A ruthenium complex and a preparation method and application thereof

Abstract

The application discloses a ruthenium complex and a preparation method and application thereof, and has the following structural formula: wherein X ‑ represents an anion. The ruthenium complex has a strong photodynamic therapy effect on a human non-small cell lung cancer cell line (A549 cells). The ruthenium complex has a strong ability to inhibit the growth and proliferation of the human non-small cell lung cancer cells under light (IC 50 50 of 0.84 muM), and the cytotoxicity of the ruthenium complex is only 14.56 muM under dark conditions, and the photo treatment index PI is as high as 17.3. This is of great significance to the research on metal drugs for resisting non-small cell lung cancer.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical chemistry, and in particular to a ruthenium complex, its preparation method, and its application. Background Technology

[0002] Lung cancer, also known as primary bronchogenic carcinoma, is a common malignant tumor of the lung originating from the trachea, bronchial mucosa, or glands. Based on histopathological characteristics, it is mainly classified into non-small cell lung cancer (NSCLC) and small cell lung cancer. NSCLC, which includes various types such as adenocarcinoma and squamous cell carcinoma, accounts for a relatively high proportion of patients. Therefore, researching drugs for the treatment of NSCLC is of great significance.

[0003] Non-small cell lung cancer (NSCLC) has been a hot research topic in lung cancer treatment due to its complex biological characteristics and diverse clinical manifestations. In recent years, transition metal iridium complexes have become promising photosensitizers (PS) in photodynamic therapy (PDT) due to their unique photophysical properties, such as large Stokes shift, strong spin coupling, high luminescence efficiency, long phosphorescence lifetime, and efficient triplet exciton generation. These novel photosensitizers can induce photochemical reactions within cells by absorbing light of specific wavelengths, thereby inducing tumor cell death and providing a new strategy for the treatment of NSCLC.

[0004] Despite significant advancements in the application of ruthenium complexes in phototherapy (PDT), the treatment of non-small cell lung cancer (NSCLC) still faces numerous challenges. First, NSCLC exhibits high heterogeneity; tumors from different patients show significant differences in gene expression, metabolic pathways, and the immune microenvironment, making single-treatment strategies often ineffective. Second, the issues of metastasis and recurrence in NSCLC remain to be addressed. Even with comprehensive treatment including surgical resection and radiotherapy / chemotherapy, some patients still experience recurrence or distant metastasis, leading to treatment failure.

[0005] Therefore, to further improve the treatment outcomes of non-small cell lung cancer (NSCLC) and reduce the risk of recurrence and metastasis, it is necessary to continuously explore new treatment strategies and drugs. This includes developing novel photosensitizers with higher efficacy and lower side effects, researching targeted drugs that target specific sites in NSCLC, and exploring novel treatment methods such as immunotherapy and gene therapy. Through these efforts, it is hoped that more effective treatment options will be available for NSCLC patients, improving their survival rate and quality of life. Summary of the Invention

[0006] This invention aims to address at least one of the technical problems existing in the prior art. To this end, this invention proposes a ruthenium complex with a novel structure that inhibits the proliferation of non-small cell carcinoma, providing a new direction for the treatment of non-small cell carcinoma.

[0007] According to one aspect of the present invention, a ruthenium complex having the following structural formula is provided:

[0008]

[0009] Among them, X - Represents anions.

[0010] According to a preferred embodiment of the present invention, at least the following beneficial effects are achieved: the ruthenium complex of the present invention exhibits a strong photodynamic therapeutic effect on the human non-small cell lung cancer cell line (A549 cells). Under light irradiation, it has a strong ability to inhibit the growth and proliferation of human non-small cell lung cancer cells (IC549). 50 The phototoxicity was 0.84 μM, while under dark conditions, its cytotoxicity was only 14.56 μM, and the phototherapy index (PI) was as high as 17.3. This is of great significance for the research of metal drugs for the treatment of non-small cell lung cancer.

[0011] In some embodiments of the present invention, X in the complex - Halogen ions, trifluoromethanesulfonate ions, or PF6 - .

[0012] In some preferred embodiments of the present invention, X in the complex - For PF6 - It can improve the solubility of ruthenium complexes, thereby enhancing their antitumor effects.

[0013] According to another aspect of the present invention, a method for preparing the above-mentioned complex is provided, comprising the following steps:

[0014] S1. with Ru 3+ The precursor compound was prepared by heating 2,9-dimethyl-2,9-phenanthroline (2,9-dmp) in a solvent.

[0015] S2. React the precursor compound obtained in step S1 with AgX and 1,6-dihydroxyphenazine to generate a ruthenium complex.

[0016] The preparation method according to a preferred embodiment of the present invention has at least the following beneficial effects: the preparation method of the present invention is simple to operate and has good prospects for industrial application.

[0017] In some embodiments of the present invention, step S1 specifically includes mixing ruthenium(III) trichloride or its hydrate, a metal halide and 2,9-dimethyl-1,9-phenanthroline and adding it to a solvent, and reacting under heating.

[0018] In some preferred embodiments of the present invention, Ru 3+ The molar ratio of metal halide and 2,9-dimethyl-1,4-phenanthroline is 2:14-16:4-4.4.

[0019] In some preferred embodiments of the present invention, Ru 3+ The molar ratio of metal halide and 2,9-dimethyl-1,4-phenanthroline is 2:15:4.

[0020] In some embodiments of the present invention, the solvent is selected from at least one of anhydrous N,N-dimethylformamide (DMF) and anhydrous acetonitrile.

[0021] In some embodiments of the present invention, step S1, the reaction under heating includes at least one of the following conditions:

[0022] 1) The temperature is 120–160℃;

[0023] 2) The time is 6 to 14 hours;

[0024] 3) The heating method is heating reflux.

[0025] In some preferred embodiments of the present invention, in step S1, the reaction under heating includes at least one of the following conditions:

[0026] 1) The temperature is 140℃;

[0027] 2) The time is 8 to 12 hours;

[0028] 3) The heating method is heating reflux.

[0029] Preferably, the metal halide is selected from lithium chloride. Lithium chloride and other metal halides provide a certain amount of chloride ions to prevent the formation of trisubstituted ruthenium, and can be other trivalent ruthenium halides.

[0030] In some embodiments of the present invention, step S2 specifically includes dissolving the precursor compound and AgX in an alcohol solvent, reacting them under heating, and then reacting them with 1,6-dihydroxyphenazine under alkaline and heating conditions to obtain the ruthenium complex.

[0031] In some embodiments of the present invention, the AgX is silver hexafluorophosphate, silver trifluoromethanesulfonate, or silver halide.

[0032] In some embodiments of the present invention, the alcohol solvent is at least one of methanol or ethanol.

[0033] In some embodiments of the present invention, the temperature of the two heating processes in step S2 is independently selected from 80 to 85°C, and the time is independently selected from 0.5 to 13 hours.

[0034] In some preferred embodiments of the present invention, the first heating time in step S2 is 1 hour and the second heating time is 12 hours.

[0035] In some preferred embodiments of the present invention, the heating temperature in step S2 is 85°C for both heating processes.

[0036] In some embodiments of the present invention, the molar ratio of the precursor compound to AgX and 1,6-dihydroxyphenazine is 1:2 to 2.2:1 to 1.1.

[0037] In some preferred embodiments of the present invention, the molar ratio of the precursor compound to AgX and 1,6-dihydroxyphenazine is 1:2:1.

[0038] In some preferred embodiments of the present invention, the pH of the alkaline conditions is 12 to 14. An alkaline environment is created by adding alkaline substances such as sodium hydroxide.

[0039] According to another aspect of the present invention, the use of the above-mentioned complex in the preparation of antitumor drugs is proposed.

[0040] According to a preferred embodiment of the present invention, the application has at least the following beneficial effects: the complex of the present invention can generate superoxide anions under light irradiation. Superoxide anions are generally associated with oxidative stress in organisms and can participate in various physiological and pathological processes as signaling molecules. Therefore, it can kill tumor cells or inhibit their growth by inducing oxidative stress. The complex of the present invention has a strong ability to generate superoxide anions after light irradiation, which can induce oxidative stress in tumor cells. Therefore, it has good anti-tumor potential, thus indicating its promising application prospects in the field of anti-tumor drugs.

[0041] In some embodiments of the present invention, the antitumor drug is an anti-non-small cell lung cancer drug. The complex of the present invention has a strong inhibitory effect on the proliferation of non-small cell lung cancer cells and has good application prospects in the treatment of non-small cell lung cancer.

[0042] In some embodiments of the present invention, the non-small cell lung cancer is A549 cell line lung cancer.

[0043] In some embodiments of the present invention, the anti-non-small cell lung cancer drug is a photodynamic therapy drug.

[0044] In some embodiments of the present invention, the excitation wavelength of the photodynamic therapy drug is 400–635 nm.

[0045] In some embodiments of the present invention, the excitation wavelength is 635 nm.

[0046] In some embodiments of the present invention, the medicament further includes a pharmaceutically acceptable carrier and / or excipient. That is, the medicament or photosensitizer uses a ruthenium complex as the main active ingredient, is mixed with a pharmaceutically acceptable carrier and / or excipient to prepare a composition, and is then formulated into a clinically acceptable dosage form.

[0047] In some embodiments of the present invention, the excipient refers to a diluent, binder, lubricant, disintegrant, solubilizer, stabilizer, and other pharmaceutical matrix that can be used in the pharmaceutical field.

[0048] In some embodiments of the invention, the different pharmaceutical excipients used in the drug dosage form may vary depending on the specific medical application. Pharmaceutical excipients can be used to adjust the solubility and bioavailability of photocatalysts, increase their stability, modulate the host's immune response, and act as emulsifiers, antioxidants, aerosol propellants, tablet binders, and tablet disintegrants. Preferred pharmaceutical excipients include, but are not limited to, binders / fillers, coating agents, disintegrants, lubricants, and sweeteners adapted to the use of photosensitizers.

[0049] In some embodiments of the present invention, the carrier is a functional pharmaceutical excipient acceptable in the pharmaceutical field, including surfactants, suspending agents, emulsifiers, and some novel pharmaceutical polymers, such as cyclodextrin, chitosan, polylactic acid (PLA), polyglycolic acid-polylactic acid copolymer (PLGA), hyaluronic acid, etc.

[0050] In some embodiments of the present invention, there are no particular limitations on the dosage form of the above-mentioned drugs. The active substance can be administered together with an assimilated edible carrier, an inert diluent, or directly combined with food. Drug dosage forms include, but are not limited to, hard-shell or soft-shell gelatin capsules, tablets, pills, powder for injection, solutions, suspensions, elixirs, syrups, wafers, gels, buccal or sublingual tablets, films, suppositories, and enemas.

[0051] In other embodiments of the invention, the photocatalyst of the invention can be formulated without any formulation adjuvants or using other drug delivery systems known in the prior art, such as forming components with liposomes, vectored and non-vectored proteins, organic and inorganic nanoparticles, nanoemulsions and microemulsions, nanocrystals, individual solvents or suitable solvent mixtures, with components such as lactose, polyvinylpyrrolidone (PVP), etc.

[0052] In some embodiments of the present invention, the prepared drug may be administered orally, via any part of the gastrointestinal tract (e.g., mouth, pharynx, esophagus, stomach, small intestine (duodenum, jejunum, ileum), large intestine (cecum, colon, rectum) and anus), or via parenteral route (e.g., intravenous, subcutaneous, intraperitoneal or local). If certain drugs are unstable under gastric conditions, they may be prepared as enteric-coated tablets.

[0053] According to another aspect of the present invention, an antitumor metal photosensitizer is provided, wherein the active ingredient of the antitumor metal photosensitizer comprises the above-mentioned ruthenium complex.

[0054] Other features and advantages of the invention will be set forth in the description which follows, and will be apparent in part from the description, or may be learned by practicing the invention. Attached Figure Description

[0055] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the description of the embodiments taken in conjunction with the following drawings, in which:

[0056] Figure 1 The ultraviolet absorption spectrum of the ruthenium complex prepared in the embodiments of the present invention is shown below.

[0057] Figure 2 This is a graph showing the test results of the photocatalytic oxidation of NADH by the ruthenium metal complex prepared in the embodiments of the present invention;

[0058] Figure 3 This is a graph showing the test results of the photocatalytic oxidation of NADPH by the ruthenium metal complex prepared in the embodiments of the present invention;

[0059] Figure 4 This is a graph showing the test results of the ability of the ruthenium metal complex prepared in the embodiments of the present invention to generate singlet oxygen.

[0060] Figure 5 The figure shows the results of dark toxicity and phototoxicity tests on the ruthenium complex prepared in the embodiments of the present invention against human non-small cell lung cancer cells (A549). Detailed Implementation

[0061] The following will clearly and completely describe the concept and technical effects of the present invention in conjunction with embodiments, so as to fully understand the purpose, features and effects of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are all within the scope of protection of the present invention. Unless otherwise specified, the experimental methods used in the embodiments are conventional methods; the materials and reagents used, unless otherwise specified, are commercially available. Unless otherwise specified, the same parameter value is the same in all embodiments. The embodiments described below are exemplary and are only used to explain the present invention, and should not be construed as limiting the present invention.

[0062] In the description of this invention, it should be understood that the orientation descriptions, such as up, down, front, back, left, right, etc., are based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing this invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limiting this invention.

[0063] The term "room temperature" as used in this invention refers to any temperature between 25 and 5°C, and specifically 25°C in the embodiments.

[0064] Example

[0065] This example demonstrates the preparation of a ruthenium complex that can be excited by red light, and its structural formula is as follows:

[0066]

[0067] The specific preparation process is as follows:

[0068] S1. 2,9-Dimethyl-1,9-phenanthroline (0.416 g, 2 mmol), ruthenium(III) trichloride hydrate (0.208 g, 1 mmol), and lithium chloride (0.632 g, 15 mmol) were added to a reaction tube along with N,N-dimethylformamide (3 mL). The mixture was then heated under reflux at 140 °C for 8 hours. After cooling the reaction mixture to room temperature, acetone (8 mL) was added and the mixture was refrigerated at 0 °C overnight. The mixture was filtered to obtain a dark purple precipitate. The precipitate was washed alternately with ice water and ice-cold acetone to obtain Ru(2,9-dmp)₂Cl₂ precursor in 35.4% yield.

[0069] The chemical reaction equations for the above reactions are shown below:

[0070]

[0071] The precursor S2.Ru(2,9-dmp)2Cl2 (120 mg, 0.12 mmol) and silver hexafluorophosphate (60 mg, 0.24 mmol) were dissolved in ethanol (15 mL). The mixture was heated to reflux at 85 °C for 1 hour and then cooled to room temperature. After filtration through diatomaceous earth, the filtrate was heated to reflux at 85 °C for 12 hours with 1,6-dihydroxyphenazine (0.06 mmol, 13 mg) and sodium hydroxide (0.27 mmol, 10 mg) and then cooled to room temperature. After drying and purification, a ruthenium complex purple powder was obtained with a yield of 40.8%.

[0072] The chemical reaction equations for the above reactions are shown below:

[0073]

[0074] The product obtained in step S2 above was subjected to structural characterization, and the mass spectra obtained were: ESI-MS [CH3OH, m / z]: 729.05 [M-PF6] - ] + .

[0075] The 1H NMR spectrum of the product is as follows: 1 HNMR (500MHz, DMSO-d6) δ10.27 (s, 1H), 8.71 (d, J = 8.2Hz, 1H), 8.66 (d, J = 8.2Hz, 1H), 8.58 (d, J = 8.2Hz, 1H), 8.27–8.23 (m, 2H), 8.17 (d, J = 8.2Hz, 1H), 8.12 (d, J = 8.7Hz, 1H), 7.99 (d, J = 8.2Hz, 1H), 7.89 (d, J = 8.7Hz, 1H), 7.70 (d, J = 8.3Hz, 1 H), 7.62 (d, J=8.2Hz, 1H), 7.42 (t, J=8.1Hz, 1H), 7.35 (d, J=8.2Hz, 1H), 6.97 (d, J=8.3Hz, 1H), 6.70 (d, J=7.5Hz, 1H), 6 .62 (t, J=8.3Hz, 1H), 6.38 (d, J=7.9Hz, 1H), 5.33 (d, J=9.0Hz, 1H), 2.62 (s, 3H), 2.31 (s, 3H), 2.26 (s, 3H), 1.59 (s, 3H).

[0076] Test case

[0077] To verify the application effect of the above-mentioned complex, its performance was tested, as follows:

[0078] 1. Absorption spectroscopy determination of ruthenium metal complexes

[0079] The ruthenium metal complexes prepared in the above procedure were dissolved in acetonitrile (MeCN) to form 10 μM sample solutions. The absorbance of the novel red-light-excited ruthenium metal complexes in acetonitrile was then characterized using a double-beam UV-Vis spectrophotometer. The results are as follows: Figure 1 As shown.

[0080] from Figure 1 As can be seen from the embodiments of the present invention, the complexes prepared in the embodiments of the present invention have good light absorption capacity in organic solvents.

[0081] 2. Determination of the photocatalytic oxidation ability of ruthenium metal complexes for NADH and NADPH

[0082] Because under light irradiation, metal complexes can oxidize reduced coenzyme I (NADH) and reduced coenzyme II (NADPH) to their oxidized forms, NAD. + and NADP + Therefore, a ruthenium-containing complex (10 μM) and NADH or NADPH (A 339 The nm (1.0 nm) was mixed in a cuvette, and its ability to oxidize NADH / NADPH under light conditions was measured. The results are as follows: Figure 2 , 3 As shown.

[0083] As can be seen from the figure, the ruthenium complex has a significant photocatalytic oxidation ability for NADH and NADPH.

[0084] 3. Determination of the ability of ruthenium metal complexes to generate superoxide anions

[0085] The ability of ruthenium complexes to generate superoxide anions was determined using the superoxide anion probe dihydrorhodamine 123 (DHR123). The change in fluorescence intensity of the test sample and the DHR123 mixture under different illumination times was monitored using a Techcomp FL970 fluorescence spectrophotometer, which reflects the superoxide anion generation ability.

[0086] At λex = 465 nm, a mixed solution of ruthenium complex (10 μM) and DHR123 was excited in a 1 cm quartz tube. The entrance and exit slits were set to 2.5 nm. The superoxide anion generation capacity was measured under 635 nm illumination. Figure 4 The ruthenium complex shown has the ability to generate superoxide anions after being exposed to light.

[0087] 4. Photodynamic therapy effect of ruthenium complex on human non-small cell lung cancer cell lines

[0088] Resazurin solution is blue and is commonly used as an acid-base indicator (orange to deep purple at pH 3.8) and a redox indicator. In cell viability assays, resazurin can penetrate cells and be irreversibly reduced to pink by living cells, simultaneously producing the red fluorescence of resorufin. The absorbance or fluorescence intensity of resorufin is positively correlated with cell number and reducing capacity; therefore, cell proliferation can be analyzed using an enzyme-linked immunofluorescence assay (ELISA).

[0089] The experimental steps for the azure blade are as follows:

[0090] (1) First, revive one tube of A549 tumor cells and culture them in fresh complete culture medium (DMEM medium + 10 vol% fetal bovine serum + 1 vol% penicillin-streptomycin mixture). After passage twice, start the experiment.

[0091] (2) When the cells reach the logarithmic growth phase, seed them into two 96-well plates at a density of 5000 cells / well (each well is cultured with 100 μL of culture medium, one plate is the light group and the other is the dark control group), and incubate them in a 37°C, 5% CO2 incubator.

[0092] (3) After the ruthenium complex adheres to the wall, remove the original culture medium and add 100 μL of ruthenium complex at concentrations of 100, 50, 10, 1, 0.1, 0.01 and 0.001 mM to each well. Shake gently and incubate in a carbon dioxide incubator (37℃, 5% CO2) in the dark.

[0093] (4) After incubation for 6 hours, the cell culture plates of the light-illuminated group were placed under a 635nm light source for 45 minutes (light dose of 63.7 J / cm²). 2 Then, the cells were returned to the incubator and incubated in the dark for another 42 hours (the cells in the dark control group were kept in the incubator in the dark throughout the incubation).

[0094] (5) After incubation for 42 hours, the culture medium was discarded from each well, and 80 μL of resazurin (100 mg / mL) was added to each well. The cells were then incubated at 37°C for another 4 hours. The EX540 / EM590 ratio was detected using the fluorescence plate of an ELISA reader, and the cell proliferation inhibition rate was calculated. The IC50 value was then determined. 50 Value (drug concentration when the inhibition rate is equal to 50%).

[0095] The results are as follows Figure 5 As shown in the figure, the ruthenium complex at different concentrations under dark and light conditions was detected by the resazurite assay, demonstrating its cytotoxic effect on human non-small cell lung cancer cell line (A549 cells). It can be seen that under dark conditions, the IC50 value for the ruthenium complex against human non-small cell lung cancer cell line (A549 cells) was significantly lower. 50 The IC50 concentration was 14.56 μM, and under light conditions, it inhibited the activity of human non-small cell lung cancer cell lines.50 The concentration was 0.84 μM, and the phototherapy index (PI) was as high as 17.3, indicating that the ruthenium complex of the present invention has a strong photodynamic therapy effect.

[0096] The embodiments of the present invention have been described in detail above, but the present invention is not limited to the above embodiments. Within the scope of knowledge possessed by those skilled in the art, various changes can be made without departing from the spirit of the present invention.

Claims

1. A ruthenium complex, characterized in that: It has the following structural formula: Among them, X - Represents anions.

2. The ruthenium complex according to claim 1, characterized in that: X in the complex - For PF6 - Trifluoromethanesulfonate ions or halide ions.

3. The method for preparing the ruthenium complex according to claim 1 or 2, characterized in that: Includes the following steps: S1. The precursor compound was prepared by heating ruthenium(III) trichloride or its hydrate and 2,9-dimethyl-1,4-phenanthroline in a solvent; S2. The precursor compound obtained in step S1 is reacted with AgX and 1,6-dihydroxyphenazine to generate a ruthenium complex, wherein the meaning of X in AgX is the same as the meaning of X in the structural formula of the ruthenium complex.

4. The method for preparing the ruthenium complex according to claim 3, characterized in that: Step S1 specifically includes mixing ruthenium(III) trichloride or its hydrate, a metal halide and 2,9-dimethyl-1,9-phenanthroline and adding them to a solvent, and reacting them under heating.

5. The method for preparing the ruthenium complex according to claim 4, characterized in that: The reaction includes at least one of the following conditions: I) The molar ratio of ruthenium(III) trichloride or its hydrate, metal halide, and 2,9-dimethyl-1,4-phenanthroline is 2:14~16:4~4.4; II) The solvent is selected from at least one of anhydrous N,N-dimethylformamide and anhydrous acetonitrile; III) The reaction temperature is 120~160℃; IV) The reaction time is 6-14 hours; V) The heating method is heating reflux.

6. The method for preparing the ruthenium complex according to claim 4, characterized in that: The metal halide is selected from lithium chloride.

7. The method for preparing the ruthenium complex according to claim 3, characterized in that: Step S2 specifically includes dissolving the precursor compound and AgX in an alcohol solvent, reacting them under heating, and then reacting them with 1,6-dihydroxyphenazine under alkaline and heating conditions to obtain the ruthenium complex.

8. The method for preparing the ruthenium complex according to claim 7, characterized in that: The reaction includes at least one of the following conditions: i) The AgX is silver hexafluorophosphate, silver trifluoromethanesulfonate, or silver halide; ii) The alcohol solvent is at least one of methanol or ethanol; iii) The temperatures for the two heating processes in step S2 are independently selected from 80~85℃, and the times are independently selected from 0.5~13h; iv) The molar ratio of the precursor compound to AgX and 1,6-dihydroxyphenazine is 1:2~2.2:1~1.1; v) The pH of the alkaline conditions described is 12-14.

9. The use of the ruthenium complex according to claim 1 or 2 in the preparation of antitumor drugs, characterized in that: The antitumor drug is an anti-non-small cell lung cancer drug.

10. The application according to claim 9, characterized in that: The non-small cell lung cancer mentioned is A549 cell line lung cancer.

11. The application according to claim 9, characterized in that: The drug for treating non-small cell lung cancer is a photodynamic therapy drug.

12. The application according to claim 11, characterized in that: The excitation wavelength of the drugs in photodynamic therapy is 465~635nm.

13. The application according to claim 12, characterized in that: The excitation wavelength is 635 nm.

14. The application according to claim 9, characterized in that: The antitumor drug has at least one of the following characteristics: (1) The drug also includes pharmaceutically acceptable carriers and / or excipients; (2) The dosage form of the drug includes at least one of hard-shell or soft-shell gelatin capsules, tablets, pills, powder injections, solutions, suspensions, elixirs, syrups, dry films, gels, buccal or sublingual tablets, films, suppositories and enemas; (3) The raw materials for preparing the drug also include at least one of the following: liposome forming components, carrierd or uncarrierized proteins, organic or inorganic nanoparticles, nanoemulsions, microemulsions, nanocrystals, and solvents; (4) The routes of administration of the drug include oral, gastrointestinal or parenteral.

15. The application according to claim 14, characterized in that: The excipients refer to at least one of the following: diluents, coating agents, binders, lubricants, disintegrants, solubilizers, or stabilizers that can be used in the pharmaceutical field.

16. The application according to claim 14, characterized in that: The carrier is a functional pharmaceutical excipient acceptable in the pharmaceutical field, including at least one of surfactants, suspending agents, or emulsifiers.

17. The application according to claim 14, characterized in that: The carrier includes at least one of cyclodextrin, chitosan, polylactic acid, polyglycolic acid-polylactic acid copolymer, or hyaluronic acid.

18. An antitumor metal photosensitizer, characterized in that: The active ingredient of the antitumor metal photosensitizer includes the ruthenium complex as described in claim 1 or 2.

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