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Expert Opinion on Drug Delivery
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/iedd20
Nano Antiviral Photodynamic Therapy: a Probable
Biophysicochemical Management Modality in
SARS-CoV-2
Khatereh Khorsandi, Sepehr Fekrazad, Farshid Vahdatinia, Abbas Farmany &
Reza Fekrazad
To cite this article: Khatereh Khorsandi, Sepehr Fekrazad, Farshid Vahdatinia, Abbas Farmany
& Reza Fekrazad (2021) Nano Antiviral Photodynamic Therapy: a Probable Biophysicochemical
Management Modality in SARS-CoV-2, Expert Opinion on Drug Delivery, 18:2, 265-272, DOI:
10.1080/17425247.2021.1829591
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REVIEW
Nano Antiviral Photodynamic Therapy: a Probable Biophysicochemical
Management Modality in SARS-CoV-2
Khatereh Khorsandi
a
, Sepehr Fekrazad
b
, Farshid Vahdatinia
c
, Abbas Farmany
c
and Reza Fekrazad
d,e
a
Department of Photodynamic, Medical Laser Research Center, YARA Institute, ACECR, Tehran, Iran;
b
School of Medicine, Tehran University of
Medical Sciences, Tehran, Iran;
c
Dental Research Center, Dental School, Hamadan University of Medical Sciences, Hamadan, Iran;
d
Radiation
Sciences Research Center, Laser Research Center in Medical Sciences, AJA University of Medical Sciences, Tehran, Iran;
e
International Network for
Photo Medicine and Photo Dynamic Therapy (INPMPDT), Universal Scientific Education and Research, Tehran, Iran
ABSTRACT
Introduction: COVID-19 disease has shocked the world by its spread and contagiousness. At this time,
there is no valid vaccine and no proven drug treatment for COVID-19 patients. Current treatments are
focused on Oxygenation, Cytokine Storm management, anti-inflammatory effects, and antiviral therapy.
Antiviral photodynamic therapy (aPDT) is based on the reaction between a photo-sensitive agent and a light
source in the presence of oxygen which can produce oxidative and free radical agents to damage the virus’
structures. Recent studies show that nanotechnology can improve aPDT’s outcome. The aim of this study
was to find out the potential therapeutic effects of Nano antiviral photodynamic therapy on COVID-19.
Areas covered: This review evaluates Nano Antiviral Photodynamic Therapy: A Probable Biophysicochemical
Management Modality in SARS-CoV-2. Data were extracted from published different studies published on
PUBMED, SCOPUS, and Web of Science.
Expert opinion: Studies indicating that aPDT and Nano-based aPDT can be useful in viral pulmonary
complications like Influenza, SARS-CoV, and MERS, but there was no direct study on SARS-Cov-2. Recent
studies showed that Nano-based aPDT could relate to control of the stages of viral infections.
Altogether, further investigations for the application of nanomedicine in antimicrobial photodynamic
inactivation are needed for COVID-19 Management.
ARTICLE HISTORY
Received 24 July 2020
Accepted 24 September 2020
KEYWORDS
COVID-19; SARS-CoV-2;
photodynamic therapy;
antiviral Photodynamic
therapy; virus; nanoparticle
1. Introduction
At the end of 2019, a group of patients with pneumonia of
an unknown cause was observed in Wuhan, Hubei Province,
China [1 This unknown agent was later considered to be
a new coronavirus (CoV) named 2019-nCoV [2]. Afterward,
the World Health Organization (WHO) announced
a standard format of Coronavirus Disease-2019 (COVID-19),
according to its nomenclature, for this novel coronavirus
pneumonia on 11 February 2020. At the early stage, the
virus is considered to be reproduced in the Mucosal epithe-
lium of upper respiratory tract (nasal cavity and pharynx)
followed by further reproduction in the lower respiratory
tract and gastrointestinal mucosa [3]. In the first 41 cases
[4], the most common symptoms were fever, cough, and
myalgia or fatigue. In some cases, sputum production, head-
ache, hemoptysis, and diarrhea were also seen in the
patients. The white blood cell count is rather normal (with
lymphopenia) and patients suffer bilateral involvement of
the lungs in 98% of the cases under CT scan. The difference
between patients’ CT scan in the intensive care unit (ICU)
and non-ICU patients was that in the first group their char-
acteristic CT findings were bilateral ground-glass opacity
and subsegmental areas of consolidation vs bilateral multi-
ple lobular and sub-segmental areas of consolidation [2,4].
Clinically, fatal cases of human SARS-CoV, MERS-CoV, and
SARS-CoV-2 infections showed exhibit severe respiratory dis-
tress requiring mechanical ventilation with pathological proof
of Acute Respiratory Distress Syndrome [5–7]. SARS-CoV-2 uses
human angiotensin-converting enzyme 2 (ACE2) as its entry
receptor just like SARS-CoV (2), (4). Genetical features and
inflammatory findings play a major role in the occurrence of
ARDS based on previous studies. More than 40 candidate
genes including ACE2, interleukin 10 (IL-10), tumor necrosis
factor (TNF), and vascular endothelial growth factor (VEGF)
among others have been considered to be associated with
the development or outcome of ARDS [8]. Increased levels of
plasma IL-6 and IL-8 are considered to be associated with
ARDS [9]. Uncontrolled pulmonary inflammation is most likely
the leading cause of death in SARS-CoV-2 infection. The result
of a recent study concluded that rapid viral replication and
cellular damage, virus-induced ACE2 downregulation and
shedding, and antibody-dependent enhancement are the
causes of aggressive inflammation caused by SARS-CoV-2 [10].
Dysfunction of the renin-angiotensin system [2] worsens
inflammation and causes vascular permeability. This is
a detrimental outcome of the pulmonary ACE2 function loss
which is considered to be related to acute lung injury [11]. At
the moment there are no specific drugs or vaccines for this
virus so systematic treatment strategies are recommended for
CONTACT Reza Fekrazad rezafekrazad@gmail.com Radiation Sciences Research Center, Laser Research Center in Medical Sciences, AJA University of
Medical Sciences, Tehran, Iran
EXPERT OPINION ON DRUG DELIVERY
2021, VOL. 18, NO. 2, 265–272
https://doi.org/10.1080/17425247.2021.1829591
© 2020 Informa UK Limited, trading as Taylor & Francis Group
clinical practice. Vaccines are far from being produced and
some nonspecific treatments are yet to be considered.
Chloroquine is an approved drug for malaria and rheuma-
toid arthritis. It has been found very effective in COVID-19
patients. Different theories are thought to be responsible for
its effects. First, it can change the acidity of an intercellular
compartment which the virus uses to enter the cells. Second, it
can inhibit the virus’ binding with the outer surface of cells.
Lastly, its immunomodulatory effects have been proven unlike
SARS although the evidence is still limited. Interferon
(SNG001) is an inhaled form of interferon β which helps the
lungs’ own immune system (INF-β) that is suppressed by the
coronavirus. Remdesivir (viral replication inhibitor) and
Famipiravir which were found more satisfying in the recent
studies. Tocilizumab (ACTEMRA) a monoclonal antibody block-
ing IL-6. Kaletra as an anti-HIV drug is a combination of
Lopinavir and Ritonavir which has been used previously in
SARS and MERS-CoV. hrsACE2 (human recombinant soluble
angiotensin-converting enzyme 2) is a modified version of
ACE2 which prevents SARS-CoV-2 entry significantly. Also,
convalescent plasma or hyperimmune immunoglobulins may
be helpful for both free virus and infected cell immune clear-
ance [12]. However, at this time, there is still no valid treat-
ment for this disease but potential treatments are based on
antiviral and anti-inflammatory treatments to inhibit the cyto-
kine storm and increasing tissue oxygenation.
Photodynamic therapy (PDT) depends on the reaction of
a photosensitizer with oxygen and the presence of light which
produces reactive oxygen species (ROS), rebuilt oxygen, etc. ROS
causes cell apoptosis and necrosis without injuring the adjoining
tissues. In PDT, both endocellular and extracellular ROS are
discharged. Numerous classifications of photodynamic therapy,
for instance, photo-activated disinfectants, antimicrobial photo-
dynamic therapy, Nanomaterial-based antibacterial photody-
namic therapy, and antiviral photodynamic therapy (aPDT),
have been explored as innovative methods of bacterial, fungal,
and viral infection inhibitors like Herpes and Papilloma. These
therapies’ strengths range from no long-term toxicity or DNA
alterations, rapid removal of microorganisms, less injury to near
tissues, access to places with complicated anatomy to low
hazard bacteremia chiefly in immune-suppressed patients and
high repetition without the formation of bacterial and viral
resistance. Diverse techniques with different photosensitizers
and laser protocols with special absorption wavelengths and
other physical parameters have been used which is
a challenge due to their penetration depths.
Nanomedicine is the medical application of nanotechnol-
ogy in the diagnosis and treatment of human disease. It uses
nanoparticles with dimensions usually ranged between 1 and
200 nm. One of the most critical functions of medical nano-
technology is drug delivery vehicles which could improve
drug availability at the target to make the maximum thera-
peutic benefit [13]. Nanomaterials can improve the solubility
of poorly water-soluble drugs, prolong the circulation time in
the bloodstream, decrease the enzymatic degradation of
drugs, reduce undesirable side effects, and enhance the drug
bioavailability [14,15]. Despite the efficacy of aPDT, inefficient
PS uptake by bacteria cannot result in efficient treatment.
Recently, nano-aPDT has also been developed to improve
the photochemical and photophysical effectiveness of aPDT
in the presence of nanoparticles [16]. Various nanoparticles
(NPs) have been used to enhance the antimicrobial PDT with
the aim of improving photosensitizer (PS) solubility, photo-
chemistry, photophysics, and targeting [17].
Different databases as Pubmed, Web of Science, Cochrane,
Scopus, and Google Scholar were searched by COVID-19,
SARS-CoV-2, Photodynamic therapy, Antiviral Photodynamic
therapy, Virus, Laser therapy, nanoparticle keywords in
English. The initial 232 studies were found and after reviewing,
64 of them were found suitable for this study.
The goal of this study was to look into different potential
therapeutic effects of nano-based aPDT in COVID-19 treatment
and management.
2. Nano antiviral photodynamic therapy
Several approaches have been suggested to combine nano-
particles and aPDT for antimicrobial applications. One use of
nanoparticles is to enhance the binding and uptake of PS by
the microbial cells, while another use is to improve the micro-
bial photoinactivation kinetics [17]. There are two basically
various paths to apply nanoparticles in PS delivery: covalent
conjugation where a chemical bond is utilized to attach the PS
to nanoparticles as is shown in Figure 1(a) and noncovalent
encapsulation or incorporation in various Nano-containers
(Figure 1(b)).
Photosensitizers could be modified by encapsulation in
delivery systems such as liposomes [18], micelles [16,17],
gold nanoparticles [19,20], polymer nanoparticles [21], cera-
mic-based nanoparticles [22]and carbon nanotubes [23].
Photosensitizers could be modified by attaching them to den-
drimers (Figure 1(a)). Dendrimers are extremely complex mole-
cules that are sequentially accumulated by solution reactions.
They have a core, branches, and end groups [24], which can
be conjugated or loaded with PS molecules. Dendrimers can
be fabricated with various sizes and lipophilicity in order to
Article highlights
●Antiviral Photodynamic Therapy is a valuable, minimally invasive, and
irresistible (unlike antiviral drugs) treatment modality for support and
treatment of viral diseases.
●This method has been proven to be effective as a new adjuvant
therapy for the management of viral lung diseases.
●Nano Antiviral Photodynamic Therapy as a type of aPDT in combina-
tion with Nanomedicine may be useful in the management of
COVID–19.
●In this method, biophysicochemical reaction between photon and
chemical substances induced a novel effective and relatively safe
treatment modality.
●Blood transfusion safety by virus decontamination is currently the
main usage of aPDT and plasma decontamination is done for the
therapeutic use of plasma of the previously infected patients.
●This study can promote other scientists to work on this new platform.
This box summarizes the key points contained in the article.
266 K. KHORSANDI ET AL.
enhance their cellular uptake and can be designed to take
a high drug payload [25]. Opposite to conventional PS, den-
drimer-PS conjugates show good ROS production even at high
concentrations as the individual PS molecules are separated
from each other by the dendrimer framework so they cannot
self-quench. Typical dendrimers are ionic dendrimer-PS con-
jugates where a porphyrin or phthalocyanine core has large
dendritic wedges attached to the periphery, which sterically
prevent aggregation of the central tetrapyrrole molecules [26].
Antiviral photodynamic therapy (aPDT) has been applied to
inactivate microorganisms using photosensitizers. The viruses and
bacteriophages inactivation by photosensitization have been
used with success from first decades of last century. Since 1970s,
PDT was first used clinically against viruses [27]. Although photo-
dynamic inactivation effect has been shown against viruses, it has
been slow in gaining acceptance mainly because of several limita-
tions such as the hydrophobicity of photosensitizers, poor target
specificity, and limited tissue penetration ability. Most photosen-
sitizers are hydrophobic and aggregate easily in aqueous solutions
which could affect their photochemical, photophysical, and
photobiological properties [28]. Furthermore, several photosensi-
tizers also have poor target specificity, which cause collateral
damage to healthy cells and tissues. In addition, current light
source used is either ultraviolet (UV) or short-wavelength visible
light as most of the photosensitizers absorb in relatively short
wavelengths that possess limited tissue penetration ability that
restricted the light to be delivered to the target sites [29].
3. Up-conversion nanoparticles (UCNs)
Up-conversion nanoparticles (UCNs)-based photodynamic inac-
tivation strategy could potentially overcome the limitations
faced by the current approaches [30,31]. Lim et al. designed
and synthesized near-infrared (NIR)-to-visible UCNs that consist
of sodium yttrium fluoride (NaYF
4
) nanocrystals co-doped with
ytterbium (Yb
3
þ) and erbium (Er3þ) ions. Figure 2 illustrates the
UCN structure and mechanism of action for the UCN-based
photodynamic inactivation strategy. The UCNs synthesized
were coated with a layer of high molecular weight polyethyle-
neimine (PEI). The chosen photosensitizer molecules, zinc phtha-
locyanine (ZnPc), were attached to the surface of NIR-to visible
UCNs. Upon exposure to NIR light at 980 nm, the ZnPc attached
UCNs (ZnPc-UCNs) emit visible light which is being absorbed by
the photosensitizers. The excited photosensitizers then convert
nearby molecular oxygen to ROS, resulting in viral inactivation
[32]. They showed that these nanoparticles could inactivate
Dengue virus serotype 2 (DENV2, New Guinea C strain) and
Adenovirus type 5 (Ad5V) viruses photodynamically in suspen-
sion and a murine model. In vivo pathogenicity was not observed
when light treated virus suspension was inoculated into the
mice, suggesting that this UCN-based strategy is able to reduce
virus infectivity to a level that did not pose threat to mice [32].
This encouraging result reflects the potential clinical values of
this strategy for other viruses including newly emerged virus
COVID-19. Moreover, the ability to surface-modified nanoparti-
cles for bioconjugation with targeting ligands and antibodies
gives this strategy an advantage to overcome low target speci-
ficity of the conventional PDT technique which causes collateral
damage to other healthy cells [33,34].
4. Metal nanoparticles
Metal nanoparticles have been studied for their antimicrobial
potential and have proven to be antibacterial agents against
Figure 1. (a) Photosensitizers covalently bind to nanoparticles including: Dendrimers macromolecules with bio targeting properties such as antibodies, Lipid-
conjugated PS self-assemble into liposomes and solid nanoparticles can be conjugated to PS. (b) Noncovalent encapsulation of photosensitizers including:
nanomicelles, nanocapsules, nanospheres and liposomes. PS: Photosensitizer.
EXPERT OPINION ON DRUG DELIVERY 267
both gram-negative and gram-positive bacteria specially [35–38].
A few studies have been done to determine the viruses’ interac-
tions with metal nanoparticles. Metal nanoparticles, especially
silver or gold-based ones, have demonstrated to have virucidal
activity against several kinds of viruses, and surely to decrease
cultured cells viral infectivity [39]. Recently some studies have
shown that metal nanoparticles can be effective antiviral agents
against HIV-1 [40–43], hepatitis B virus [44], respiratory syncytial
virus [45], herpes simplex virus type 1 [46,47], monkeypox virus
[48], influenza virus [49] and Tacaribe virus (55).
5. Quantum dots (QDs)
Quantum dots (QDs) as semiconductor NPs have several phy-
sicochemical properties that make them a potentially new
class of PS. These small NPs have high quantum yields,
a constant composition, high photo-stability, and fluorescent
emission properties that can be tunable by size. They are
relatively simple and inexpensive to synthesize, are non-
cytotoxic in the absence of light, but have the potential to
induce cytotoxicity under UV irradiation or IR depending on
their sizes and colors [51]. Dragnea et al. described the incor-
poration of CdSe/ZnS semiconductor quantum dots (QDs) into
viral particles [52]. The QDs were collected inside the capsids
of brome mosaic virus as a simple icosahedral virus. The result
was a virus-like particle of similar size to the native virus, using
easily manipulated PEG coatings to facilitate future industrial
applications [53].
6. Titanium dioxide (TiO
2
)
TiO
2
is able to mediate photo-
oxidation and could generate ROS on light absorption by
electron transfer reactions involving oxygen and water. The
main problem with the use of TiO
2
-NPs for medical applica-
tions is that their absorption is basically in the UV region of
electromagnetic spectrum. Researchers have emphasized on
shifting the absorbance spectrum of TiO
2
toward the visible
region through doping with other elements [54,55].
Researchers are attempting to dope TiO
2
with platinum or
nitrogen or other materials in order to shift its activation
wavelength from UV to visible range [56] and make different
types of titanium nanostructures such as TiO
2
nanotubes [57].
With respect to public health and viral safety, a number of
publications deal with the elimination of viruses from air/
water using APDT [58,59] and the development of self-
sterilizing materials and surfaces based on PS-loading [60–
62]. Specifically, inorganic materials have been evaluated
[59,63]. The use of inorganic materials, namely if employing
inexpensive and environmentally friendly materials and sun-
light as the natural light source offers considerable potential
for this application of APDT. One example using a simple,
inexpensive inorganic compound and sunlight is TiO
2
photo-
catalysis for APDT of viruses [64,65]. In the context of viral
safety, TiO
2
based APDT has been proposed for inactivation of
viral samples in laboratory safety [66], also has even been
discussed for the destruction of biowarfare agents and could
be useful for disinfection of oral with considering the dose of
aPDT and concentration of PS [67].
7. Fullerenes (C
60
)
Fullerenes have a molecular diameter at the lower end of the
nanoparticle scale (1 nm), but they have very large photo-
stability and generate a combination of both singlet oxygen
(type 2) and also type I reactive oxygen species including
superoxide or hydroxyl radicals.
Fullerene and its derivatives could potentially demonstrate
antiviral activity, which has strong impacts on the HIV-infection
treatment. The fullerene derivatives antiviral activity is due to
many biological properties such as their unique molecular archi-
tecture and antioxidant activity. It has been displayed that full-
erene derivatives could inhibit and make a complex with HIV
protease [68,69]. Dendrofullerene 1 has demonstrated the lar-
gest anti-protease activity [70–72]. Derivative 2, the trans-2 iso-
mer, is a potential inhibitor of HIV-1 replication. Water-insoluble
fullerene (C
60
) derivatives have antiviral activity on enveloped
viruses. After visible-light illumination for 5 h of semliki forest
virus (SFV, Togaviridae) or vesicular stomatitis virus (VSV,
Rhabdoviridae)(79). In the presence of C
60
, the infectivity of
Figure 2. (a) Schematic illustration of different wavelengths penetration depth in a tissue model; (b) Up-conversion nanoparticle could convert the NIR excitation to
visible emission for photosensitizer activation and by producing reactive singlet molecular oxygen (ROD) could destroys virus particles.
268 K. KHORSANDI ET AL.
these viruses is missed. This effect is attributed to the production
of singlet oxygen and is equally efficient in solutions that con-
tained proteins. Various dyes could produce singlet oxygen gen-
eration [73]. The examination that fullerenes and its derivatives
do not have an immunogenetic effect further endorses their
possibility as pharmaceutical compounds.
The H1N1 influenza A virus, which originated in swine, leads
to a global pandemic in 2009, and the highly pathogenic H5N1
avian influenza virus has also led epidemics in southeast Asia in
recent years. Influenza A RNA polymerase contains PA, PB1, and
PB2 subunits, and the N-terminal domain of PA subunit shows
endonuclease activity. To know potential new anti-influenza
compounds, Shoji et al (2013) screened 12 fullerene derivatives
utilizing an in vitro PA endonuclease inhibition assay. They
showed 8 fullerene derivatives that inhibited the endonuclease
activity of the PA N-terminal domain or full-length PA protein
in vitro. In a cell culture model, they found that several fullerene
derivatives inhibit influenza A viral infection and expression of
influenza A nucleoprotein and nonstructural protein 1. These
results confirm that fullerene derivatives are good candidates
for improving the novel anti-influenza drugs [74].
The antiviral potential of Buckminster’s fullerene (C
60
, 10)
and its derivatives was demonstrated by inhibiting HIV-1 pro-
tease – in the absence of light [74]. A few years later the
photodynamic antiviral activity of C
60
was shown. The PDT
with fullerene has been reviewed by a number of authors [75]
and their possible role in photodynamic viral inactivation has
been addressed as well [70].
8. Graphene and graphene oxide (GO)
Graphene is generally called as the simplest structure among all
carbon nanomaterials. Hu et al. used a graphene oxide-aptamer
conjugate to target the phage MS2 as a model virus [76], while
Akhavan et al. showed that photoirradiation of graphene-
tungsten oxide composites resulted in protein destruction and
RNA efflux in MS2 [77]. It should be mentioned that graphene
materials bear potential not only for APDT of viruses but also for
deactivation of viruses via alternative mechanisms, e.g., via selec-
tive binding. Deokar et al. recently synthesized sulfonated mag-
netic NPs functionalized with graphene oxide. This nano-
structure exhibited a high antiviral activity against HSV-1 via
photothermal destruction [78]. Likewise, polyglycerol sulfate
functionalized graphene sheets were shown to selectively bind
and thus inhibit the African swine fever virus, one of the most
dangerous pig diseases and critical for livestock breeding [74].
9. Carbon nanotubes
The carbon nanotube (CNT) is known for its various biomedi-
cal applications due to their unique physicochemical proper-
ties. CNTs were classified as single-walled and multi-walled
carbon nanotubes due to the number of carbon sheets. The
NIR radiation absorption by CNTs proposed their utilization as
novel photosensitizers in aPDT [79]. The functionalization,
conjugation, or encapsulation of CNTs with other photosensi-
tizers is a strong tool for aPDT against infectious diseases.
Banerjee et al. have conjugated PpIX to multi-walled car-
bon nanotubes and revealed that this conjugate was able to
reduce influenza A virus infectivity in mammalian cells [80].
At all, high surface area of nanoparticles could be poten-
tially modified with antibodies for specific targeting (Figure 3).
For some cases such as newly emerged COVD-19, these nano-
particles could target the lung cells that have the receptor of
special antibodies and in this case these infected cells could
be destroyed.
10. Conclusion
For the best usage of aPDT in practice, we should consider all
factors. Different pathways such as environmental, intratracheal,
and intravenous have proven to homogeneously expose all
affected areas in the lung without complications.
The objective of this study was to review aPDT and its effects
on influenza viruses, MERS-CoV, and orthomyxoviruses estab-
lished in the last decade to introduce its fields of application
and development and its potential therapeutic power in COVID
19. Blood transfusion safety by virus decontamination is currently
the main usage of aPDT and plasma decontamination is done for
the therapeutic use of plasma of the previously infected patients.
There is no specific photosensitizer for this antiviral photother-
apy because they significantly depend on the target virus and
the area of application. Curcumin, Nano-Curcumin, methylene
blue, and Riboflavin combined with red and blue wavelengths
with precise methods. aPDT is a valuable, minimally invasive, and
irresistible (unlike antiviral drugs) treatment modality for support
and treatment of viral diseases. Also, the synergistic effects of
Figure 3. Schematic representation of application of different nanoparticles in
antiviral PDT. Nanothechnology based antiviral photodynamic inactivation strat-
egy could potentially overcome the limitations faced by the current approaches.
EXPERT OPINION ON DRUG DELIVERY 269
aPDT and classic methods should be studied. Recent studies
show that aPDT may be useful in the management of COVID–
19 with minimal side effects and drug interactions. This method
has been proven to be effective as a new adjuvant therapy for
the management of viral lung diseases. More animal and human
studies are done to reach a meticulous protocol. This study can
promote other scientists to work on this new platform.
Biophysical reaction between photon and chemical substances,
chemical reaction between chemical substances form
a biophysical reaction induced as a novel effective and relatively
safe treatment modality. In short, Nano antiviral photodynamic
therapy is a valuable support against viral diseases due to the rise
of resistance against antivirals while recent studies confirmed
this hypothesis. Altogether, a further investigation for the appli-
cation of nanomedicine in antimicrobial photodynamic inactiva-
tion is needed for COVID-19 Management.
11. Expert opinion
Antiviral photodynamic therapy is a valuable, minimally inva-
sive, and irresistible (unlike antiviral drugs) treatment modality
for the support and treatment of viral diseases such as COVID-
19. Nano Antiviral Photodynamic Therapy as a type of Antiviral
photodynamic therapy in combination with Nanomedicine
may be useful in the management of COVID-19 with minimal
side effects and drug interactions.
The combination of these two novel methods with each of
them having some abilities and limitations has more boundaries
indeed. Due to the relatively small size of nanoparticles and their
resemblance to all viruses such as SARS-Cov-2, these particles can
help us with the rapid and accurate detection of viruses. For
example, in the nasal and oral cavity with the interaction of light
sources (laser, LED, …) with suitable parameters of this method
and suitable nanoparticles may induce fluorescence and phos-
phorescence effects may help us find viruses. Furthermore, due
to the high accuracy of this method, we may be able to quantify
the number of viral agents and even distinguish between viral
cells and their dead remainder. For treatment, by manipulation of
physical parameters in light sources and various nanoparticles, we
may be able to eradicate viruses with two different mechanisms
which are photochemical and photothermal reactions. In photo-
thermal phenomenon, oxygen and other chemical particles are
not required because viral agents are being eradicated solely by
the rise in temperature, whereas, in photochemical system, we
need chemical agents such as singlet oxygen and other chemical
destructors of viral agents.
There are of course some limitations in this combined tech-
nology. Drug–drug delivery to specific tissues is hard to achieve
specially because viruses penetrate in deep tissues. Delivering
Nanoparticles to more superficial tissue such as the nasal cavity,
oral cavity, blood, and gastrointestinal tract is relatively easier
than deep tissues such as lungs. Also, we need more penetrating
lasers with suitable parameters to activate these nanoparticles.
Perhaps in the future, different lasers with various wavelengths
in the electromagnetic field would be invented for better and
more penetration such as which may be useful for organs like
lungs and other deep organs. Plus, high power laser therapy is
being used in physical medicine and physiotherapy field to
access deep tissues, recently. Maybe by replacing our currently
used laser therapy method with this type of laser therapy we
may be able to solve this problem soon. Lately, there have been
some discussions surrounding a novel concept of sonodynamic
therapy in which ultrasonic waves penetrating deep tissues may
be useful in another way to solve this problem. This technology
is new and laboratory and transrational and clinical studies are
need to be done in near future.
Finally, the future of medicine does not appear to be promis-
ing without these novel types of science specially against com-
plicated and life-threatening disease such as COVID-19 that has
no treatment and may be with us for a long time even after the
production of its vaccine exactly like Influenza which we are all
still struggling with after many years of the invention of its
vaccine. The ultimate goal of this combined method is selective
detection and specific targeting of viruses of all kinds with high
accuracy both in the primary and late stages of diseases in all
tissues of the body specially the deep ones. We may be able to
use monoclonal antibodies adhered to these nanoparticles for
a more specific attack of the injured tissues for viral eradication.
In this method, biophysicochemical reaction between
photon and chemical substances induced a novel effective
and relatively safe treatment modality. Nano-based aPDT
could relate to control of the stages of viral infections.
Finally, this hypothesis promotes scientists for further investi-
gations for the application of Nanomedicine in antimicrobial
photodynamic inactivation for COVID-19 Management.
Funding
This paper was not funded.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any
organization or entity with a financial interest in or financial conflict with
the subject matter or materials discussed in the manuscript. This includes
employment, consultancies, honoraria, stock ownership or options, expert
testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other
relationships to disclose.
ORCID
Reza Fekrazad http://orcid.org/0000-0001-5188-8829
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