exhibit outcomes. 49
Lopinavir loaded polymeric nanoparticles have been coated with macrophage membranes,
neutralizing pro anti-inflammatory cytokines and suppressing macrophage/neutrophil activation.
The improved ability to target irritation in addition to improved therapeutic results ensuing
within the reduction of viral masses are the crucial benefits of those Nano systems.49
Zhou et al.50 illustrated a revolutionary tool with prophylactic and therapeutic makes use of.
Plasma membrane-ACE2-extracellular vesicles have been deployed for neutralizing SARS-CoV-
2 (pseudo-type and actual) in human ACE2 transgenic mice, with efficient blocking off
outcomes stated towards viral loads of authentic SARSCoV-2, as a consequence defensive the
host from lung infection caused by means of SARS-CoV-2 contamination. 50 usually, antiviral
agents target a novel viral site, as a result go through obstacles of infectiveness towards viruses
due to their numerous mutations and get away techniques. 51–53 as an example, biomimetic
proteolipid bilayer decoy receptor nanosponges constructed molecularly (100- nm Nanospheres)
have been explored towards SARS-CoV-2, and tested promising inhibitory results. This Nano
system neutralized SARS-CoV-2 infections in animal/human cells and also trapped the viral
particles. Intravenous (I)-injected nanosponge-based totally systems may be appropriate for
multivalent capturing of SARS-CoV-2 within the body; but, preclinical and scientific reviews are
required to recognize the underlying mechanisms and its efficacy towards numerous mutated
versions of SARS-CoV-2.51 specially, the emergence of recent variations of situation (VOCs) of
SARS-CoV-2 (inclusive of Omicron and its unique versions) induced health professionals to re-
examine the effectiveness of to be had techniques and consider extra comprehensive and
essential research to higher control the continued pandemic in addition to viable future
outbreaks.53,54 Li et al.55 designed human lung spheroid cell-derived ACE2 nanodecoys for
binding and neutralizing SARS-CoV-2, in addition to protective host lung cells from
contamination those nanodecoys without a significant toxicity might be transported via
inhalation remedy and remained within the lungs for over 72h after transport, accelerating viral
clearance and decreasing lung damage. Such Nano decoys with particular properties and
performance may be considered as ability inhibitory and therapeutic agents against COVID-19. 55
those nanosponge-like nanodecoys may be deployed to resolve vital problems concerning drug
improvement and nanotherapy, which includes the discount of off-target results (the
development of focused on capabilities) and undesirable bio distribution. Extensively, complexes

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of Nano systems encompassing viruses may be used for the improvement of vaccine
manufacturing technology; cellular membrane-mimicking Nano decoys with their capability to
trap and detain pathogenic viruses have to be similarly evaluated for the systemic safety towards,
and prevention of, infectious diseases.14,56
Numerous Nano trappers were designed to neutralize and capture SARS-CoV-2 and inhibit viral
infections, as exemplified by using functionalized nanosponges that carry out as Nano trappers
towards SARS-CoV-2. Chen et al.57 functionalized liposomal based Nano trappers the use of
anti-SARS-CoV-2-neutralizing antibodies, phagocytosis-particular phosphatidylserines, or
recombinant ACE2 proteins to capture SARS-CoV-2 with whole blockage of viral
contamination; those Nano trappers illustrated excessive in vitro and in vivo biosafety and
biocompatibility, representing an progressive Nano-based approach for inhibiting SARS-CoV-2
contamination.57 It seems that those innovatively designed nanosponges- and different Nano trap-
based totally Nano formulations have superb capacity for application as nasal sprays or
inhalers7058 for easy and direct transport/accumulation within the respiratory device.
Furthermore, extra formulations for particular concentrated on of those Nano systems to special
sites of SARS-CoV-2 exposure show promise.

6. APPLICATION OF NANOSPONGES IN HEALTHCARE AND

ENVIRONMENT

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Nanosponges In Agriculture
Functionalize nanosponges (FNS) in agriculture has added the advantage of plant growth and
advances their appearance. Those Nanosponges have outstanding advantages within the
reduction of herbicide and fertilizer usages. It helps to improve productivity by its quality levels
both in cultivation and environmental safety.59
Topical Agents
An extensive range of substances can be incorporated into an articulated product such as cream,
liquid, ointment, gel, powder, and lotion. By emulsion solvent diffusion method, the econazole
nitrate NSs were fabricated and composed of hydrogel as a local depot for continuous drug
release33,60 During pharmacokinetics studies on the mouse, the developed formulations of NS-4
are non-irritating in mouse skin. So, the formulation can meet the requirements for human
exposure, and it can be utilized for topical drug release for the use of celecoxib.61
Nanosponges For Solubility Enhancement
Additionally, β-cyclodextrin NSs have gained greater attention as it helps to enhance the
bioavailability and solubility of drugs like naproxen and ketoprofen. 26 The solubility of the drug
resveratrol was also increased by entrapment into cyclodextrin based NS.62
Nanosponges As Provider For Biocatalyst And Protein Transport
A few NSs can selectively trap some families of protein molecules from the blood and
subsequently may be utilized in safe guarding the ones proteins from present process enzymatic
degradation. In cyclodextrin NS, proteins and other macromolecules were encapsulated such the
beneficial enzymes trypsin, alpha amylase, cellulose, and pectinase.63,64
Nanosponges As Chemical Sensors
The controlled release of oxygen from a photochirogenesis reaction offers the exciting state
chirality transmission from chiral host to a prochiral substrate. Lee et al. prepared graphite Nano
fiber-supported porous porous Pt–Ag NSs and mesoporous platinum NSs as electro catalysts for
the oxygen reduction reaction.65,66
Removal Of Organic Pollutants From Water
Moura and Lago worked on the oil spill remediation utilizing floatable hydrophobic NSs
produced from catalytic growth of carbon nanotubes and Nano fibers on vermiculite. 67 The β-
cyclodextrin NSs are insoluble in water; consequently, they have the capacity to encapsulate the

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organic pollution from water. A few NS impregnation of ceramic porous filters ensuing in hybrid
organic/inorganic filter out modules may verify the purification of water in a selection of water
pollution. This enhances the elimination of polycyclic aromatic hydrocarbons (PAHs) properly
approximately 95%. Characterization of the pollutant group of insecticides (simazine), mono
aromatic hydrocarbons (BTX), and tri-halogen methane's (THMs) also can be eliminated.68
Cancer Therapy
Any other diterpenoid isolated from the tree bark of Taxus brevifolia is paclitaxel (Taxol), and
that they own anticancer movement towards Kaposi’s sarcoma, breast, and head and neck,
ovarian, pancreatic, and lung cancer. NSs have proven 5 instances advanced activity than direct
injection to cure tumor increase. In drug transport system, the anticancer drugs have been loaded
in virus sized sponges wherein the receptors present at the surface of the tumor cells may want to
chemically link to those NSs. Then the sponges have been injected into the body in which they
arrive in contact with the most cancers cells, get connected to the cellular surface, and are
covered into the cellular, wherein those sponges unload their drug in a sustainable rate. 69 As a
result, the NS-loaded anticancer drugs have been showing progressed activity towards most
cancers.
Other Application
Some other compound, quercetin, become encapsulated in 5 distinct varieties of NSs composed
of 5 distinct concentrations of β-cyclodextrin and diphenyl carbonate, with size starting from 40
to 100 nm. The solubility in addition to antioxidant ability of the NS-loaded quercetin became
determined to be advanced in assessment to most effective quercetin. The NS encapsulated
quercetin became additionally much extra solid within the simulated GI fluid as compared to free
quercetin. The NS encapsulated quercetin also exhibited better photo stability than free
quercetin.70 NSs have been also determined to be useful as a service to pulmonary, head, and
nasal analysis. In infections like rhinovirus, respiratory syncytial virus (RSV), HBV, HSV,
influenza virus, and HIV, the Nano carriers resource to supply antiviral pills or small interfering
RNA to the nasal epithelia in addition to lungs. a number of the drugs used as Nano carrier are
acyclovir (Eudragit-based totally), zidovudine, interferon-α, and saquinavir. 71 Omar et al.
evolved griseofulvin (GRI)–loaded β-cyclodextrin (β-CD)–based totally NSs for enhancing the
dissolution rate, bitter flavor masking, and improved oral bioavailability. The examine became
performed by using performing ultra-sonication technique in which the fabrication of the plain

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NSs (NS1, NS2, and NS3) have been done with β-CD and the cross-linker diphenyl carbonate at
distinct molar ratios (1:2, 1:4, and 1:6), respectively. This resulted in 1:4 (NS2) as the maximum
suitable ratio of β-CD to the cross-linker diphenyl carbonate that would be used for GRI
loading.72

7. CURRENT DEVELOPMENT IN SARS-COV-2 MANAGEMENT

Nanosponges which can be developed from human macrophages or pulmonary type II epithelial
cells have appropriate attractant of SARS-CoV-2 virus, and after capturing, they can be
eliminated. So, it becomes used within the improvement of protecting measures of SARS-CoV-
2.73 Depending at the modern structure of SARS-CoV-2, the researchers have advanced two

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kinds of cellular NSs, particularly, human lung epithelial type II cell nanosponge (epithelial-NS)
and human macrophage nanosponge (MΦ-NS). The NSs contained the identical receptors on
which the viruses depend for their access, and it became guess that when binding with those NSs,
coronavirus will no longer be able to infect the cell. Incubating with NSs, SARS-CoV-2 can be
neutralized and could in turn lose its ability to infect the cells. Nanosponges can create confusion
for viral mutations and viral species. Also, it can discover host cell which remains as the target
for the virus and acts towards the virus to neutralize it. But the fast rate of mutation will create
several challenges for therapeutics and prevention improvement. Each epithelial-NS and MΦ-NS
proved its ability to neutralize SARS-CoV-2 in a concentration-dependent manner. 18 Cellular
NSs have higher surface heparin density that has the ability to bind strongly with the viral S
proteins, which allows further restrictions towards SARS-CoV-2.45
Cellular NSs act as versatile tools for biological neutralization in evaluation to the traditional
neutralization techniques. They mimic inclined host cells instead of accommodating the systems
of the causative agents for the design of therapeutics.52
The coating of NSs with PLGA center inside the membrane of cellular targets in virus showed a
good result. While examined with Vero E6 cells, they may effectively input into the cell and
block the SARS-CoV-2 infection. While the cellular NSs have been administered into the lungs
of mice, especially there was no such toxicity located in them. NSs are agnostic to many species
of viruses and viral mutations, and that is why they could protect the current and upcoming rising
coronaviruses.57 Nanoparticles covered in human lung and immune cell membranes act as decoys
to neutralize SARS-CoV-2 in cell culture and assist to avoid the host cell to purpose infection. At
five mg/ml, the lung and macrophage membrane cloaked sponge’s restriction 93% and 88% of
SARS-CoV-2, respectively. Cloaking NSs with the cell membranes of macrophages conferred
the extra benefit of soaking up circulating inflammatory cytokine proteins attached within the
immune response along with the infection. But additional research is required to measure
the NSs’ efficacy in animal disorder models, together with long-term biocompatibility. 74
Several nanomaterial-based totally detection techniques have developed in the course of
COVID-19. On the stage of the infection, the entry of host is done with higher affinity from
SARSCoV-2 surface spike protein to its receptor human angiotensin converting enzyme 2
(ACE2). To conquer this, Nano traps have been evolved which successfully blocked this binding
through abrogation of SARS-CoV-2 access and also caused subsequent phagocytosis. The

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engineered Nano traps have been composed of a polymeric core, a liposome shell, a
phosphatidylserine ligand, surface ACE2/neutralizing antibodies, and food and Drug
administration (FDA)–authorized polylactic acid (PLA). This material was effective due to its
small size and it is prepared for mass manufacturing, powerful, convenient to apply,
biocompatible, and secure. NSs have been also evolved, however it become an alternative for
viable remedy as it became essential to acquire the sample from every affected person to make
customized NSs that are much like chimeric antigen receptor T (car-T) cell therapy. In
comparison, Nano traps obstructed both, the entry of the cell and prompt virus’s phagocytic
clearance.57
Gold nanoparticles (AuNPs) are also evolved for identity of IgG and IgM antibodies in case of
SARS-CoV-2 with minimal diagnostic time, i.e., much less than 10 min, however this caused
degradation of the pattern. In nanotechnology, the sample collection kit become organized which
contained an RNA stabilization fluid which safeguarded the sample in transportation. 73 AuNPs
have been made to have interaction with polyclonal antibodies which targeted the envelope
protein, membrane protein, and spike protein of SARS-CoV-2 that resulted in 98% specificity
and 96% sensitivity. Much like this, AuNPs have been coupled with an N-acetylneuraminic acid,
a glycan moiety which binds to SARS-CoV-2 S protein (glycan-AuNPs). For detection, the
sample became loaded in lateral float immunoassay strip (LFIA) that resulted inside the
collecting of AuNPs on the check line via the interaction of the S protein and the glycan in virus-
like nanoparticles (VLPs). Colorimetric signal become generated for visible detection, and
furthermore, this device detected SARS-CoV-2 VLPs with spike protein concentration of
5 μg/ml. Selenium nanoparticles (SeNPs) have been included with SARS-CoV-2 nucleoprotein
to note virus-unique IgG and IgM in LFIA. This confirmed improved sensitivity of
approximately 800 times higher than the AuNP-based LFIA. any other nanoparticle poly(lactic-
co-glycolic) (PLGA) became functionalized with 3,3′,5,5′-tetramethylbenzidine denoted as
TMB-PLGA NPs and that is couples’ antibodies towards the SARS-CoV-2 S protein. This
approach analyzed SARS-CoV-2 RNA in 10 min, and attention became in femtogram/ml range
and easy to perform. Any other material, fluorescent europium chelate nanoparticles (FNPs),
became conjugated with S9.6 antibodies that effectively bound RNA–DNA hybrid strands. At
the same time as evaluating with rtPCR checks, it resulted with 99% specificity and 100%
sensitivity.75 Lung spheroid cells (LSCs) are the mixture of lung epithelial and mesenchymal

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cells. Consequently fabrication of LSC membrane Nano vesicles as ACE2 Nano decoys was
performed by using resident lung cells as they expressed ACE2. This LSC-Nano decoys (act as
cellular mimics) bind to SARS-CoV-2 spike (S) protein and turns on a phagocytosis for viral
eradication. Inhalation of the LSC Nano decoys complements the clearance of SARS-CoV-2
mimics of the lungs and did now not elicit any toxicity. Moreover, Nano decoy technology
became extremely translatable because currently parental cells had been in primary scientific
trial level so it was a ability therapy for pulmonary fibrosis.55
In the course of COVID-19 infections, Novochizol (chitosan nanoparticles) helped for easy
encapsulation of drug moieties into the lungs. They have been greater useful because it had low
toxicity, biodegradation capacity, excellent applicability, and proper mucoadhesive properties. It
was found that even after the restoration from SARS CoV-2 infection, the affected person had
gastrointestinal infection. To conquer this, chitosan nanoparticles showed managed release of the
drug which benefited on the pulmonary and intestinal level. The mixture of carbon quantum dots
(CQDs) and boric acid exhibited inhibitory impact on human CoV-2. On this examine the
conversation among them with receptor and S protein caused the blockage of virus binding to the
cells. This helped to manipulate the spread of SARS-CoV-2 infection at exclusive levels. 76
Nanotechnology-based vaccine production has additionally emerged in SARS-CoV-2 duration.
VLPs and lipid nanoparticles (LNPs) are the most nanoparticles used for synthesis of vaccines.
LNP-based totally mRNA vaccines are one of the main, secure, and swiftly manufactured
vaccines towards COVID-19. The mRNA is encapsulated into LNPs comprising SM-102 (a
artificial amino lipid), ldl cholesterol, PEG 2000-dimyristoyl glycerol, and 1,2-distearoyl-sn-
glycero-3-phosphocholine (DSPC). This directed to powerful anti-SARS-CoV-2 vaccination. In
case of VLP-mediated vaccines, they do not require any enhance immunization, and they're
made up with a famous protein named ferritin. The improvement of vaccine towards SARS-
CoV-2 is because nanoparticles can advantage excellent balance to the antigens, present antigens
multivalently, and co-deliver adjuvants with the antigens.75

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8. CONCLUSION
For obtaining therapies delivery at the appropriate target tissue areas and for controlling
medication release per patient virus load and other symptoms, research into Nano-enabled
therapeutic cargos has shown to be highly helpful. Such Nano medicine medications can be
created by combining sophisticated surface-active functional Nano system methods with

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elements of pharmacology. This pharmacologically relevant Nano cargo displayed adaptable

qualities that gave the go-ahead to design and develop therapeutics for regulating COVID-19 in a
tailored way, together with specifically created stimuli-responsive systems. A important
approach for developing novel diagnostics, medical imaging, Nano therapeutics, vaccinations,
and biomaterials for regenerative medicine, Nano medicine has an influence on all medical
professions.

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