LitCovid-sentences  

PMC:7299399 / 11390-49391 JSONTXT 12 Projects

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Id Subject Object Predicate Lexical cue
T53 0-57 Sentence denotes Nanotechnology Tools to Inactivate SARS-CoV-2 in Patients
T54 58-255 Sentence denotes The main target of SARS-CoV-2 is the respiratory tract (upper airways, lung),36 although other organs might also be infected (e.g., gut, kidney) and vasculature21 also appears to be a prime target.
T55 256-329 Sentence denotes The expression of ACE2 probably determines uptake by different tissues.37
T56 330-588 Sentence denotes In addition to discussing immune-based approaches, because the lung is the most critically affected organ, we will center our discussion on the various options to inactivate the virus in the deep lung and to target the essential host cells for drug delivery.
T57 589-751 Sentence denotes The virus reaches the alveoli and enters alveolar epithelial type II cells (AECII), due to the relatively high abundance of ACE2 and a permissive cellular milieu.
T58 752-903 Sentence denotes These cells serve as a reservoir of the virus, which finally spreads throughout the lung, leading to the lung function impairment seen in severe cases.
T59 904-1126 Sentence denotes Airborne nanomaterials are optimally suited to penetrate into the deep lung due to the physicochemical properties of such aerosols, existing on the same size scale particles that penetrate most readily to the deep airways.
T60 1127-1286 Sentence denotes Hence, nanomedicine is already actively pursuing ideas to deliver drugs, therapeutic proteins, and mRNAs by exploiting nanodevices for pulmonary delivery.38,39
T61 1287-1447 Sentence denotes Moreover, the rapid emergence of SARS-CoV-2 has exposed one of the main weaknesses in the current medical landscape: the lack of broad-spectrum antiviral drugs.
T62 1448-1544 Sentence denotes At present, there are only a handful of approved antivirals, and they are mostly virus-specific.
T63 1545-1639 Sentence denotes Hence, when a new virus emerges, little can be done pharmacologically to slow down its spread.
T64 1640-1823 Sentence denotes Some research efforts have been focused on the development of broad-spectrum drugs, which could potentially offer some efficacy against future emerging viruses (and maybe SARS-CoV-2).
T65 1824-1997 Sentence denotes The various approaches developed over the years are mainly based on the creation of entry inhibitors.40,41 A highly conserved part in viruses is the attachment ligand (VAL).
T66 1998-2280 Sentence denotes In most known respiratory viruses,42 the VAL targets either heparan sulfate proteoglycans (HSPG)43 or sialic acids (SA).44 Both HSPG and SA mimics have shown in vitro ability to bind to viruses, blocking their interaction with cell membranes, and often in a broad-spectrum way.45−47
T67 2281-2668 Sentence denotes In the context of nanomedicine, many nanomaterials have been developed, ranging from polymers48 to dendrimers,49 oligomers, NPs,50 liposomes,51 and small molecules.52 However, successful clinical translation has been hindered by the fact that, upon dilution, these compounds lose efficacy as the virus-compound complex dissociates leaving viruses free to restart their replication cycle.
T68 2669-3407 Sentence denotes Recently, it has been shown that this limitation can be overcome by synthesizing NPs that, after binding, are able to inhibit viral infectivity irreversibly by permanently damaging the virion, refueling the hope for a true, broad-spectrum antiviral drug.53 Because the focus is also on the development of a drug specific to SARS-CoV-2, a good entry inhibitor could be based on blocking the S spike protein interaction with the cellular ACE2 receptor.19,21−23 Regardless of the specific approach, it is imperative that novel, effective antivirals be based on compounds that exhibit very low or negligible toxicity profiles, as patients will most likely need to receive those drugs for extended periods of time and will already be weakened.
T69 3408-3504 Sentence denotes For these reasons, when designing antiviral drugs, clearance mechanisms have to be kept in mind.
T70 3505-4027 Sentence denotes An example of this process is the recent redesign of broad-spectrum antiviral NPs into equally effective modified cyclodextrins.54 Moreover, nanotechnology may offer nanotheranostic approaches to fill the existing gap between diagnostics and therapy.55−57 The simultaneous management of both diagnostics and therapy for those suffering from COVID-19 or in future pandemics, as for many other diseases, is an additional potential strategy to take into consideration in which nanomaterials have proven to be effective tools.
T71 4028-4338 Sentence denotes The advantages of the capabilities of nanotechnology and nanomaterials for combined therapeutics and diagnostics has been widely explored in cancer research; however, there have been considerable efforts in the past few years to extend the scope of this approach to other areas including infectious diseases.58
T72 4340-4399 Sentence denotes Nanomaterial-Based Vaccine Development and Immunomodulation
T73 4400-4569 Sentence denotes Following the publication of the genetic sequence of SARS-CoV-2 on January 11, 2020, intense research efforts have been devoted to developing a vaccine against COVID-19.
T74 4570-4906 Sentence denotes With unprecedented speed, this extraordinary scientific mobilization led the first vaccine candidate to enter the Phase I human clinical trial on March 16, 2020, and other novel candidates are rapidly following.59 Up to May 22, 2020, there are 10 COVID-19 candidate vaccines in clinical evaluations and 114 in preclinical development.60
T75 4907-5115 Sentence denotes Concerning vaccine and immunization research, nanomaterials can assist in multiple ways to boost the upregulation required by the immune system and to direct the immune response specifically against antigens.
T76 5116-5356 Sentence denotes Immune-targeted nanotherapeutics can be developed through their rational manufacture at the nanoscale level by designing nanomaterials that are able to amplify host’s immune response, for instance as adjuvants in the context of vaccination.
T77 5357-5904 Sentence denotes The development of a vaccine will rely either on the direct administration of viral antigens (e.g., in the form of recombinant proteins, vectored vaccines, or whole inactivated or attenuated virus) or RNA- or DNA-encoding viral antigens.27 Candidate antigens for immunization are surface proteins such as the immunogenic spike protein (S1), which is already targeted by antibodies of convalescent patients.27 Because the S1 protein is also essential for cellular uptake, many researchers are using this protein as the primary target for a vaccine.
T78 5905-6067 Sentence denotes There are many issues related to the delivery of a drug, protein, or RNA into the patient as the cargo is often degraded, not bioavailable, or is swiftly cleared.
T79 6068-6194 Sentence denotes Nanotechnology provides multiple solutions to these challenges though, as nanocarriers can overcome some of these limitations.
T80 6195-7045 Sentence denotes Biocompatible polymeric-, lipid-based, or inorganic NPs can be tuned with respect to their physicochemical properties to encapsulate cargo proteins with high loading efficiency, improving protein delivery and pharmacokinetics over conventional approaches.38 Intranasal delivery of polymer-encapsulated antigen triggers a strong immune response, and the success of vaccination depends on the appropriate type of polymer in combination with the antigen.61,62 Similarly, researchers have developed lipid and lipid-based NPs as delivery platforms for mRNAs or siRNAs to enable the synthesis of key viral proteins for vaccination or to inactivate critical viral target genes, respectively.39 The field of therapeutic mRNAs to support vaccination has gained momentum, as well,63 at least in part due to nanotechnology-enabled strategies for cargo delivery.
T81 7046-7146 Sentence denotes Moreover, the versatility of nanoplatforms as antigen-presenting systems offers great opportunities.
T82 7147-7464 Sentence denotes Considering the possibility of random viral mutations that may alter the antigen shape, functionalizing nanomaterials with a wide number of molecules at the same time to target the virus, or motifs that are specific for pathogens, will increase the efficiency of vaccines and their ability to prevent viral infection.
T83 7465-7946 Sentence denotes Several companies are working on mRNA vaccines encoding SARS-CoV-2 proteins such as the spike protein, encapsulated in nanoliposomes with specific physicochemical properties that are potentially akin to those documented for immunization against certain tumor antigens.64 The design of such nanocarriers, which will need to escape recognition by scavenger cells and to be nontoxic and nonimmunogenic, is a challenge that will require substantial time prior to clinical availability.
T84 7947-8041 Sentence denotes On March 16, 2020, Moderna, through a partnership with the Vaccine Research Center at the U.S.
T85 8042-8603 Sentence denotes National Institutes of Health, enrolled the first participants into a Phase I clinical trial testing an mRNA vaccine (mRNA-1273) encapsulated in lipid NPs—a record time of just 63 days following sequence selection (NCT04283461).65 The enrollment of the first cohort of participants (18 to 55-year-old healthy subjects) concluded on April 16, 2020.66 CureVac and BioNTech (in partnership with Pfizer) are currently working on similar vaccines; Pfizer/BioNTech, in particular, have recently started the recruitment in Phase I/II trials (NCT04368728, NCT04380701).
T86 8604-8841 Sentence denotes A DNA plasmid vaccine by Inovio Pharmaceuticals (INO-4800) has showed promising results in mice and guinea pigs according to a recent article published in Nature Communications(67) and has entered Phase I testing in humans (NCT04336410).
T87 8842-9069 Sentence denotes Another candidate COVID-19 vaccine for Phase I clinical trial is from the University of Oxford and AstraZeneca (NCT04324606).68 Around 1110 people will take part in the trial, which started recruitment at the end of April 2020.
T88 9070-9176 Sentence denotes The vaccine is based on a chimpanzee adenovirus vaccine vector (ChAdOx1) and the SARS-CoV-2 spike protein.
T89 9177-9310 Sentence denotes Chimpanzee adenoviral vectors against different pathogens have been already tested in thousands of subjects with demonstrated safety.
T90 9311-9409 Sentence denotes To date, ChAdOx1 has been administered to six rhesus macaques exposed to high doses of SARS-CoV-2.
T91 9410-10045 Sentence denotes The vaccine was unable to prevent infections, although it reduced the severity of the disease: no signs of virus replication were observed in the lungs, with significantly lower levels of respiratory disease and no lung damage compared to control animals, according to a recent article deposited in bioRxiv.69 Another adenoviral vector vaccine developed by CanSino Biological Inc. and Beijing Institute of Biotechnology using a genetically engineered replication-defective adenovirus type 5 vector to express the SARS-CoV-2 spike protein (Ad5-nCoV) is currently being tested in Phase I/II trials (NCT04398147, NCT04341389, NCT0431312).
T92 10046-10234 Sentence denotes Although vaccines based on novel DNA and mRNA technologies might be promising, there are no such kinds of vaccines on the market, and it is unknown whether they can be effective in humans.
T93 10235-10467 Sentence denotes Moderna, for instance, has generated preliminary safety data on different mRNA-based vaccines targeting other respiratory viruses, but their more advanced program (on a cytomegalovirus vaccine) is still in Phase II clinical testing.
T94 10468-10864 Sentence denotes However, on May 18, Moderna announced that mRNA-1273 elicited antibody titers above the levels observed in convalescent individuals (and therefore considered potentially protective) in all eight initial participants across the 25 and 100 μg dose cohorts of the Phase I trial (NCT04283461).70 The company, after having received a fast-track approval from the FDA, is now moving on Phase II trials.
T95 10865-11621 Sentence denotes Conversely, strong evidence exists regarding the efficacy of protein-based vaccines such as recombinant-protein, viral-vector, attenuated, or inactivated vaccines across different infectious diseases, with licensed vaccines already existing for all of these platforms.27 All of the aforementioned approaches are currently being explored in the context of SARS-CoV-2.27 An inactivated vaccine developed by the China National Pharmaceutical Group (Sinopharm), in collaboration with the Wuhan Institute of Biological Products, is currently tested in a Phase I/II trial (ChiCTR2000031809), and a second inactivated vaccine (in collaboration with the Beijing Institute of Biological Products) has been currently approved for clinical testing (ChiCTR2000032459).
T96 11622-11932 Sentence denotes A third aluminum salt (alum) adjuvanted inactivated vaccine, developed by Beijing-based Sinovac Biotech’s, was able to provide partial or complete protection in rhesus macaques, according to a recent article published in Science,71 and is currently being tested in Phase I/II trials (NCT04383574, NCT04352608).
T97 11933-12156 Sentence denotes Live-attenuated vaccines are intrinsically immunogenic (e.g., due to the presence of viral DNA), but extensive safety tests are required due to the rare possibility of reversion to a pathogenic form able to cause infection.
T98 12157-12396 Sentence denotes Vaccine candidates based in this application have previously been designed for SARS-CoV with high stability.72,73 Recombinant-protein vaccines and inactivated vaccines are safer but might require adjuvants to increase their immunogenicity.
T99 12397-12467 Sentence denotes In the context of SARS-CoV-2, adjuvants are important for two reasons.
T100 12468-12742 Sentence denotes First, adjuvants might increase the efficacy of the vaccine, especially in subjects with impaired immunological function, such as the elderly, or in subjects with comorbidities resulting in immune dysfunctions; in these patient cohorts, SARS-CoV-2 has a high lethality rate.
T101 12743-12901 Sentence denotes Second, adjuvants can reduce the amount of vaccine protein(s) required per dose, which could facilitate scaling-up vaccine production in a reduced time frame.
T102 12902-14119 Sentence denotes Beyond alum, which is in fact a nanoscale material74 that was developed in the 1920s for the tetanus and diphtheria toxoids,75 approval for a new adjuvant did not occur until 1997, with the introduction of the oil-in-water emulsion of squalene oil and polysorbate 80 and sorbitan trioleate surfactants (MF59) in the seasonal influenza vaccine for the elderly.76 The use of MF59 was further expanded to pandemic and avian influenza vaccines.77 Other adjuvants in licensed vaccines have been approved since 2000, as well: (a) AS03 (used for pandemic and avian influenza vaccines), similar to MF59, but including α-tocopherol as an additional immune stimulant; (b) AF 03 (used for pandemic influenza vaccines), an alternative squalene emulsion containing polyoxyethylene, cetostearyl ether, mannitol, and orbitan oleate;78 (c) AS 01 (used for herpes zoster vaccine), a liposome-based vaccine adjuvant system containing two immunostimulants, 3-O-desacyl-4′-monophosphoryl lipid A (MPL, a Toll-like receptor 4 agonist) and saponin QS-21, which activates the ACT-NLRP3 inflammasome pathway;79 and (d) AS04 (used for hepatitis B and human papilloma virus vaccines), which is a combination of MPL and aluminum hydroxide.76,80
T103 14120-14490 Sentence denotes In this context, the concept of “nanoimmunity by design” relies on the rational design of distinct physicochemical properties and specific functionalization of nanomaterials intended for fine-tuning their potential effects on the immune system.81 Nanomaterials have emerged as promising tools for immune modulation, either stimulating or suppressing the immune response.
T104 14491-14628 Sentence denotes In fighting SARS-CoV-2, these properties may find applications for both prevention and therapy and in the context of vaccine development.
T105 14629-15526 Sentence denotes Mounting evidence indicates that nanomaterials such as graphene,82 nanodiamonds,83 carbon nanotubes,84 and polystyrene particles85 bear an intrinsic capacity to activate the immune system, depending on their functionalization.86 For instance, graphene oxide functionalized with amino groups (GO-NH2) induces activation of STAT1/IRF1 interferon signaling in monocytes and T cells, resulting in the production of T cell chemoattractants, and macrophage 1 (M1) 1/T-helper 1 (Th1) polarization of the immune response, with negligible toxicity.82 Remarkably, the ability of licensed adjuvants such as AS01 and AS03 to enhance adaptive immunity has been linked to their capacity to boost STAT1/IRF1 interferon signaling.87 In addition, recent SARS-CoV and MERS-CoV studies suggest that the development of a Th1-type response is central for controlling infection, which also may be true for SARS-CoV-2.88
T106 15527-16139 Sentence denotes Several groups and consortia have been screening and characterizing nanomaterials according to their immunomodulatory properties and absence of cytotoxicity.56,57,82−84,86 The development of an adjuvant for clinical use is a lengthy process that requires extensive Phase III randomized trials in large and diverse cohorts of subjects, and the process generally requires several years.76 Pharmaceutical giants such as GlaxoSmithKline (GSK), which owns the ASs mentioned above and other adjuvant platforms, are engaged in several partnerships to embed their adjuvant systems with SARS-CoV-2-protein-based vaccines.
T107 16140-16322 Sentence denotes A full-length recombinant SARS-CoV-2 glycoprotein nanoparticle vaccine adjuvanted with the saponin-based Matrix M developed by Novavax is in Phase I clinical testing (NCT04368988).89
T108 16323-16547 Sentence denotes Although it is unlikely that novel adjuvants would be used in the context of the current pandemic, the SARS-CoV-2 pandemic offers an opportunity to reflect on the potential of nanotechnology for vaccine adjuvant development.
T109 16548-16766 Sentence denotes In this context, it is critical to stream coherent pipelines covering in vitro and in vivo experiments specifically to select candidate materials that might be tested for clinical implementation as vaccine adjuvants.90
T110 16767-17247 Sentence denotes In this view, the status of nanomaterial-based vaccine adjuvants has been reviewed.91,92 In particular, immunomodulatory effects induced on the innate immune signaling have been demonstrated.91 For example, nanomaterials such as GO can elicit an inflammasome sensor (NLRP3)-dependent expression of IL-1β in macrophages.93 Notably, alum, the most commonly used adjuvant in human vaccines, induces the release of this cytokine in macrophages through the same NRLP-induced mechanism.
T111 17248-17350 Sentence denotes These results suggest that nanomaterials such as GO and alum may be useful for medical applications.94
T112 17351-17545 Sentence denotes Considering that new vaccine development typically requires years to be approved and applied to the general population, there is also an urgent need to study how to improve treatment approaches.
T113 17546-17781 Sentence denotes According to the first Phase III clinical studies, the antiviral drug Remdesivir, which was recently approved by the FDA for COVID-19 treatment in the United States, seems to be a promising treatment for adults diagnosed with COVID-19.
T114 17782-18101 Sentence denotes Nano-based strategies have already been applied to enhance the effectiveness of Remdesivir in the context of other emerging viral infections (Nipah virus),95 suggesting the suitability of nanotechnology to assist with similar strategies for the treatment of COVID-19 as well as other possible pandemics in the future.96
T115 18103-18157 Sentence denotes Can Nanotechnology Help to Control the Cytokine Storm?
T116 18158-18736 Sentence denotes One of the main features of COVID-19 is the triggering of a cytokine storm in the body, also known as cytokine release syndrome (CRS), which results from an excessive immune response and leads to the severe deterioration of patient health.25,97,98 This inflammatory storm is one of the major causes of the acute respiratory distress syndrome (ARDS) that is often associated with multiple-organ failure, representing the leading causes of death in critical patients.98 In particular, the role of interleukin (IL)-6 has been highlighted in patients requiring assisted ventilation.
T117 18737-18900 Sentence denotes Ongoing clinical trials are testing drugs that block the receptor of IL-6 (Tocilizumab, an anti-IL-6 receptor antibody, and Sarilumab) or IL-6 itself (Siltuximab).
T118 18901-19133 Sentence denotes Whereas a well-regulated cytokine response that is rapidly triggered by the host’s innate immunity can serve to prevent and to counteract an infection, an excessive, unbalanced, prolonged immune response can seriously harm the body.
T119 19134-19244 Sentence denotes Therefore, therapeutic strategies aimed at effectively suppressing the cytokine storm are under investigation.
T120 19245-19626 Sentence denotes Nanomaterials have been exploited to adjust the immune response to an optimized level, and such proprieties might be explored to inhibit cytokine releases.99 Nanosystems can enhance the specificity/efficiency of immunosuppressant delivery to target immune cells, with consequent reductions in drug dose, drug distribution to nontarget tissues and organs, and possible side effects.
T121 19627-19923 Sentence denotes In addition, specific nanotools can be designed to evade the immune system and to enhance the solubility of poorly soluble immunosuppressant agents; the potential of finely tuning their surface charge opens possibilities for encapsulation strategies and offers accommodation for a high drug load.
T122 19924-20030 Sentence denotes All of these mechanisms may also occur simultaneously, enhancing the activity of immunosuppressive agents.
T123 20031-20453 Sentence denotes Concerning the role of macrophages in COVID-19, the presence of ACE2-expressing CD68+CD169+ macrophages containing SARS-CoV-2 nucleoprotein antigen and showing an increased release of IL-6 was observed in infected spleen and lymph nodes.100 Notably, immunohistochemical and immunofluorescence analyses of lymph nodes and spleen tissue from autopsy samples of patients who died from COVID-19 revealed lymphocytic apoptosis.
T124 20454-20663 Sentence denotes The tissues infected by SARS-CoV-2 also showed an upregulated expression of Fas, suggesting a role for CD169+ macrophages in viral spreading, aberrant inflammation, and activation-induced lymphocyte apoptosis.
T125 20664-20940 Sentence denotes Moreover, histological examinations of biopsy samples of patients who died from COVID-19 revealed an increased alveolar exudate due to the extended neutrophil and monocyte infiltrate in lung capillaries with fibrin deposition, probably leading to difficulties in gas exchange.
T126 20941-21541 Sentence denotes Through nanomedicine, we envision therapeutic approaches aimed at targeting specific immune subpopulations to avoid these complications, and different nanomaterials have already been explored for their specific impact on different immune cell subpopulations.82,83,86 Octadecylamine-functionalized and dexamethasone-adsorbed nanodiamond promotes anti-inflammatory and proregenerative behavior in human macrophages in vitro.101 A low dose of this functionalized nanodiamond also reduced macrophage infiltration and expression of proinflammatory mediators iNOS and tumor necrosis factor (TNF)-α in mice.
T127 21542-21657 Sentence denotes Overall, these results suggest that nanodiamond particles may be useful as an inherently immunomodulatory platform.
T128 21658-22004 Sentence denotes Finally, the indiscriminate systemic suppression of the immune system may increase the susceptibility to sepsis due to underlying secondary bacterial infections that can exacerbate critical conditions in patients, causing death.102 Risk factors for mortality include acquired bacterial infections by opportunistic organisms and primary pathogens.
T129 22005-22225 Sentence denotes Using nanocarriers to achieve targeted delivery of immunosuppressive drugs, or the specific and controlled inhibition of only a specific immune cell subpopulation, can play a critical role in limiting such complications.
T130 22226-22393 Sentence denotes The fast and complete removal of pro-inflammatory cytokines from the bloodstream has been shown to increase survival significantly in patients with early stage sepsis.
T131 22394-22586 Sentence denotes Adsorption of cytokines from serum by extracorporeal perfusion through porous carbons is one of the most promising ways for their selective, quick, and complete removal from blood circulation.
T132 22587-23282 Sentence denotes Hierarchical carbon materials with tuned porosity have shown effective adsorption of many cytokines, including IL-6 and even the largest ones, such as TNF-α.103 Based on their demonstrated outstanding performance in removing sepsis-associated pro-inflammatory cytokines from blood, mesoporous carbon adsorbents with hierarchical structure, tuned pore size, and surface chemistry, as well as graphene with open and accessible surfaces104 have significant potential to quickly remove inflammatory cytokines associated with CRS and to prevent mortality arising from an uncontrolled inflammatory cascade, thereby providing enough time for the defense mechanisms of the human body to fight the virus.
T133 23284-23323 Sentence denotes Photodynamic Inactivation of SARS-CoV-2
T134 23324-23465 Sentence denotes In addition to drug- and vaccine-based antiviral strategies, photodynamic therapy (PDT) stands as a unique approach to inactivate SARS-CoV-2.
T135 23466-23789 Sentence denotes Using a light-based method, PDT attacks target cells via the excitation of photosensitive agents, called photosensitizers (PSs), with radiation characterized by a wavelength corresponding to its absorption spectrum to generate reactive oxygen species (ROS) in the presence of oxygen, which ultimately results in cell death.
T136 23790-24383 Sentence denotes Photodynamic therapy is primarily used for the clinical treatment of various oncological disorders.105 It was not until the 1970s that PDT was first used clinically against viruses,106 exploiting ROS production to damage virus proteins, nucleic acids, and—if present—lipids.107 Even though there are research efforts for PDT-based virotherapies against different viruses, including herpes simplex virus, human papilloma virus, and human immunodeficiency virus,106−109 clinical use of PDT is limited due to hydrophobicity of PSs, poor target specificity, and limited tissue penetration ability.
T137 24384-24752 Sentence denotes Most PSs are hydrophobic and aggregate in aqueous solutions, affecting their photochemical and photobiological properties.106,110 For this reason, Lim et al. have proposed a promising approach for photodynamic inactivation of viruses with NPs, developing sodium yttrium fluoride (NaYF4) upconversion NPs (UCNs) with zinc phthalocyanine PSs grafted onto their surfaces.
T138 24753-24876 Sentence denotes Unlike most PSs, these UCNs are coated with polyethylenimine (PEI), which render them hydrophilic and easier to manipulate.
T139 24877-25218 Sentence denotes These UCNs showed antiviral activity against Dengue virus serotype 2 and adenovirus type 5, which were used as models of enveloped and non-enveloped viruses, respectively.110 MXenes111,112 are a large family of 2D transition metal carbides, nitrides,113 and carbonitrides114 that exhibit unique electronic, optical, and catalytic properties.
T140 25219-25560 Sentence denotes They have the general formula Mn+1XnTx, where M is an early transition metal (Ti, Zr, V, Mo, etc.), X is C and/or N, Tx represents the surface functional groups (=O, −OH, −F, −Cl), and n = 1–4.115,116 Some examples include Ti3C2Tx, V2CTx, and Nb2CTx, with over 30 stoichiometric compositions already synthesized with more than 100 predicted.
T141 25561-25808 Sentence denotes Biocompatible MXenes, such as Ti3C2Tx, are hydrophilic and are among the most efficient light-to-heat transforming materials.117 The plasmon resonance extinction maxima of Ti3C2Tx is at 780 nm, enabling the use of near-infrared (IR) light for PDT.
T142 25809-25947 Sentence denotes Several other MXenes have absorption maxima in the IR range and have shown outstanding performance in PDT and theranostic applications.118
T143 25948-26619 Sentence denotes Fullerene and graphene are also good candidates for virus inactivation by PDT and have proved to be effective against Semliki Forest virus (SFV), vesicular stomatitis virus (VSV), HSV-1, HIV-1, mosquito iridovirus (MIV), and influenza A virus (IAV), as well as the phage MS2.107 In addition, several 2D nanomaterials, including graphene-based materials, MXenes, black phosphorus, graphitic carbon nitride, tungsten disulfide, and molybdenum disulfide, have been reported to improve the efficacy of PDT considerably for cancer treatment.56,57 Therefore, determining if such nanomaterial-based PDT protocols could be exploited to inactivate SARS-CoV-2 is of great interest.
T144 26621-26668 Sentence denotes Biomimetic Engineering of Nanodelivery Systems:
T145 26669-26701 Sentence denotes Artificial Viruses in the Making
T146 26702-26977 Sentence denotes In an effort to engineer the next generation of nanoscale vectors, scientists have moved from using inorganic components aimed at obtaining inert structures to utilizing biological building blocks that are able to convey additional functionalities to the resulting construct.
T147 26978-27216 Sentence denotes To cope with the complexity of the body and to evade the multiple layers of defense that tissues and organs have, it is critical to rely on the ability of certain materials to interact with, rather than to eschew, the biology of our body.
T148 27217-27459 Sentence denotes Every NP system conceived to date faces one common fate: whether injected, inhaled, ingested, or absorbed through our epithelia, all will at some point come into contact with the mixture of fluids and organic compounds that comprise the body.
T149 27460-27917 Sentence denotes Under such conditions, every material reacts in a unique way according to the conditions they individually face (i.e., the tissue or body region they are in), their composition (i.e., organic or inorganic), and their physical properties (i.e., size, shape, surface charge).119 Inorganic NPs can function as globular protein mimics because of their similar size, charge, shape, and surface features that can be chemically functionalized to resemble proteins.
T150 27918-28034 Sentence denotes These similarities can be used in biotechnology to control virus pathways or cell receptor interactions with NPs.120
T151 28035-28235 Sentence denotes Among the many attempts, the legendary accomplishments, and the epic failures, we could list thousands of different NPs, differing from one another thanks to the creative endeavors of their designers.
T152 28236-28497 Sentence denotes Despite their remarkable differences and researchers’ endeavors to make them one of a kind, they all aim to achieve one goal: to deliver in a specific way one particular form of payload, while remaining as unnoticed as possible by the body’s defense mechanisms.
T153 28498-28708 Sentence denotes For everyone who has made an effort to create their own version of such a silver bullet, it has come to mind that nature in its incredible variety had already invented a few ingenious solutions to this problem.
T154 28709-28851 Sentence denotes In the world of nano-based drug delivery, one entity dominates as the quintessential example of precision, efficiency, and stealth: the virus.
T155 28852-29039 Sentence denotes Not by chance, these two worlds share many features that span from the physical laws that govern their assembly and stability to the chemical similarities in their overall composition.121
T156 29040-29205 Sentence denotes Historically, the field of nanomedicine and the global endeavor to generate NPs for drug delivery arose from one of the greatest struggles in medicine: gene therapy.
T157 29206-29382 Sentence denotes At the core of that approach was the idea that viruses could be used as Trojan horses to deliver the correct sequence of the gene into the cells that harbored the mutated copy.
T158 29383-29564 Sentence denotes In order to identify the virus that offered the best delivery service, a cadre of viral strains and species were tested, adapted, and engineered to fit the aims and hit the targets.
T159 29565-30056 Sentence denotes It took decades of trial and error, of progressive adjustments, and a few tragic mistakes to identify the viruses that could provide the ideal backbone to develop viral vectors able to ferry genetic cargo into the target cell.122 In the midst of that global challenge, nanotechnology offered a safer and more controllable alternative: to generate bespoke structures that could replace viral vectors and do the same job, delivering a payload from the point of injection to the site of action.
T160 30057-30281 Sentence denotes Fast forward a few decades, and the promises made by both worlds seem to have finally become reality, with a number of active clinical trials, some clinical success stories, and a few commercial products in the market space.
T161 30282-30404 Sentence denotes Interestingly, the two worlds seem to have maintained a safe distance so as to avoid any collision or dangerous proximity.
T162 30405-30844 Sentence denotes Exchange of ideas between the fields of gene therapy and nanomedicine is limited, and the potential for disciplinary growth through knowledge exchange has remained elusive to scientists in both fields.5 Many scientists have suggested that nanotechnologists could find inspiration in the mechanisms devised by viruses to elude immune surveillance, to overcome biological barriers, and to deliver their genetic payload with high specificity.
T163 30845-31016 Sentence denotes Similarly, gene therapists would find high-tech solutions to their scalability and safety issues in looking at the new generations of biomimetic particles being generated.
T164 31017-31290 Sentence denotes The principles of biomimicry and bioinspiration have been used to design and to engineer drug-delivery technologies that reproduce or recapitulate biological materials, for what pertains to not only their structure and chemistry but also, more importantly, their functions.
T165 31291-31831 Sentence denotes In drug delivery, surface recognition and nanoscale interactions between materials and biological entities are key to the success of the delivery strategy, and the use of biological building blocks such as membrane proteins has been proposed as a way to convey targeting and shielding moieties simultaneously.123 One can only hope that the recent events and global attention that viruses are capturing in the scientific world will spur a renewed interest in finding ways to adapt viral features and mechanisms of action to the world of NPs.
T166 31832-32043 Sentence denotes Increased focus in this field would be useful to create virus-like NPs able to circulate in the blood system, overcoming the endothelial barrier, and to deliver their therapeutic payload with high efficiency.124
T167 32045-32150 Sentence denotes Interference with Cellular Uptake, Immobilization, and Inactivation of the Virus Outside of the Host Cell
T168 32151-32258 Sentence denotes Nanomaterials can be synthesized with a high specific surface area of a few hundred square meters per gram.
T169 32259-32394 Sentence denotes Therefore, dependent on the surface properties, nanomaterials efficiently adsorb biomolecules and form a so-called biomolecular corona.
T170 32395-32535 Sentence denotes This passive, nontargeted adsorption might be utilized to bind viruses, provided that the selected nanomaterial is relatively biocompatible.
T171 32536-33039 Sentence denotes Viral surface proteins are often modified by sugar moieties or encompass positively charged amino acid patches that bind to lectins or glycosaminoglycans (GAGs) of heparan sulfate (HS), respectively.32 Robust interactions of virus particles with these host receptors is ensured by multivalent binding, which is likely why single-molecule inhibitors often are not capable of efficiently perturbing this key event but multivalent NPs are superior to block binding of different viruses to the host cell.125
T172 33040-33234 Sentence denotes Gold NPs capped with mercaptoethanesulfonate are effective inhibitors of HSV type 1 infection as they mimic cell-surface-receptor heparan sulfate and, therefore, competitively bind to the virus.
T173 33235-33340 Sentence denotes Interestingly, polyvalent sulfated Au NPs inhibit virus binding to the host cell dependent on their size.
T174 33341-33518 Sentence denotes Nanoparticles of diameters equal to and larger than the virus diameter (in this case, the stomatitis virus) more efficiently inhibit the binding to cells than smaller particles.
T175 33519-33756 Sentence denotes Most likely, larger NPs efficiently cross-link virions, whereas smaller NPs simply decorate the viral surface.126 Papp et al. found that gold NPs decorated with SA effectively inhibited the binding of influenza virus to the target cells.
T176 33757-34303 Sentence denotes In this case, viral recognition via its surface protein hemagglutinin of SA on the host cell membrane was a prerequisite for cellular entry.127 More recently, Cagno et al. reported antiviral NPs (Au and iron oxide core) with long and flexible linkers mimicking HS that strongly bind and inactivate viruses such as respiratory syncytial virus in vitro and in vivo in a lung infection model and even led to irreversible viral deformation.53 Hence, there is ample evidence that biocompatible, functionalized NPs can act as broad-spectrum antivirals.
T177 34304-34494 Sentence denotes Notably, the receptor-binding domain of the spike S1 protein of SARS-CoV-2 binds not only to ACE2 but also to heparin128 and, thus, might be targeted by similar approaches as outlined above.
T178 34495-34903 Sentence denotes One of the most recent strategies to inhibit viral uptake is based on administration of recombinant ACE2 to inhibit binding competitively via the spike S1 protein.21 Knowing that multivalency is key to block virus–host interactions reliably, researchers have speculated that a nanostructured carrier could not only improve delivery and cargo stability but also might dramatically enhance binding strength.129
T179 34905-34985 Sentence denotes Speeding up the Nanomedicine-Based Approaches for COVID-19 by In Silico Analysis
T180 34986-35620 Sentence denotes Currently, repurposing drug molecules is a key strategy for identifying approved or investigational drugs outside the scope of the original medical indication that can be used to fight COVID-19.130,131 There are various advantages to this strategy, including already-established safety profiles, fast transition to clinical studies, and less investment needed, compared to the process of developing an entirely new drug.132,133 Therefore, these advantages have the potential to result in less risky and more rapid returns on investment in the development of repurposed drugs, benefits that are particularly important during pandemics.
T181 35621-35754 Sentence denotes In addition to rapid diagnosis, making recommendations to physicians about rapid treatment methods can save the lives of many people.
T182 35755-36014 Sentence denotes Combining in silico tools such as molecular docking, molecular dynamics, and computational chemistry with large drug databases provides a great advantage in selecting “possible candidates” from among thousands of pharmaceutically active substances (Figure 3).
T183 36015-36177 Sentence denotes In silico analyses should be supported by the literature, expert opinions (pharmacologists and clinicians), and, when possible, preclinical and clinical findings.
T184 36178-36337 Sentence denotes After selecting the best candidates following in silico analyses, detailed in vitro and in vivo experimentation should be undertaken prior to clinical studies.
T185 36338-36597 Sentence denotes Recently, various drug-repurposing studies have been published to assist in the global COVID-19 pandemic response.134−136 Such studies aim to identify whether already-approved drugs have the capacity to interact with viral proteins or receptors on host cells.
T186 36598-36712 Sentence denotes Figure 3 Schematic of how in silico analysis can be used to select candidate drug molecules for clinical studies.
T187 36713-36736 Sentence denotes MD, molecular dynamics.
T188 36737-36969 Sentence denotes In nanomedicine, computational models have recently garnered attention; such work may help to identify how nanomaterials interact with biological systems and to determine how the efficacy of these nanotherapeutics could be improved.
T189 36970-37798 Sentence denotes Computational models indicate how NPs are taken up by healthy cells or tumor cells, enabling better predictions regarding the pharmacokinetic and pharmacodynamic properties of these materials.134 For example, Lunnoo et al. used a coarse-grained molecular dynamics (MD) simulation to observe the internalization pathways of various Au nanostructures (nanospheres, nanocages, nanorods, nanoplates, and nanohexapods) into an idealized mammalian plasma membrane.137 Other studies have simulated how different NPs can target tumor cells and deliver drugs.138,139 Therefore, in silico approaches that are currently used for drug repurposing, including molecular docking, molecular dynamics, and computational chemistry, constitute valuable tools to aid preclinical and clinical studies of nanomaterials directed for disease treatment.
T190 37799-38001 Sentence denotes Considering the urgent need for nanomedicine against the current pandemic, in silico analyses may be especially useful in guiding the rational design of new NP formulations required to fight SARS-CoV-2.