Disinfecting dispensable nanoparticle-based compositions

Abstract

Disclosed herein are fast and residual disinfectant compositions comprising metal-associated cerium oxide nanoparticles. Also disclosed are methods of making the disinfectant compositions. Also disclosed are films comprising the disclosed compositions, and methods of disinfecting surfaces.

Description

BACKGROUND

[0001] Coronaviruses are easily transmitted, and transmission is believed to occur primarily through respiratory droplets produced by infected persons, and through contact with surfaces that harbor droplets containing the SARS-CoV-2 virus. [1] Early studies have shown that these viruses can survive on most common types of surfaces for 2-3 days. [2] Most known available disinfectants, while able to neutralize multiple types of viruses, generally require a reaction time of about 30 seconds to 10 minutes. [3] It is impractical to attempt to disinfect surfaces within these time ranges, which can pose a problem. Furthermore, current disinfectants require constant reapplication within high-touch areas as they do not provide residual protection against viruses and bacteria. BRIEF DESCRIPTION OF DRAWINGS

[0002] Figure 1 RAD compositions are shown as applied and post-application. The mechanism of viral inactivation by cerium oxide nanoparticles (CNP) is shown in the bottom right corner box.

[0003] Figure 2 A shows x-ray photoelectron spectroscopy (XPS) survey scans of silver-modified cerium oxide nanoparticles (AgCNP), Figure 2 B shows unique multiplet cerium signals used to quantify the Ce 3+ / Ce 4+ ratio, Figure 2 C shows silver peaks detailing the silver chemical environment in AgCNP, Figure 2 D is high resolution transmission electron microscopy (hrTEM) of silver-modified CNP, Figure 2 E is x-ray diffraction of pure phase CNP.

[0004] Figure 3 shows a flowchart of the synthesis of AgCNP1 and AgCNP2.

[0005] Figure 4 is a model for the synthesis of AgCNP1 and AgCNP2.

[0006] Figure 5 shows material characteristics of AgCNP1 and AgCNP2. Figure 5 A is a transmission electron microscopy (TEM) image of AgCNP1 showing spherical particles (20 nm in size) rich in Ag nanoparticles (2-5 nm in size). Figure 5 B is a TEM micrograph of AgCNP2 showing agglomerated Ce02 particles designed with Ag nanoparticles of different sizes (5 to 20 nm). Tafel analysis was performed on AgCNP1 and AgCNP2, Figure 5C shows the unique corrosion potential of each formulation (465.386 mV and 217.374 mV, respectively). Figure 5 D is the Nyquist representation of AgCNP1 and AgCNP2 in the range 10 Hz to 100 kHz.

[0007] Figure 6 AgCNP-virus interactions were measured in situ by impedance spectroscopy. Figure 6 A-C show the incubation of AgCNP1 with the envelope coronavirus OC43; Figure 6 D-F relate to the incubation of AgCNP2 with the non-enveloped rhinovirus, measured at regular time intervals of 30 minutes (2 and 4 hours of incubation for rhinovirus and OC43 virus, respectively).

[0008] Figure 7 is an electrochemical model of the AgCNP-virus interaction in situ.

[0009] Figure 8 is a physical model of the virus / nanoparticle interaction:

[0010] Liposome / xanthine: xanthine oxidase. Figure 8 A is the fitted electrochemical impedance spectrum, Figure 8 B shows the equivalent circuit, Figure 8 C is the fitted circuit element values.

[0011] Figure 9 is a graph showing the efficacy of AgCNP2 dried on a glass slide against RV14.

[0012] Figure 10 is a graph showing the repeat efficacy of AgCNP. DETAILED DESCRIPTION

[0013] Disclosed herein is a fast and residual acting disinfectant (RAD) composition (e.g., nanoRAD) to control the spread of SARS-CoV-2 and other pathogens through contact with surfaces. The disclosed method employs a select medium containing fast-responding metal-associated cerium oxide nanoparticles where the oxidation response / mechanism is designed to run several “disinfectant” reactions in parallel. The first is an oxidation reaction involving the viral spike glycoprotein that inhibits virus-host cell interactions, thereby inactivating infectivity. The second mechanism is membrane peroxidation of the viral envelope to induce lysis; thereby rendering the virus ineffective. Each disinfection mechanism can be achieved through the cerium oxide surface reaction. These mechanisms are self-regenerative as the nanoparticles are not used up during disinfection, thereby allowing the nanoRAD to have residual disinfecting capacity. In other embodiments, the particles can be made more effective by doping with silver: resulting in further production of free radicals in application. Doping the nano cerium oxide with fluorine or similar chemistry can reduce the reaction rate of the first two mechanisms to well below 30 seconds. The combination (coaction) of disinfection mechanisms will further reduce the overall rate event, allowing for fast disinfection through multiple parallel pathways and dry disinfection efficacy at safe contact concentrations.

[0014] According to one embodiment, a dispensable composition is disclosed comprising metal-associated cerium oxide nanoparticles (mCNP) and an excipient. The metal associated with the cerium oxide nanoparticles can include, but is not limited to, silver, gold, ruthenium, vanadium, copper, titanium, nickel, platinum, titanium, tin, and iron. In one specific example, the metal is silver and comprises 10% or less by weight of the particle. In some embodiments, the excipient is selected from water, chloroform, dichloromethane, acetone, methyl ethyl ketone, cyclohexane, ethyl acetate, diethyl ether, a lower alcohol, a lower glycol, THF, DMSO, or DMF. The mCNP can also be doped with fluorine.

[0015] In other embodiments, methods for producing mCNPs are disclosed. When the metal is silver, AgCNPs are produced by a method comprising: dissolving a cerium precursor salt and a silver precursor salt, such as cerium nitrate and silver nitrate; oxidizing the dissolved cerium precursor salt and silver precursor salt with an admixture containing peroxide; and precipitating nanoparticles with an admixture containing ammonium hydroxide. Alternatively, AgCNPs are produced by a method comprising the following steps: (i) dissolving a cerium precursor salt and a silver precursor salt, such as cerium nitrate and silver nitrate; (ii) oxidizing and precipitating the dissolved cerium precursor salt and silver precursor salt with an admixture containing ammonium hydroxide; (iii) washing and resuspending the precipitated nanoparticles in water; (iv) treating the resuspended nanoparticles with hydrogen peroxide; and (v) washing the nanoparticles from step (iv) to remove ionized silver.

[0016] In other embodiments, methods for sterilizing surfaces are disclosed by dispensing a dispensable composition onto a surface. These and other embodiments will be further described below.

[0017] Definitions

[0018] Unless specifically specified or obvious from the context, as used herein, the term "about" is understood to mean within the normal tolerance range in the art, such as within 2 standard deviations of the mean. "About" can be understood as within 30%, 25%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, 0.05%, or 0.01% of the specified value. Unless the context otherwise requires, all numerical values ​​provided herein are modified by the term "about".

[0019] As used herein, the terms "disinfection" or "disinfect" refer to the reduction or elimination of pathogenic microorganisms (including bacteria and viruses) on a surface. The term "residual disinfectant" as used herein refers to any sprayable disinfectant capable of disinfecting a surface in dry form for at least 24 hours. Residual disinfectants lasting up to 24 hours can disinfect by reducing viral load by 3 log and bacterial load by 5 log within 10 minutes. Residual disinfectants lasting more than one day (sprayed or otherwise applied) can disinfect by reducing viral load by 3 log and bacterial load by 3 log within 2 hours.

[0020] The term "rapid disinfection" as used in this article refers to the near-instantaneous elimination of pathogenic microorganisms on surfaces. When applied in wet form, rapid disinfectants have a disinfection residence time of approximately one minute or less.

[0021] The terms "metal-associated cerium oxide nanoparticles," "metal-associated cerium oxide nanoparticles," or "mCNP" refer to cerium oxide nanoparticles doped with or otherwise bonded to a metal (such as silver, gold, copper, platinum, nickel, iron, titanium, ruthenium, vanadium, etc.). The term mCNP includes AgCNP. In one embodiment, the metal-associated cerium oxide nanoparticles have particle sizes ranging from 1 nm to 50 nm, or 5 nm to 100 nm, or 5 nm to 25 nm.

[0022] As used herein, the term "nanoRAD" refers to a disinfectant containing cerium oxide nanoparticles bonded to a metal (such as silver) as both an active agent and an excipient. As taught herein, the disclosed nanoRAD compositions may include excipients (such as organic acids), surfactants, desiccants, and / or polymers, etc.

[0023] As used herein, the term "dispensing" generally refers to the ejection of the composition from a container or dispensing system. Dispensing can be accomplished, for example, by using an air exchange pump, an opening, etc. There are no limitations herein on the amount or manner in which the composition is dispensed. In some embodiments, the composition can be dispensed as a fine mist, similar to an atomized spray, which can be achieved by using, for example, a nozzle or atomizer. In other embodiments, the composition can be dispensed under high or low pressure as a single stream of liquid (droplets, etc.). In embodiments of the invention, any form of dispensing that meets the needs of a particular environment can be utilized.

[0024] As used herein, the term "pump" refers to a device capable of dispensing a composition located within a container. A pump can be an "air exchange" pump, which functions by injecting air or the like into the container. The injected air then displaces and dispenses some or all of the composition within the container. The amount of composition dispensed depends on the amount of air injected and the amount of composition within the container. More specifically, a pump can inject air into a container and dispense the composition from a nozzle or other opening.

[0025] The term "dominant 4+ surface charge" refers to the concentration of cerium ions on the surface and implies the presence of [Ce+] on the surface of cerium oxide nanoparticles. 3+ ]:[Ce 4+ The [Ce] ratio is less than 50%. In one specific embodiment, cerium oxide nanoparticles with a dominant 4+ surface charge have 40% or less [Ce] ratio. 3+ ]:[Ce 4+ ]Compare.

[0026] The term "dominant 3+ surface charge" refers to the [Ce3+] surface charge on the surface of cerium oxide nanoparticles. 3+ ]:[Ce 4+The ratio is greater than 50%. In one specific embodiment, [Ce] 3+ ]:[Ce 4+ The percentage is greater than 60%.

[0027] The term "wet chemical synthesis" refers to a method for producing CNPs that involves dissolving a cerium precursor salt in water and then adding hydrogen peroxide. In one specific embodiment, the CNPs remain stable for a predetermined period of time, typically at least 15-30 days.

[0028] Overview

[0029] Current disinfectant sprays disinfect only upon application. The disclosed RAD composition, however, possesses the unique ability to create a temporary, persistent disinfectant film on the surface upon application. This sustained disinfectant activity is due to the regenerative (catalytic) properties of the cerium oxide nanoparticle (CNP) nanosurface reaction sites, which allow for continuous disinfection of the surface when new viruses or bacteria come into contact with it. This provides an attractive solution for surfaces where permanent disinfectant films are not readily applied. The RAD composition is a solution capable of controlling the spread of COVID-19 and hospital-acquired infections (HAIs) through surface contact in a manner currently unavailable and uniquely suited as both disinfectant sprays and temporary films.

[0030] With the emergence of COVID-19, many businesses and governments have been working to figure out how to get people into public places or public spaces in a way that reduces the spread of the coronavirus. In India, walk-through sprinkler systems have been used to spray disinfectant directly onto shoppers as they enter markets. [4] Due to the high transmissibility of the coronavirus, many people are scrambling to find solutions to control its spread even when the benefits are still unclear.

[0031] Like many respiratory viruses, coronaviruses spread through respiratory droplets. This means that when people are in an area, sneezing, talking, and coughing can deposit respiratory droplets on surfaces. On normal surfaces, these droplets will retain any virus already embedded in a stable form when using commercially available disinfectant sprays, until the disinfectant spray is applied, or some time after application (potentially up to 2 to 3 days). Permanent antiviral films have been investigated to help control the spread of SARS-CoV-2. Permanent films have specific adhesion requirements to the surfaces they are applied to prevent delamination. Furthermore, these films are primarily designed to prevent surface wetting as an indirect measure against viral transmission, rather than directly inactivating viral species. RAD compositions have the ability to maintain surface disinfection for a longer period compared to currently available surface disinfection capabilities. Permanent disinfectant films are difficult to adapt to existing surfaces and may require replacement / modification of components or materials to provide their benefits. When commercially available, RAD compositions combine the advantages of commercially available sprays and films, providing the acute disinfection capabilities of a spray with little to no durability and some of the advantages of a permanent film.

[0032] The Centers for Disease Control and Prevention (CDC) has developed guidelines for surface disinfection in childcare facilities through the National Center for Child Health and Early Education Health and Safety. [6] The recommended disinfection schedule includes guidelines for before use, after use, and daily (at the end of each day), Table 1. It should be noted that this recommended schedule is linked from the COVID-19 Daycare Facility Guidelines on the CDC website. [7] The table selects frequently touched surfaces that may contribute to the spread of the coronavirus. Many of these are only recommended to be cleaned at the end of the day. Given the high infectivity of SARS-CoV-2 and the fact that many people are asymptomatic but are carriers of the virus, these cleaning measures are insufficient. They provide an opportunity for someone to sneeze, cough, or talk near the surface and deposit respiratory droplets without ever actually touching the surface physically. However, applying a RAD composition to extend the disinfection time after application would make this disinfection schedule more reliable in preventing the spread of the virus through surfaces.

[0033] Table 1: Routine schedule for cleaning, sanitizing and disinfection (adapted from [6])

[0034]

[0035]

[0036] Unlike other available surface disinfectants, the disclosed RAD compositions offer a capability currently lacking in surface disinfectants: a temporary, lasting disinfectant film. This feature makes RAD compositions an attractive alternative solution for consumers in high-risk locations for coronavirus transmission.

[0037] In one implementation, a rapid-acting disinfectant (RAD) spray is provided that controls the spread of viruses (e.g., SARS-CoV-2) through contact with contaminated surfaces. The RAD spray employs a selective medium containing rapidly reacting doped CNPs, whose oxidation reaction is designed to perform multiple disinfection mechanisms in parallel (Table 2). Figure 1 The operational concept of how the RAD composition works to combat respiratory viruses such as coronavirus reactive oxygen species (ROS) is shown, which is one of the mechanisms used in conjunction with other direct CNP surface reaction mechanisms (membrane peroxidation and S protein oxidation) to improve the disinfection rate and the disinfection efficiency of each individual CNP.

[14] The combination (synergistic effect) of disinfection mechanisms improves the overall disinfection rate, allowing for rapid and effective disinfection through multiple parallel pathways. Upon application, the disclosed RAD composition has the unique ability to generate a temporary, persistent disinfectant film on the surface to which it is applied. The CNP has a regenerative property that allows for persistent disinfection of the surface when it encounters a new virus from respiratory droplets or physical transmission. This provides an attractive solution for surfaces where permanent disinfectant films are not readily applied, allowing for application to a variety of surface types regardless of the ability of the surface to adhere the film. In one specific embodiment, the RAD composition is a solution that is able to control the spread of COVID 19 and other pathogens that come into contact with surfaces in a manner that is currently unavailable and unique as a disinfectant spray and a temporary film. These mechanisms will be discussed in more detail herein.

[0038] Table 2: Nano RAD is a fast-acting, residual disinfectant spray that provides continuous and safe disinfection for several days after initial application and surface disinfection.

[0039]

[0040] Currently, CNPs have been experimentally used in vitro as broad-spectrum antiviral agents. Due to their unique chemical properties (e.g., enhanced catalytic activity), they are being used as an alternative method for preventing viral infections. It is speculated that when nanoparticles are hydrated by biofluids (e.g., respiratory droplets), surface redox reactions generate ROS, accompanied by oxidative stress, inducing lipid peroxidation of the viral envelope, affecting viral stability, leading to oxidation of surface receptor proteins, thereby causing the virus to lose its infectivity (i.e., by modifying receptors to prevent host cell-virus interaction).

[0041] Different types of nanoparticles have been shown to be antiviral agents, such as gold, silver and cerium oxide. Among them, CNP has minimal or no toxicity to normal-typic cells and modulates redox-related cellular processes, enabling cell survival or death, and exhibits unique catalytic activity toward oxygen metabolites depending on the synthetic program. Cerium oxide can exist in two forms: 1) Ce2O3 with a hexagonal

[27] and 2) CeO2 with a cubic fluorite lattice. This endows nano-cerium oxide with the following properties: oxygen storage and release, catalysis [27, 28] and solar / fuel cell

[29] .

[0042] In the case of CNPs, the creation of oxygen vacancies leads to the positioning of two electrons in the 4f state. [27, 30, 31] This results in two coordinated cerium cations (from Ce) having a thermodynamically stable structure. 4+ To Ce 3+ ) / reduction of oxygen. [27, 31] Furthermore, at the nanoscale, the available surface area and orientation of the crystal plane in cerium nanoparticles highly modulate catalytic performance. It has been previously shown that the (100) plane family of cerium nanoparticles exhibits the highest reactivity due to their relatively high interatomic spacing in the crystal planes with the highest atomic density

[32] . This was previously illustrated by changing the morphology of cerium nanoparticles, which can be controlled by changing the synthetic method of preparation and determining Madelungenergies in different crystal planes

[34] .

[0043] These oxygen vacancies become sites of catalytic activity and vary with particle size.

[35] CNPs exhibit different enzyme-mimicking activities depending on their surface chemistry. Catalase-mimicking activity is high due to the presence of the +4 surface oxidation state, while superoxide dismutase activity is high due to the greater Ce content. 3+ And increase. Furthermore, CNP(Ce 3+ To Ce 4 These mixed valence states in CNPs have the ability to switch between oxidation states within the crystal system. When their valence states change, CNPs can scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS). In biological systems, important biological and environmental reactions occur through co-oxidants and antioxidants. Co-oxidants generate hydroxyl radicals (OH), hydrogen peroxide (H₂O₂), and superoxide anions (O₂O₂). - This can induce oxidative stress (which may destroy viruses). Under normal and carcinogenic conditions, catalytic CNPs are used to reduce reactive oxygen species in various organs of the body via redox reactions. [18, 38-40]

[0044] CNPs have been used as antimicrobial agents

[41] and antiviral agents.

[42] Cerium nanoparticles act as antibiotics by acting directly on bacterial structures or indirectly through chemical modification. CNPs can interact directly with the bacterial cell wall, leading to cell wall instability and lysis. Alternatively, the particles can act indirectly; reacting with intracellular chemicals and components. Each mechanism leads to bacterial cell death. At physiological pH, the positive charge on CNPs results in antimicrobial activity of antibacterial substances based on these mechanisms, mediated by initial membrane adhesion.[43, 44] In the case of viruses, the geometry and surface charge of CNPs play an important role as antiviral agents. By attaching CNPs to the viral surface prior to cell penetration / viral uptake, unique biochemical properties and virus-motivated intercellular cascades can be altered. Lozovski et al. demonstrated that narrow, small-sized CNP distributions have the most significant effect on viruses containing both DNA and RNA.[42, 45] This is due to the localized effect of released ions causing phosphatase-mimicking activity and interference with calcium-dependent membrane processes. Furthermore, these ionic substances have been shown to modulate metabolic processes, particularly in or near mitochondria (e.g., electron transport chain events).

[46] CNPs readily attach to phosphate groups, resulting in inorganic, insoluble cerium phosphate.

[47] In addition, CNPs have been shown to accelerate the breaking of highly resistant phosphodiester bonds in nucleic acids.

[46] When CNPs interact with cell surface proteins, they can lead to alterations in cell surface properties. These may include the colloidal properties of membranes and their fluidity, thereby affecting the ability of viruses to enter living cells. Specially designed nano-cerium oxide, with or without silver doping, is a candidate for comprehensive antiviral therapy and inactivation of surface contamination caused by emerging COVID-19 and other viruses and pathogens.

[0045] Description of the embodiments

[0046] This invention describes cerium oxide nanoparticles doped or otherwise bonded to metals such as silver, gold, copper, platinum, nickel, iron, titanium, ruthenium, vanadium, etc. The use of metal and metal oxide nanomaterials has been investigated in various antibacterial / antiviral applications, providing a broader basis for understanding pathogen toxicity. Transition metal-based materials have demonstrated excellent broad-spectrum antibacterial activity and antiviral efficacy.

[0047] mCNPs can be spherical, rod-shaped, star-shaped, or polygonal. In a preferred embodiment, the mCNPs are spherical, meaning they are more or less approximately spherical. Preferably, the average diameter of the spherical mCNPs is about 24 nm or less, about 20 nm to about 24 nm, or about 3 nm to about 5 nm. In one embodiment, the average diameter of the spherical cerium oxide nanoparticles, measured by transmission electron microscopy, is 3 nm to 5 nm. In embodiments where the mCNPs are not spherical, the average size between the two opposite sides of the nanoparticles is preferably 24 nm or less.

[0048] mCNP has a cerium oxide core with an outer surface. This surface is characterized by the percentage of Ce(3+) ions relative to Ce(4+) ions thereon. While not intended to limit the amount used, some preferred ranges for the Ce(3+):Ce(4+) percentage when used in the methods of the present invention are: about 80%:20% to about 20%:80%, about 75%:25% to about 25%:75%, about 60%:40% to about 25%:75%, or about 57%:43% to about 27%:73%. In some embodiments, the percentage of Ce(3+) relative to Ce(4+) is >50% Ce(3+).

[0049] Silver-associated cerium oxide nanoparticles

[0050] This disclosure includes two different types of nanoparticles, AgCNP1 and AgCNP2. In some embodiments, a combination of the two exists because they appear to have slightly different modes of action. The silver-modified cerium oxide formulation (AgCNP) is synthesized using two distinct formulations (AgCNP1, AgCNP2), each utilizing a different chemical reaction against an aqueous silver solution. AgCNP1 is synthesized via a previously developed two-step method ( Figure 3A , Figure 4 This synthesis can be scaled up or down to a large or small process. In short, a solution containing AgCNP-like components, silver-modified cerium oxide nanoparticles, and silver secondary phases is formed via an alkaline forced hydrolysis reaction. The product material is washed with deionized water (dH₂O) and then treated with ammonium hydroxide. Ammonium hydroxide acts as an etchant and a phase-transfer complex: mediating the dissolution / stabilization of silver ions dissolved in the aqueous phase. Specifically, this reaction leads to the formation of Tollens' reagent (Ag[(NH₃)₂OH)₂). aq The resulting single-particle solution was then washed with dH₂O to remove excess alkali and counterions / bystander ions. AgCNP₂ utilizes the stability of silver ions to hydrogen peroxide oxidation (…). Figure 3BSpecifically, cerium nitrate and silver nitrate are dissolved, followed by the addition of hydrogen peroxide, which leads to the selective oxidation of silver by cerium ions, transforming into a metallic silver phase on the cerium oxide surface. The unique synthesis conditions of these particles suggest potentially entirely different particle properties. In some embodiments, the synthesis can be scaled up to large or small methods.

[0051] Examples of small-scale methods for AgCNP2:

[0052] 1. Dissolve 109 mg of cerium nitrate hexahydrate (99.999% purity) in 47.75 mL of dH2O at the bottom of a 50 mL square glass container.

[0053] 2. Add 250 μL of 0.2 MgNO3 (99% purity) aqueous solution to the above cerium solution and vortex the solution for 2 minutes: machine: vortexer.

[0054] 3. From here, quickly add 2 mL of 3% hydrogen peroxide (reserve) to the above solution, and then immediately vortex at the highest speed for 2 minutes (in a vortex mixer).

[0055] 4. The solution was stored at room temperature in the dark, with the bottle (50 mL square-bottomed glass) cap loosened to allow the release of the gradually forming gas; under these conditions, the solution was aged for up to 3 weeks (monitoring the color of the solution from yellow to clear) to produce a total volume of 50 mL of solution.

[0056] 5. Then dialyze the granules with 2L dH2O for more than 2 days (dialysis tube), changing the water every 12 hours, and store them under the same conditions as aging.

[0057] Two unique formulations of cerium oxide nanoparticles were produced using surfaces modified with silver nanophases. Material characterization revealed that the silver components in each formulation were distinct from each other, decorating the cerium oxide surface as numerous small nanocrystals (AgCNP1) or as a Janus-type two-phase structure (AgCNP2). Preferably, the average diameter of AgCNP1 was about 20 to 24 nm, and the average diameter of AgCNP2 was about 3 to 5 nm. Each synthesis also possessed a unique mixture of valence atoms relative to Ce on AgCNP2. 4+ AgCNP2 has a significantly larger proportion of Ce 3+The unique valence characteristics and the combination of chemically active silver phases result in high catalytic activity for each formulation. AgCNP2 exhibits high superoxide dismutase activity, while AgCNP1 possesses both catalase and superoxide dismutase-like mimicry activities, attributed to the catalase activity of cerium oxide and the superoxide dismutase activity derived from the silver phase. Furthermore, electrochemical analysis revealed that silver incorporated into each formulation is substantially more stable against redox-mediated degradation compared to the pure silver phase, contributing to increased lifetime in catalytic applications. The use of each formulation in influencing antiviral properties demonstrates the specific activity of each: among the virus species tested, AgCNP1 showed significant activity against OC43 coronavirus, and AgCNP2 showed activity against RV14 rhinovirus. In-situ electrochemical impedance spectroscopy collected for each virus / particle system during their respective incubation periods reflects the unique interactions observed for each pair. Each equivalent circuit component, along with the developed model / test system (using simulated virus-like particles, model proteins, and oxygen radical-generating enzyme / substrate systems), demonstrates the mode of action of pairing influencing antiviral responses. The results of these studies identify the primary physical interaction mechanism for OC43 / AgCNP1 and the oxidative and chemical interactions for RV14 / AgCNP2.

[0058] While not intended to limit the amount used, when used in the methods of the present invention, a preferred amount of silver percentage related to AgCNP is from about 6% to about 10% or less.

[0059] Implementation of the composition

[0060] In one embodiment, a dispensable composition comprising mCNP (e.g., AgCNP) and excipients is provided. Examples of excipients include solvents, such as, but not limited to, water or aqueous (water-based) solutions (where water is at least the major component), lower alcohols (C6 or lower), lower diols (C6 or lower), THF, DMSO, DMF, etc. They can be used alone or as mixtures of various components with water. Examples that do not constitute a limitation on non-aqueous carriers or mixtures thereof are chloroform, dichloromethane, acetone, methyl ethyl ketone, cyclohexane, ethyl acetate, diethyl ether, lower alcohols (C4 or less), lower diols (C4 or less), THF, DMSO, and DMF.

[0061] The dispensable composition may also include fragrances. Examples of fragrances include, but are not limited to, lemon oil, orange oil, bergamot oil, ylang-ylang oil, patchouli oil, lemongrass oil, boad rose oil, clove oil, eucalyptus oil, cedarwood oil, lavender oil, natural fragrances such as sandalwood oil, vetiver oil, geranium oil, limonene oil, peppermint oil, rose oil, jasmine oil, and litz accubeba oil; hydrocarbon fragrances (e.g., limonene, α-pinene, camphene, p-cymene, phen Chen, etc.); and ether fragrances (e.g., 1,8-cineole, rose oxide, cedrol methyl ether). Bar), p-cresol methyl ether, isopentylphenyl ethyl ether, 4-phenyl-2,4,6-trimethyl-1,3-dioxane, anethole, etc.), S-class fragrances (e.g., ethyl acetate, ethyl propionate, methyl butyrate, ethyl isobutyrate, ethyl butyrate, butyl acetate, ethyl 2-methylbutyrate, isopentyl acetate, ethyl 2-methylvalerate (manganate)), hexyl acetate, allyl hexanoate, tricyclodecenyl propionate (VERTOPRO; fluorocycloene), allyl heptaate, isoborneol acetate, linaloyl acetate, citronellol acetate, 2-tert-butylcyclohexyl acetate (narcidol), etc.), alcohol fragrances (e.g., linolenic acid, 3-octanol, 2,6-dimethyl-heptanol, 10-undecenol, geraniol, nerol, citronellol, rosin oil, mill Senol, tetrahydrolinalool, thymol, terpineol, cedrol, 2,4-dimethyl-3-cyclohexane-1-methanol, 4-isopropylcyclohexanol, nerolidol, 9-decenol, cis-3-hexenol, trans-2-hexenol, eugenol, etc.), aldehyde fragrances (e.g., citronellol, secondary aldehyde, benzaldehyde, aldehyde C-6, aldehyde C-7, aldehyde C-8, aldehyde C-9, aldehyde C-10, tripral, p-ethyldimethylhydrocinnamaldehyde, etc.), synthetic fragrances (e.g., floralzone, 2-tridecenal, aldehyde C11, etc.) or blended fragrances with these.

[0062] According to other implementations, as taught herein, the substrate can be coated with a thin film of metal-associated cerium oxide nanoparticles. The substrate can take the form of any surface on which human contact is made or on which exhaled droplets are typically placed, such as paper towels, toilet paper, countertops, HVAC filters, air purifiers, electric fans, refrigerators, microwave ovens, dishwashers / dryers, rice cookers, pots, pot lids, IH heaters, washing machines, vacuum cleaners, lighting fixtures (lamp, appliance body, lampshade, etc.), hygiene products, toilets, washbasins, mirrors, bathrooms (walls, ceilings, floors, etc.), building materials (interior wall, ceiling materials, flooring, exterior walls, etc.), interior products (curtains, carpets, tables, chairs, sofas, shelves, beds, bedding, etc.), eyeglasses, belts, handrails, doors, knobs, clothing, filters for household appliances or similar products, stationery, kitchenware, medical supplies (coats, masks, gloves, etc.), medical devices and equipment, and materials used in the interiors of automobiles, trains, airplanes, small boats, and ships. Examples of substrate materials include glass, ceramics, plastics, resins (such as acrylic resins), paper, fibers, metals, wood, etc.

[0063] In another embodiment, antiviral foams can also be produced for a variety of applications. For example, polyurethane foams can be manufactured using a formulation produced by mixing isocyanate with a polyol (a molecule having three or more hydroxyl groups), a chain extender (a bifunctional hydroxyl molecule), a catalyst to promote the reaction, a surfactant, a heat and / or UV stabilizer, and a blowing agent. The blowing agent can be water, as it produces carbon dioxide gas when it reacts with the isocyanate. Methods for manufacturing antiviral foams include producing metal-associated cerium oxide nanoparticles using a surfactant (using a surfactant compatible with the system or the same surfactant used in the system) or a urethane forming component, and adding these to the foam formulation. Another alternative method involves producing the nanoparticles in an aqueous medium, for example by mixing them with a desired surfactant in water, and then adding this aqueous mixture as both a blowing agent and an antiviral source to the foam formulation.

[0064] According to other embodiments, antiviral inks comprising cerium oxide nanoparticles bonded to silver or another metal can be formed using techniques known in the field of printing inks. Such inks can be printed using a variety of techniques, such as inkjet printing, aniline printing, gravure printing, and screen printing. In some cases, such as inkjet printing, the size of the functionalized particles should be less than about 50 nm. Three-dimensional antiviral products (mask materials and normally contacted hard objects) can be formed by 3D printing, wherein the 3D printed composition contains antiviral materials taught herein, such as AgCNP.

[0065] Spray formulations

[0066] This invention also includes a spray formulation of nano-RADs. In typical embodiments, the formulation comprises nano-RADs, a desiccant, an organic acid, a surfactant, water, and a polymer binder. In some embodiments, the nano-RAD may contain one or more mCNPs, depending on the desired sterilization mechanism. When applied to a substrate, the nano-RAD spray produces a sterilizing film. In some embodiments, the amount of nano-RAD is about 0.01 to 10% by weight. In some embodiments, the amount of the desiccant (such as ethanol or isopropanol) is about 0 to 40% by weight. In some embodiments, about 0.5 to 2% by weight of citric acid or other organic acid is provided to the spray formulation. Other desiccants include alcohols or mixtures of alcohols, such as ethanol, isopropanol, n-propanol, and mixtures thereof; fatty alcohols, including but not limited to cetyl alcohol, myristyl alcohol, stearyl alcohol, octanol, decanol, and lauryl alcohol, and mixtures thereof; hexanol and / or other aliphatic or aromatic alcohols. Organic acids that may be used in the disclosed compositions include, but are not limited to, lactic acid, citric acid, salicylic acid, glycolic acid, mandelic acid, benzoic acid, and combinations thereof.

[0067] The nano-RAD can also be mixed with compatible surfactants, diluents, and polymer binders selected according to the application. Surfactants can act as detergents, wetting agents, emulsifiers, foaming agents, or dispersants. In some embodiments, the amount of surfactant is about 0.5 to 3% by weight. Suitable surfactants are, for example, laurylamine oxide, myristamine oxide, other amphoteric agents, tergitol 15-S-15, or other secondary alcohol ethoxylates. In some embodiments, the amount of laurylamine oxide is about 0.25 to 2% by weight, and the amount of tergitol 15-S-15 is about 0 to 1% by weight. In some embodiments, a suitable diluent is water, in an amount of about 15 to 45% by weight. The polymer binder is used to produce transparent, flexible, oxygen-permeable films that adhere to glass, plastics, and metals. Suitable polymer binders are, for example, poly(2-ethyl-2-oxazoline) or polyvinylpyrrolidone (PVP)-vinyl acetate copolymers. In some embodiments, the amount of PVP-vinyl acetate copolymer is about 1 to 30% by weight. In some embodiments, the amount of poly(2-ethyl-2-oxazoline) is about 1 to 25% by weight.

[0068] Other polymers suitable for the disclosed compositions include polyox hydrogel polymers, stearyl alcohol, cellulose polymers, cationic hydroxyethyl cellulose (e.g., Ucare; JR30), hydroxypropyl methylcellulose, hydroxypropyl cellulose (Klucel), chitosan pyrrolidone carboxylate (Kytamer), behenyl alcohol, zinc stearate, emulsified waxes (including but not limited to Incroquat and Polawax), addition polymers of acrylic acid, and resins (such as... ETD 2020), Guar gum, gum arabic, acrylate / stearyl ether-20 methacrylate copolymer, agar, alginate, alginic acid, ammonium acrylate copolymer, ammonium alginate, ammonium chloride, ammonium sulfate, amylopectin, attapulgite, bentonite, C9-15 alcohol, calcium acetate, calcium alginate, calcium carrageenan, calcium chloride, octanol, carbomer 910, carbomer 934, carbomer 940P, carbomer 940, carbomer 941, carboxymethyl hydroxyethyl cellulose, carboxymethyl hydroxypropyl guar gum, carrageenan, cellulose, cellulose gum, cetearyl alcohol, cetyl alcohol, corn starch, dammar resin, dextrin, diphenylamine sorbitol, ethylene dihydrogenated shea butteramide, ethylene diamide, ethylene distearate, gelatin, guar gum, guar gum hydroxypropyltrimethylammonium chloride, lithium montmorillonite, hyaluronic acid, hydrated silica, hydroxybutyl methyl... Fiberglass, hydroxyethylcellulose, hydroxyethyl ethylcellulose, hydroxyethyl stearamide-MIPA, isocetyl alcohol, isostearyl alcohol, ebony gum, kelp, lauryl alcohol, soybean gum, magnesium aluminum silicate, magnesium silicate, magnesium trisilicate, methoxy polyethylene glycol (PEG)-22 / dodecyl glycol copolymer, methylcellulose, microcrystalline cellulose, montmorillonite, myristyl alcohol, oat flour, oleyl alcohol, palm kernel alcohol, pectin, PEG-2M, PEG-5M, polyacrylic acid, polyvinyl alcohol, potassium alginate, potassium aluminum polyacrylate, potassium carrageenan, potassium chloride, potassium sulfate, potato starch, propylene glycol alginate, sodium acrylate / vinyl alcohol copolymer, sodium carboxymethyl dextran, sodium carrageenan, sodium cellulose sulfate, sodium chloride, sodium polymethacrylate, sodium aluminosilicate, sodium sulfate, stearalkonium bentonite, stearalkonium hydrate Hectorite, stearyl alcohol, tallow, triethylamine hydrochloride, tragacanth gum, tridecanol, magnesium aluminum trimethylamine silicate, wheat flour, wheat starch, xanthan gum, rosin alcohol, linoleic acid acrylate, aluminum behenate, aluminum octanoate, aluminum di-linoleate (such as aluminum distearate and aluminum isostearate), beeswax, behenamide, butadiene / acrylonitrile copolymer, C29-70 acid, calcium behenate, calcium stearate, candelilla wax, palm wax, ceresin, cholesterol, cholesterol hydroxystearate, coconut alcohol, copal, glyceryl distearate malate, dihydroabiol, dimethyl laurylamine oleate, lauric acid / cetyl alcohol Ethyl alcohol / ethylene glycol copolymer, erucamide, ethyl cellulose, triacetyl hydroxystearate, triacetyl ricinoleate, ethylene glycol dibenzenehexyl ester, ethylene glycol di-octanoate, ethylene glycol distearate, hexanediol distearate, hydrogenated C6-14 olefin polymer, hydrogenated castor oil, hydrogenated cottonseed oil, hydrogenated lard, hydrogenated herring oil, hydrogenated palm kernel oil glycerides, hydrogenated palm kernel oil, hydrogenated palm oil, hydrogenated polyisobutylene, hydrogenated soybean oil, hydrogenated shea butter amide, hydrogenated shea butter glycerides, hydrogenated vegetable oil glycerides, hydrogenated vegetable oil, Japanese wax, jojoba wax, lanolin alcohol, shea butter, lauryl amide.Methyl dehydrorosinate, methyl hydrogenated rosinate, methyl rosinate, methyl styrene / vinyl toluene copolymer, microcrystalline wax, montmorillonite wax, montmorillonite wax, tetradecanoic acid wax, myristyloctadecanol, octadecene / maleic anhydride copolymer, octadecyl stearyl stearate, oleamide, oleostearine, small crown coconut wax, oxidized polyethylene, ceresin, paraffin wax, pentylenetetrazol. Hydrogenated rosin esters, pentaerythritol tetracaprylate, pentaerythritol rosin ester, pentaerythritol tetrarosin ester, pentaerythritol tetrabenzyl ester, pentaerythritol tetraoleate, pentaerythritol stearate, ophthalmic anhydride / glycerol / capric acid glycidyl ester copolymer, ophthalmic / triphenyltrihydride / ethylene glycol copolymer, polybutene, polybutylene terephthalate, polydipentene, polyethylene, polyisobutylene, polyisoprene, polyvinyl butyral, polyvinyl alcohol laurate, didecanoate, di... Propylene glycol diisocyanate, propylene glycol diisocyanate, propylene glycol dilaurate, propylene glycol dinonanoate, propylene glycol distearate, propylene glycol icosanoate, PVP / eiconsene copolymer, PVP / hexadecene copolymer, rice bran wax, ammonium bentonite stearate, lithium octadecylammonium montmorillonite (hydrazine), stearamide, stearamide DEA-distearate, stearamide DIBA-stearate, stearamide MEA-stearate Fatty acid esters, stearyl ketone, stearoyl erucamide, octadecyl stearate, glyceryl stearoyl stearate, synthetic beeswax, synthetic wax, trihydroxystearic acid, triisononanoin, triisostearic acid, triisostearic acid trilinoleic acid tri ... Examples include, but are not limited to, guar gum, yellow polysaccharide gum, alginate (E400), sodium alginate (E401), potassium alginate (E402), ammonium alginate (E403), calcium alginate (E404 - brown algae polysaccharide), agar (E406, a polysaccharide obtained from red algae), carrageenan (E407, a polysaccharide obtained from red algae), locust bean gum (E410, a natural gum derived from raspberry seeds), pectin (E440, a polysaccharide obtained from apples or citrus fruits), gelatin (E441, partially hydrolyzed from animal collagen), and 1,5-pentanediol 4-t-enylcyclohexanol (Symsitive 1609).

[0069] Examples of pump spraying compositions:

[0070] • 0.01-5% by weight of nano-RAD (active)

[0071] • 0-40% by weight of ethanol (isopropanol or other desiccant)

[0072] • 0.5-2% citric acid by weight

[0073] 0.5-3% surfactant

[0074] • 0.25-2% laurylamine oxide (myristylamine oxide or other amphoteric agents)

[0075] • 0-1% Tergitol 15-S-15 (Nonionic surfactant: secondary alcohol ethoxylate)

[0076] 15-45% water

[0077] • 1-25% poly(2-ethyl-2-oxazoline) (polymer binder) or similar polymer

[0078] In some implementations, the nano-RAD aerosol formulation produces a rehydrated film upon application and exhibits potentially sustained disinfection behavior upon rehydration. AgCNP can extract water from gaseous water particles for reactivation, and the polymer film produced by the aerosol formulation is also hydrophilic, which facilitates the use of a water layer on the surface of the gaseous water particles for reactivation disinfection.

[0079] According to other embodiments, a container is provided having a pump for dispensing the composition described herein. The pump can be designed in any manner that meets the limitations of the composition and the container, and dispenses the composition in a desired manner. Furthermore, the pump may include tubing extending into the container, thereby facilitating the pump's ability to dispense liquids. Those skilled in the art will understand that pumps including optional tubing, nozzles, etc., can be in fluid communication with the composition within the container. The pump can also be designed to be "detachably coupled" to the container, meaning it can be detached from and reconnected to the container once or multiple times.

[0080] Another embodiment relates to an apparatus comprising a container portion for receiving a quantity of the dispensable composition disclosed herein and a nozzle. In a specific embodiment, the apparatus includes a container adapted to receive the composition; and a pump coupled to the container, the pump including the nozzle and in fluid communication with the composition, the pump being configured to dispense the composition from the nozzle by injecting air into the container to displace the composition. In a specific embodiment, the pump also includes a tube extending into the container and in fluid communication with the composition.

[0081] In another embodiment, the device includes a fluid-sealed container pressurized with propellant and a valve for dispensing a dispensable composition upon activation. Suitable propellants for dispersing the composition are well known in the art. Common examples of propellants include, but are not limited to, hydrocarbons, ethers, compressed gases, chlorofluorocarbon propellants, liquid propellants, or mixtures thereof.

[0082] Some examples of the types of distribution containers that can be used in accordance with the teachings herein include, but are not limited to, the types of devices disclosed in U.S. Patent Nos. 3,061,202, 3,986,644, 4,669,664, 5,358,179, 3,995,778, 4,202,470, 3,992,003, Chinese Patent No. 1042,213, U.S. Patent Publication No. 20,180,370,715, U.S. Patent No. 2,863,699, and U.S. Patent No. 3,333,743.

[0083] Biocompatibility and safety

[0084] Recognizing the interest in the toxicology of cerium oxide nanoparticles, the reactivity of cerium salts has been studied, which has sparked interest in the toxicology of cerium oxide nanoparticles

[21] . Another study examined changes in the surface charge and size of CNPs and their effects on cellular uptake.

[48] In addition, another study was conducted using fluorescent conjugates of CNPs to analyze the kinetics and subcellular localization of cerium oxide nanoparticles.

[49] Since bare oxide nanomaterials may not be as biocompatible in mammals as soft materials, a study focused on PEG functionalization was conducted to determine whether polyethylene glycolation would alter the catalytic properties of CNPs, but it did not.

[50]

[0085] There are various methods for synthesizing nano-cerium oxide particles, including wet chemical methods, solvothermal methods, microemulsion methods, precipitation methods, hydrolysis methods, and hydrothermal methods. [51, 52] Depending on the synthesis method used, these nanoparticles range in size from 3-5 nm to over 100 nm and have surface charges ranging from -57 mV to +45 mV. The synthesis method can also affect the shape of the CNPs. Coatings and surfactants may also be present and contaminate the formulation, such as cyclohexamethylenetetramine (HMT)

[53] or ethylene glycol.

[54] Many studies reporting the toxicity of nano-cerium oxide have focused on NPs produced by hydrothermal methods. This type of CNP often has sharp edges that can cause cell damage.

[55] However, CNPs synthesized by a wet chemical formulation are more biocompatible and have almost zero toxicity. This lack of toxicity has been observed in human umbilical vein endothelial cells (HUVECs).

[56]

[0086] Although it is a nontoxic, neutral pH normal cell, it remains highly effective in killing cancer cells due to the acidic chemical environment and the pH-sensitive redox activity of nano-cerium oxide

[57] . The protective effects of these CNPs previously reported have also been observed. In a review article, 38 reports demonstrated the protective effects of CNPs in cell culture and animal studies.

[51] It should be noted that many cell types and animal models have been exposed to nano-cerium oxide and have shown beneficial effects. These cells include RAW 264.7 macrophages, BEAS-2B lung cells, H9c2 cardiomyocytes, A549 lung cells, HT22 hippocampal neurons, organoid neurons, and many others. Animal models include Tubby mutant mice, EAE models, C57BL / 6 mice, diabetic Wistar rats, and ectopic tumor mouse models.

[0087] Example

[0088] Example 1 : Formulation of pure phase and silver-modified cerium oxide nanoparticles to induce ROS in simulated biological fluids.

[0089] COVID-19 and other influenza-like viruses pose a substantial threat to human health due to the high infectivity of the biofluids released by infected individuals. Human-to-human infection is particularly evident in first-response and medical settings due to contact with contaminated surfaces in highly trafficked areas. Current disinfection measures are either unavailable in these settings or exhibit limited effectiveness due to mechanical kinetic limitations. Studies have shown that nano-cerium oxide and silver-nano-cerium oxide exhibit ROS-inducing effects at high reaction rates due to nanoscale / surface effects in the presence of virus-laden biofluids. The generated ROS induces significant oxidative stress, leading to membrane peroxidation and cytolysis, as well as oxidation and inactivation of viral cell receptor surface structures, resulting in viral inactivation. Literature on nanophase silver and cerium oxide presents speculative ROS-generating reaction schemes under relevant conditions (see FIG1).

[0090] 2Ag (0) +O2+H2O→Ag2O+O2 - +2H +

[0091] 2Ce 3+ +Ag₂O + 2H⁺ + →2Ce 4+ +2Ag (0) +H2O / free radical initiation

[0092] (i)O2 - +Ag₂O + 2H⁺ + →H₂O₂ + Ag₂O / Surface diffusion; Superoxide combination

[0093] (ii)O2 - +2H₂O+Ce + →H₂O₂ + Ce 4+ SOD activity simulation based on cerium oxide

[0094] (iii)O2 - +Ce 3+ +2H + →H₂O₂ + Ce 4+ / Cerium oxide SOD simulated activity

[0095] AgO x +H₂O₂→Ag + +H2O+H + Peroxide-mediated oxidative dissolution

[0096] 1.1 Particles were synthesized and preliminarily characterized using various solution-based methods. Given the strong influence of the chemical environment on the surface chemistry of nanomaterials and the cerium redox ratio (i.e., involving Ce) demonstrated in the nanomedicine literature as promoting the formation of unique ROS, 3+ and Ce 4+ The effect of fraction (relative material composition) on several synthetic methods was investigated. Pure-phase cerium oxide nanoparticles were synthesized through several unique methods that have previously been shown to induce ROS generation. In one embodiment, a hydrogen peroxide-based oxidation reaction was used to produce high Ce content. 3+ / Ce 4+ A proportionate nano-cerium oxide formulation was prepared. Specifically, cerium nitrate hexahydrate was dissolved in water to a concentration of 5 mM, followed by the addition of 3% hydrogen peroxide under stirring. The particles were allowed to stand for a period of time to allow the cerium oxide surface to degrade excess peroxide.

[0097] To produce products richer in Ce 4+The formulation was synthesized a second time using a forced hydrolysis method. Specifically, the particles were formed from cerium nitrate hexahydrate precursors in an aqueous solution. Hydrogen peroxide limited the formation of the metallic phase and the silver oxide phase (i.e., preventing the formation of secondary, dissimilar silver nanophases). Therefore, some syntheses utilized peroxides as oxidants in the silver-modified cerium oxide nanoparticle formulation. First, the formulation was produced in situ, in which cerium nitrate and silver nitrate were dissolved, then directly oxidized by hydrogen peroxide, and aged to allow degradation of the peroxides via catalytic degradation of the cerium oxide surface. Second, a mixed forced hydrolysis method was performed, in which the dissolved salts were first oxidized by peroxides, followed by precipitation by the addition of 30% ammonium hydroxide. The particles were collected by centrifugation at 10,000 rpm and washed three times with deionized water. The combination of direct peroxide-mediated oxidation and forced hydrolysis mediated the change in the redox ratio of cerium. Third, a solution was prepared in which co-dissolved cerium nitrate and silver nitrate underwent ammonium hydroxide-mediated oxidation / precipitation, followed by washing and resuspending in deionized water. From here, hydrogen peroxide is added, and the solution is allowed to stand with stirring to promote the dissolution of the secondary phase silver nanomaterials. The particles are then washed to remove ionized silver. Oxide particles are formed via a unique chemical reaction through oxidation with peroxide or ammonium hydroxide, which strongly influences the product silver-cerium nanoparticles. The effect of silver fraction (mass percentage; 2%, 5%, 10%, 20%) was investigated in each nanomaterial candidate formulation. Particle size and surface charge were evaluated by dynamic light scattering and zeta potential measurements. Furthermore, silver phase characteristics and Ce... 3+ / Ce 4+ Qualitative evaluation was performed by monitoring peaks at approximately 320 nm and 252 / 298 nm, respectively. Figure 4 ).

[0098] 1.2 The ROS generation chemical activity of the formulations generated in 1.1 was analyzed. Specifically, the activities of catalase and superoxide dismutase were assessed using standard bioassay kits. Hydroxyl radical generation activity was assessed by analyzing the degradation of the added methylene blue dye. Assays were performed in model biological fluid solutions (e.g., NaCl / HCl buffer at pH 6, room temperature). Reaction rates associated with each reaction were collected and compared. The effect of silver release / ionization in these reactions was evaluated. Ionization reactions were first monitored by UV-Vis measurements at constant time points (i.e., analysis of silver ion peak evolution), followed by spectroelectrochemistry (i.e., monitoring UV-Vis peak characteristics while performing galvanometry and voltammetry / Tafel analysis at open-circuit potential to detail the silver corrosion process). Furthermore, the effect of chloride concentration on the reaction (rate) was determined by titration and Tafel analysis. The efficacy of nanomaterials in inducing lipid peroxidation was analyzed using a commercial lipid peroxidation assay kit (MDA assay). The collective results of these studies were used to modify the synthesis parameters in 1.1 to generate Ag-CNP formulations with high reaction rates that induce ROS production.

[0099] Example 2: Characterization of nanoparticles and analysis of efficacy and toxicity.

[0100] Preliminary work on CNPs has demonstrated which forms of CNP lead to different types of biological behavior. It has been shown that both CNPs and Ag-CNPs produce ROS, which inactivates the phospholipid bilayer of enveloped viruses—leading to rapid and widespread cytolysis and inactivation of these viruses, preventing them from infecting cells.

[0101] 2.1 Characterization of formulations exhibiting high ROS generation reaction rates in terms of size, morphology, and chemical composition. High-resolution transmission electron microscopy (hrTEM; to visualize the size, morphology, and particle characteristics of nanomaterials), small-angle X-ray diffraction (SAXS; to characterize the crystallization characteristics of silver and cerium oxide phases), and X-ray photoelectron spectroscopy (XPS; to analyze / evaluate chemical composition, cerium redox ratio, and silver oxidation / chemical environment, such as… Figure 2 (As shown).

[0102] 2.2 CNP and Ag-CNP were assessed for reduced infectivity from viral suspensions using plaque assays or TCID50 assays. From this, RT-PCR was used to analyze the viral genome. Dose- and time-dependent viral inactivation was established for each formulation.

[0103] Two methods were used to determine the ability of CNP and Ag-CNP to inactivate a range of human pathogenic viruses. First, different concentrations of virus were incubated in solutions of fixed concentrations of CNP or Ag-CNP. At different times after mixing, samples were removed from the samples, diluted, and analyzed for residual infectivity. Whether a plaque assay or TCID50 was used depended on the virus. Real-time PCR was used to determine residual particles (regardless of infectivity). Samples were analyzed in triplicate, and data are expressed as fold change in infectivity compared to the initial virus levels shown in our previous publications. [61, 62] Temperature was a major factor in viral stability and was tested along with incubation time and the concentration of CNP or Ag-CNP.

[0104] First, the above tests were performed using a prototype laboratory strain of coronavirus to enable rapid progress and demonstrate productivity. To determine the antiviral specificity of CNP, virus #2 (Zika virus) was tested to determine whether other enveloped positive-sense RNA viruses with structures similar to CoV were also sensitive to inactivation. Virus #3 (rhinovirus) was tested to see if sensitivity extended to positive-sense RNA viruses lacking a lipid bilayer. Virus #4 (influenza A virus) was tested to see the sensitivity of enveloped negative-sense RNA viruses, the results of which would influence the mechanism of action. Virus #5 (vaccinia virus VV) was tested to see the inactivation of DNA-encapsulated viruses. Based on published work showing that VV is more resistant to chemical treatment than RNA viruses

[61] (Bracey et al., 2019), a sensitivity gradient is expected to emerge - CoV > influenza > VV. Results for non-enveloped rhinoviruses will be important as they will guide future research on whether inactivation is lipid-dependent or nucleic acid-dependent.

[0105] If inactivation of any enveloped RNA virus (e.g., coronavirus, Zika virus, influenza virus) is observed, it indicates that the envelope has been disrupted by CNP or Ag-CNP. This involves sedimentation of a sucrose gradient in a sample comprising individual CNPs, individual viruses, and incubated CNP plus virus as identified above. After centrifugation, the fractions are collected and the location of the viral fractions is analyzed by Western blotting. Intact viruses precipitate near the bottom of the tube, while broken viral bodies remain at the top of the gradient. Direct interaction between CNPs and viral bodies is detected by crosslinking experiments and testing the gradient fraction of CNPs co-precipitated with particles.

[0106] Example 3: Formulation of optimized silver-modified cerium oxide nanoparticle aerosols and carrier components.

[0107] The dispersion of disinfectants mediated by aerosols or pump sprays allows for rapid and widespread deployment onto general surfaces without significant consideration for material properties or topology. Incorporating Ag-CNP into aerosols or sprays provides a portable system for general surface disinfection, offering high disinfection rates and persistent disinfectant activity even after drying. Furthermore, the storage of this nanomaterial in an aerosol medium facilitates the long-term preservation of its active ingredients, thus maintaining activity before administration.

[0108] 3.1: Ag-CNPs were dispersed in solvents of varying volatility (e.g., alcohols, ethers). Depending on the particle preparation method, dispersion was accomplished either by suspending the particles in a candidate dispersant after a washing step, or by dialysis to remove the aqueous phase. Colloidal stability was assessed using dynamic light scattering (i.e., measuring the solubility-dynamic radius and aggregation characteristics of the particles relative to hrTEM measurements as a function of size) and zeta potential (surface solvent coordination affects stability; a zeta potential >25 mV is considered highly stable). Harmless ligands (e.g., small, non-reactive, polar organic substances such as sugars) could be added to confer better stability by harmonizing the particle surface. The optimal dispersant (or propellant) was based on greater volatility (thus enabling efficient hydration mediated by a virus-containing biofluid after spraying) and the colloidal stability of the nanoparticles.

[0109] 3.2 Ag-CNP was suspended in a dispersant medium and diluted in a biofluid model solution. ROS generation was monitored by analyzing changes over time to estimate the efficiency of the carrier medium during vaporization. Reaction rates were compared to their activity in the pure model medium.

[0110] Example 4: Optimization of formulations for surface and thin film performance.

[0111] Different methods are possible for forming temporary films from formulation solutions. These methods include the formation of weak films from formulation suspensions, van der Waals adhesion of Ag-CNPs to surfaces, and weak electrostatic interactions of NPs to surfaces. The microcrystalline nature of the active components of the formulation will allow for the formation of temporary films based on one or more of these mechanisms.

[0112] 4.1 Efficacy of the spray formulation on virus-laden surfaces and efficacy of the dried formulation as a film when applying virus / biofluid. The test formulation was sprayed onto a virus-inoculated test surface to determine initial efficacy. The efficacy of the spray as a (dried) film was analyzed by dispersing particles on the test surface, followed by virus inoculation, and determining the infectivity of the interacting virus.

[0113] The films were incubated for different times, infected, and treated for infectivity and total particles as described above. AgCNP2 was applied to slides and allowed to dry for 1 hour. Rhino14 was fed to AgCNP2-treated and untreated slides. Over a two-hour period, the virus titer on the AgCNP2-treated slides decreased at a significantly higher rate than on the untreated slides. Figure 9 Residual efficacy analyses of AgCNP1 and AgCNP2 against OC43 and RV14, respectively, showed that AgCNP maintained its efficacy for several hours. Figure 10 ).

[0114] Example 5: Optimization of metal-mediated nanoceria for inactivation of human coronaviruses and rhinoviruses through surface disruption.

[0115] In this study, two unique silver-modified cerium oxide nanoparticle formulations (AgCNP1 and AgCNP2) were produced and characterized, and their antiviral efficacy was tested. Figure 5 Microscopy and photoelectron spectroscopy revealed significant differences in the redox composition of cerium, formulation particle size, and the presence of the silver phase in the cerium oxide matrix. Electrochemical and bandgap measurements provided insights into the properties of silver and the silver / cerium oxide interface, and evidence that they are stabilized by the cerium oxide phase. Antiviral efficacy was determined by assessing a unique set of virus types, demonstrating the specificity of AgCNP formulations in their antiviral activity against specific viruses. In this paper, antiviral efficacy against rhinovirus RV14 and coronavirus OC43 was determined and compared. For the first time, in-situ electrochemical impedance spectroscopy was performed, confirming the specificity of the AgCNP formulation / virus type interaction during incubation. Based on this data, and results from a similarly designed system, a general pattern of action for describing the antiviral activity of highly effective virus / AgCNP formulation pairs was identified.

[0116] 5.1 Material synthesis and colloidal properties:

[0117] Silver-modified cerium oxide formulations (AgCNP) are synthesized using two distinct formulations (AgCNP1, AgCNP2), each utilizing a different chemical reaction in response to an aqueous solution of silver. AgCNP1 is synthesized via a previously developed two-step method (…). Figure 5 The synthesis involves the formation of a solution containing AgCNP-like nanoparticles, silver-modified cerium oxide nanoparticles, and a silver secondary phase via an alkaline forced hydrolysis reaction. The product material is washed with dH₂O and subsequently treated with ammonium hydroxide. Ammonium hydroxide acts as an etchant and phase-transfer complex, mediating the dissolution / stabilization of silver ions dissolved in the aqueous phase. Specifically, the reaction leads to the formation of Tollens' reagent (Ag[(NH₃)₂OH)₂). aqThe resulting single-particle solution was then washed with dH₂O to remove excess alkali and counterions / bystander ions. AgCNP₂ utilizes the stability of silver ions to hydrogen peroxide oxidation. Specifically, cerium nitrate and silver nitrate are dissolved, followed by the addition of hydrogen peroxide, resulting in the selective oxidation of silver by cerium ions and the transformation into a metallic silver phase on the cerium oxide surface. The unique synthesis conditions of these particles suggest potentially entirely different particle properties.

[0118] The colloidal properties of the particles were evaluated for kinetic stability, surface potential, and hydrodynamic diameter. Dynamic light scattering (DLS) measurements for each sample are collected in Table 3, correlated with larger particle sizes (including specific hydrated spheres) for each formulation, with AgCNP1 particles having a diameter approximately three times larger (Table 3). Furthermore, zeta potential measurements indicated that AgCNP2 had a larger surface potential than AgCNP1, each exhibiting positive polarity. These characterizations suggest that AgCNP2 particles exhibit greater kinetic stability than AgCNP1 (AgCNP1: moderate precipitation after 1 week of aging at room temperature; AgCNP2: no significant precipitation after more than 5 months). AgCNP1 particles also showed turbidity in a 1 mg / mL solution, while AgCNP2 was completely translucent under similar conditions, indicating that greater Mie scattering is associated with larger particle size. Particles from each synthesis were observed to demonstrate unique fundamental and functional material properties.

[0119] Table 3. Physicochemical properties of AgCNP formulations.

[0120]

[0121]

[0122] 5.3 Electrochemical characterization

[0123] XPS results indicated that each formulation possessed unique silver properties; therefore, the stability of the silver phase in each formulation was evaluated using common electrochemical techniques. Electrochemical measurements were performed... Figure 5(C, D) To determine the activity of the silver phase in AgCNP formulations and its sensitivity to electron transfer processes. In the XPS results, AgCNP1 was confirmed to have a larger Tafel potential than AgCNP2 (Table 3) (465.4 mV vs. 217.4 mV, respectively), indicating stronger stability to electron transfer and higher oxidation properties. Interestingly, AgCNP1 exhibited a Tafel current that was twice the value observed for AgCNP2 (0.027 μA vs. 0.013 μA, respectively). These values ​​are relatively low, indicating the overall stability of the silver phase in each formulation. However, the larger current value of AgCNP1 at higher potentials was revealed from the XPS spectra, where the silver content in a portion of the samples was found to be oxide. Silver infiltration into the cerium oxide surface / subsurface increases the Tafel potential (i.e., has a stabilizing effect on the silver phase) while improving the phase's registry at its interface, thus improving charge transfer as a Tafel current. TEM images confirmed that the silver-cerium oxide interface in AgCNP1 had a larger area than that in AgCNP2. Tafel analysis (Table 3) showed that the anodic β values ​​were significantly larger than the cathodic β values ​​in both samples, indicating that the oxidation process was kinetically favored by electron transfer at the Tafel potential. While electrochemical methods can provide information about fundamental charge transfer processes, this characterization only provides nominal information at the atomic or chemical level.

[0124] 5.5 Selective inactivation of two human respiratory viruses with AgCNP1 and AgCNP2:

[0125] To determine the extent to which cerium nano-oxide and silver-modified cerium nano-oxide could inactivate human coronavirus OC43, the reaction was prepared to include 10 per milliliter. 5 Viral infection units (TCID50) along with buffer and nanoparticles. Alternatively, a buffer-only reaction may include water as a carrier control. 10 5 Introduced virus at TCID50 / mL was determined to be time-zero infectious. After 6 hours of incubation, the buffer-controlled reaction alone showed 10 4 TCID50 / mL residual infectious virus. Unmodified nano-cerium oxide, CNP2 and CNP1 had almost no effect on the viral titer, and the reaction remained at approximately 5 × 10⁻⁶. 4 TCID50 / mL. Notably, AgCNP1 treatment resulted in complete inactivation of the infectious virus, while AgCNP2 treatment reduced the infectious virus titer to approximately 10. 3 TCID50 / mL. Time-course studies were performed using a reaction prepared as described above, containing only buffer, AgCNP1, or AgCNP2. Infectivity was determined after 0, 2, 4, and 6 hours of incubation. As early as 4 hours, AgCNP1 treatment reduced the OC43 viral titer from the initial value of 10. 5TCID50 / mL decreased to less than 10 2 TCID50 / mL. In summary, these data indicate that AgCNP1 is highly effective in inactivating coronavirus OC43, while AgCNP2 has a moderate ability to inactivate OC43.

[0126] To determine the optimal effective AgCNP1 concentration for inactivating coronavirus OC43, from 10 5 The reaction was prepared starting at TCID50 / mL OC43, along with buffer and incremental concentrations of AgCNP1. Infectivity was determined at 5 minutes and 4 hours of incubation. After the 5-minute timepoint, all AgCNP1 concentrations (approximately 10) were considered. 4 -10 5 The TCID50 / mL titers were similar. In contrast, treatment with 0.77 mg / mL AgCNP1 for 4 hours resulted in no detectable OC43 viral infectivity, while treatment with 0.2 mg / mL AgCNP1 reduced infectivity to approximately 10. 2 TCID 50 / mL. The result of AgCNP1-OC43 inactivation was confirmed by another infectious method. 10 4 Plaque-forming units (PFU) / mL OC43, incubated with a separate buffer for 4 hours, restored all infectivity, resulting in undetectable OC43 plaques in assays compared to incubation with 0.77 mg / mL AgCNP1. In summary, these data demonstrate the time- and dose-dependent infectivity of AgCNP1 for inactivated coronavirus OC43.

[0127] Next, we attempted to determine the extent to which cerium nanoparticles and silver-modified cerium nanoparticles could inactivate the human respiratory pathogen rhinovirus 14 (RV14), a non-enveloped icosahedral RNA virus. RV14 was incubated with either a separate buffer or the nanoparticles shown. A separate buffer reaction was prepared using water as a carrier control. Measurements were taken at 6 × 10⁻⁶. 5 RV14 virus was introduced at TCID50 / mL, and the time was expressed as zero point. After 6 hours of incubation, the buffer-only reaction retained 6 × 10⁻⁶. 5 Infectivity of TCID50 / mL input. Unmodified nano-cerium oxide CNP2 and CNP1 had almost no effect on the infectivity of RV14. Importantly, AgCNP1 treatment reduced the infectious viral titer to 5 × 10⁻⁶. 2 TCID50 / mL, while AgCNP2 treatment resulted in complete inactivation of the infectious virus. In time-course studies, 6 × 10 5Incubation of RV14 at TCID50 / mL with a single buffer for 6 hours showed no loss of infectivity. In contrast, incubation with AgCNP2 for 2 hours resulted in a very rapid decrease in infectivity of RV14 to undetectable levels. Incubation with AgCNP1 compared to AgCNP2 showed slower inactivation of RV14, with viral titers decreasing to approximately 10 after 6 hours. 2 TCID50 / mL. In summary, these data indicate that both AgCNP1 and AgCNP2 can inactivate the infectivity of RV14, with AgCNP2 exhibiting a stronger anti-RV14 effect.

[0128] 5.6 In-situ bioelectrochemical impedance spectroscopy characterization of AgCNP disinfectant activity:

[0129] Both formulations exhibited basic disinfectant activity against unique subgroups of viral species, and HA assay results indicated a unique mode of action for each test case. To investigate the characteristics of each formulation, two test cases, namely AgCNP1 / OC43 and AgCNP2 / rhinovirus (…), were tested. Figure 6 Electrochemical impedance spectroscopy (EIS) was performed. EIS is a non-destructive characterization technique that relies on applying small-amplitude potentials at frequencies varying within a fixed range. Decomposing the measured current into contributions from unique frequency regions allows for the identification of characteristic electrochemical processes. EIS is a major technology in manufacturing, particularly for the energy and semiconductor industries. In this paper, total impedance is measured using data fitted with simple circuit diagrams (i.e., fitted circuit elements representing chemical components / processes). In recent years, this technique has been applied to study alterations in cell properties caused by physical or chemical stimuli. Among these studies, the conditions under which cell membrane properties change are most frequently investigated. Giaever and Keese's ECIS model provides a simple interpretation of cell-matrix EIS data, where impedance components are unconvoluted into resistance and cell membrane capacitance in the charge flow regions between biological particles and between particles and the electrode matrix. In cell health studies, these model components are diagnostic: each component changes upon the introduction of toxic agents (e.g., pore formation, lesion area contraction, membrane oxidation). Furthermore, these reactions are necessarily frequency-dependent, with specific bands recognized by unique biological processes. Three regions are highlighted, denoted as α (<10kHz), β (10kHz <100mHz), and γ (GHz). Specific biochemical processes can be identified by observing changes in impedance spectra over time in the presence of a test reagent (e.g., AgCNP).

[0130] In this study, the impedance spectra of the test cases were all different from each other. Figure 6 For AgCNP1 ( Figure 6Spectra collected during an 8-hour sterilization period (AB) were used for the infectivity assays described above. The spectra showed nearly uniform impedance characteristics, with significant amplitude differences only at high frequencies (decreasing with time; 100 Hz to 100 kHz), denoted by Bode. In the phase and logarithmic (frequency) representations, there was a significant, time-dependent shift towards higher frequencies in the phase peaks. These results were confined to the α-dispersion region: we expected the spectral variations to be related to ion diffusion, particularly in the cell membrane and its physical interactions. Similar peak spectral features represent the superposition of two physical processes with different time constants, which can be attributed to specific changes on the cell membrane through fitting and circuit modeling (hereinafter). AgCNP2 ( Figure 6 The DE (determined spectral signature) exhibited similar initial spectral characteristics (two components) during a 4-hour incubation period. However, as incubation time increased, the spectra became more complex: exhibiting two observable “peaks” that could be decomposed into a four-component function. The differences between these spectra confirm distinct particle-virus interactions and indicate the presence of additional physical elements. Considering the observed phase shift towards higher frequencies, the data suggest the existence of a constant phase element component (resistance dominated by resistance as frequency increases). Spectral fitting validated these characteristics with a general plot structure across all test cases, except at unique time points (…). Figure 6 C, Figure 6 The specific AgCNP and the variable elements of viral interaction on F) Figure 6 C, Figure 6 (Indicated by dashed lines in F). Variable elements are suitable as parallel resistors and capacitors for AgCNP1:OC43, and as constant-phase elements for AgCNP2:RV14, as shown by the phase-to-impedance characteristics of the spectrum. In particular, the parallel elements conform to the time-dependent behavior of the AgCNP1:OC43 interaction, with values ​​varying from high resistance and moderate capacitance to significantly lower values. Specifically, the resistance value changes drastically with incubation. The results collectively confirm the proposed particle-virus interaction leading to changes in membrane integrity / permeability; the reduced resistance is associated with reduced membrane density, permeability, and capacitance, as well as the physical interaction with the oxide nanoparticles. The constant-phase variable component of RV14:AgCNP2 is a frequency-dependent element simulating an imperfect dielectric. In the case of this system, increasing the incubation group leads to increasingly imperfect properties of the model dielectric: causing the resistance characteristics to evolve from the initial characteristics to those similar to OC43. To better explain and attribute the observed in-situ features to unique physicochemical processes, a physical model was constructed and unique controlled reactions were investigated.

[0131] 5.7 Development of a physical model for bioelectrochemical impedance spectroscopy:

[0132] Simulation systems were fabricated for the RV14 and OC43 virus systems to identify the unique antiviral mechanisms generated during in-situ EIS measurements. Specifically, we aimed to reproduce the characteristics of the virus at the interface between the virus and the electrolyte. Therefore, two unique systems were fabricated to mimic the dense protein structure of the RV14 surface and the envelope surface of OC43. For measurements related to RV14, bovine serum albumin was used, while liposomes were used for the lipid membrane of OC43. All measurements were performed under the same electrolyte conditions as in-situ measurements to control for solution-based impedance contributions (i.e., 0.1 M Tris-HCl, pH 7.5). Liposomes are commonly used in virus research, including as viral mimicry vectors for drug / gene delivery therapies, and as virus-like particles. In this study, liposomes were synthesized to approximately the size of the OC43 coronavirus (approximately 120 nm) to appropriately mimic any physical interactions between AgCNP and the liposomes. In each experimental case, the viral mimicry material was dispersed in solution and drop-coated onto the surface of a glassy carbon electrode in a manner similar to that used for in-situ virus measurements. In each case, the behavior of the simulated material appears to reflect the observed behavior of the relevant virus, exhibiting corresponding AgCNP formulation dependence. Figure 4 The EIS spectra of virus analogs of virus:particle pairs collected and effective in infectious assays are shown. Notably, the fitted spectra result in an equivalent circuit similar to the in-situ data. In particular, the circuit diagram is identical to that produced in the in-situ study, except that the components on the right side of the figure remain variable. For the liposome / AgCNP1 system ( Figure 7 A, Figure 7 In F), we observed that the variable element is a parallel resistor and capacitor, and maintains this property during incubation. However, we see that the values ​​of these elements change during the incubation period, resulting in a related phase shift due to their properties changing from more capacitive to resistive. Correlation fitting materials for the BSA / AgCNP2 system emerged ( Figure 7 E, Figure 7 G) and correlated with in-situ data from RV14 / CNP2. However, we observed that the spectra in the simulated system were less clear than those seen in the viral system. These minor differences in properties can be attributed to small-scale (topological) differences between the systems. Specifically, BSA is a single globular protein, while RV14 is an aggregate of proteins with a coarser surface topology. The differences in spectra can be attributed to different physicochemical environments; however, the spectra suggest that the overall interactions between the particles and the virus / analogue are similar. Considering the evolution of additional resistive properties in the model, we decided to identify any specific chemical changes that occurred. Therefore, the oxygen radical generation system, known to induce lipid peroxidation by simultaneously producing superoxide and hydrogen peroxide in proportion, was used as a positive control for activity.

[0133] In these experiments, the effect of positive control on free radical oxygen release was assessed by observing relevant changes in the spectra. (The following is a list of observations / analyses.) Figure 7 B) For the BSA / AgCNP2 spectrum ( Figure 7 C), oxidation reproduced the additional peaks observed in the RV14 / AgCNP2 system. The observed characteristics were also reproduced in the Lipo / AgCNP1 system. Figure 8 This confirms that the changes in the spectral characteristics of the virus system did not originate from the chemical attack during AgCNP1 incubation.

[0134] refer to:

[0135] [1] https: / / www.cdc.gov / coronavirus / 2019-ncov / community / organizations / cleaning-disinfection.html. https: / / nih.gov / news-events / news-releases / new-coronavirus-stable-hours-surfaces.

[0136] [2] https: / / www.epa.gov / pesticide-registration / list-n-disinfectants-use-against-star-cov-2. https: / / timesofindia.indiatimes.com / city / kolkata / new-market-sprinklers-to-spray-disinfectant-solution-on-shoppers / articleshow / 75017812.cms.

[0137] [3] https: / / nrckids.org / files / appendix / Appendixk.pdf. https: / / www.cdc.gov / coronavirus / 2019-ncov / community / schools-childcare / guidance-for-childcare.html#CleanDisinfect.

[0138] [4] ​ ​ ​

[0139] [5]Antiseptics and Disinfectants Market Size,Share&Trends AnalysisReport By Type(Quaternary Ammonium,Chlorine),Product Type(Medical DeviceDisinfectants),By End Use,And Segment Forecasts,2019-2026.

[0140] [6] ​

[0141] [7] ​ ​

[0142] [8]R.A.Yokel,S.Hussain,S.Garantziotis,P.Demokritou,V.Castranova,F.R.Cassee,The yin:an adverse health perspective of nanoceria:uptake,distribution,accumulation,and mechanisms ofits toxicity,EnvironmentalScience:Nano 1(5)(2014)406-428.

[0143] [9]W.T.Self,E.Bossy-Wetzel,S.Seal,J.Dowding,Neuronal protection bycerium oxide nanoparticles,Google Patents,2018.

[0144]

[10] W.T.Self,S.Seal,Nanoparticles of cerium oxide having superoxidedismutase activity,Google Patents,2009.

[0145]

[11] B.A.Rzigalinski,S.Seal,D.Bailey,S.Patil,Cerium oxidenanoparticles and use in enhancing cell survivability,Google Patents,2009.

[0146]

[12] S.Seal,H.Cho,S.Patil,A.Mehta,Cerium oxide nanoparticleregenerative free radical sensor,Google Patents,2012.

[0147]

[13] P.Brenneisen,S.Seal,A.Karakoti,Redox active cerium oxidenanoparticles and associated methods,Google Patents,2017.

[0148]

[14] Cerium Oxide Nanoparticles Market:Market by Application(EnergyStorage,Polishing Agent,Personal Care,Pharmaceuticals);Report ID:GVR-1-68038-547-2,August 2017.

[0149]

[15] D.-s.Tsai,T.-S.Yang,Y.-S.Huang,P.-W.Peng,K.-L.Ou,Disinfectioneffects of undoped and silver-doped ceria powders of nanometer crystallitesize,International journal of nanomedicine 11(2016)2531.

[0150]

[16] E.Grulke,K.Reed,M.Beck,X.Huang,A.Cormack,S.Seal,Nanoceria:factorsaffecting its pro-and anti-oxidant properties,Environmental Science:Nano 1(5)(2014)429-444.

[0151]

[17] G.Sener,S.A.Hilton,M.J.Osmond,C.Zgheib,J.P.Newsom,L.Dewberry,S.Singh,T.S.Sakthivel,S.Seal,K.W.Liechty,Injectable,self-healablezwitterionic cryogels with sustained microRNA-cerium oxide nanoparticlerelease promote accelerated wound healing,Acta biomaterialia 101(2020)262-272.

[0152]

[18] V.Shah,S.Shah,H.Shah,F.J.Rispoli,K.T.McDonnell,S.Workeneh,A.Karakoti,A.Kumar,S.Seal,Antibacterial activity of polymer coated ceriumoxide nanoparticles,PLoS One 7(10)(2012).

[0153]

[19] L.Alili,M.Sack,A.S.Karakoti,S.Teuber,K.Puschmann,S.M.Hirst,C.M.Reilly,K.Zanger,W.Stahl,S.Das,Combined cytotoxic and anti-invasiveproperties of redox-active nanoparticles in tumor-stroma interactions,Biomaterials 32(11)(2011)2918-2929.

[0154]

[20] C.Korsvik,S.Patil,S.Seal,W.T.Self,Superoxide dismutase mimeticproperties exhibited by vacancy engineered ceria nanoparticles,ChemicalCommunications(10)(2007)1056-1058.

[0155]

[21] E.G.Heckert,A.S.Karakoti,S.Seal,W.T.Self,The role of cerium redoxstate in the SOD mimetic activity ofnanoceria,Biomaterials 29(18)(2008)2705-9.

[0156]

[22] J.Chen,S.Patil,S.Seal,J.F.McGinnis,Rare earth nanoparticlesprevent retinal degeneration induced by intracellular peroxides,NatNanotechnol 1(2)(2006)142-50.

[0157]

[23] T.Pirmohamed,J.M.Dowding,S.Singh,B.Wasserman,E.Heckert,A.S.Karakoti,J.E.S.King,S.Seal,W.T.Self,Nanoceria exhibit redox state-dependent catalase mimetic activity,Chemical Communications 46(16)(2011)2736-2738.

[0158]

[24] S.Babu,J.Cho,J.Dowding,E.Heckert,C.Komanski,S.Das,J.Colon,C.Baker,M.Bass,W.Self,S.Seal,Multicolored redox active upconverter ceriumoxide nanoparticle for bio-imaging and therapeutics,Chemical Communications46(37)(2010)6915-6917.

[0159]

[25] S.Seal,Lanthanide doped nanocrystalline ceria coating forincreasing oxidation resistance ofstainless steel and associated methods,Google Patents,2013.

[0160]

[26] M.H.Kuchma,C.B.Komanski,J.Colon,A.Teblum,A.E.Masunov,B.Alvarado,S.Babu,S.Seal,J.Summy,C.H.Baker,Phosphate ester hydrolysis of biologicallyrelevant molecules by cerium oxide nanoparticles,Nanomedicine:Nanotechnology,Biology and Medicine6(6)(2010)738-744.

[0161]

[27] A.Karakoti,S.Singh,J.M.Dowding,S.Seal,W.T.Self,Redox-activeradical scavenging nanomaterials,Chemical Society Reviews 39(11)(2010)4422-4432.

[0162]

[28] Q.Fu,H.Saltsburg,M.Flytzani-Stephanopoulos,Active nonmetallic Auand Pt species on ceria-based water-gas shift catalysts,Science 301(5635)(2003)935-938.

[0163]

[29] S.Seal,E.L.Petersen,S.Deshpande,S.Patil,S.C.Kuiry,Use of oxidenanoparticles in soot reduction,Google Patents,2008.

[0164]

[30] C.T.Campbell,C.FI.F.Peden,Chemistry-Oxygen vacancies andcatalysis on ceria surfaces,Science 309(5735)(2005)713-714.

[0165]

[31] F.Esch,S.Fabris,L.Zhou,T.Montini,C.Africh,P.Fornasiero,G.Comelli,R.Rosei,Electron localization determines defect formation on ceriasubstrates,Science 309(5735)(2005)752-755.

[0166]

[32] A.Kumar,S.Babu,A.S.Karakoti,A.Schulte,S.Seal,Luminescenceproperties of europium-doped cerium oxide nanoparticles:role ofvacancy andoxidation states,Langmuir 25(18)(2009)10998-11007.

[0167]

[33] U.M.Bhatta,I.M.Ross,T.X.Sayle,D.C.Sayle,S.C.Parker,D.Reid,S.Seal,A.Kumar,G.n.Mobus,Cationic surface reconstructions on cerium oxidenanocrystals:an aberration-corrected HRTEM study,ACS nano 6(1)(2012)421-430.

[0168]

[34] T.Sakthivel,S.Das,A.Kumar,D.L.Reid,A.Gupta,D.C.Sayle,S.Seal,Morphological phase diagram ofbiocatalytically active ceria nanostructures asa function ofprocessing variables and their properties,ChemPlusChem 78(12)(2013)1446-1455.

[0169]

[35] S.Deshpande,S.Patil,S.V.Kuchibhatla,S.Seal,Size dependencyvariation in lattice parameter and valency states in nanocrystalline ceriumoxide,Applied Physics Letters 87(13)(2005)133113.

[0170]

[36] C.Walkey,S.Das,S.Seal,J.Erlichman,K.Heckman,L.Ghibelli,E.Traversa,J.F.McGinnis,W.T.Self,Catalytic properties and biomedicalapplications of cerium oxide nanoparticles,Environmental Science:Nano 2(1)(2015)33-53.

[0171]

[37] T.Pirmohamed,J.M.Dowding,S.Singh,B.Wasserman,E.Heckert,A.S.Karakoti,J.E.King,S.Seal,W.T.Self,Nanoceria exhibit redox state-dependentcatalase mimetic activity,Chemical communications 46(16)(2010)2736-2738.

[0172]

[38] M.Hijaz,S.Das,I.Mert,A.Gupta,Z.Al-Wahab,C.Tebbe,S.Dar,J.Chhina,S.Giri,A.Munkarah,Folic acid tagged nanoceria as a novel therapeutic agent inovarian cancer,BMC cancer 16(1)(2016)220.

[0173]

[39] I.Kalashnikova,J.Mazar,C.J.Neal,A.L.Rosado,S.Das,T.J.Westmoreland,S.Seal,Nanoparticle delivery of curcumin induces cellularhypoxia and ROS-mediated apoptosis via modulation ofBcl-2 / Bax in humanneuroblastoma,Nanoscale 9(29)(2017)10375-10387.

[0174]

[40] A.Shcherbakov,N.Zholobak,N.Y.Spivak,V.Ivanov,Advances andprospects of using nanocrystalline ceria in cancer theranostics,RussianJournal ofInorganic Chemistry 59(13)(2014)1556-1575.

[0175]

[41] N.M.Zholobak,V.K.Ivanov,A.B.Shcherbakov,Interaction of nanoceriawith microorganisms,Nanobiomaterials inAntimicrobial Therapy,Elsevier2016,pp.419-450.

[0176]

[42] V.Lozovski,V.Lysenko,V.Piatnytsia,O.Scherbakov,N.Zholobak,M.Spivak,Physical point of view for antiviral effect caused by theinteraction between the viruses and nanoparticles,Journal ofBionanoscience 6(2)(2012)109-112.

[0177]

[43] A.Arumugam,C.Karthikeyan,A.S.Haja Hameed,K.Gopinath,S.Gowri,V.Karthika,Synthesis ofcerium oxide nanoparticles using Gloriosa superbaL.leafextract and their structural,optical and antibacterial properties,Materials Science and Engineering:C 49(2015)408-415.

[0178]

[44] A.Thill,O.Zeyons,O.Spalla,F.Chauvat,J.Rose,M.Auffan,A.M.Flank,Cytotoxicity of Ce02 nanoparticles for Escherichia coli.Physico-chemicalinsight of the cytotoxicity mechanism,Environmental science&technology 40(19)(2006)6151-6156.

[0179]

[45] V.Lozovski,V.Lysenko,V.Pyatnitsia,M.Spivak,Can nanoparticles beuseful for antiviral therapy?,Semiconductor Physics Quantum Electronics&Optoelectronics(2011).

[0180]

[46] P.Janos,J.Ederer,M.Dosek,J.Stojdl,J.Flenych,J.Tolasz,M.Kormunda,K.Mazanec,Can cerium oxide serve as a phosphodiesterase-mimetic nanozyme?,Environmental Science:Nano 6(12)(2019)3684-3698.

[0181]

[47] S.Singh,T.Dosani,A.S.Karakoti,A.Kumar,S.Seal,W.T.Self,Aphosphate-dependent shift in redox state of cerium oxide nanoparticles and its effectson catalytic properties,Biomaterials 32(28)(2011)6745-6753.

[0182]

[48] A.Vincent,S.Babu,E.Fleckert,J.Dowding,S.M.Hirst,T.M.Inerbaev,W.T.Self,C.M.Reilly,A.m.E.Masunov,T.S.Rahman,S.Seal,Protonated NanoparticleSurface Governing Ligand Tethering and Cellular Targeting,ACS Nano 3(5)(2009)1203-1211.

[0183]

[49] S.Singh,A.Kumar,A.Karakoti,S.Seal,W.Self,Unveiling the mechanismof uptake and sub-cellular distribution of cerium oxide nanoparticles,Molecular Biosystems 6(10)(2010)1813-1820.

[0184]

[50] A.S.Karakoti,S.Singh,A.Kumar,M.Malinska,S.V.Kuchibhatla,K.Wozniak,W.T.Self,S.Seal,PEGylated nanoceria as radical scavenger withtunable redox chemistry,Journal of theAmerican Chemical Society 131(40)(2009)14144-14145.

[0185]

[51] S.Das,J.M.Dowding,K.E.Klump,J.F.McGinnis,W.Self,S.Seal,Ceriumoxide nanoparticles:applications andprospects in nanomedicine,Nanomedicine 8(9)(2013)1483-1508.

[0186]

[52] C.Sun,H.Li,L.Chen,Nanostructured ceria-based materials:synthesis,properties,and applications,Energy&Environmental Science 5(9)(2012)8475-8505.

[0187]

[53] J.M.Dowding,S.Das,A.Kumar,T.Dosani,R.McCormack,A.Gupta,T.X.Sayle,D.C.Sayle,L.von Kalm,S.Seal,Cellular interaction and toxicity depend onphysicochemical properties and surface modification of redox-activenanomaterials,ACS nano 7(6)(2013)4855-4868.

[0188]

[54] A.S.Karakoti,S.Das,S.Thevuthasan,S.Seal,PEGylated inorganicnanoparticles,Angewandte Chemie International Edition 50(9)(2011)1980-1994.

[0189]

[55] E.-J.Park,J.Choi,Y.-K.Park,K.Park,Oxidative stress induced bycerium oxide nanoparticles in cultured BEAS-2B cells,Toxicology 245(1)(2008)90-100.

[0190]

[56] S.Das,S.Singh,J.M.Dowding,S.Oommen,A.Kumar,T.X.T.Sayle,S.Saraf,C.R.Patra,N.E.Vlahakis,D.C.Sayle,W.T.Self,S.Seal,The induction ofangiogenesis by cerium oxide nanoparticles through the modulation ofoxygen inintracellular environments,Biomaterials 33(31)(2012)7746-7755.

[0191]

[57] M.Sack,L.Alili,E.Karaman,S.Das,A.Gupta,S.Seal,P.Brenneisen,Combination of conventional chemotherapeutics with redox-active cerium oxidenanoparticles—Anovel aspect in cancer therapy,Molecular cancer therapeutics13(7)(2014)1740-1749.

[0192]

[58] J.B.Johnson,D.S.Lyles,M.A.Alexander-Miller,G.D.Parks,Virion-associated complement regulator CD55 is more potent than CD46 in mediatingresistance of mumps virus and vesicular stomatitis virus to neutralization,Journal ofvirology 86(18)(2012)9929-9940.

[0193]

[59] C.R.Fox,G.D.Parks,Parainfluenza virus infection sensitizes cancercells to DNA-damaging agents:implications for oncolytic virus therapy,Journalofvirology 92(7)(2018)e01948-17.

[0194]

[60] J.Mazar,Y.Li,A.Rosado,P.Phelan,K.Kedarinath,G.D.Parks,K.A.Alexander,T.J.Westmoreland,Zika virus as an oncolytic treatment ofhumanneuroblastoma cells requires CD24,PloS one 13(7)(2018).

[0195]

[61] D.N.Bracey,T.M.Seyler,A.H.Jinnah,T.L.Smith,D.A.Ornelles,R.Deora,G.D.Parks,M.E.Van Dyke,P.W.Whitlock,Aporcine xenograft-derived bone scaffoldis a biocompatible bone graft substitute:An assessment of cytocompatibilityand the alpha-Gal epitope,Xenotransplantation 26(5)(2019)e12534.

[0196]

[62] P.W.Whitlock,T.M.Seyler,G.D.Parks,D.A.Ornelles,T.L.Smith,M.E.VanDyke,G.G.Poehling,A novel process for optimizing musculoskeletal allografttissue to improve safety,ultrastructural properties,and cell infiltration,JBJS 94(16)(2012)1458-1467.

[0197]

[63] Walls,A.C.;Park,Y.-J.;Tortorici,M.A.;Wall,A.;McGuire,A.T.;Veesler,D.,Structure,function,and antigenicity ofthe SARS-CoV-2 spikeglycoprotein.Cell 2020,181(2),281-292.e6.

[0198]

[64] Walls,A.C.;Xiong,X.;Park,Y.-J.;Tortorici,M.A.;Snijder,J.;Quispe,J.;Cameroni,E.;Gopal,R.;Dai,M.;Lanzavecchia,A.,Unexpected receptor functionalmimicry elucidates activation ofcoronavirus fusion.Cell 2019,776(5),1026-1039.e15.

[0199]

[65] Baker,A.N.;Richards,S.-J.;Guy,C.S.;Congdon,T.R.;Hasan,M.;Zwetsloot,A.J.;Gallo,A.;Lewandowski,J.R.;Stansfeld,P.J.;Straube,A.,The SARS-COV-2 spike protein binds sialic acids and enables rapid detection in alateral flow point of care diagnostic device.ACS central science 2020,6(11),2046-2052.

[0200]

[66] Waman,V.P.;Sen,N.;Varadi,M.;Daina,A.;Wodak,S.J.;Zoete,V.;Velankar,S.;Orengo,C.,The impact of structural bioinformatics tools andresources on SARS-CoV-2 research and therapeutic strategies.Briefings inbioinformatics 2021,22(2),742-768.

[0201]

[67] Li,X.;Yu,J.;Zhang,Z.;Ren,J.;Peluffo,A.E.;Zhang,W.;Zhao,Y.;Wu,J.;Yan,K.;Cohen,D.,Network bioinformatics analysis provides insight into drugrepurposing for COVID-19.Medicine in Drug Discovery 2021,100090.

[0202]

[68] Bauer,D.C.;Tay,A.P.;Wilson,L.O.;Reti,D.;Hosking,C.;McAuley,A.J.;Pharo,E.;Todd,S.;Stevens,V.;Neave,M.J.,Supporting pandemic response usinggenomics and bioinformatics:A case study on the emergent SARS-CoV-2outbreak.Transboundary and emerging diseases 2020,67(4),1453-1462.

[0203]

[69] Robson,B.,Bioinformatics studies on a function ofthe SARS-CoV-2spike glycoprotein as the binding ofhost sialic acid glycans.Computers inbiology and medicine 2020,122,103849.

Claims

1. A dispensable composition comprising metal-associated cerium oxide nanoparticles and an excipient, wherein the excipient comprises water; The metal includes silver, the metal-associated cerium oxide nanoparticles are silver-associated cerium oxide nanoparticles, at least a portion of the metal-associated cerium oxide nanoparticles are spherical, and the average diameter of the spherical metal-associated cerium oxide nanoparticles includes a size of 20 nm to 24 nm or a size of 3 nm to 5 nm, wherein the metal-associated cerium oxide nanoparticles have been deionized. The metal-associated cerium oxide nanoparticles thereon are also doped with fluorine; and The metal-associated cerium oxide nanoparticles are synthesized by the following method: Solvothermal method, microemulsion method, precipitation method and hydrothermal method.

2. The dispensable composition according to claim 1, wherein the amount of silver is less than 10% by weight.

3. The dispensable composition according to any one of claims 1 to 2, wherein the excipient further comprises a substance selected from chloroform, dichloromethane, acetone, methyl ethyl ketone, cyclohexane, ethyl acetate, diethyl ether, lower alcohols, THF, DMSO or DMF.

4. The dispensable composition according to any one of claims 1 to 2, wherein the size of the metal-associated cerium oxide nanoparticles is less than 100 nm.

5. The dispensable composition according to any one of claims 1 to 2, wherein the metal-associated cerium oxide nanoparticles comprise a dominant 3+ surface charge.

6. The dispensable composition according to any one of claims 1 to 2, wherein the metal-associated cerium oxide nanoparticles comprise a dominant 4+ surface charge.

7. The dispensable composition according to any one of claims 1 to 2, wherein the silver-associated cerium oxide nanoparticles are produced by a method comprising: Dissolve cerium precursor salts and silver precursor salts, and oxidize the dissolved cerium precursor salts and silver precursor salts.

8. The dispensable composition according to any one of claims 1 to 2, wherein the silver-associated cerium oxide nanoparticles are produced by a method comprising: Dissolve cerium precursor salts and silver precursor salts; Dissolved cerium precursor salts and silver precursor salts are oxidized by peroxides; Nanoparticles were precipitated using ammonium hydroxide.

9. The dispensable composition according to any one of claims 1 to 2, wherein the silver-associated cerium oxide nanoparticles are produced by a method comprising (i) dissolving a cerium precursor salt and a silver precursor salt; (ii) oxidizing the dissolved cerium precursor salt and silver precursor salt with hydrogen peroxide, and then precipitating the oxidized system with ammonium hydroxide; (iii) washing and resuspending the precipitated nanoparticles in water; (iv) treating the resuspended nanoparticles with hydrogen peroxide; and (v) washing the nanoparticles from step (iv) to remove ionized silver.

10. A disinfectant formulation comprising a dispensable composition according to any one of claims 1 to 9, a desiccant, an organic acid, a surfactant, a polymer binder, and water; The desiccant is selected from ethanol and isopropanol; or The desiccant is ethanol.

11. The formulation according to claim 10, wherein the formulation comprises one or more dispensable compositions according to any one of claims 1 to 9.

12. The formulation according to claim 10, wherein the amount of the dispensable composition according to any one of claims 1 to 9 is 0.1 to 10 by weight.

13. The formulation according to claim 10, wherein the amount of ethanol is 0 to 40 by weight.

14. The formulation according to claim 10, wherein the organic acid is citric acid.

15. The formulation according to claim 14, wherein the amount of citric acid is 0.5 to 2 by weight.

16. The formulation according to claim 10, wherein the surfactant is selected from laurylamine oxide, myristamine oxide, and tergitol 15-S-15.

17. The formulation according to claim 10, wherein the amount of the surfactant is 0.5 to 3 by weight.

18. The formulation according to claim 16, wherein the surfactant is laurylamine oxide and tergitol15-S-15.

19. The formulation according to claim 18, wherein the amount of laurylamine oxide is 0.25 to 2 by weight.

20. The formulation according to claim 18, wherein the amount of tergitol 15-S-15 is 0 to 1 by weight.

21. The formulation according to claim 10, wherein the polymer binder is selected from poly(2-ethyl-2-oxazoline) and polyvinylpyrrolidone-vinyl acetate copolymer.

22. The formulation of claim 21, wherein the polymer binder is poly(2-ethyl-2-oxazoline).

23. The formulation according to claim 22, wherein the amount of poly(2-ethyl-2-oxazoline) is 1 to 25 by weight.

24. The formulation according to claim 21, wherein the amount of the polyvinylpyrrolidone-vinyl acetate copolymer is 1 to 30 by weight.

25. A disinfecting film comprising the composition of any one of claims 1 to 9 placed on a substrate.

26. The disinfection film according to claim 25, wherein the disinfection film is capable of residual disinfection.

27. The disinfectant film according to claim 26, wherein the residual disinfection occurs within 15 to 30 minutes.

28. The disinfection film according to claim 25, wherein the disinfection film is capable of rapid disinfection.

29. The disinfection film according to claim 28, wherein the rapid disinfection occurs within 1 minute.

30. The disinfectant film according to claim 25, wherein the disinfectant film is effective for 1 to 14 days.

31. The disinfection film according to any one of claims 25 to 30, wherein the disinfection film is activated when exposed to water.

32. The disinfectant film according to any one of claims 25 to 30, wherein the dried disinfectant film can be reactivated by exposure to water.

33. A method for disinfecting a surface as a non-disease diagnosis and treatment method, the method comprising dispensing a dispensable composition according to any one of claims 1 to 9 onto the surface.

34. A fabric comprising the dispensable composition of any one of claims 1 to 9 disposed on the surface of the fabric.

35. The fabric of claim 34, wherein the fabric is configured to include at least a portion of garments and any PPE.

Images