Application of MPBA-IR-780 compound in the preparation of drugs for tumor treatment

Abstract

The invention discloses an application of an MPBA-IR-780 compound in the preparation of a drug for treating tumors. The compound contains a phenylboronic acid structure and a heptamethine cyanine structure, and is synthesized by an elimination reaction between a chlorine-containing structure in IR-780 and a thiol group in mercaptophenylboronic acid. The compound is based on the reaction of an IR-780 fluorescent dye molecule with a mercaptophenylboronic acid series compound (MPBA), and the two are linked by a covalent bond to obtain a series of tumor diagnosis and treatment drugs that can be used for PTT, BNCT, and PTT-BNCT combined therapy; the compound contains both a structure that can emit near-infrared fluorescence and has a high photothermal conversion efficiency and a boron atom, so it has a strong absorption peak in the near-infrared region and converts the absorbed energy into heat, becoming a photoconversion agent for tumor photothermal therapy, and its preparation process is simple, reliable, and easy to implement.

Description

Technical Field

[0001] The present invention relates to the fields of chemical technology and medicine, and to the synthesis of drug compounds for combined therapy of tumor photothermal therapy and boron neutron capture therapy, and specifically to the reaction of heptamethine cyanine fluorescent small molecule IR-780 with mercaptophenylboric acid (MPBA) and its homologues, and to a method for separating and purifying the products and their medical application. Background Art

[0002] Malignant tumors have become one of the diseases with the highest mortality rate today. The exploration of its treatment methods has never stopped. Currently, common tumor treatment methods include surgery, chemotherapy, radiotherapy, and immunotherapy. In clinical practice, surgical resection of tumor tissue is usually selected, and then various methods are combined to perform lesions, metastases, lymph node dissection, etc. to achieve the best treatment effect. Photothermal therapy (PTT) and boron neutron capture therapy (BNCT) are relatively new technologies in various tumor treatment methods. They have accumulated research for many years and have been gradually promoted and applied in clinical practice. In existing studies, in order to reduce side effects and radiation risks, BNCT usually uses a one-time irradiation treatment method, while PTT often performs multiple repeated phototherapy due to the limited photothermal effect. The combined treatment of the two methods may first kill a large number of cancer cells through the BNCT method, and then continue to clear residual lesions through repeated PTT treatment, or first use the PTT method to limit the growth of tumor tissue during the tumor stage, and then use the BNCT method to kill tumor tissue, thereby obtaining better treatment effects.

[0003] Photothermal therapy is a treatment method that injects materials with high photothermal conversion efficiency into the human body, gathers them near tumor tissues through targeted recognition, and converts light energy into heat energy under the irradiation of an external light source (generally near-infrared light) to kill cancer cells. Among them, photosensitizers with high photothermal conversion efficiency are the key to PTT. The most studied ones include precious metal nanoparticles such as gold, silver, platinum, etc.; carbon nanomaterials such as graphene, carbon nanorods, etc.; compounds composed of metal elements and non-metal elements such as copper sulfide, zinc sulfide, etc.; organic fuels such as indocyanine green, Prussian blue series dyes and various derivatives of the above materials. 2-(2-(2-chloro-3-(2-(3,3-dimethyl-1-propylindol-2-methylene)ethylidene)cyclohex-1-en-1-yl)vinyl)-3,3-dimethyl-1-propyl-3H-indol-1-ium iodide (IR-780) is one of them. It belongs to the indocyanine green series of dyes. It has maximum absorption at a wavelength of 750-830nm and is converted into heat, which heats up the tumor tissue and kills tumor cells. The external light source used in PTT is mainly near-infrared light, and it is even expected to use infrared light. The purpose is to obtain a greater tissue penetration depth while reducing the direct damage of the light source to the tissue. However, due to the maximum absorption wavelength of the photosensitizer, the main research is still near-infrared light, and it is often only effective for superficial tumors that can be directly penetrated by near-infrared light, such as epithelial cell cancer. In addition, in order to obtain a better therapeutic effect, PTT often requires multiple and repeated irradiations to effectively kill tumor cells.

[0004] Boron neutron capture therapy is a cellular-scale targeted binary radiotherapy method. The principle of BNCT in killing tumor cells is that non-radioactive isotopes 10 B undergoes a nuclear fission reaction after being bombarded by thermal neutrons, producing an alpha particle and a 7 Li atoms and alpha particles have a lethal effect on cells, but their range of action is only the size of a cell, so they can effectively kill cancer cells while hardly damaging the surrounding normal tissues. The necessary conditions for BNCT are neutron irradiation and the ability to be enriched in tumor cells in sufficient quantities. 10 B atoms, containing 10 Compounds containing boron atoms are called boron carriers or boron drugs. Currently, only 4-dihydroxyboryl-L-phenylalanine (L-BPA) and sodium 11-hydrogen mercapto-12-boronide (BSH) have been approved for clinical use. Currently, the BNCT method has been clinically studied on superficial tumors such as melanoma, brain glioma, and head and neck tumors, but obtaining more effective boron drugs is still the key to the effectiveness of this method.

[0005] Based on IR-780 dye, Chinese invention patents CN111004624A and CN113476602A disclose a novel near-infrared fluorescent probe molecule, which connects two molecules of IR-780 with one molecule of 1,2-diphenyl-1,2-di(4-hydroxyphenyl)ethylene to form a compound combining IR-780 with a tetraphenylethylene (TPE) structure, which is used for photothermal therapy and photodynamic therapy, and has the function of integrated diagnosis and treatment; Chinese invention patent CN105038295A discloses a near-infrared fluorescent compound based on a cyanine dye as a skeleton, which combines IR-780 with piperazine and 4-chloro-7-nitro-2,1,3-benzoxadiazole in sequence, and the resulting compound can be used for near-infrared fluorescence identification of hydrogen sulfide molecules; Chinese invention patent CN102491930A discloses a near-infrared fluorescent probe molecule based on IR-780 As the parent, the fluorescent probe molecule that responds to pH value obtained by combining with isopropylamine, benzylamine, methylethylamine, N-methylaniline, ethylenediamine, hexamethylenediamine, p-phenylenediamine, etc. has a very high fluorescence quantum yield; Chinese invention patent CN104099089A discloses a near-infrared mesoporous silicon fluorescent nanoprobe formed by combining IR-780 with mesoporous silicon, which has good biocompatibility; Chinese invention patent ZL201510312670 discloses a fluorescent probe molecule obtained by combining IR-780 with a 1,8-naphthaleneimide structure, which can selectively identify glutathione (GSH); Chinese invention patent CN108329404A discloses a drug-loaded micelle obtained by combining IR-780 with chitosan stearic acid and encapsulating doxorubicin drugs, which can target tumor cells and quickly release drugs under near-infrared light, induce tumor cell apoptosis and improve the anti-tumor treatment effect. However, the above-mentioned modifications and alterations of IR-780 only involve fluorescent probes or photothermal therapy, and do not link the structure of boron-containing compounds and be used for PTT-BNCT combined therapy.

[0006] In the field of BNCT boron carrier research, Li Jiyuan et al. summarized the development history and existing research types of boron carriers in the past few decades in "An Unpopular Direction Entering the Dawn: A Brief History of the Development of Boron Carriers" (Science China·Chemistry, 2020, 50(10):1296), including boron-containing small molecules, boron-containing biomacromolecules, boron-containing nanomedicines, etc. Chinese invention patents CN109942608A and CN109988187A respectively disclose a polyboron phenylalanine compound containing nitroimidazole and a phenylalanine compound containing carborane. Both molecules can be used for BNCT treatment, but they do not involve diagnosis and treatment or photothermal therapy. Chinese invention patent CN111204736A discloses a boron-containing carbon quantum dot. Since the quantum dot has in vivo and in vitro fluorescence properties, it can be used for BNCT treatment and fluorescence diagnosis, but does not involve photothermal therapy; Chinese invention patents CN1988848A and CN1968705A both disclose a carbon borane-containing 5,10,15,20-tetraphenylporphyrin compound, which can be used for BNCT treatment and photodynamic therapy (PDT), but this molecule has no fluorescence properties and does not involve fluorescence diagnosis and photothermal therapy.

[0007] In the reports on boron carriers in the known BNCT field, there is no scheme of using boron carriers obtained by directly combining boron-containing compound structures with fluorescent molecules such as IR-780 for PTT-BNCT combined treatment.

[0008] In summary, an MPBA-IR-780 compound for BNCT-PTT combined therapy is prepared, which can be a boron carrier in BNCT, and at the same time has high photothermal conversion efficiency, and is also a photosensitizer in PTT. Moreover, this type of compound can also be used as a tumor fluorescent probe, which is of great significance for realizing the combination of imaging detection and therapeutic preparations. Summary of the invention

[0009] The purpose of the present invention is to provide a class of drugs for PTT-BNCT combined treatment and a preparation method thereof, specifically, the reaction of MPBA and its homologues with IR-780, and the product molecules contain both a structure that can emit near-infrared fluorescence and has a high photothermal conversion efficiency and a boron atom.

[0010] To this end, the present invention proposes the following technical solutions:

[0011] A MPBA-IR-780 compound contains a phenylboronic acid structure and a heptamethine cyanine structure, and its synthetic structural formula is as follows:

[0012]

[0013] Preferably, the MPBA (Mercaptophenylboricacid) and its homologues include 4-mercaptophenylboric acid, 3-mercaptophenylboric acid, 2-mercaptophenylboric acid and mixtures thereof;

[0014] Preferably, the compound is synthesized by an elimination reaction between the chlorine-containing structure in IR-780 and the thiol group in mercaptophenylboronic acid; the synthesis route comprises: dissolving MPBA or its homologues and IR-780 in an organic solvent at room temperature, wherein the amount of MPBA or its homologues to IR-780 is in a molar ratio of 1 to 3:1;

[0015] Then, an organic base is added, and the molar ratio of the organic base to IR-780 is 1:2-1;

[0016] The reaction is carried out under an inert atmosphere, the reaction temperature is 20-70°C, and the reaction time is 12-48h;

[0017] After the reaction was completed, the product was separated and purified by column chromatography.

[0018] Preferably, the organic base includes triethylamine and pyridine; the inert atmosphere includes nitrogen and argon;

[0019] The organic solvent includes, but is not limited to, water, methanol, ethanol, chloroform, dichloromethane, chloroform, dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF) and a mixture thereof.

[0020] Preferably, the amount of the organic solvent used is about 100 to 2000 times the mass of IR-780.

[0021] Preferably, the column chromatography mobile phase is a mixed solution of methanol and dichloromethane, and the ratio of the two is methanol / dichloromethane is 1:5-1:20.

[0022] Preferably, part or all of the boron atoms in the compound structure are 10 Boron atoms enriched in the B isotope are therefore good at absorbing neutrons for boron neutron capture therapy of tumors;

[0023] Preferably, part or all of the compound structure is 10 The structure of the B isotope-enriched boron atom is derived from 10 B enriched mercaptophenylboronic acid and its homologues.

[0024] Preferably, the MPBA-IR-780 compound is used in the preparation of drugs for treating tumors.

[0025] The present invention has at least the following advantages:

[0026] (1) The present invention is based on the reaction of IR-780 fluorescent dye molecules with mercaptophenylboronic acid series compounds (MPBA), and the two are linked by covalent bonds to obtain a series of tumor diagnosis and treatment drugs that can be used for PTT, BNCT and PTT-BNCT combined treatment. Among them, MPBA and its homologues have boron elements and can be used as boron carriers for BNCT treatment; this drug can be administered once and then used for photothermal-boron neutron capture therapy combined with the two methods. This drug has a certain tumor targeting property, and its preparation process is simple, reliable and easy to implement.

[0027] (2) The present invention provides an MPBA-IR-780 compound, specifically, MPBA and its homologues react with IR-780. The compound contains both a structure that can emit near-infrared fluorescence and has a high photothermal conversion efficiency and a boron atom. The application of the compound will provide a new drug and treatment plan for tumor treatment.

[0028] 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.

[0029] 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

[0030] 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.

[0031] Figure 1 The synthetic route of MPBA-IR-780 compound;

[0032] Figure 2 The hydrogen nuclear magnetic resonance (H NMR) of MPBA-IR-780 compound 1 H-NMR) spectrum;

[0033] Figure 3 is the ultraviolet (UV) absorption spectrum of the MPBA-IR-780 compound;

[0034] Figure 4 It is a temperature rise curve of the solution when the MPBA-IR-780 compound is dissolved in dimethyl sulfoxide (DMSO) solution and irradiated by 808nm laser;

[0035] Figure 5 The results of MPBA-IR-780 acting on HepG2 human liver cancer cells at different doses;

[0036] Figure 6 Results of PTT treatment of tumor-bearing mice using MPBA-IR-780. DETAILED DESCRIPTION

[0037] 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.

[0038] 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 previous and next associated objects are in an "or" relationship.

[0039] 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.

[0040] Example 1

[0041] In conjunction with the accompanying drawings, this example illustrates the synthetic structure of the MPBA-IR-780 compound of the present invention.

[0042] A MPBA-IR-780 compound is synthesized from MPBA and its homologues and IR-780. The compound contains a phenylboronic acid structure and a heptamethine cyanine structure. The synthesis reaction is as shown in the attached Figure 1 As shown, Figure 1 This is the synthetic route of MPBA-IR-780 compound.

[0043] The MPBA (Mercaptophenylboricacid) and its homologues include 4-mercaptophenylboric acid, 3-mercaptophenylboric acid, 2-mercaptophenylboric acid and a mixture thereof. The compound is synthesized by an elimination reaction between the chlorine-containing structure in IR-780 and the thiol group in mercaptophenylboric acid. The specific synthesis route is: dissolving MPBA or its homologue and IR-780 in an organic solvent at room temperature, wherein the amount of MPBA or its homologue to IR-780 is 1 to 3:1 in a molar ratio;

[0044] Then, a certain amount of organic base such as triethylamine, pyridine, etc. is added, and the molar ratio of the organic base to IR-780 is 1:2-1;

[0045] The reaction is carried out under an inert atmosphere such as nitrogen, argon, etc. The usable reaction temperature is 20-70°C, and the preferred reaction temperature is 25-45°C; the reaction time is 12-48h, and the preferred reaction time is 24-36h;

[0046] After the reaction is completed, the product is separated and purified by column chromatography; wherein the mobile phase of the column chromatography is a mixed solution of methanol and dichloromethane, the ratio of the two being methanol / dichloromethane being 1:5-1:20, and the preferred ratio being 1:10-1:15; the product is soluble in common organic reagents.

[0047] Among them, the available organic solvents include but are not limited to water, methanol, ethanol, chloroform, dichloromethane, chloroform, dimethyl sulfoxide (DMSO), N, N-dimethylformamide (DMF) and mixtures thereof. The preferred organic solvents are dichloromethane and dimethyl sulfoxide, and the amount of the organic solvent used is about 100 to 2000 times the mass of IR-780.

[0048] Some or all of the boron atoms in the structure of this compound are 10 Boron atoms enriched in the B isotope are therefore more likely to absorb neutrons for boron neutron capture therapy of tumors. 10 The structure of the B isotope-enriched boron atom is derived from 10 B enriched mercaptophenylboronic acid and its homologues, through 10 B-enriched 4-mercaptophenylboronic acid, 3-mercaptophenylboronic acid, 2-mercaptophenylboronic acid and their mixture were synthesized with IR-780 in the same manner as described above.

[0049] In this embodiment, the preparation process of the compound is simple, reliable and easy to implement. The compound has the potential to become a drug for photothermal-boron neutron capture combined therapy. This drug can be administered once and then used for photothermal-boron neutron capture combined therapy combining the two methods, and this drug has a certain tumor targeting. Because the compound contains both a structure that can emit near-infrared fluorescence and has a high photothermal conversion efficiency and a boron atom, it has a strong absorption peak in the near-infrared region and converts the absorbed energy into heat, becoming a photoconversion agent for tumor photothermal therapy.

[0050] Example 2

[0051] In this example, 4-mercaptophenylboronic acid (4-MPBA) was prepared and reacted with heptamethine cyanine dye IR-780.

[0052] Weigh 37.5 mg IR-780 and 7 mg 4-MPBA, dissolve in 25 mL dichloromethane, add 55 μL triethylamine dropwise under magnetic stirring, and react at room temperature for 24 h under nitrogen atmosphere.

[0053] After the reaction, the product was separated and purified by column chromatography using a mixture of methanol and dichloromethane in a ratio of 1:12.5 as the mobile phase. The liquid corresponding to the 4-MPBA-IR-780 product point was collected, and the solvent was removed by rotary evaporation to obtain 4-MPBA-IR-780 solid.

[0054] The compound drug obtained in this example was subjected to characterization test.

[0055] As attached Figure 2 As shown, Figure 2 The hydrogen nuclear magnetic resonance (H NMR) of MPBA-IR-780 compound 1 H-NMR) spectrum. Figure 2 H NMR ( 1 The differences in peaks between substances can be seen in the H-NMR spectrum, and the new structural molecule of MPBA-IR-780 was formally formed through comparative analysis.

[0056] As attached Figure 3 As shown, Figure 3 This is the ultraviolet (UV) absorption spectrum of the MPBA-IR-780 compound. Figure 3 In the mid-ultraviolet (UV) absorption spectrum, the original characteristic ultraviolet absorption peak of IR-780 at around 250nm disappeared, and a new absorption peak of phenylboronic acid structure appeared at 250-450nm, which proved that 4-MPBA had successfully combined with IR-780 to form a new molecule.

[0057] As attached Figure 4 As shown, Figure 4This is a temperature rise curve of the MPBA-IR-780 compound dissolved in dimethyl sulfoxide (DMSO) solution when irradiated by 808nm laser. The obtained compound was dissolved in dimethyl sulfoxide (DMSO) and the solution temperature rose after irradiation by 808nm laser. 4-MPBA-IR-780 is similar to IR-780 molecules, and both have obvious photothermal effects.

[0058] Example 3

[0059] Different from Example 2, 3-mercaptophenylboronic acid (3-MPBA) was used to react with IR-780 to obtain a drug molecule that has the potential to be used in photothermal-boron neutron capture combined therapy.

[0060] Example 4

[0061] Different from Example 2, 2-mercaptophenylboronic acid (2-MPBA) was used to react with IR-780 to obtain a drug molecule that has the potential to be used in photothermal-boron neutron capture combined therapy.

[0062] Example 5

[0063] Different from Example 2, an excess of 4-MPBA was used, and other conditions were the same, to obtain a drug molecule with potential for photothermal-boron neutron capture combined therapy, but the yield was slightly higher.

[0064] Example 6

[0065] Different from Example 2, the reaction solvent was replaced by an equal volume of dimethyl sulfoxide from dichloromethane to obtain a drug molecule that has the potential to be used in photothermal-boron neutron capture combined therapy.

[0066] Example 7

[0067] Different from Example 2, the reaction time was extended to 48 h, and a drug molecule with potential for photothermal-boron neutron capture combined therapy was obtained.

[0068] Example 8

[0069] Different from Example 2, the ratio of methanol / dichloromethane in the mobile phase of the column chromatography was changed to 1:15, and drug molecules with potential for photothermal-boron neutron capture combined therapy could also be obtained.

[0070] Example 9

[0071] Different from Example 2, the reaction temperature was changed to reflux (40° C.) in dichloromethane to obtain a drug molecule that has the potential to be used in photothermal-boron neutron capture combined therapy.

[0072] Example 10

[0073] In this example, MPBA-IR-780 was applied to HepG2 human liver cancer cells, and the viability of the cells was observed under near-infrared light irradiation.

[0074] HepG2 human liver cancer cells were inoculated in a 24-well plate. After the cells were in a semi-confluent state, the cells were given MPBA-IR-780 drugs. During the drug administration process, DMSO was used as an organic auxiliary agent with a concentration of 1%; the drug concentration was 0-30μM. After drug administration, the cells were incubated at 37±0.5℃ and 5% CO2 for 30 minutes. The cells were repeatedly cleaned with PBS until the drugs that were not taken up by the cells were completely washed away. Then, the cells were irradiated with 800nm ​​near-infrared light for PTT treatment. The light power was 5W / cm 2 ; The irradiation time was 5 minutes; the cells were then cultured for 24 hours at 37±0.5°C and 5% CO2, and the cell viability index was detected using the CCK-8 method to evaluate the therapeutic effect.

[0075] As attached Figure 5 As shown, Figure 5 The results are shown in Figure 2. The results show that MPBA-IR-780 acts on HepG2 human liver cancer cells at different doses. Figure 5 The results in the figure are based on the cell viability index and the drug / drug+PTT treatment. The results show that the cell group irradiated with near-infrared light is significantly better than the cell group without illumination. At a drug concentration of 10-30μM, the simultaneous application of PTT treatment has a significant killing effect on HepG2 tumor cells.

[0076] Embodiment 11

[0077] In this example, MPBA-IR-780 was used to perform PTT treatment experiments on tumor-bearing mice.

[0078] The tumor-bearing mice were randomly divided into 3 groups, 6 in each group, and 0.9% NaCl saline and 0.2 mg / mL MPBA-IR-780 were injected into the tail vein on day 0 and day 7, respectively, with a dosage of 5 μL / g×mouse body weight (g). One of the groups received PTT treatment 48 h after each administration (the specific operation was to irradiate the tumor site with near-infrared light for 5 min after the mice were anesthetized by breathing), and the other group did not receive PTT treatment, and the changes in mouse body weight and tumor volume were observed.

[0079] The results are attached Figure 6 As shown, Figure 6 Results of PTT treatment of tumor-bearing mice using MPBA-IR-780. Figure 6The changes in tumor volume of the three groups of mice during the 20-day observation period show that the tumor volume of the mice treated with drug and PTT was significantly reduced compared with the control group, showing an obvious tumor treatment effect.

[0080] Example 12

[0081] Different from the above-mentioned embodiment, the 10 B-enriched MPBA was used for synthesis to obtain 10 B-enriched MPBA-IR-780 becomes a boron carrier in BNCT treatment. Combined with the good effects of PTT treatment in the aforementioned embodiments, BNCT further kills tumor cells and obtains better tumor treatment effects. The method that can be used is usually a single BNCT treatment combined with multiple PTT treatments. PTT treatment is usually before BNCT treatment, or after BNCT treatment. The above is only a preferred embodiment of the present application, which does not limit the scope of protection of the present application. For those skilled in the art, the present application may have various changes and variations. Within the spirit and principles of the present application, changes, modifications, replacements, integrations and parameter changes to these embodiments without departing from the principles and spirit of the present application are all within the scope of protection of the present application.

Claims

1. A MPBA-IR-780 compound, characterized in that The compound contains a phenylboronic acid structure and a heptamethine cyanine structure, and its structural formula is shown below: 。 2. A MPBA-IR-780 compound according to claim 1, characterized in that, The MPBA and its homologues include 4-mercaptophenylboronic acid, 3-mercaptophenylboronic acid, 2-mercaptophenylboronic acid and mixtures thereof.

3. A MPBA-IR-780 compound according to any one of claims 1 or 2, characterized in that Some or all of the boron atoms in the compound structure are 10 Boron atoms enriched in the B isotope.

4. The MPBA-IR-780 compound according to claim 3, characterized in that: Part or all of the compound structure is 10 The structure of the B isotope-enriched boron atom is derived from 10 B enriched mercaptophenylboronic acid and its homologues.

5. A method for preparing a MPBA-IR-780 compound according to any one of claims 1 to 4, characterized in that: The compound is synthesized by an elimination reaction between the chlorine-containing structure in IR-780 and the thiol group in mercaptophenylboronic acid; The synthesis route comprises: dissolving MPBA or its homologues and IR-780 in an organic solvent at room temperature, wherein the molar ratio of MPBA or its homologues to IR-780 is 1-3:1; Then, an organic base is added, and the molar ratio of the organic base to IR-780 is 1:2~1; The reaction is carried out under an inert atmosphere, the reaction temperature is 20-70°C, and the reaction time is 12-48h; After the reaction was completed, the product was separated and purified by column chromatography.

6. The method for preparing a MPBA-IR-780 compound according to claim 5, characterized in that: The organic base includes triethylamine and pyridine; the inert atmosphere includes nitrogen and argon; The organic solvent includes water, methanol, ethanol, chloroform, dichloromethane, chloroform, dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF) and a mixture thereof.

7. The method for preparing a MPBA-IR-780 compound according to claim 6, characterized in that: The amount of the organic solvent used is 100 to 2000 times the mass of IR-780.

8. The method for preparing a MPBA-IR-780 compound according to claim 7, characterized in that: The column chromatography mobile phase is a mixed solution of methanol and dichloromethane, and the ratio of the two is methanol / dichloromethane is 1:5-1:

20.

9. Use of the MPBA-IR-780 compound according to any one of claims 1 to 4 in the preparation of drugs for treating tumors.

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