Cell killing agents, disinfecting compositions and methods for physically destroying target cells in vitro

Abstract

To provide a cell killing agent capable of suppressing side effects and the emergence of drug-resistant bacteria and more effectively and efficiently killing cancer cells and various pathogenic bacteria.SOLUTION: Provided is a cell killing agent comprising: a particle that is a photocatalyst; a substance provided on the surface of the particle to specifically recognize target cells; and a modifying substance provided on the surface of the particle and having cell permeability to a target cell. The particle is composed of a compound semiconductor. The compound semiconductor comprises a first semiconductor and a second semiconductor. The particle has a core-shell structure in which one of the first semiconductor and the second semiconductor serves as a core and the other thereof serves as a shell. The band structure of the particle is type II. The highest energy level in the valence band of the first semiconductor is more positive than the oxidation potential of water. The lowest energy level in the conductive band of the second semiconductor is more negative than the reduction potential of water.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a cell killing agent , murder The present invention relates to compositions for fungi and methods for physically disrupting target cells in vitro. [Background technology]

[0002] Chemotherapy is the most common conventional cancer treatment. In chemotherapy, anticancer drugs are administered to cancer cells that are dividing and proliferating, but they also affect fast-dividing normal cells, which can easily cause side effects such as nausea, hair loss, and white blood cell reduction.

[0003] In addition, antibiotics and antiviral drugs are used to treat infectious diseases against pathogenic bacteria and viruses. However, genetic mutations occur frequently in these pathogenic bacteria and viruses, and there is a risk that antibiotics and antiviral drugs will lose their effectiveness if drug-resistant bacteria and viruses are developed.

[0004] As an alternative to the above-mentioned drug-based treatments, photocatalytic treatments are being considered. For example, Patent Document 1 discloses an antitumor agent that includes titanium oxide particles and a nonionic water-soluble polymer that is bonded to the surface of the titanium oxide particles via various functional groups. Patent Document 1 proposes a mechanism in which the titanium oxide particles are activated to generate radical species by irradiating the antitumor agent with ultrasound or ultraviolet light after administration to a cancer patient, and the generated radical species kill cancer cells. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] JP 2008-201797 A Summary of the Invention [Problem to be solved by the invention]

[0006] The present invention has been made in view of the above circumstances, and provides a cell killing agent that can suppress side effects and the emergence of drug-resistant bacteria, and can kill cancer cells and various pathogenic bacteria more effectively and efficiently. Also provided are a pharmaceutical composition, a supplement composition, a sterilizing composition, and a method for physically destroying target cells in vitro, using the cell killing agent. [Means for solving the problem]

[0007] That is, the present invention includes the following aspects. (1) Particles that are photocatalysts; A substance provided on the surface of the particle that specifically recognizes a target cell; A modifying substance provided on the surface of the particle and having cell permeability to the target cell, the particles are made of a compound semiconductor; the compound semiconductor includes a first semiconductor and a second semiconductor; the particle has a core-shell structure in which one of the first semiconductor and the second semiconductor is a core and the other is a shell, The band structure of the particles is type II, the highest energy level in the valence band of the first semiconductor is more positive than the oxidation potential of water; A cell-killing agent, wherein the lowest energy level in the conduction band of said second semiconductor is more negative than the reduction potential of water. (2) The cell-killing agent described in (1), wherein a portion of the core is exposed at the surface of the particle. (3) The cell killing agent according to (1) or (2), wherein the compound semiconductor is at least one selected from the group consisting of metal oxides, metal nitrides, metal oxynitrides, metal carbonitrides, II-VI group semiconductors, and III-V group semiconductors. (4) The cell killing agent according to any one of (1) to (3), wherein the optical absorption edge of the first semiconductor is 700 nm or more and 1000 nm or less. (5) The cell killing agent according to any one of (1) to (4), wherein the particles have an average particle size of more than 1 nm and not more than 1000 nm. (6) The cell killing agent according to any one of (1) to (5), wherein the average particle diameter of the core of the particles is 1 nm or more and 20 nm or less. ( 7 2. A sterilizing composition comprising the cell killing agent according to any one of (1) to (6). ( 8 2. A method for physically disrupting target cells in vitro, comprising: Contacting a target cell with the cell killing agent according to any one of (1) to (6) above, and allowing the cell killing agent to be incorporated into the target cell; Irradiating the target cells into which the cytotoxic agent has been taken with light, causing a photocatalyst contained in the cytotoxic agent to decompose water contained within the target cells by the energy of the light, generate hydrogen and oxygen, and then expanding the target cells with the hydrogen and oxygen, thereby physically destroying them; The method includes: ( 9 ) the target cell is a pathogenic bacterium, 8 ) The method according to claim 1. Effect of the Invention

[0008] According to the cell killing agent of the above embodiment, it is possible to provide a cell killing agent that suppresses side effects and the emergence of drug-resistant bacteria, and can more effectively and efficiently kill cancer cells and various pathogenic bacteria. [Brief description of the drawings]

[0009] [Figure 1A] FIG. 1 is a diagram showing the structure of a photocatalyst according to a first embodiment of the present invention. [Figure 1B] FIG. 2 is a diagram showing the band structure of the photocatalyst according to the first embodiment of the present invention. [Figure 2A] FIG. 4 is a diagram showing the structure of a photocatalyst according to a second embodiment of the present invention. [Figure 2B] FIG. 4 is a diagram showing the band structure of a photocatalyst according to a second embodiment of the present invention. [Diagram 3] FIG. 4 is a diagram showing the structure of a photocatalyst according to a third embodiment of the present invention. [Figure 4]FIG. 11 is a diagram showing the structure of a photocatalyst according to a fourth embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The cell killing agent, pharmaceutical composition, supplement composition, sterilizing composition, and method for physically destroying target cells in vitro according to one embodiment of the present invention (hereinafter abbreviated as "this embodiment") are described in detail below.

[0011] <Cell killing agent> The cell killing agent of the present embodiment contains photocatalyst particles as an active ingredient.

[0012] As used herein, "containing as an active ingredient" means containing a therapeutically effective amount of photocatalyst. As used herein, "therapeutically effective amount" means an amount of photocatalyst, or a combination of photocatalyst and one or more active agents, that induces a biological, medical effect or response desired by a physician, clinician, veterinarian, researcher, or other appropriate professional when administered in accordance with a desired treatment regimen. A preferred therapeutically effective amount is an amount that improves the symptoms of the disease of interest. Also, "therapeutically effective amount" includes a prophylactically effective amount, i.e., an amount suitable for preventing a disease state.

[0013] The particles are composed of a compound semiconductor. In this case, "compound semiconductor" means a semiconductor formed by bonding two or more elements.

[0014] The band structure of the particles is type II. The type II band structure is composed of a second semiconductor, which is a compound semiconductor having a conduction band located at a level where the probability of electrons generated by light absorption is high, and a first semiconductor, which is a compound semiconductor having a valence band located at a level where the probability of holes generated by light absorption is high. In this embodiment, the compound semiconductor constituting the particle includes the first semiconductor and the second semiconductor. The electrons and holes generated by light absorption are separated between different semiconductors, which increases the carrier lifetime. In other words, the type II band structure of the particle can increase the activity of the photocatalyst.

[0015] In a particle, the energy levels (quantum levels), from highest to lowest, are the minimum energy level of the conduction band of the first semiconductor, the minimum energy level of the conduction band of the second semiconductor, the maximum energy level of the valence band of the first semiconductor, and the maximum energy level of the valence band of the second semiconductor.

[0016] The particles have a core-shell structure with either the first or second semiconductor as the core and the other as the shell. Of these, it is preferable that the particles have a core-shell structure with the first semiconductor as the core and the second semiconductor as the shell. This allows efficient cell expansion.

[0017] The first semiconductor constituting the particles is not particularly limited as long as the highest energy level in the valence band is more positive than the oxidation potential of water. The second semiconductor is not particularly limited as long as the lowest energy level in the conduction band is more negative than the reduction potential of water. By using the first semiconductor and the second semiconductor that satisfy such a relationship, the electrons in the conduction band generated by light absorption are used to reduce water (specifically, reduce hydrogen ions derived from water) to generate hydrogen, and the positive holes in the valence band generated by light absorption are used to oxidize water to generate oxygen. In other words, a photocatalyst useful for water splitting can be configured. Specific examples of such compound semiconductors include metal oxides, metal nitrides, metal oxynitrides, metal carbonitrides, II-VI group semiconductors, and III-V group semiconductors. Examples of metal oxides include titanium oxides such as TiO2 and SrTiO3; tantalum oxides such as Ta2O5 and KTaO3; ZnO, ZnGaO, ZrO2, and Nb2O5. Examples of metal nitrides include Ta3N5 and Nb3N5. Examples of metal oxynitrides include NbON and TaON. An example of the metal carbonitride is TaCN. Examples of II-VI group semiconductors include CdTe, CdSe, ZnSe, and CdS. Examples of III-V semiconductors include GaN, InGaN, GaP, InP, and GaAs. Among them, preferred materials for the first semiconductor include Ta3N5, Nb3N5, TaON, NbON, TaCN, CdSe, CdS, InGaN, and the like. Also, preferred materials for the second semiconductor include metal oxides such as TiO2, SrTiO3, and ZnO.

[0018] In the particles, among the compound semiconductors exemplified above, the second semiconductor is preferably formed from a metal oxide. By forming the second semiconductor from a metal oxide, the stability of the particles is improved, and when used in an environment where water is present (i.e., inside the cells of the target cells), deterioration of the semiconductor material can be suppressed, and the durability of the photocatalyst can be improved.

[0019] When the cytocidal agent of this embodiment is administered into the body of a subject, it is preferable that the optical absorption edge of the first semiconductor constituting the particles is 700 nm or more, since visible light is easily absorbed by components in the living body and ultraviolet light causes significant damage to cells. By using a photocatalyst composed of a compound semiconductor that absorbs light in the near-infrared region of 700 nm or more, the efficiency of light utilization in the living body is high and damage to normal cells can be minimized. On the other hand, it is preferable that the optical absorption edge of the first semiconductor is 1000 nm or less, since the energy required for water decomposition can be obtained. Examples of compound semiconductors having an optical absorption edge in the range of 700 nm to 1000 nm include InGaN, NbON, and TaCN.

[0020] Among these, the combination of the first semiconductor and the second semiconductor (first semiconductor / second semiconductor) in the particles is preferably InGaN / TiO2, NbON / TiO2, or TaCN / TiO2.

[0021] The average particle size of the particles is not particularly limited as long as it is a size that can be taken up by target cells, but is preferably greater than 1 nm and less than 1000 nm, more preferably greater than 1 nm and less than 500 nm, even more preferably greater than 1 nm and less than 300 nm, and particularly preferably greater than 1 nm and less than 100 nm. When the average particle size of the particles is equal to or larger than the lower limit, deterioration of the photocatalytic properties due to crystal defects can be suppressed, whereas when the average particle size is equal to or smaller than the upper limit, the particles are easily taken up by target cells.

[0022] In addition, the average particle diameter of the core of the particles is not particularly limited as long as the average particle diameter of the particles falls within the above range, but is preferably 1 nm or more and 20 nm or less, more preferably 1 nm or more and 15 nm or less, and even more preferably 1 nm or more and 10 nm or less. When the average particle size of the core is not less than the above lower limit, deterioration of the photocatalytic properties due to crystal defects can be suppressed, whereas when it is not more than the above upper limit, it is easily taken up by target cells.

[0023] The average particle size of the particles can be measured, for example, from a transmission electron microscope (TEM) image, and is obtained by calculating the average value of the measured particle size values ​​of a plurality of particles (for example, about 100 to 500 particles) using known image analysis software. At this time, all particles contained in one visual field are measured, and the plurality of visual fields are measured until the number of measurements exceeds a lower limit, and then the measurement is set to end when the lower limit is exceeded. Alternatively, the average particle size can be estimated by measuring the particle size by dynamic light scattering, analyzing the particle size by photon correlation spectroscopy, or measuring the particle size by small angle scattering, and analyzing the scattering curve using NANO-Solver. In this specification, the particle size is a circle equivalent diameter.

[0024] The average particle size of the cores can be measured, for example, using a dispersion of core particles produced as an intermediate during the production of the photocatalyst, using a method similar to the method for measuring the average particle size of the particles described above. Alternatively, since the core and shell of a particle are made of different compound semiconductors, if the densities of the materials in these compound semiconductors are different, the particle diameter of the core and the particle diameter of the entire particle can be measured simultaneously based on the difference in electron transmittance.

[0025] The particle has a cell-permeable modifying substance (hereinafter, sometimes simply referred to as a "modifying substance") and a substance that specifically recognizes target cells (hereinafter, sometimes simply referred to as a "specific recognition substance") on its surface. The cell-permeable modifying substance on the surface of the particle allows the particle to penetrate the cell membrane of the target cells. Furthermore, the cell-permeable substance on the surface of the particle allows the cell killing agent of this embodiment to be efficiently taken up only by the target cells. One or more types of modifying substance and one or more types of specific recognition substance may be used, or one or more types of substance that combines cell permeability and the property of specifically recognizing target cells may be used.

[0026] The cell-permeable modifying substance and the substance that specifically recognizes the target cell may be supported on the surface of the particle. Note that, as used herein, "supported" means that the particle and the cell-permeable modifying substance, and the particle and the substance that specifically recognizes the target cell are directly or indirectly bound to each other and are not separated from each other. For example, the cell-permeable modifying substance and the substance that specifically recognizes the target cell can be supported on the surface of the particle via chemical bonding by functional groups such as carboxyl groups, amino groups, thiol groups, and hydroxyl groups, or by physical adsorption. Alternatively, at least one of the cell-permeable modifying substance and the substance that specifically recognizes a target cell may be in a state in which the entire surface of the particle is covered.

[0027] The cells that are targeted by the cell killing agent of this embodiment are not particularly limited, but examples thereof include cancer cells, pathogenic bacteria, and the like.

[0028] Cancer cells are cells that derive from somatic cells and acquire the ability to proliferate indefinitely, and are malignant neoplasms that invade surrounding tissues or cause metastasis. Examples of cancers from which cancer cells originate include breast cancer (e.g., invasive ductal carcinoma, non-invasive ductal carcinoma, inflammatory breast cancer, etc.), prostate cancer (e.g., hormone-dependent prostate cancer, hormone-independent prostate cancer, etc.), pancreatic cancer (e.g., pancreatic ductal carcinoma, etc.), gastric cancer (e.g., papillary adenocarcinoma, mucinous adenocarcinoma, adenosquamous carcinoma, etc.), lung cancer (e.g., non-small cell lung cancer, small cell lung cancer, malignant mesothelioma, etc.), colon cancer (e.g., gastrointestinal stromal tumor, etc.), rectal cancer (e.g., gastrointestinal stromal tumor, etc.), colorectal cancer (e.g., For example, familial colorectal cancer, hereditary nonpolyposis colorectal cancer, gastrointestinal stromal tumor, etc.), small intestine cancer (for example, non-Hodgkin's lymphoma, gastrointestinal stromal tumor, etc.), esophageal cancer, duodenal cancer, tongue cancer, pharyngeal cancer (for example, nasopharyngeal cancer, oropharyngeal cancer, hypopharyngeal cancer, etc.), head and neck cancer, salivary gland cancer, brain tumors (for example, pineal astrocytoma, pilocytic astrocytoma, diffuse astrocytoma, anaplastic astrocytoma, etc.), neurilemmoma, liver cancer (for example, primary liver cancer, extrahepatic bile duct cancer, etc.), kidney cancer (for example, renal cell carcinoma, transitional cell carcinoma of the renal pelvis and ureter, etc.), gallbladder cancer, pancreatic cancer, endometrial cancer, cervical cancer, ovarian cancer (e.g., epithelial ovarian cancer, extragonadal germ cell tumor, ovarian germ cell tumor, ovarian low malignant potential tumor, etc.), bladder cancer, urethral cancer, skin cancer (e.g., intraocular (eye) melanoma, Merkel cell carcinoma, etc.), hemangioma, malignant lymphoma (e.g., reticulum cell sarcoma, lymphosarcoma, Hodgkin's disease, etc.), melanoma, thyroid cancer (e.g., medullary thyroid carcinoma, etc.), parathyroid cancer, nasal cavity cancer, paranasal sinus cancer, bone tumors (e.g., Examples of cancers that may be present include, but are not limited to, osteosarcoma, Ewing's tumor, uterine sarcoma, soft tissue sarcoma, metastatic medulloblastoma, angiofibroma, dermatofibrosarcoma protuberans, retinal sarcoma, penile cancer, testicular tumor, pediatric solid tumors (e.g., Wilms' tumor, pediatric renal tumor, etc.), Kaposi's sarcoma, Kaposi's sarcoma caused by AIDS, maxillary sinus tumor, fibrous histiocytoma, leiomyosarcoma, rhabdomyosarcoma, chronic myeloproliferative disorder, leukemia (e.g., acute myeloid leukemia, acute lymphoblastic leukemia, etc.), and the like.

[0029] Pathogenic bacteria are bacteria that infect humans and animals such as pets such as dogs and cats, and cause diseases or pathological symptoms. Specific examples of pathogenic bacteria include pathogenic Escherichia coli (including enteropathogenic E. coli, enteroinvasive E. coli, enterotoxigenic E. coli, enterohemorrhagic E. coli, and enteroaggregative E. coli), Salmonella, Listeria, Campylobacter, Staphylococcus aureus, and Clostridium perfringens, but are not limited to these.

[0030] Specific examples of cell-permeable modifying substances include polyethylene glycol, membrane-permeable peptides, sugar chains, and liposomes.

[0031] The substance that specifically recognizes a target cell may be any substance that specifically recognizes a target cell, and specifically includes, for example, a ligand, an antibody, an antibody fragment, an aptamer, etc., for a receptor present on the surface of the target cell. The antibody can be prepared, for example, by immunizing an animal such as a mouse with an antigen, a receptor, or a fragment thereof present on the surface of the target cell as an antigen. Alternatively, the antibody can be prepared, for example, by screening a phage library. Examples of the antibody fragment include Fv, Fab, scFv, etc. The above antibody is preferably a monoclonal antibody. Alternatively, the antibody may be a commercially available antibody.

[0032] An aptamer is a substance that has a specific binding ability to a target substance. Examples of aptamers include nucleic acid aptamers and peptide aptamers. Nucleic acid aptamers that have a specific binding ability to a target peptide can be selected, for example, by the systematic evolution of ligand by exponential enrichment (SELEX) method. Furthermore, peptide aptamers that have a specific binding ability to a target peptide can be selected, for example, by the two-hybrid method using yeast.

[0033] The cell killing agent of this embodiment contains a photocatalyst having the above-mentioned configuration, and thus the photocatalyst can be selectively incorporated into the target cells. The incorporated photocatalyst decomposes water in the cells by irradiating light energy, generating hydrogen and oxygen. The generated hydrogen and oxygen become bubbles. The volume of the generated hydrogen and oxygen expands to about 1200 times the volume of the water before decomposition. Since this expanding force is stronger than the force maintaining the cell membrane or cell wall, the target cells can be physically destroyed (burst) by the expanding force.

[0034] The amount of hydrogen and oxygen generated in the living body by the photocatalyst (cytotoxic agent) is extremely small, and therefore has little effect on the human body. In addition, the cytotoxic agent remains in the blood for a certain period of time after administration, and is then excreted from the body. Therefore, it is presumed that the cytotoxic agent of this embodiment suppresses the occurrence of side effects in subjects more than conventional anticancer drugs. In addition, unlike drugs, the cytotoxic agent of this embodiment is less likely to cause drug-resistant bacteria. Furthermore, the photocatalyst, which is the active ingredient of the cell killing agent of the present embodiment, has a type II band structure and can decompose water more efficiently than a conventional photocatalyst made of titanium oxide, so that the cell killing agent of the present embodiment can kill cancer cells and various pathogenic bacteria more effectively and efficiently.

[0035] The cell killing effect of the cell killing agent of this embodiment on target cells can be controlled by the efficiency of the photocatalyst, the number of photocatalysts taken up into the cells of the target cells, the intensity of the irradiated light energy, and the speed at which water is decomposed by the photocatalyst.

[0036] The efficiency of the photocatalyst and the speed at which water is split by the photocatalyst can be controlled by appropriately selecting the above-mentioned compound semiconductors. Among them, photocatalysts in which the combination of the particle core and shell is InGaN / TiO2 are efficient and can split water quickly.

[0037] The number of photocatalysts taken into one target cell can be adjusted appropriately depending on the average particle size of the particles, but for example, when the average particle size of the particles is more than 1 nm and less than 100 nm, it can be 1 to 100,000, preferably 100 to 50,000, and more preferably 1000 to 30,000. By having the number of photocatalysts taken in be equal to or more than the lower limit, a more sufficient cell killing effect can be exerted, while by having the number be equal to or less than the upper limit, it can be more easily taken into the target cell.

[0038] The intensity of the light energy to be irradiated is, for example, 0.01 mW / cm 2 It can be more than 0.1mW / cm 2 It is preferable that the power consumption is 1 mW / cm or more. 2 It is more preferable that the intensity of the irradiated light energy is equal to or greater than the lower limit. By setting the intensity of the irradiated light energy to equal to or greater than the lower limit, the activity of the photocatalyst can be more fully expressed. On the other hand, since the activity of the photocatalyst increases as the intensity of the light energy increases, the upper limit is not particularly limited.

[0039] The photocatalyst may further comprise a labeling substance. By further comprising a labeling substance, it is possible to confirm that the excitation light is irradiated as intended. As the labeling substance, a fluorescent substance that emits fluorescence by excitation light of the same wavelength as the excitation light of the photocatalyst can be appropriately selected and used. Specific examples of the fluorescent substance include known quantum dots, indocyanine green (ICG), protoporphyrin, porphyrin analogs (photosensitizers such as photofrin and laserphyrin), 5-aminolevulinic acid (5-ALA; metabolite protoporphyrin IX (PP IX)), near-infrared fluorescent dyes (e.g., Cy5.5, Cy7, AlexaFluor, rhodamine, etc.), and other known fluorescent dyes (e.g., GFP, FITC (Fluorescein), TAMRA, etc.).

[0040] [Photocatalyst structure] The structure of the photocatalyst is described below. In the following description, in comparing two types of semiconductors, the semiconductor with the higher energy levels of the valence band and the conduction band is the "first semiconductor", and the semiconductor with the lower energy levels of the valence band and the conduction band is the "second semiconductor".

[0041] (First embodiment) Fig. 1A is a diagram showing the structure of a photocatalyst according to a first embodiment of the present invention. As shown in Fig. 1A, a particle 10 is composed of a core 11, a shell 12 covering the core 11, and a modifier substance (modifier substance) 13 having cell permeability bound to the particle surface, i.e., the shell, and a substance (specific recognition substance) 14 that specifically recognizes a target cell. The core 11 is formed from a second semiconductor, and the shell 12 is formed from a first semiconductor.

[0042] Fig. 1B is a diagram showing the band structure of the photocatalyst according to the first embodiment of the present invention. In Fig. 1B, "H2 / H2O" represents the reduction potential of water, "O2 / H2O" represents the oxidation potential of water, and "Eg" represents the band gap. In Fig. 1B and subsequent figures, "H2 / H2O", "O2 / H2O", and "Eg" have the same meanings. In FIG. 1B, particle 10 has a band structure that allows for a charge-separated state with a high probability of electrons being present in the core.

[0043] 1B, the particle 10 has a type II band structure. When light having an energy equal to or greater than the energy corresponding to the band gap is absorbed in the particle 10, electrons in the valence band (e - ) is excited into the conduction band, and a hole (h + ), and electrons in the conduction band (e - ) are then generated. The electrons in the conduction band of the first semiconductor move to the conduction band of the second semiconductor, and the holes in the valence band of the second semiconductor move to the valence band of the first semiconductor. This creates holes (h + ) are abundant in the valence band of the first semiconductor, i.e., in shell 12, and electrons (e -) are abundant in the conduction band of the second semiconductor, i.e., in the core 11. And the holes (h + ) is used in the oxidation reaction of water to produce oxygen (O2), and electrons (e - ) is used in the reduction reaction of water to produce hydrogen (H2).

[0044] In particle 10, the generated hole (h + ) and electrons (e - ) are located in different semiconductors and spatially separated, so carrier recombination is suppressed. Therefore, the carrier life is increased, and the energy conversion efficiency in the photocatalyst can be improved. In addition, the positive holes (h + ) and electrons (e - ) and the generated holes (h + ) and electrons (e-) are close to the surface of the particle 10, which is the active surface of the photocatalyst, so that holes (h + ) and electrons (e - ) can be efficiently used in the oxidation or reduction of water, and the oxygen (O2) and hydrogen (H2) generated by these reactions can effectively kill target cells.

[0045] Second embodiment Fig. 2A is a diagram showing the structure of a photocatalyst according to a second embodiment of the present invention. As shown in Fig. 2A, a particle 20 is composed of a core 21, a shell 22 covering the core 21, and a modifier substance 23 and a specific recognition substance 24 bound to the particle surface, i.e., the shell. The core 21 is formed of a first semiconductor, and the shell 22 is formed of a second semiconductor.

[0046] 2B is a diagram showing the band structure of the photocatalyst according to the second embodiment of the present invention, in which the particle 20 has a band structure that allows a charge separation state in which the probability of holes existing in the core is high.

[0047] As shown in FIG. 2B, the particle 20 has a type II band structure. When light having an energy equal to or greater than the energy corresponding to the band gap is absorbed in the particle 20, electrons in the valence band (e - ) is excited into the conduction band, and a hole (h + ), and electrons in the conduction band (e - ) are then generated. The electrons in the conduction band of the first semiconductor move to the conduction band of the second semiconductor, and the holes in the valence band of the second semiconductor move to the valence band of the first semiconductor. This creates holes (h + ) are abundant in the valence band of the first semiconductor, i.e., in shell 22, and electrons (e - ) are abundant in the conduction band of the second semiconductor, i.e., in the core 21. And the holes (h + ) is used in the oxidation reaction of water to produce oxygen (O2), and electrons (e - ) is used in the reduction reaction of water to produce hydrogen (H2).

[0048] In particle 20, the generated hole (h + ) and electrons (e - ) are located in different semiconductors and spatially separated, so carrier recombination is suppressed. Therefore, the carrier life is increased, and the energy conversion efficiency in the photocatalyst can be improved. In addition, the positive holes (h + ) and electrons (e - ) and the generated holes (h + ) and electrons (e - ) and the surface of the nanoparticle 20, which is the active surface of the photocatalyst, are close to each other, so that the holes (h + ) and electrons (e - ) can be efficiently used in the oxidation or reduction of water, and the oxygen (O2) and hydrogen (H2) generated by these reactions can effectively kill target cells.

[0049] Third embodiment FIG. 3 is a diagram showing the structure of a photocatalyst according to a third embodiment of the present invention. As shown in FIG. 3, the particle 30 is composed of a core 31, a partial shell 32 partially covering the core 31, and a modifier 33 and a specific recognition substance 34 bound to the particle surface, i.e., the shell. The core 31 is formed of a first semiconductor, and the partial shell 32 is formed of a second semiconductor. The particle 20 in the second embodiment differs only in that the partial shell 32 is formed so as to partially cover the core 31, and the shell 22 is not formed so as to cover the entire core 21. The relationship between the band structure of each semiconductor and the band structure of the nanoparticle 30 is the same as that of the second embodiment shown in FIG. 2B, and therefore will not be described.

[0050] In the particle 30, a part of the core 31 is exposed on the surface of the nanoparticle 30, and thus the holes (h + ) and the catalytic surface become closer, and the generated holes (h + ) can be used more efficiently in the oxidation reaction of water. In other words, oxygen (O2) can be released more efficiently, resulting in a higher cell killing effect.

[0051] For the particle 10 in the first embodiment, similarly to this embodiment, it is also possible to configure the shell to cover only a part of the core, rather than the entire core. With this configuration, the electrons (e - ) and the catalytic surface become closer, and the generated electrons (e - This allows hydrogen (H2) to be more efficiently used in the reduction reaction of water, which means that hydrogen (H2) can be released more efficiently, resulting in a higher cell killing effect.

[0052] (Fourth embodiment) FIG. 4 is a diagram showing the structure of a photocatalyst according to the fourth embodiment of the present invention. As shown in FIG. 4, a particle 40 is composed of a core 41, a partial shell 42 partially covering the core 41, and a modifier 43 and a specific recognition substance 44 bound to the particle surface, i.e., the shell. The core 41 is formed of a first semiconductor, and the partial shell 42 is formed of a second semiconductor. The particle 30 in the third embodiment differs only in that the modifier 43 is formed so as to cover the entire shell, and further, the specific recognition substance 44 is bound to the modifier 43. The relationship between the band structure of each semiconductor and the band structure of the nanoparticle 40 is the same as that of the second embodiment shown in FIG. 2B, so the description will be omitted. The modifier 43 is a liposome having a lipid bilayer structure.

[0053] In the particle 40, since the modifier 43 is a liposome, the particle 40 can be taken up into the target cell by endocytosis or phagocytosis, or fusion of the liposome membrane with the cell membrane.

[0054] Similarly to the present embodiment, the particle 10 in the first embodiment and the particle 20 in the second embodiment can also be configured so that the modifier 13 or 23 covers the entire shell, and further, the specific recognition substance 44 binds to the modifier 43. With such a configuration, the particle 10 or 20 can be taken up into the target cell by endocytosis or phagocytosis, or fusion of the liposome membrane with the cell membrane.

[0055] [Photocatalyst manufacturing method] In this embodiment, the photocatalyst can be produced, for example, by first producing intermediate particles made of a compound semiconductor that forms a core, and then coating the surface of the intermediate particles with a compound semiconductor that forms a shell, and then supporting a modifier and a specific recognition substance on the surface of the particles, or by further coating the particles with a modifier and then binding a specific recognition substance onto the modifier.

[0056] The compound semiconductor that forms the core is added to the reaction solvent and mixed, and then the mixed solution is held in a temperature-controllable reaction vessel such as an autoclave vessel at a temperature of about 200° C. to about 400° C. for about 30 minutes to about 3 hours to grow the crystals of the core particles. The particle size of the particles can be appropriately adjusted by changing the heating temperature and heating time. The reaction solvent can be appropriately selected depending on the type of compound semiconductor used to form the core, and examples thereof include diphenyl ether. The obtained core may be used as it is for the reaction with the compound semiconductor that forms the subsequent shell, but from the viewpoint of obtaining a photocatalyst with high purity, it is preferable to purify the core and remove unreacted raw materials, etc. Examples of the method for purifying the core include a method of washing the core with a mixed solvent of a solvent capable of dispersing the particles and a solvent for dissolving and removing unreacted raw materials, etc.

[0057] Next, a layer made of a compound semiconductor that forms a shell is formed on the surface of the core, and the surface is covered. For example, a method for forming a layer made of a compound semiconductor that forms a shell can be a sol-gel method when a shell of a metal oxide is formed, and a shell is formed by hydrolyzing a metal alkoxide on the core particles. Specifically, a metal alkoxide and a reaction promoter such as a surfactant or ammonia water are added to a dispersion of the core particles, and the mixture is stirred at about room temperature for several hours to grow a crystal made of a compound semiconductor that forms a shell on the surface of the core particles, thereby obtaining a photocatalyst.

[0058] In addition, the coverage of the core with the shell can be controlled by changing the heating temperature and heating time during shell formation, the amount of shell material added, etc. For example, by shortening the heating time, the growth of the compound semiconductor forming the shell can be interrupted before it completely covers the core particle, and it is possible to obtain particles 30 in which the shell 32 partially covers the core 31, as in the particle 30 in the third embodiment described above.

[0059] The method for supporting the modifier and the specific recognition substance on the particle surface can be a physical or chemical bond directly or via a linker, etc. Examples of the bonding mode include a coordinate bond, a covalent bond, a hydrogen bond, a hydrophobic interaction, and physical adsorption, and any known bonding method can be used.

[0060] <Pharmaceutical Composition> The pharmaceutical composition of this embodiment is a pharmaceutical composition used for the prevention or treatment of cancer, and contains the above-mentioned cell killing agent.

[0061] According to the pharmaceutical composition of the present embodiment, cancer can be effectively prevented or treated while suppressing side effects and the emergence of drug-resistant bacteria.

[0062] The pharmaceutical composition of this embodiment may further contain a pharma- ceutically acceptable carrier.

[0063] As the pharmaceutically acceptable carrier, those generally used in the preparation of pharmaceutical compositions can be used without any particular limitation. More specifically, for example, binders such as gelatin, corn starch, gum tragacanth, gum arabic, etc.; excipients such as starch and crystalline cellulose, swelling agents such as alginic acid, solvents for injections such as water, ethanol, glycerin, etc.; adhesives such as rubber-based adhesives and silicone-based adhesives, etc. can be mentioned.

[0064] The pharmaceutical composition of the present embodiment may further contain additives, such as lubricants such as calcium stearate and magnesium stearate, sweeteners such as sucrose, lactose, saccharin and maltitol, flavorings such as peppermint and saffron oil, stabilizers such as benzyl alcohol and phenol, buffers such as phosphates and sodium acetate, solubilizers such as benzyl benzoate and benzyl alcohol, antioxidants, and preservatives.

[0065] The pharmaceutical composition of this embodiment can be formulated by appropriately combining the cell killing agent with the pharma- ceutically acceptable carriers and additives described above, and mixing them in a unit dosage form required for generally accepted pharmaceutical practice.

[0066] When the pharmaceutical composition of the present embodiment is a dispersion containing water, it is preferable to store it in a light-shielding container or the like in order to suppress the activity of the photocatalyst. Alternatively, it is preferable to prepare it just before use.

[0067] The pharmaceutical composition of the present embodiment may be in a dosage form for oral use or a dosage form for parenteral use, but is preferably in a dosage form for oral use.Drug forms for oral use include, for example, tablets, capsules, elixirs, microcapsules, etc.Drug forms for parenteral use include, for example, injections, ointments, patches, etc.

[0068] The pharmaceutical composition of the present embodiment may be used in combination with a therapeutic agent for another disease. For example, the cell killing agent may be used in combination with an anticancer agent, an antibiotic, or the like, to more effectively prevent or treat the target disease. The cytocidal agent and the other drug may be in the same formulation or in separate formulations. Each formulation may be administered by the same administration route or by separate administration routes. Furthermore, each formulation may be administered simultaneously, sequentially, or separately at a certain time or period. In one embodiment, the cytocidal agent and the other drug may be in the form of a kit containing them.

[0069] The pharmaceutical composition of the present embodiment may be used in combination with a labeling substance. For example, the cell killing agent may be used in combination with a labeling substance to visualize the delivery of the photocatalyst to the affected area of ​​the disease. Examples of labeling substances include radioisotopes and fluorescent substances. As the radioisotope, a positron-emitting nuclide can be used. Specifically, for example, 55 Co, 64 Cu, 66 Ga, 68 Ga, 76 Br, 89 Zr, 124I. For labeling the photocatalyst with these positron-emitting nuclides, known methods can be used.

[0070] Examples of fluorescent substances include those exemplified above as cell killing agents.

[0071] [Administration method] Subjects to which the antibody is administered include, but are not limited to, humans, monkeys, dogs, cows, horses, sheep, pigs, rabbits, mice, rats, guinea pigs, hamsters, and cells thereof. Among these, mammals or mammalian cells are preferred, and humans or human cells are particularly preferred.

[0072] Administration to patients or animals can be performed by methods known to those skilled in the art, such as intrathecal injection, intraarterial injection, intravenous injection, subcutaneous injection, local injection, intranasal injection, transbronchial injection, intramuscular injection, transdermal injection, or oral injection. The dosage varies depending on the patient's weight and age, the patient's symptoms, the method of administration, etc., but those skilled in the art can appropriately select an appropriate dosage.

[0073] [Light irradiation method] The light source for irradiating the patient or animal with light after administration of the pharmaceutical composition of this embodiment may be any light source that irradiates light with an energy level equal to or greater than that required for the photocatalyst to decompose water, i.e., light with a wavelength shorter than about 1000 nm (>about 1.23 eV), and examples of such light include sunlight, LED, xenon lamp, mercury lamp, laser, etc. That is, after administration of the pharmaceutical composition of this embodiment, the photocatalyst can be activated by exposing the body surface to sunlight. Alternatively, for the purpose of active treatment, light can be irradiated from the body surface using the above-mentioned light source (excluding sunlight), or light can be irradiated to the affected area using a catheter or the like equipped with the above-mentioned light source (excluding sunlight). When a catheter equipped with a laser is used, this can be called phototherapy combining a laser and a photocatalyst.

[0074] <Preventive and therapeutic methods> In one embodiment, the present invention provides a method for preventing cancer, comprising administering to a subject an effective amount of the cell-killing agent. Examples of cancers that are the target of the cancer prevention method of this embodiment include the same cancer types exemplified in the above "Cell Killing Agent". The subject may be a healthy individual, a cancer patient, or a person who may develop cancer. In addition, the subject is not limited to humans, and includes various mammals exemplified in the above "Pharmaceutical Composition".

[0075] In one embodiment, the present invention also provides a method for treating cancer, comprising administering an effective amount of the cell-killing agent to a human or animal patient in need of treatment.

[0076] Alternatively, in one embodiment, the present invention provides a method for treating a cancer, comprising administering to a human or animal patient in need of treatment an effective amount of the cell killing agent; Irradiating a tumor site of the subject with light; The present invention provides a method for treating cancer, comprising:

[0077] As described above, the cytotoxic agent has high catalytic activity, and after administration of the cytotoxic agent, exposure to sunlight alone can be sufficient to exert a cytotoxic effect, but in order to perform treatment more effectively, light can also be actively irradiated. Examples of light sources and irradiation methods include those exemplified in the above "pharmaceutical composition". Examples of cancers that can be treated by the cancer prevention method of this embodiment include the same types of cancers as those exemplified in the above "cell killing agent." Furthermore, examples of animals to be treated include various mammals other than humans exemplified in the above "pharmaceutical composition."

[0078] In one embodiment, the present invention also provides use of the cell-killing agent for the prevention or treatment of cancer. In one embodiment, the present invention also provides use of the cell-killing agent for the manufacture of a pharmaceutical composition for use in the prevention or treatment of cancer.

[0079] <Supplement Composition> The supplement composition of this embodiment is a supplement composition used for preventing cancer and contains the above-mentioned cell killing agent.

[0080] According to the supplement composition of the present embodiment, cancer can be effectively prevented while suppressing side effects and the emergence of drug-resistant bacteria. As described above, the photocatalyst in the present embodiment generates only a very small amount of hydrogen and oxygen in the living body, so it has little effect on the human body, and after administration, it remains in the blood for a certain period of time and is then excreted from the body. Therefore, it is considered that there is little problem in taking it every day from the viewpoint of safety.

[0081] The supplement composition of the present embodiment can further contain known additives that are generally used in food and drink.Additives include, for example, sweeteners such as sugar, fructose, isomerized liquid sugar, glucose, aspartame, stevia, etc., acidulants such as citric acid, malic acid, tartaric acid, etc., excipients such as dextrin and starch, binders, diluents, flavorings, buffers, thickeners, gelling agents, colorants, stabilizers, emulsifiers, dispersants, suspending agents, preservatives, etc.

[0082] The supplement composition of this embodiment may be in a solid form such as a powder or gel, a semi-solid form such as a sol tablet, or a liquid form such as a dispersion.

[0083] When the supplement composition of this embodiment is a dispersant containing water, it is preferable to store it in a light-blocking container or the like in order to suppress the activity of the photocatalyst.

[0084] The supplement composition of this embodiment can be incorporated as a food additive into special purpose foods, nutritional functional foods, nutritional supplements, health foods, foods for specified health uses, and foods with functional claims.

[0085] The amount of photocatalyst in the supplement composition of this embodiment may be an amount that can exert its cell killing effect, and considering the oral administration amount of the above-mentioned pharmaceutical composition and the general intake amount of the target food and drink, the daily intake amount per adult can be about 0.01 μg to 1 g, preferably about 0.05 μg to 100 mg, more preferably about 0.1 μg to 10 mg. For example, in the case of a solid form, it can be 0.5% by mass to 50% by mass, and in the case of a liquid form, it can be 0.1 w / v% to 10 w / v%.

[0086] <Bactericidal composition> The sterilizing composition of the present embodiment contains the above-mentioned cell killing agent.

[0087] The sterilizing composition of the present embodiment can effectively sterilize bacteria, particularly pathogenic bacteria, while suppressing the emergence of drug-resistant bacteria.

[0088] The sterilizing composition of the present embodiment has a sufficient sterilizing effect even with the cell killing agent alone, but may further contain additives having sterilizing and antibacterial effects. Examples of additives having antibacterial effects include sodium sulfite, sodium benzoate, sorbic acid, potassium sorbate, sodium dehydroacetate, butyl paraoxybenzoate, propionic acid, ethylparaben, propylparaben, butylparaben, polyphosphoric acid, polylysine, milt protein extract, ethanol, glycine, glycerin fatty acid ester, sodium acetate, thiamine lauryl sulfate, licorice oil extract, chitosan, moso bamboo extract, lysozyme, rosemary extract, cationic surfactants (benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, etc.), etc.

[0089] The sterilizing composition of the present embodiment can contain other components generally blended into sterilizing compositions, for example, powders such as inorganic pigments and extender pigments, anionic surfactants, cationic surfactants, amphoteric surfactants, nonionic surfactants, esters of fatty acids and polyhydric alcohols such as higher fatty acid alkanolamides and fatty acid monoglycerides, moisturizers, lower alcohols, thickeners, chelating agents, preservatives, colorants, fragrances, and other known additives, within the scope that does not impair the effect of the sterilizing composition of the present embodiment.

[0090] The sterilization composition of this embodiment may be in a solid form such as a powder or gel, a semi-solid form such as a sol tablet, or a liquid form such as a dispersion using water or alcohol (ethanol, etc.) as a solvent.

[0091] When the sterilizing composition of the present embodiment is a dispersant containing water, it is preferable to store it in a light-shielding container or the like in order to suppress the activity of the photocatalyst.

[0092] The amount of photocatalyst in the sterilization composition of this embodiment may be any amount that can exert its cell-killing effect, and can be appropriately adjusted taking into consideration the number of photocatalysts to be taken up into the target cells in the above-mentioned cell-killing agent; for example, in the case of a solid, it can be 0.5% by mass or more and 50% by mass or less, and in the case of a liquid, it can be 0.1% by mass or more and 10% by mass or less.

[0093] [Sterilization method using a sterilizing composition] As a sterilization method using the sterilizing composition, sterilization can be performed by contacting the sterilizing composition of the present embodiment with an object to be sterilized and then irradiating the object with light.

[0094] The object to be sterilized is not particularly limited, but since the sterilization method using the sterilization composition of the present embodiment does not involve heating, it is suitable for use with objects made of heat-sensitive materials or objects that are difficult to sterilize by heating.

[0095] Examples of methods for contacting the sterilizing composition with the target include spraying, misting, immersion (dipping, soaking, etc.), etc. Alternatively, the liquid sterilizing composition can be contacted with the target in the form of a wet wiper impregnated with a base fabric such as paper, nonwoven fabric, absorbent cotton, rayon stable cotton, or a combination of these with a plastic film, etc. Among these, spraying or atomizing is preferred.

[0096] In addition, examples of the light source include the same ones as those exemplified for the pharmaceutical composition above. The intensity of the light to be irradiated may be the same as those exemplified for the cell killing agent above.

[0097] <Method of physically destroying target cells in vitro> The method of the present embodiment is a method for physically destroying target cells in vitro, comprising: contacting the cell killing agent with a target cell to allow the cell killing agent to be incorporated into the target cell; irradiating the target cells into which the cell killing agent has been incorporated with light; Includes.

[0098] According to the method of the present embodiment, the target cells into which the cytotoxic agent has been taken up are irradiated with light, and the photocatalyst contained in the cytotoxic agent decomposes the water contained within the target cells by the energy of the light, generating hydrogen and oxygen. The target cells are then expanded by the hydrogen and oxygen, and the target cells can be effectively physically destroyed in vitro. When the target cells are bacteria, the method of this embodiment can also be called a bactericidal method.

[0099] The target cells include those exemplified as the above-mentioned cell killing agents, and among them, pathogenic bacteria are preferable.

[0100] Methods for contacting the cell killing agent with the target cells include the same methods as those exemplified for the above-mentioned sterilizing composition. In addition, examples of the light source include the same ones as those exemplified for the pharmaceutical composition above. The intensity of the light to be irradiated may be the same as those exemplified for the cell killing agent above. EXAMPLES

[0101] The present invention will be described below with reference to examples, but the present invention is not limited to the following examples.

[0102] [Example 1] (Cancer cell destruction test) 1. Preparation of Cell Killing Agents After adding diphenyl ether, GaI3, InI3, and NaNH2 as a reaction solvent, they were mixed and the mixed solution was kept at a temperature of 300°C for 1 hour. 60 Ga 40 Core particles of photocatalytic crystals were grown, each having an average particle size of 5 nm, and made of N (first semiconductor). The average particle size of the core particles was measured by TEM and dynamic light scattering. Thereafter, the core particles were purified by repeating a centrifugation process using alternately toluene to disperse the core particles and ethanol to remove unnecessary raw materials from the particles, and then dispersed in cyclohexane. Next, titanium tetraisopropoxide, octylphenol ethoxylate as a surfactant, and aqueous ammonia were added to the obtained dispersion of core particles, and hydrolysis was carried out to obtain In 60 Ga 40 Type II core-shell InGaN (core) / TiO (shell) particles were obtained by forming TiO (second semiconductor) with an average particle size of 0.3 nm around the core particle made of N. The average particle size of TiO was measured by TEM and dynamic light scattering. Next, a methanol solution of sodium 3-mercaptopropionate and tetramethylammonium hydroxide was added to the resulting chloroform dispersion of InGaN / TiO2 particles and reacted at 70℃ to modify the carboxyl groups. Furthermore, in order to impart cell permeability and the ability to specifically recognize target cells, a membrane-permeable peptide, arginine peptide (R8), and thiol-terminated folic acid-modified polyethylene glycol, which selectively binds to cancer cells, were mixed with the carboxyl group-modified particles to obtain a photocatalyst for destroying cancer cells.

[0103] 2.Cancer cell destruction test The photocatalyst dispersion (200 nmol / L) obtained in "1." above was sprayed onto HeLa cells, and allowed to be taken up into the cells by endocytosis. The number of photocatalysts taken up per cell was measured by light absorption, and was found to be approximately 20,000. The specific method for measuring the number of photocatalysts taken up per cell by light absorption was as follows: first, a photocatalyst dispersion with a known concentration was sprayed onto the culture medium of HeLa cells to allow the photocatalyst to be taken up, and the remaining photocatalyst dispersion was then recovered. The difference between the concentration of the photocatalyst dispersion before spraying and the concentration of the recovered photocatalyst dispersion was then compared in terms of the amount of light absorption to calculate the amount of photocatalyst taken up. Next, infrared light with a wavelength of 700 nm (energy density 0.1 mW / cm) was applied to the cells. 2 ) for 10 minutes. This caused the water in the cells to be broken down by the photocatalyst, generating hydrogen and oxygen. The cells expanded due to the bubbles of hydrogen and oxygen, which physically destroyed the cell membranes and killed the cancer cells. The death of the cancer cells was confirmed by visual observation using an optical microscope. [Industrial Applicability]

[0104] The cell killing agent of this embodiment can suppress side effects and the emergence of drug-resistant bacteria, and can kill cancer cells and various pathogenic bacteria more effectively and efficiently. [Explanation of symbols]

[0105] 10,20,30,40…particles (photocatalyst) 11,21,31,41...Core 12,22,32,42…Shell 13, 23, 33, 43...Modifiers with cell permeability (modifiers) 14, 24, 34, 44…Substances that specifically recognize target cells (specific recognition substances)

Claims

1. Particles that are photocatalysts; A substance provided on the surface of the particle that specifically recognizes a target cell; A modifying substance provided on the surface of the particle and having cell permeability to the target cell, the particles are made of a compound semiconductor; the compound semiconductor includes a first semiconductor and a second semiconductor; the particle has a core-shell structure in which one of the first semiconductor and the second semiconductor is a core and the other is a shell, The band structure of the grain is type II, the highest energy level in the valence band of the first semiconductor is more positive than the oxidation potential of water; A cell-killing agent, wherein the lowest energy level in the conduction band of said second semiconductor is more negative than the reduction potential of water.

2. The cell-killing agent of claim 1 , wherein a portion of the core is exposed from the shell at the surface of the particle.

3. The cell killing agent according to claim 1 or 2, wherein the compound semiconductor is at least one selected from the group consisting of metal oxides, metal nitrides, metal oxynitrides, metal carbonitrides, II-VI group semiconductors, and III-V group semiconductors.

4. The cell killing agent according to any one of claims 1 to 3, wherein the optical absorption edge of the first semiconductor is 700 nm or more and 1000 nm or less.

5. The cell killing agent according to any one of claims 1 to 4, wherein the average particle size of the particles is greater than 1 nm and not greater than 1000 nm.

6. The cell killing agent according to any one of claims 1 to 5, wherein the average particle diameter of the core of the particle is 1 nm or more and 20 nm or less.

7. A bactericidal composition comprising the cell killing agent according to any one of claims 1 to 6.

8. 1. A method for physically disrupting target cells in vitro, comprising: Contacting a target cell with the cell killing agent according to any one of claims 1 to 6 to allow the cell killing agent to be incorporated into the target cell; and irradiating the target cells into which the cell-killing agent has been incorporated with light.

9. The method of claim 8 , wherein the target cell is a pathogenic bacterium.

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