In addition to ultraviolet light, these lights can also kill viruses

In our daily life, we have used ultraviolet rays for sterilization intentionally or unintentionally. The most common example is drying quilts. Some experts believe that the new coronavirus may disappear naturally when the weather is warm, partly based on the principle of ultraviolet sterilization. So can ultraviolet light really kill viruses? In fact, in addition to ultraviolet light, visible light and infrared light also have powerful sterilization capabilities. So, how does this light kill pathogens such as bacteria, fungi, and viruses? What scenarios can these light-mediated sterilization technologies be applied to?

In recent years, researchers have developed a series of light-mediated sterilization technologies, which can be used in various scenes in daily life, can also be used to inactivate viruses to prepare vaccines, and can also be directly used in wound treatment. According to previous studies [1], these technologies can target various types of biological weapons such as bacteria, fungi, and viruses. Therefore, for the new coronavirus that is currently raging in various countries, these technologies should also play an important role in the defense and treatment of the new coronavirus.

Compared with chemical disinfectants, fungicides and anti-infectives, light has many advantages:

is environmentally friendly and pollution-free.

is relatively safe and non-toxic.

will not cause excessive damage to the surrounding biological medium, whether it is inorganic, organic or living.

The production cost is relatively low.

The reaction speed is very fast, usually only a few seconds.

can be applied to human skin, wounds, mucous membranes and other exposed parts without causing undue harm.

There is no report showing that microbial cells are resistant to light-based anti-infective therapies.

We are here to introduce several light-mediated sterilization methods, hoping to inspire the prevention and treatment of the new coronavirus.

Different wavelengths of light and its effects

First of all, what are the “components” of light that we usually talk about? Which of them are harmful to the human body, and which of them will be beneficial to sterilization, sterilization, etc., if used properly?

Light can be classified according to its wavelength range and whether it can produce ionization effects when interacting with substances. According to the ascending order of wavelength, it can be divided into gamma rays, X rays, ultraviolet rays, visible light, infrared rays, microwaves and radio waves. The shorter the wavelength, the higher the frequency and the greater the energy. Due to the electromagnetic properties of light, it can cause various phenomena when it interacts with matter. For example, when a light wave with a wavelength of less than 100 nanometers interacts with a substance, it will cause the material atoms to ionize; as the wavelength increases, the energy carried by the light wave is not enough to cause ionization, but it can excite electrons and make the substance at high energy. State and induce changes in its molecular structure.
Because the sterilization technology based on ultraviolet, visible light and infrared is widely used in daily life, scientific research and medical treatment, here we mainly develop from these aspects.

Ultraviolet sterilization principle and application

Ultraviolet (UV) has a wavelength range between X-ray (≤100nm) and visible light (>400nm), approximately in the range of 100-400nm. According to the interaction between ultraviolet light and molecules, it can be divided into four types. These types of ultraviolet light have different physiological effects on substances.

Vacuum UV (VUV) wavelength range is 100-200nm. At low doses, it can also react instantly with oxygen atoms and organic molecules, which is harmful.

Ultra-short ultraviolet UVC light with a wavelength range of 200-280 nanometers. UVC can be completely absorbed by the atmosphere, and no natural UVC rays irradiate the earth’s surface. Ultraviolet rays located in this band have a sterilization effect. People usually say “ultraviolet sterilization”, the effective “component” is UVC[2], which can be obtained by artificial light source (such as UVC LED or mercury lamp).

UVC has a weak penetrating ability. Most of it will be absorbed by the stratum corneum and epidermis of the human skin, and only a very small part will hit the dermis. Only when UVC acts on the dermis will it cause skin cell cancer, so UVC is generally considered It has little effect on human skin (except babies and people allergic to UVC). However, since there is no cuticle protection for the eyes, UVC has a harmful effect on human eyes, so when using UVC to disinfect the room, people should try not to enter it. If you must enter, you must wear special protective glasses and protective clothing.

Far ultraviolet UVB wavelength range of light between 280-315 nanometers. This wavelength of light can cause skin “sun burn”, which is related to photocarcinogenesis and photoaging. The main purpose of applying sunscreen is to combat it.

Near-ultraviolet UVA wavelength range of light between 315-400 nanometers. Among them, the shorter wavelength UVA (315-340 nanometers, UVA1) can also produce harmful effects on the skin due to its ability to generate active oxygen. Its penetrating power is very strong, it can penetrate most transparent glass and plastic, and it can also reach the dermis of the skin, destroy the elastic fibers and collagen fibers, and tan the skin.

Among the various wavelengths of ultraviolet rays, only ultra-short ultraviolet rays UVC have the effect of sterilization and disinfection. When irradiating bacteria, viruses and other microorganisms with ultra-short ultraviolet rays, the ultra-short ultraviolet rays with a wavelength of 254 nanometers can be absorbed by the pyrimidines and purines in the nucleic acids of these microorganisms, prompting the nucleic acids to produce some light products through base dimerization. Thereby destroying the molecular structure of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) in microbial cells. When DNA is damaged, it is difficult for nucleic acid to replicate. Even if replication is possible, it usually has defects, making bacteria unable to survive. In addition, when multi-wavelength ultra-short ultraviolet rays are used to irradiate microorganisms, ultra-short ultraviolet rays may also affect aromatic amino acids, which in turn affects the structure and function of proteins, and makes bacteria unable to survive.

Ultrashort ultraviolet is a mature disinfection method that can be used to kill many pathogens, including anthrax, smallpox, viral hemorrhagic fever, pneumonic plague, bubonic plague, terrestrial fever, drug-resistant tuberculosis, influenza pandemic and severe Potential bioterrorism agents for diseases such as acute respiratory syndrome.

Due to its bactericidal effect on microorganisms, the application of ultraviolet rays has also been extended to the food processing industry, sewage purification, ventilation and air-conditioning system disinfection, room and surface disinfection, etc. Some people also use it to kill human pathogens transmitted through water (Bacteria, viruses and protozoa).

In the field of food processing, ultraviolet light shows great potential in surface disinfection of fresh-cut fruits and vegetables. It can slow down the deterioration of fruits and vegetables, extend storage life, and become a chemical fungicide such as titanium dioxide (TiO2) and chlorine. Effective alternatives.

Ultraviolet lamp can effectively fight various microorganisms, and does not produce chemical residues or other by-products, and does not affect water quality, so it can also be used for sewage treatment. There are also companies that install ultraviolet lamps on faucets and drinking fountains.

Another important use of ultraviolet light is air disinfection. A variety of fungi, bacteria, and viral pathogens may be transmitted by droplets in the air, such as Mycobacterium tuberculosis, influenza virus, SARS coronavirus, Aspergillus and other Legionella bacteria. 30 minutes of ultraviolet light can effectively reduce the microbial in the air. concentration. Therefore, in addition to the ultraviolet lamps widely used in surgical operating rooms and microbiological laboratories, installing ultra-short ultraviolet lamps in air handling devices and ventilation systems can also reduce the concentration of airborne bacteria, fungi and viruses in indoor air.

The initial success of air disinfection in surgical operating rooms stimulated the promotion and application of ultra-short ultraviolet rays in hospitals. For example, installing ultra-short ultraviolet lamps in infant wards and neonatal intensive care units can prevent respiratory infections; ultra-short ultraviolet rays can also be used to reduce the colonization of microorganisms in the trachea and treat respiratory-related pneumonia.

Once the potential of ultraviolet rays to kill bacteria, viruses, fungi and other microorganisms is understood, people are more and more interested in increasing the utilization of ultraviolet rays. But in fact, UV sterilization has two defects in dealing with bacteria:

First, ultraviolet light not only affects bacteria, but also has adverse effects on mammalian cells. Second, the spores of bacteria have strong resistance to ultraviolet light, which is worrying to some extent. For example, the dormant spores of Bacillus subtilis and other bacillus are 5 to 50 times more resistant to ultraviolet radiation than the corresponding growing cells.

The reason why    spores have such a tenacious resistance is mainly because there is a unique DNA repair enzyme in the spores called spore photoproduct lyase (SP lyase). During the germination of endospores, SP lyase can specifically repair DNA damage induced by ultraviolet rays. Bacterial spores are extremely resistant to physical damage such as heat, ionization, ultraviolet and gamma radiation, osmotic pressure, and drying. Spores can also protect bacteria from chemical and biological disinfectants, such as iodine, peroxides, and alkylating agents. Therefore, even rough physical and chemical methods cannot remove bacterial spores.

The so-called wildfire is endless, and the spring breeze blows again. Therefore, it is urgent to expand other more effective sterilization methods.

Photocatalytic sterilization technology

Ultra-short ultraviolet UVC can directly act on and kill various pathogens without damaging the body, while near-ultraviolet UVA has no bactericidal effect and has certain harm to the human body. However, when the near-ultraviolet UVA in the ultraviolet rays is used in combination with some photocatalytic media (such as titanium dioxide and psoralen), it can have unexpected effects.

(1) Photocatalyst sterilization technology

Titanium dioxide is a chemically stable inert substance that can continuously exert antibacterial effects under light conditions. It has three main crystal types: anatase, rutile and brookite. Studies have shown that anatase enzyme is the most effective photocatalyst, while rutile has lower activity. Surprisingly, the mixture of anatase and rutile, or when the anatase enzyme is doped with metals such as sulfur, anions, or silver, has a more efficient photocatalytic effect than 100% anatase. And the inactivation effect of the virus is better. In addition, compared to bulk titanium dioxide materials, titanium dioxide nanoparticles have better performance in inactivating pathogens. Researchers refer to those photo-semiconductor materials with photocatalytic function represented by nano-scale titanium dioxide as photocatalysts.

When near ultraviolet UVA is irradiated on titanium dioxide, incident photons will activate the production of active oxygen. The photocatalytic surface of titanium dioxide directly contacts the cell wall, causing oxidative damage to the cell wall. Cells that were initially damaged by oxidative damage are still alive. However, the loss of local cell walls makes the cytoplasmic membranes of these cells vulnerable to oxidative damage. As a result, photocatalysis gradually increases the permeability of the cells, which ultimately leads to the leakage of cell contents. , Which in turn leads to cell death. In addition, it seems that titanium dioxide can also enter the membrane to damage cells, causing direct damage to intracellular components, thereby accelerating cell death

Photocatalyst sterilization technology has a good sterilization effect on a variety of microorganisms, and can widely kill Gram-negative and Gram-positive bacteria, fungi (single cell and filamentous), protozoa, algae, mammalian viruses and Phage.

In recent decades, the incidence of antibiotic-resistant bacterial infections has risen sharply, and has therefore become one of the most important issues in the field of public health. Titanium dioxide has the potential to inactivate antibiotic-resistant bacteria. Researchers have discovered that UVA-activated titanium dioxide can be used to inactivate methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Acinetobacter baumannii (MDRAB), and vancomycin-resistant enterococci in suspension. When UVA is present, titanium dioxide can effectively reduce the content of resistant microorganisms in the suspension.

For those bacterial spores that are resistant to ultraviolet light, photocatalyst sterilization technology can also play a certain role. Studies have shown that this technology can reduce the survival rate of anthrax spores and kill about 25% of spores.

In medicine, photocatalyst technology can sterilize wards and operating rooms, and can also be used to treat tumors; in terms of oral health, photocatalyst technology can be used for tooth cleaning and bleaching; in terms of beauty and health, nano-titanium dioxide can also be used to make sunscreen cosmetics , Most sunscreens in Japan contain titanium dioxide [3].

(2) Psoralen and UVA inactivation method (PUVA)

Psoralen is a natural furanocoumarin, extracted from a plant called Amiqin in Egypt. They are also found in celery, parsley, carrots, parsnips and other vegetables. Since ancient times, people have known that after eating these foods, exposure to the sun can cause photosensitive skin reactions similar to sunburn.

In 1982, psoralen was combined with UVA light (PUVA) and began to be used to treat psoriasis (commonly known as psoriasis, which is a chronic inflammatory skin disease). Patients took oral psoralen compounds or used supplements in the bath. Osteostatin, under the stimulation of UVA, psoralen can promote the synthesis of melanin and deposit it under the skin, thereby effectively curing skin diseases such as vitiligo and psoriasis.

Psoralen molecule has the correct structure and shape, can be inserted between two strands of DNA in a double helix structure, and induces the formation of inter-strand covalent cross-links between the reverse complementary nucleic acid strands under light, thereby destroying the DNA structure. Therefore, PUVA has been used to inactivate bacteria, viruses and protozoa in platelets and plasma blood components.

The photochemical inactivation activity of PUVA can kill pathogens, but it can maintain its metabolic capacity (Killed But Metabolically Active, KBMA), which means that this method can inactivate the entire microorganisms, but still maintain immunogenicity, so Can be used for vaccine development. Some research groups have developed recombinant and pathogen-derived KBMA vaccines using intact microorganisms. These microorganisms have been proven to be harmless and immunogenic. This technology can prevent specific diseases and reduce the occurrence of infectious diseases in animal models. Brings new hope.

In addition, PUVA can also be used to inactivate many other viruses, such as Dengue virus, Chikungunya virus, SARS-CoV, etc. Some researchers use acid lime and synthetic psoralen to enhance the sun’s disinfection effect on water. They conducted laboratory evaluations of the Norovirus, E. coli and MS2 phage contained therein, and found that the synergistic effect of psoralen and acid lime extract with ultraviolet radiation can accelerate the inactivation of microorganisms.

The mechanism and application of blue light inactivating pathogens

Although the bactericidal effect of ultraviolet light is well known, it has the risk of causing skin damage and carcinogenesis. A more serious defect is that ultraviolet light has no or only weak killing effect on bacterial spores. Bacterial preparations used in biological weapons are usually selected from bacteria that exhibit antibiotic resistance or can form endospores and biofilms, so that they can be more resistant to existing antibacterial treatment options. In order to exert the greatest destructive ability. For these reasons, researchers still need to study the highly toxic bacteria, fungi and viruses in order to successfully defeat possible biological warfare.

Current research shows that blue light in visible light also has a sterilizing effect, and its wavelength range is 435-450 nanometers. Compared with ultraviolet radiation, blue light can not only kill antibiotic-resistant bacteria and bacterial spores, but also has much less harm to mammalian cells. Therefore, the use of visible light for sterilization has obvious advantages.

Blue light with a wavelength of 405 nm shows a broad-spectrum antibacterial effect on Gram-negative bacteria and Gram-positive bacteria. At present, some people have proposed using blue light as an alternative therapy to treat some bacterial infections that are resistant to methicillin and penicillin. The mechanism of blue light killing antibiotic-resistant bacteria may be that it can be absorbed by the porphyrin produced by the bacteria, leading to an increase in free radicals, which in turn affects cell plasma membrane proteins and DNA, or directly affects the bacteria’s light-resistant pigment.

“On the other hand, high-intensity blue light with a wavelength of 405 nanometers can also effectively inactivate Bacillus cereus, Bacillus megaterium, Bacillus subtilis and Clostridium difficile. This is an oxygen-dependent process. The 405-nanometer blue light may interact with the photo-induced chromophore in the bacteria, such as coproporphyrin, and then produce singlet oxygen in Bacillus and Clostridium, which is toxic to cells. Of reactive oxygen species, thereby causing damage to bacteria.

However, it should be noted that blue light can not only regulate the vitality of bacteria, inhibit the formation of biofilms, enhance the photo-inactivation effect on bacteria, but also enhance the virulence factors of bacteria.

High-intensity 405-nanometer light can be used in medical, military and agricultural fields to prevent and control the exposure of Bacillus anthracis and Bacillus cereus, as well as disinfection of air, contact surfaces and medical equipment. The blue light treatment devices and blue light washing machines for acne that are currently on the market are also based on the principle of blue light sterilization.

photodynamic therapy

Photodynamic therapy (PDT) is a non-invasive treatment method that uses non-toxic photosensitizers and harmless visible or near-infrared light to generate singlet oxygen and other reactive oxygen species. These reactive oxygen species can act on nucleic acids, proteins, and Biological macromolecules such as saturated fatty acids cause cell damage. For example, when using photodynamic therapy to treat cancer, reactive oxygen species can cause damage to these key biomolecules in tumor cells and trigger cell apoptosis. The biological targets of photodynamic therapy (proteins, lipids, nucleic acids) are the main components of all kinds of microorganisms and their derivatives. Therefore, photodynamic therapy can destroy all known biological weapons.

The short-lived reactive oxygen species produced by photodynamic inactivation is the main cause of damage to the key molecular targets of the virus. Singlet oxygen and other reactive oxygen species (hydrogen peroxide, superoxide, and hydroxyl radicals) can attack different viral targets, such as viral envelopes, proteins, capsids, core proteins, and nucleic acids, thereby making the virus lose its infectivity. Studies have shown that enveloped viruses can be inactivated due to protein damage. Since photodynamic inactivation can damage viral proteins, even non-enveloped viruses can be effectively inactivated.

For different types of mammalian viruses and bacteriophages, whether they are enveloped or non-enveloped viruses, whether they are DNA or RNA viruses, different types of photosensitizers can all play an effective role in the photodynamic inactivation of the virus. effect.

Photodynamic inactivation is one of the few treatments that can inactivate toxins and virulence factors produced by pathogens. The photodynamic effects of reactive oxygen species can attack the oxidized molecular characteristics of toxin molecules themselves, such as sulfur atoms, aromatic rings, heterocycles, unsaturated double bonds, amino groups, etc. These oxidation reactions can interfere with the conformation of the toxin or change its functional group, thereby destroying its biological function.

It is recommended to use photodynamic therapy for sterilization operations because it has two significant advantages:

One is that photodynamic therapy is more environmentally friendly than other chemical disinfectants. After disinfecting houses or cars, the remaining photosensitizer can be decomposed by sunlight;

“The second reason is that photodynamic therapy has high selectivity. It can selectively target specific cells or tissue types through photosensitizers, and it can also selectively target certain areas by controlling the illuminated area.

By using appropriate photosensitizers and light, photodynamic therapy can be used to kill pathogens in water, vehicles and equipment and other surfaces, food, skin, and wounds. It can even treat pathogens that cause humans or animals before systemic invasion occurs. Local infection.

Femtosecond laser’s antibacterial effect

Femtosecond Lasers can be used for sterilization in addition to myopia surgery. Femtosecond laser refers to a laser with a pulse time of 10-15 seconds, which can destroy transparent or semi-crystalline biological tissues and is a new method to kill pathogens.

Femtosecond lasers use different mechanisms to inactivate different microorganisms: when inactivating viruses, the femtosecond laser can break hydrogen bonds and hydrophobic bonds in the protein shell of the virus particle, separate weak protein connections, or cause viral capsids and Envelope proteins selectively aggregate to inactivate the virus; while inactivating bacteria, the inactivation of bacteria is related to the DNA damage caused by visible femtosecond laser irradiation.

Research found that the visible femtosecond laser or near-infrared sub-picosecond fiber laser can inactivate a variety of viruses, including M13 bacteriophage, murine cytomegalovirus, tobacco mosaic virus, human papilloma virus and human immunodeficiency virus.

Conclusion

Light-mediated technology has a wide range of applications in combating all known pathogens. Wavelengths ranging from short ultraviolet to near infrared (used alone or in combination with photosensitizers) can be used to kill or inactivate Gram-positive bacteria and leather. Ran’s negative bacteria, fungi, endospores, parasites, viruses, and even protein toxins.

With different types of microorganisms and their derivatives, different wavelengths of light used, and whether photosensitizers are used, the mechanism by which light-mediated technologies work may also be different, but these technologies mainly target two types of targets, such as UVC And PUVA targets the nucleic acids of pathogens, while blue light and photodynamic therapy target photolyzed oxidized proteins. Therefore, when any large-scale biological attack occurs, you can try to use these light-mediated sterilization technologies to respond.

Notes and references

[1] Fatma Vatansever, Cleber Ferraresi and et al., Can biowarfare agents be defeated with light? Virulence 4:8, 796–825

[2] Note: We know that ultraviolet light is invisible light, but why do ultraviolet lamps in daily life mostly emit blue-violet light? In fact, although the ultraviolet wavelength of germicidal ultraviolet lamps is 254 nanometers, it belongs to invisible light and is invisible to the naked eye. However, in the mercury spectrum emitted by the low-pressure mercury in the lamp after being bombarded by electrons, in addition to the main component of ultraviolet light with a wavelength of 254 nanometers, it also includes blue and violet light in the visible light range. In this way, the ultraviolet lamp can not only play the bactericidal effect of ultraviolet rays, but also remind the user whether the ultraviolet lamp is turned on in the environment where the user is located, thereby preventing the harm of ultraviolet rays to the human body.

[3] Wang Yuhui, Xu Gaotian, Development and Application of Photocatalyst Technology, Chemical Engineer, 1002-1224 (2004) 12-0038-04

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