Coptis alkaloid iridium photosensitizer as well as preparation method and application thereof

Abstract

The invention discloses a rhizoma coptidis alkaloid iridium photosensitizer as well as a preparation method and application thereof, belongs to the technical field of antitumor drugs, provides a rhizoma coptidis alkaloid iridium photosensitizer with high phototoxicity and a preparation method thereof, and provides application of the rhizoma coptidis alkaloid iridium photosensitizer in the aspect of tumor photodynamic therapy. The iridium photosensitizer prepared by the invention has ultrahigh singlet oxygen generation capacity which is higher than that of a reference substance rose bengal B (RB), shows higher phototoxicity (half inhibitory concentration IC50 is equal to 1.65 mu M, and in-vivo photoinhibition rate is 58.21%) in mouse hepatoma carcinoma cells HepG-2, can achieve an excellent photodynamic therapy effect at extremely low concentration, and can be used for preparing a medicine for treating liver cancer. The toxicity to normal liver cancer cells is relatively low.

Description

Technical Field

[0001] The invention belongs to the technical field of anti-tumor drugs, and particularly relates to a coptis alkaloid iridium photosensitizer and a preparation method and application thereof. Background Art

[0002] Photodynamic therapy (PDT) is a tumor treatment method based on the production of reactive oxygen species (ROS) that can kill diseased tissue cells after photosensitizers absorb photon energy, thereby achieving therapeutic effects. Photosensitizers can absorb photon energy under light conditions and convert to an excited state, which then interacts with the surrounding oxygen to produce reactive oxygen species (ROS), such as singlet oxygen ( 1 O 2 ). These ROS can damage the surrounding cell structures and cause the diseased cells to die. Since this process can be carried out in a specific location and will not affect the surrounding healthy tissues, PDT is considered to be a relatively safe treatment with fewer side effects. In recent years, photodynamic therapy has been shown to have good effects on skin cancer, oral cancer, early obstructive lung cancer, head and neck cancer and other diseases.

[0003] On the other hand, iridium (III) complexes have outstanding photophysical properties, long-lived triplet excited states, and the ability to efficiently transfer energy to oxygen or to undergo electron transfer with various acceptor molecules to produce phototoxic reactive oxygen species, making them a promising candidate for photosensitizers. In addition, iridium (III) complexes also show good water solubility and stability, which is crucial for improving the biocompatibility and therapeutic effect of photosensitizers in vivo.

[0004] Although the application of iridium (III) complexes in the field of PDT shows great potential, there are still many challenges to be solved, such as further improving the selectivity of photosensitizers, reducing toxicity, improving drug delivery systems, etc. In addition, more preclinical studies and clinical trials are needed to verify the safety and effectiveness of iridium-based photosensitizers. With the advancement of nanotechnology and drug design, it is expected that iridium (III) complexes will play a more important role in the field of photodynamic therapy in the future.

[0005] As a medicinal material extracted from the Ranunculaceae family, the dried root and rhizome of Coptis chinensis plays an important role in traditional medicine. It is well-known for its significant effects of clearing away heat and dampness and purging fire and detoxifying. It has been used as a traditional Chinese medicine for more than two thousand years. The main active ingredients of Coptis chinensis are various alkaloids it contains, such as berberine, worenine and jatrorrhizine, which give Coptis chinensis a wide range of pharmacological effects, including anti-inflammatory, antibacterial, antifungal and anti-tumor properties.

[0006] In recent years, with the deepening of research on the modernization of traditional Chinese medicine, efforts have been made to explore how to combine traditional Chinese medicine active ingredients with modern medicinal chemistry to develop more effective drugs; however, up to now, there have been no reports on the use of alkaloids in Coptis chinensis as ligands to synthesize iridium complexes. Due to their unique electronic structure and biological activity, iridium complexes have shown potential application value in the fields of anti-tumor drugs. Therefore, combining alkaloids in Coptis chinensis with iridium to form new complexes may become a new direction for the development of new drugs and promote the application of Coptis chinensis in modern medicine. Summary of the invention

[0007] To achieve the above purpose, the present invention uses coptis alkaloid rhizome as an active skeleton to synthesize an iridium photosensitizer, which has a high singlet oxygen generation ability and exhibits high phototoxicity to liver cancer cells HepG-2 in vivo and in vitro. Therefore, the present invention proposes a coptis alkaloid iridium photosensitizer and a preparation method and application thereof. The chemical structural formula of the coptis alkaloid iridium photosensitizer is:

[0008]

[0009] Furthermore, the preparation method of the coptis alkaloid photosensitizer comprises the following steps:

[0010] Step S1, placing jatrorrhizine hydrochloride and 4-bromomethyl-4'-methyl-2,2'-bipyridine in a reaction bottle at a molar ratio of 1:0.9 to 1.2, and then undergoing a substitution reaction to obtain 9-(4'-methyl-2,2'-bipyridine)methyljatrorrhizine ligand (L);

[0011] Step S2, dissolving the ligand L and dichlorotetrakis[2-(2-pyridyl)phenyl]diiridium(III) in anhydrous methanol solvent at a molar ratio of 1:0.9-1.3, and then undergoing coordination reaction to obtain the target Coptis chinensis alkaloid iridium photosensitizer (1-Ir).

[0012] Furthermore, the reaction system in step S1 is in an anaerobic state.

[0013] Furthermore, the reaction temperature of the reaction system in step S1 is 65-90° C., and the reaction time is 4-6 hours.

[0014] Furthermore, the reaction system in step S2 is in an oxygen-free and water-free state.

[0015] Furthermore, the reaction temperature of the reaction system in step S2 is 65-90° C., and the reaction time is 8-24 hours.

[0016] Furthermore, a Coptis chinensis alkaloid iridium photosensitizer is prepared according to the above method.

[0017] Furthermore, the aforementioned Rhizoma Coptidis alkaloid iridium photosensitizer is used in the preparation of drugs for photodynamic therapy of tumors.

[0018] Furthermore, the tumor is a subcutaneous tumor.

[0019] Compared with the prior art, the advantages and effects of this application are as follows:

[0020] 1. The coptis alkaloid iridium photosensitizer of the present invention has the characteristics of simple structure, which makes its synthesis path more direct and reduces the complexity in the production process. At the same time, since coptis alkaloids are used as raw materials, they are naturally present in coptis plants. Compared with some artificially synthesized compounds, this type of natural product is easier to obtain and the cost is relatively low. In addition, coptis alkaloids themselves are widely used in traditional Chinese medicine, and their safety has been verified by long-term clinical use, which also provides a favorable basis for the research and development of new drugs.

[0021] 2. The iridium photosensitizer of the coptis alkaloid of the present invention has an ultra-high singlet oxygen production capacity, which is higher than the reference Bengal Rose Red B, and has excellent core performance. This new photosensitizer has shown great potential in the treatment of tumors and is expected to become an important breakthrough in the field of anti-tumor drug technology, with broad application prospects.

[0022] 3. The Rhizoma Coptidis alkaloid iridium photosensitizer of the present invention is effective under laser (535nm, 100mW / cm -2 ) irradiation, it has extremely high phototoxicity to cancer cells, with a half inhibitory concentration IC 50 As low as 1.65μM, the photoinhibition rate in vivo is 58.21%. Excellent therapeutic effects can be achieved at extremely low concentrations, which can effectively reduce the dosage and cost of medication.

[0023] The above description is only an overview of the technical solution of the present application. In order to more clearly understand the technical means of the present application so that it can be implemented in accordance with the contents of the specification, and to make the above and other purposes, features and advantages of the present application more obvious and easy to understand, the following is a detailed description of the preferred embodiments of the present application in conjunction with the accompanying drawings as follows.

[0024] Based on the detailed description of the specific embodiments of the present application in combination with the accompanying drawings below, those skilled in the art will become more aware of the above and other objects, advantages and features of the present application. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings required for use in the embodiments or the prior art descriptions are briefly introduced below. Obviously, the drawings described below are some embodiments of the present application. For ordinary technicians in this field, other drawings can also be obtained based on these drawings without creative work. In all drawings, similar elements or parts are generally identified by similar reference numerals. In the drawings, each element or part is not necessarily drawn according to the actual scale.

[0026] in:

[0027] Figure 1 The chemical formula structure diagram of the Coptis chinensis alkaloid iridium photosensitizer;

[0028] Figure 2 The synthetic route of the iridium photosensitizer of Coptis chinensis alkaloids is shown in Figure 1.

[0029] Figure 3 is the hydrogen spectrum of 9-(4'-methyl-2,2'-bipyridyl)methyl jatrorrhizine ligand (L);

[0030] Figure 4 is the carbon spectrum of 9-(4'-methyl-2,2'-bipyridyl)methyl jatrorrhizine ligand (L);

[0031] Figure 5 is the mass spectrum of 9-(4'-methyl-2,2'-bipyridyl)methyl jatrorrhizine ligand (L);

[0032] Figure 6 It is the hydrogen spectrum of 9-(4'-methyl-2,2'-bipyridyl)methyl pyridine iridium photosensitizer (1-Ir);

[0033] Figure 7 The carbon spectrum of 9-(4'-methyl-2,2'-bipyridyl)methyl pyridine iridium photosensitizer (1-Ir);

[0034] Figure 8 The mass spectrum of 9-(4'-methyl-2,2'-bipyridyl)methyl pyridine iridium photosensitizer (1-Ir);

[0035] Fig. 9 Figure A in the middle shows the degradation effect of ABDA by 1-Ir under the action of laser.

[0036] Figure B shows the degradation effect of Bengal Rose Red B on ABDA under the action of laser.

[0037] Figure C is a comparison chart of explanation speed.

[0038] Figure D shows the EPR spectrum of 1-Ir under illumination;

[0039] Fig.10 This is a statistical comparison of the effects of 1-Ir on cell survival rate under laser action and non-laser action conditions;

[0040] Fig.11 This is a comparison chart of H&E staining of the heart, liver, spleen, lung, and kidney after treatment;

[0041] Fig.12 This is a diagram showing the effect of tumor growth inhibition in vivo. Specific embodiments

[0042] To make the purpose, technical scheme and advantages of the embodiment of the present application clearer, the technical scheme in the embodiment of the present application will be clearly and completely described below in conjunction with the accompanying drawings in the embodiment of the present application. Obviously, the described embodiment is a part of the embodiment of the present application, rather than all of the embodiments. In the following description, specific details such as specific configuration and components are provided only to help fully understand the embodiments of the present application. Therefore, it should be clear to those skilled in the art that various changes and modifications can be made to the embodiments described herein without departing from the scope and spirit of the present application. In addition, for clarity and brevity, the description of known functions and structures is omitted in the embodiment.

[0043] It should be understood that the references to "one embodiment" or "this embodiment" throughout the specification mean that the specific features, structures, or characteristics associated with the embodiment are included in at least one embodiment of the present application. Therefore, the references to "one embodiment" or "this embodiment" appearing throughout the specification do not necessarily refer to the same embodiment. In addition, these specific features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

[0044] In addition, the present application may repeat reference numerals and / or letters in different examples. This repetition is for the purpose of simplicity and clarity, and does not in itself indicate the relationship between the various embodiments and / or settings discussed.

[0045] The term "and / or" in this article is only a description of the association relationship of associated objects, indicating that there can be three relationships. For example, A and / or B can mean: A exists alone, B exists alone, and A and B exist at the same time. The term " / and" in this article describes another type of association object relationship, indicating that there can be two relationships. For example, A / and B can mean: A exists alone, and A and B exist alone. In addition, the character " / " in this article generally indicates that the associated objects before and after are in an "or" relationship.

[0046] The term "at least one" in this article is merely a description of the association relationship of associated objects, indicating that there may be three relationships. For example, at least one of A and B can mean: A exists alone, A and B exist at the same time, and B exists alone.

[0047] It should also be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprises" or any other variations thereof are intended to cover non-exclusive inclusions.

[0048] Example 1

[0049] This example introduces a method for preparing a Rhizoma Coptidis alkaloid iridium photosensitizer. Figure 1 As shown, the chemical structural formula of the coptis alkaloid iridium photosensitizer is:

[0050]

[0051] For further information, please refer to Figure 2 As shown, the synthesis route of the coptis alkaloid photosensitizer is:

[0052]

[0053] Furthermore, the method for preparing the coptis alkaloid photosensitizer comprises the following steps:

[0054] Step S1, preparation of 9-(4'-methyl-2,2'-bipyridine)methyl jatrorrhizine ligand (L):

[0055] Step S101, jatrorrhizine (1 mmol) was placed in a round-bottom flask, 30 mL of anhydrous acetonitrile was added, and an argon atmosphere was maintained;

[0056] Step S102, under continuous stirring, add dropwise into the reaction flask a solution of 4'-methyl-[2,2'-bipyridine]-4-bromomethyl dissolved in acetonitrile (1.1 mmol, 5 mL), and react the reaction system at 85° C. for 6 h.

[0057] Step S103: After the temperature of the reaction liquid drops to room temperature, slowly add the reaction liquid to a beaker containing distilled water (200 mL) and continue stirring. A yellow solid is precipitated. No additional purification is required. The yellow solid obtained by suction filtration is 9-(4'-methyl-2,2'-bipyridine)methyl jatrorrhizine ligand (L).

[0058] Step S2, preparing 9-(4'-methyl-2,2'-bipyridine)methyl pyridine iridium photosensitizer (1-Ir):

[0059] Step S201, add the above ligand L (0.1 mmol), dichlorotetrakis[2-(2-pyridyl)phenyl]diiridium (0.12 mmol), dichloromethane (0.5 mL), and methanol (4.5 mL) into a 30 mL thick-walled glass tube, and react at 85° C. for 12 h under argon atmosphere.

[0060] Step S202, after the reaction is completed, cool down, evaporate naturally to remove the solvent to obtain a crude brown solid, purify by column chromatography, eluent V (methanol): V (chloroform) = 1:50, and obtain a light brown solid as the photosensitizer (1-Ir).

[0061] Example 2

[0062] This example introduces a method for preparing a Rhizoma Coptidis alkaloid iridium photosensitizer. Figure 3-4 As shown, the NMR data of 9-(4'-methyl-2,2'-bipyridine)methyl jatrorrhizine ligand (L) obtained based on Example 1 is: 1 H NMR(600MHz,DMSO-d6)δ9.85(s,1H),9.07(s,1H),8.68(d,J=4.9Hz,1H),8.55(d,J=4.9Hz,1H) ,8.43(d,J=1.5Hz,1H),8.22(d,J=1.6Hz,1H),8.13(d,J=9.0Hz,1H),8.02(d,J=9.0Hz,1H),7. 75(s,1H),7.49(dd,J=5.0,1.7Hz,1H),7.30(dd,J=5.0,1.7Hz,1H),7.15(s,1H),5.34(s,2H), 4.96(t,J=6.5Hz,2H),4.10(s,3H),4.03(d,J=10.1Hz,6H),3.21(t,J=6.2Hz,2H),2.42(s,3H). 13 C NMR(151MHz,DMSO-d6)δ155.91,155.20,150.70,150.36,149.89,149.51,149.40,148.48,147.26,145.79,144.01,137.83,133.43,128.75,127 .02,125.59,123.90,122.23,121.77,121.75,120.55,120.07,118.75,1 13.20,109.51,68.93,62.33,57.43,56.87,55.76,40.50,26.41,21.19.

[0063] Please refer to the attached Figure 5 As shown, the mass spectrum data of the obtained 9-(4'-methyl-2,2'-bipyridyl)methyl jatrorrhizine ligand (L) is: ESI-MS m / z: 520.2538.

[0064] The elemental analysis data of the obtained 9-(4'-methyl-2,2'-bipyridyl)methyl jatrorrhizine ligand (L) are:

[0065] The theoretical calculated values ​​are: C 73.83, H 5.81, N 8.07; the experimental tested values ​​are: C 73.80, H 5.82, N8.05.

[0066] After comprehensive analysis, the molecular formula of 9-(4'-methyl-2,2'-bipyridyl)methyl jatrorrhizine ligand (L) is: 32 H 30 N 3 O 4 + .

[0067] Please refer to the attached Figure 6-7 As shown, the NMR data of 9-(4'-methyl-2,2'-bipyridine)methyl pyridine iridium photosensitizer (1-Ir) obtained based on Example 1 are:

[0068] 1 H NMR(600MHz,DMSO-d6)δ9.86(s,1H),9.07(s,1H),8.71–8.65(m,2H),8.60–8.51(m,3H),8.45(s,2H),8.29 –8.22(m,2H),8.15(d,J=9.1Hz,2H),8.10–8.01(m,3H),7.96(d,J=7.8Hz,1H),7.88(td,J=7.7,1.9Hz,1H), 7.76(s,1H),7.73(dd,J=7.6,1.7Hz,1H),7.53–7.46(m,4H),7.30(dt,J=5.9,2.9Hz,2H),7.17(s,1H),5.3 6(s,2H),4.96(d,J=6.2Hz,2H),4.10(s,3H),4.05(s,3H),4.02(s,3H),3.21(d,J=6.3Hz,2H),2.42(s,3H). 13CNMR(151MHz,DMSO-d6)δ155.95,155.30,155.22,150.73,150.41,149.92,149.53,149.44,148. 96,148.50,148.11,147.30,145.84,144.04,137.87,134.60,133.45,129.62,129.22,128.80,12 8.62,127.36,127.09,126.96,125.60,124.36,123.92,123.07,122.29,121.81,121.77,120.57,120.11,118.81,113.24,109.56,68.97,62.34,57.45,56.87,55.78,40.51,36.27,26.41,21.19.

[0069] Please refer to the attached Figure 8 As shown, the mass spectrum data of the obtained 9-(4'-methyl-2,2'-bipyridine)methyl pyridine iridium photosensitizer (1-Ir) is: ESI-MS m / z: 1019.449.

[0070] The elemental analysis data of the obtained 9-(4'-methyl-2,2'-bipyridine)methyl pyridine iridium photosensitizer (1-Ir) are as follows:

[0071] The theoretical calculated values ​​are: C 55.66, H 3.89, N 6.01; the experimental tested values ​​are: C 55.64, H 3.90, N6.02.

[0072] Based on the above analysis, the molecular formula of the obtained 9-(4'-methyl-2,2'-bipyridine)methyl pyridine iridium photosensitizer 1-Ir is: 54 H 45 F 6 Ir 5 O 4 P, structural formula: [Ir(L)(bpy)]PF 6。

[0073] Example 3

[0074] This example introduces a test method for a Rhizoma Coptidis alkaloid iridium photosensitizer. Please refer to Fig. 9 As shown, further description is given based on the above examples. The singlet oxygen generating ability of the iridium photosensitizer 1-Ir was tested by ultraviolet absorption spectroscopy and electron spin resonance electron paramagnetic resonance (EPR).

[0075] First, the relative singlet oxygen yield of 1-Ir was tested by a chemical method using 9,10-anthracenediyl-bis(methylene)dimalonic acid (ABDA) as a singlet oxygen indicator and Bengal rose red B (RB) as a reference. The specific experimental steps are as follows:

[0076] A 1-Ir solution in acetonitrile (10 μM) was mixed with an ABDA solution (10 μM) and then illuminated with a laser (535 nm, 10 mW / cm -2 ) was irradiated and the absorption spectrum of the mixed solution was detected. The absorption spectrum and the absorbance at 300-400 nm were recorded every 10 min. The same experiment was carried out using Bengal Rose B as a reference.

[0077] Then, the singlet oxygen generation ability of 1-Ir was tested by using 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMP) as a singlet oxygen scavenger using electron propagation reaction (EPR) technology.

[0078] The degradation effects of iridium photosensitizer 1-Ir and reference substance RB on ABDA under laser action are shown in the attached figure. Fig. 9 As shown in A, 9B, and 9C, after laser irradiation, 1-Ir causes ABDA to degrade rapidly, and its degradation rate is significantly faster than that of the reference substance RB; and please refer to the attached Fig. 9 The EPR detection results of D showed that after 1-Ir was exposed to light for different time periods, an obvious 1:1:1 singlet oxygen characteristic signal peak could be detected.

[0079] In summary, the iridium photosensitizer 1-Ir prepared above has excellent singlet oxygen generation ability.

[0080] Example 4

[0081] This example introduces a method for testing a Rhizoma Coptidis alkaloid iridium photosensitizer. Based on the above example, the toxicity and photodynamic therapy effect of the iridium photosensitizer 1-Ir on HepG-2 cancer cells under laser action and non-laser action conditions are detected by MTT method. The specific experimental steps are as follows:

[0082] Cells in the logarithmic growth phase were cultured at 1×10 5 The cells were seeded at a density of 100 / well in a 96-well plate and placed in an incubator (37°C, 5% CO 2 ) and incubated in , and when the cell density reached 80%, medium containing different concentrations of 1-Ir was added;

[0083] For the laser irradiation group, after 1-Ir incubation for 16 h, laser (535 nm, 100 mW / cm -2 , 30min) irradiate cells;

[0084] For the non-laser irradiation group, the cells were always kept in the dark, and 0 μM was set as the control group. After incubation for 24 hours, 15 μL of MTT was added to each well, and incubation was continued for 4 hours. The absorbance of the absorption peak of each well at 540 nm was tested by an ELISA instrument, and the average and standard deviation of the absorbance of 6 wells in each group were calculated to calculate the survival rate of cancer cells.

[0085] The specific preparation method of the above-mentioned culture medium containing different concentrations of iridium photosensitizer 1-Ir is as follows: use biochemical grade dimethyl sulfoxide to prepare a 1-Ir mother solution with a concentration of 2mM, and use complete culture medium (RPMI 1640, containing 10% fetal bovine serum) to dilute the mother solution to 2.5μM, 5μM, 10μM, 20μM, and 40μM.

[0086] The above MTT test results are as follows Fig.10 As shown in Figure 2, under laser action, as the test concentration continued to increase, the survival rate of HepG-2 cells continued to decrease, and its half inhibition concentration IC was calculated. 50 =1.65μM, which is significantly higher than the non-illumination group, indicating that the iridium photosensitizer 1-Ir prepared above has excellent photodynamic therapy effect. Moreover, under the conditions of laser action and no action, the survival rate of normal liver cancer cells is still high at high concentrations of 1-Ir, indicating that the iridium photosensitizer 1-Ir prepared above has excellent biocompatibility.

[0087] Example 5

[0088] This example introduces a method for testing the iridium photosensitizer of Coptis chinensis alkaloids. Based on the above example, HepG-2 cells (2×10 6 The liver cancer tumor model was established with a tumor volume of 100 mm 3 The group treatment was started and the tumor-bearing mice were divided into 3 groups (5 mice in each group):

[0089] Group 1: no treatment;

[0090] Group 2: Tail vein injection of iridium photosensitizer 1-Ir;

[0091] Group 3: The iridium photosensitizer 1-Ir was injected into the tail vein. Two hours after the injection, the laser (535 nm, 100 mW / cm -2 , 30min) for treatment;

[0092] After 14 days of treatment (during which no mice died), all mice were killed, and tumors and major organ tissues (heart, liver, spleen, lung, and kidney) were collected, photographed, weighed, and recorded.

[0093] H&E staining results of organs after photodynamic therapy of mouse breast cancer subcutaneous tumor model with iridium photosensitizer 1-Ir Fig.11As shown, there were no obvious histopathological changes in the main organs of the experimental group, which once again showed that the iridium photosensitizer 1-Ir prepared above had excellent biocompatibility;

[0094] Also, please refer to Fig.12 The results showed that the tumor inhibition rate of the laser irradiation group reached 58.21%, which was 42.85% higher than that of the non-laser irradiation group, indicating that the iridium photosensitizer 1-Ir prepared above has excellent photodynamic therapy effect.

[0095] The above description is only the preferred embodiment of the present invention, which does not limit the protection scope of the present invention. For those skilled in the art, the present invention can be modified and varied in various ways. Within the spirit and principle of the present invention, any change, modification, replacement, integration and parameter change of these embodiments by conventional substitution or capable of achieving the same function without departing from the principle and spirit of the present invention shall fall within the protection scope of the present invention.

Claims

1. A Rhizoma Coptidis alkaloid iridium photosensitizer, characterized in that: The chemical structural formula of the coptis alkaloid iridium photosensitizer is:

2. The method for preparing a Rhizoma Coptidis alkaloid photosensitizer according to claim 1, characterized in that: The following steps are involved: Step S1, placing jatrorrhizine hydrochloride and 4-bromomethyl-4'-methyl-2,2'-bipyridine in a reaction bottle at a molar ratio of 1:0.9-1.2, and then undergoing a substitution reaction to obtain 9-(4'-methyl-2,2'-bipyridine)methyljatrorrhizine ligand (L); Step S2, dissolving the ligand L and dichlorotetrakis[2-(2-pyridyl)phenyl]diiridium(III) in anhydrous methanol solvent at a molar ratio of 1:0.9-1.3, and then undergoing coordination reaction to obtain the target Coptis chinensis alkaloid iridium photosensitizer (1-Ir).

3. The method for preparing a Rhizoma Coptidis alkaloid photosensitizer according to claim 2, characterized in that: The reaction system in step S1 is in an oxygen-free state.

4. The method for preparing a Rhizoma Coptidis alkaloid photosensitizer according to claim 3, characterized in that: The reaction temperature of the reaction system in step S1 is 65-90° C., and the reaction time is 4-6 hours.

5. The method for preparing a Rhizoma Coptidis alkaloid photosensitizer according to claim 2, characterized in that: The reaction system in step S2 is in an oxygen-free and water-free state.

6. The method for preparing a Rhizoma Coptidis alkaloid photosensitizer according to claim 5, characterized in that: The reaction temperature of the reaction system in step S2 is 65-90° C., and the reaction time is 8-24 hours.

7. A Rhizoma Coptidis alkaloid iridium photosensitizer, characterized in that: Prepared according to the method according to any one of claims 2 to 7.

8. Use of the coptis alkaloid iridium photosensitizer according to claim 1 in the preparation of drugs for tumor photodynamic therapy.

9. The use of a coptis alkaloid iridium photosensitizer according to claim 8, characterized in that: The tumor is a subcutaneous tumor.

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