Composition of albumin and mercaptododeborane and application of composition in preparation of tumor treatment drugs

Abstract

The invention relates to the technical field of tumor treatment drugs, in particular to a composition of albumin and mercaptododecane and application of the composition in preparation of tumor treatment drugs. According to the technical scheme, albumin is covalently coupled with mercaptododeborane through 34-site cysteine sulfydryl to construct a nucleation site, and mercaptododeborane is further loaded on protein at a fixed point through a nucleation effect; a sulfydryl group of the sulfydryl dodecane is combined with a sulfydryl group at the 34 site of the albumin cysteine through a disulfide bond. Through covalent coupling nucleation of free sulfydryl of albumin and sulfydryl dodecaborane, fixed-point coating of sulfydryl dodecaborane is realized by using a nucleation effect, so that the toxic risk caused by an organic solvent or chemical modification in a traditional solubilizing method is avoided, oxidative degradation and free boron ion release are effectively prevented, pH-responsive targeted release is realized, and the pH-responsive targeted release is realized. The boron accumulation amount of tumor tissues is remarkably increased, and the compound has high stability, accurate drug release property and low systemic toxicity.

Description

Technical Field

[0001] The present invention relates to the technical field of tumor therapeutic drugs, and in particular to a composition of albumin and mercapto dodecaborane and application thereof in preparing tumor therapeutic drugs. Background Art

[0002] Boron Neutron Capture Therapy (BNCT) uses thermal neutrons to bombard tumor cells with 10 B element, produces alpha particles with high energy transfer linear density and ions, thereby achieving precise killing of cancer cells. 10 After capturing a neutron, the B element undergoes a nuclear reaction, generating alpha particles and Ions have the characteristics of short range (only about 5-10 μm, covering about 1-2 cell diameters) but high energy, which can achieve precise attack on tumors at the cellular level, and theoretically minimize damage to surrounding normal tissues. Among the many boron carrier molecules, mercapto dodecaborane (such as thiol-modified dodecaborane derivatives) has a high abundance of 10 B atoms (each molecule contains 12 boron atoms) show strong potential as boron carriers and are expected to provide efficient boron delivery for BNCT.

[0003] However, the poor hydrophobicity and stability of mercapto dodecaborane itself limit its application in the field of BNCT. The dodecaborane skeleton itself has strong hydrophobicity, which makes the compound less soluble in water. Although the thiol group introduces a certain polarity, the improvement of the overall water solubility is limited. Low water solubility not only brings difficulties to the preparation and administration of drugs, but also may lead to uneven distribution of drugs in the body. Currently, the commonly used solubilization methods include chemical modification (such as the introduction of hydrophilic groups) and the addition of solubilizers (such as organic solvents, etc.). However, when polar groups are introduced or other chemical modifications are performed, the biological activity and safety of mercapto dodecaborane may be changed, resulting in increased toxicity or reduced therapeutic effect. Some solubilizers, such as cyclodextrin, PEG, Tween, etc., have certain toxicity and may cause adverse reactions in the body, including allergic reactions, inflammation, etc. In addition, the thiol group in mercapto dodecaborane is easily oxidized in the body fluid environment, especially under neutral or alkaline conditions (such as blood pH 7.4), forming a disulfide bond (-SS-). As the oxidation process proceeds, the structural stability of the borane molecule is destroyed, and then degradation occurs: the free boron ions (B 3+will be released, thus destroying the original specific targeting property of the borane compound and making it unable to act precisely on the target tissue or cell. Moreover, normal tissues are also at increased risk of exposure due to the release of boron ions, which may cause potential toxic effects or adverse reactions to normal tissues. Forming a protective layer (such as polydopamine modification) on the surface of dodecaborane thiol can isolate oxygen and water to enhance its stability, but it will increase the molecular size and surface charge of dodecaborane thiol, changing its physicochemical properties and potentially affecting its pharmacokinetic behavior in the body.

[0004] Serum albumin plays an important role in the solubilization of hydrophobic drugs due to its excellent biocompatibility and water solubility. For example, albumin-bound paclitaxel used in clinical applications wraps hydrophobic drugs by virtue of its amphiphilic structure, solving the allergic risk of traditional solvent-based drugs. However, traditional methods mainly rely on hydrophobic interactions to achieve the encapsulation of drugs by albumin. This binding method cannot precisely control the interaction sites between drugs and proteins. The drugs randomly adsorb in the internal hydrophobic cavities of proteins, which may lead to changes in the spatial conformation of albumin, resulting in recognition obstacles in key targeting functional regions such as surface glycosylation sites and receptor-binding domains, causing the loss of biological targeting.

[0005] In summary, the present application proposes a composition of albumin and dodecaborane thiol and its application in the preparation of anti-tumor drugs. Summary of the Invention

[0006] The object of the present invention is to address the problems of poor hydrophobicity and stability of the boron carrier molecule dodecaborane thiol in the background art, and to propose a composition of albumin and dodecaborane thiol and its application in the preparation of anti-tumor drugs.

[0007] In a first aspect, the present invention provides a composition of albumin and dodecaborane thiol, comprising:

[0008] Albumin, which is covalently coupled with dodecaborane thiol through the thiol group of cysteine at position 34 to construct a nucleation site, and further loads dodecaborane thiol on the protein at a fixed point through the nucleation effect;

[0009] The thiol group of the dodecaborane thiol binds to the thiol group of cysteine at position 34 of albumin through a disulfide bond. Among them, the disulfide bond stably exists in the physiological environment and reversibly breaks in the acidic microenvironment of tumors for targeted release of dodecaborane thiol.

[0010] Optionally, the pH of the physiological environment is 7.3 - 7.5, and the pH of the acidic microenvironment of tumors is 6.5 - 7.0.

[0011] Optionally, the albumin is selected from any one or more of the following: human serum albumin, ovalbumin, lactalbumin, myoalbumin, wheat albumin, and soybean albumin.

[0012] Optionally, it is characterized in that the mass ratio of the albumin to the mercapto dodecaborane is 1:1 to 1000:1.

[0013] Optionally, the composition further comprises a pharmaceutically acceptable excipient selected from one or more of a stabilizer, a buffer, a preservative, and an osmotic pressure regulator.

[0014] Optionally, the preparation form of the composition is an intravenous injection or a freeze-dried powder injection.

[0015] In a second aspect, the present application provides a drug comprising the albumin-mercapto dodecaborane composition described in the first aspect and a pharmaceutically acceptable carrier.

[0016] In a third aspect, the present application provides the use of the drug described in the second aspect in the preparation of a tumor treatment drug, characterized in that the tumor treatment is boron neutron capture therapy, and the tumor is any one of colon cancer, triple-negative breast cancer, malignant melanoma, non-small cell lung cancer, liver cancer, renal cell carcinoma, prostate cancer, ovarian cancer, and gastric cancer.

[0017] Optionally, after the drug is intravenously injected, the ratio T / N of the boron concentration in the tumor tissue to the boron concentration in the normal tissue is ≥ 3:1.

[0018] Optionally, the drug is released in the acidic microenvironment of the tumor through a pH-responsive release mechanism. 10 B, for killing tumor cells.

[0019] Compared with the prior art, the present application includes at least one of the following beneficial technical effects:

[0020] In the present application, the only free sulfhydryl group (at position Cys34) in the albumin molecule can be covalently coupled with the mercapto dodecaborane. This process has high site specificity and avoids the random binding defect of the traditional method. The rigid cage-like structure of the dodecaborane molecule can produce a "nucleation effect" on the protein surface, inducing the formation of stable aggregates of the dodecaborane molecule on the albumin molecule. This structural modification brings multiple advantages: on the one hand, the complex formed by covalent coupling can enhance the stability of the protein preparation; on the other hand, since the covalent modification is located in the non-functional region of the albumin, far from the receptor binding domain, the natural targeting property of the albumin is effectively retained.

[0021] Utilizing the property of the cleavage of sulfhydryl groups under acidic conditions, a pH-sensitive drug release mechanism was constructed, enabling the controlled release of drugs in specific environments. This technology breaks through the limitations of traditional albumin carriers that rely on physical interactions. Through site-specific covalent modification and nucleation effect regulation, the synergistic optimization of the carrier's stability, targeting, and responsiveness is achieved, showing broad application potential in the field of drug delivery and providing new ideas for solving the common technical problems of protein drug carriers. Brief Description of the Drawings

[0022] Figure 1 It is a graph of the detection results of cell uptake;

[0023] Figure 2 It is a graph of the detection results of tissue distribution. Detailed Embodiments

[0024] The technical solutions of the present invention will be further described below in conjunction with the drawings and specific embodiments.

[0025] Example 1: Preparation Scheme of Drug Compositions (A-J)

[0026] Take 2.5 mL of 20 mg / mL human serum albumin solution (dissolved in PBS); take another 0.5 mL of 100 mg / mL dodecaborane sulfhydryl solution (dissolved in chloroform). Mix the two solutions in a vial, and use an ultrasonic probe to penetrate into the vial close to the bottom of the liquid for homogenization. When ultrasonicating, use a power of 500 W, set to stop for 3 s after ultrasonicating for 2 s each time, ultrasonicate 3 times, 2 minutes each time. Subsequently, use a rotary evaporator to remove chloroform under reduced pressure at 30 °C to obtain the albumin-dodecaborane sulfhydryl composition A. The mass ratio of albumin to dodecaborane sulfhydryl is 1:1.

[0027] Example 2: Preparation Scheme of Drug Compositions (A-J)

[0028] Take 2.5 mL of 40 mg / mL human serum albumin solution (dissolved in PBS); take another 0.5 mL of 100 mg / mL dodecaborane sulfhydryl solution (dissolved in chloroform). Mix the two solutions in a vial, and use an ultrasonic probe to penetrate into the vial close to the bottom of the liquid for homogenization. When ultrasonicating, use a power of 500 W, set to stop for 3 s after ultrasonicating for 2 s each time, ultrasonicate 3 times, 2 minutes each time. Subsequently, use a rotary evaporator to remove chloroform under reduced pressure at 30 °C to obtain the albumin-dodecaborane sulfhydryl composition B. The mass ratio of albumin to dodecaborane sulfhydryl is 2:1.

[0029] Example 3: Preparation Scheme of Drug Compositions (A-J)

[0030] Take 2.5 mL of 100 mg / mL human serum albumin solution (dissolved in PBS); take another 0.5 mL of 100 mg / mL mercaptododecaborane solution (dissolved in chloroform). Mix the two solutions in a vial, and use an ultrasonic probe to penetrate into the vial to be close to the bottom of the liquid for homogenization. When ultrasonicating, use a power of 500 W, set to stop for 3 s after every 2 s of ultrasonication, ultrasonicate 3 times, 2 minutes each time. Subsequently, use a rotary evaporator to remove chloroform under reduced pressure at 30 °C to obtain the albumin-mercaptododecaborane composition C. The mass ratio of albumin to mercaptododecaborane is 5:1.

[0031] Example 4: Preparation Scheme of Pharmaceutical Compositions (A-J)

[0032] Take 2.5 mL of 100 mg / mL human serum albumin solution (dissolved in PBS); take another 0.5 mL of 50 mg / mL mercaptododecaborane solution (dissolved in chloroform). Mix the two solutions in a vial, and use an ultrasonic probe to penetrate into the vial to be close to the bottom of the liquid for homogenization. When ultrasonicating, use a power of 500 W, set to stop for 3 s after every 2 s of ultrasonication, ultrasonicate 3 times, 2 minutes each time. Subsequently, use a rotary evaporator to remove chloroform under reduced pressure at 30 °C to obtain the albumin-mercaptododecaborane composition D. The mass ratio of albumin to mercaptododecaborane is 10:1.

[0033] Example 5: Preparation Scheme of Pharmaceutical Compositions (A-J)

[0034] Take 2.5 mL of 100 mg / mL human serum albumin solution (dissolved in PBS); take another 0.5 mL of 25 mg / mL mercaptododecaborane solution (dissolved in chloroform). Mix the two solutions in a vial, and use an ultrasonic probe to penetrate into the vial to be close to the bottom of the liquid for homogenization. When ultrasonicating, use a power of 500 W, set to stop for 3 s after every 2 s of ultrasonication, ultrasonicate 3 times, 2 minutes each time. Subsequently, use a rotary evaporator to remove chloroform under reduced pressure at 30 °C to obtain the albumin-mercaptododecaborane composition E. The mass ratio of albumin to mercaptododecaborane is 20:1.

[0035] Example 6: Preparation Scheme of Pharmaceutical Compositions (A-J)

[0036] Take 2.5 mL of 200 mg / mL human serum albumin solution (dissolved in PBS); take another 0.5 mL of 20 mg / mL mercaptododecaborane solution (dissolved in chloroform). Mix the two solutions in a vial, and use an ultrasonic probe to penetrate deep into the vial to near the bottom of the liquid for homogenization. When ultrasonicating, use a power of 500 W, set to stop for 3 s after ultrasonicating for 2 s each time, ultrasonicate 3 times, 2 minutes each time. Subsequently, use a rotary evaporator to remove chloroform under reduced pressure at 30 °C to obtain the albumin-mercaptododecaborane composition F. The mass ratio of albumin to mercaptododecaborane is 50:1.

[0037] Example 7 Preparation Scheme of Pharmaceutical Compositions (A-J)

[0038] Take 2.5 mL of 200 mg / mL human serum albumin solution (dissolved in PBS); take another 0.5 mL of 10 mg / mL mercaptododecaborane solution (dissolved in chloroform). Mix the two solutions in a vial, and use an ultrasonic probe to penetrate deep into the vial to near the bottom of the liquid for homogenization. When ultrasonicating, use a power of 500 W, set to stop for 3 s after ultrasonicating for 2 s each time, ultrasonicate 3 times, 2 minutes each time. Subsequently, use a rotary evaporator to remove chloroform under reduced pressure at 30 °C to obtain the albumin-mercaptododecaborane composition G. The mass ratio of albumin to mercaptododecaborane is 100:1.

[0039] Example 8 Preparation Scheme of Pharmaceutical Compositions (A-J)

[0040] Take 2.5 mL of 200 mg / mL human serum albumin solution (dissolved in PBS); take another 0.5 mL of 5 mg / mL mercaptododecaborane solution (dissolved in chloroform). Mix the two solutions in a vial, and use an ultrasonic probe to penetrate deep into the vial to near the bottom of the liquid for homogenization. When ultrasonicating, use a power of 500 W, set to stop for 3 s after ultrasonicating for 2 s each time, ultrasonicate 3 times, 2 minutes each time. Subsequently, use a rotary evaporator to remove chloroform under reduced pressure at 30 °C to obtain the albumin-mercaptododecaborane composition H. The mass ratio of albumin to mercaptododecaborane is 200:1.

[0041] Example 9 Preparation Scheme of Pharmaceutical Compositions (A-J)

[0042] Take 2.5 mL of 500 mg / mL human serum albumin solution (dissolved in PBS); take another 0.5 mL of 5 mg / mL mercaptododecaborane solution (dissolved in chloroform). Mix the two solutions in a vial, and use an ultrasonic probe to penetrate into the vial to near the bottom of the liquid for homogenization. When ultrasonicating, use a power of 500 W, set to stop for 3 s after every 2 s of ultrasonication, ultrasonicate 3 times, 2 minutes each time. Subsequently, use a rotary evaporator to remove chloroform under reduced pressure at 30 °C to obtain the albumin-mercaptododecaborane composition I. The mass ratio of albumin to mercaptododecaborane is 500:1.

[0043] Example 10: Preparation Scheme of Drug Compositions (A-J)

[0044] Take 2.5 mL of 500 mg / mL human serum albumin solution (dissolved in PBS); take another 0.5 mL of 2.5 mg / mL mercaptododecaborane solution (dissolved in chloroform). Mix the two solutions in a vial, and use an ultrasonic probe to penetrate into the vial to near the bottom of the liquid for homogenization. When ultrasonicating, use a power of 500 W, set to stop for 3 s after every 2 s of ultrasonication, ultrasonicate 3 times, 2 minutes each time. Subsequently, use a rotary evaporator to remove chloroform under reduced pressure at 30 °C to obtain the albumin-mercaptododecaborane composition J. The mass ratio of albumin to mercaptododecaborane is 1000:1.

[0045] Example 11: Cell Uptake Experiment

[0046] (1) Experimental Grouping

[0047] Control Group 1: Blank Medium Group (Negative Control Group);

[0048] Control Group 2: Free Mercaptododecaborane Group (Positive Control Group);

[0049] Experimental Group 1: Albumin-Mercaptododecaborane Composition A (mass ratio 1:1);

[0050] Experimental Group 2: Albumin-Mercaptododecaborane Composition B (mass ratio 2:1);

[0051] Experimental Group 3: Albumin-Mercaptododecaborane Composition C (mass ratio 5:1);

[0052] Experimental Group 4: Albumin-Mercaptododecaborane Composition D (mass ratio 10:1);

[0053] Experimental Group 5: Albumin-Mercaptododecaborane Composition E (mass ratio 20:1);

[0054] Experimental Group 6: Albumin-Mercaptododecaborane Composition F (mass ratio 50:1);

[0055] Experimental group 7: Albumin-mercaptododecaborane composition G (mass ratio 100:1);

[0056] Experimental group 8: Albumin-mercaptododecaborane composition H (mass ratio 200:1);

[0057] Experimental group 9: Albumin-mercaptododecaborane composition I (mass ratio 500:1);

[0058] Experimental group 10: Albumin-mercaptododecaborane composition J (mass ratio 1000:1);

[0059] (2) Experimental procedures

[0060] Inoculate B16 tumor cells into 6-well plates respectively, and the cell seeding density is , and culture for 24 hours until the cells adhere to the wall;

[0061] Add the culture medium containing albumin-mercaptododecaborane composition with 200 μg / mL mercaptododecaborane to the experimental groups, add the same concentration of free mercaptododecaborane to the positive control group, and add the same volume of blank culture medium to the negative control group, and incubate for 1 hour, 2 hours, 4 hours, and 8 hours;

[0062] After the incubation, wash the cells three times with PBS, digest the cells with trypsin and collect them; Centrifuge (1000 rpm, 5 minutes) to collect the cells for counting, take 1×10 6 cells, use nitric acid digestion, and use ICP-MS to quantify the boron content in the cells.

[0063] (3) Experimental results

[0064] The results of cell uptake detection are as Figure 1 shown: The cell uptake amount of the experimental groups was significantly higher than that of the control groups. The experimental groups showed high cell uptake efficiency at different mass ratios, and the cell uptake amount reached the peak in the range of mass ratio from 10:1 to 500:1. This indicates that the albumin-mercaptododecaborane composition can significantly enhance the uptake of boron by tumor cells.

[0065] Example 12: Mouse tumor targeting accumulation experiment

[0066] (1) Experimental grouping

[0067] Control group 1: Normal saline (negative control group);

[0068] Control group 2: Free mercaptododecaborane group (positive control group);

[0069] Experimental group 1: Albumin-mercaptododecaborane composition A (mass ratio 1:1);

[0070] Experimental group 2: Albumin-mercaptododecaborane composition B (mass ratio 2:1);

[0071] Experimental group 3: Albumin-mercaptododecaborane composition C (mass ratio 5:1);

[0072] Experimental group 4: Albumin-mercaptododecaborane composition D (mass ratio 10:1);

[0073] Experimental group 5: Albumin-mercaptododecaborane composition E (mass ratio 20:1);

[0074] Experimental group 6: Albumin-mercaptododecaborane composition F (mass ratio 50:1);

[0075] Experimental group 7: Albumin-mercaptododecaborane composition G (mass ratio 100:1);

[0076] Experimental group 8: Albumin-mercaptododecaborane composition H (mass ratio 200:1);

[0077] Experimental group 9: Albumin-mercaptododecaborane composition I (mass ratio 500:1);

[0078] Experimental group 10: Albumin-mercaptododecaborane composition J (mass ratio 1000:1);

[0079] (2) Experimental procedures

[0080] Twenty-four 6- to 8-week-old female BALB / c nude mice were randomly divided into two groups (12 mice in each group). A human glioma xenograft model was established by subcutaneous injection of U87MG cells. The experiment began when the tumor volume reached 100 - 150 mm³;

[0081] In the experimental groups, albumin-mercaptododecaborane complexes (the same boron, 10 mg / kg) were injected via the tail vein, in the control group, free mercaptododecaborane at the same dose was injected, and in the blank group, an equal volume of normal saline was injected. The animals were sacrificed at 0.5 hour, 1 hour, 2 hours, 4 hours, 8 hours, and 24 hours after administration (3 animals at each time point);

[0082] Tumor tissues, blood, salivary glands, kidneys, livers, hearts, spleens, and lung tissues were collected. The blood residues were washed with ultrapure water, weighed, and then processed using a Tissue-Tearor homogenizer. The boron content in each sample was measured by ICP-MS.

[0083] (3) Experimental results

[0084] The results of tissue distribution detection are as Figure 2 ​Shown: At 6 hours after drug administration, the boron content in the tumor tissues of the experimental group was significantly higher than that of the control group BSH, both exceeding 10 μg / g, meeting the effective treatment threshold for boron neutron capture therapy (BNCT).

[0085] In the present invention, a specific disulfide bond covalent coupling is formed between the only free sulfhydryl group at position 34 of albumin cysteine (Cys34) and mercaptododecaborane to achieve precise molecular anchoring. This process strictly avoids the problem of uncontrollable binding sites caused by traditional physical encapsulation or random chemical modification, providing a basis for the structural certainty and high stability of the complex. Utilizing the rigid cage-like structure of the dodecaborane molecule, the "nucleation effect" is triggered after covalent coupling at the Cys34 site, inducing the directional aggregation of mercaptododecaborane molecules on the surface of albumin and forming a stable complex. This effect significantly enhances the drug loading capacity and the stability of the complex, solving the problems of low drug loading rate and easy dissociation caused by the weak interaction (such as hydrophobic interaction) dependent on traditional albumin carriers.

[0086] Among them, the covalent modification is strictly located in the non-functional domain of albumin (far from the receptor binding region), completely retaining the natural tumor targeting ability of albumin (such as the targeting delivery mediated by the SPARC receptor), ensuring that the complex is efficiently enriched in tumor tissues in vivo, and the experimental verification shows that the tumor / normal tissue boron concentration ratio (T / N ratio ≥ 3:1). Based on the stability of the disulfide bond in the physiological environment (pH 7.3 - 7.5) and the reversible cleavage property in the tumor acidic microenvironment (pH 6.5 - 7.0), an intelligent drug release system is constructed. This mechanism realizes "zero leakage" of the drug in the circulatory system, and at the same time specifically releases active 10 B at the tumor site, significantly improving the precision and efficacy of boron neutron capture therapy (BNCT).

[0087] It should be noted that the synergistic effect of covalent coupling - nucleation completely inhibits the oxidative degradation of mercaptododecaborane, avoiding systemic toxicity (such as liver and kidney damage) caused by the release of free boron ions; at the same time, it avoids the use of organic solvents or surfactants in traditional solubilization processes, reducing the toxicity risk of the preparation from the source. For the first time, the "site-specific covalent coupling" and the "nucleation effect" are synergistically applied to the design of albumin carriers, breaking through the limitations of the existing technology relying on physical interactions, and providing a general solution for the development of protein drug delivery systems with high stability, high targeting, and intelligent responsiveness.

[0088] The above specific embodiments are merely several alternative embodiments of the present invention. Based on the technical solution of the present invention and the relevant inspirations of the above embodiments, those skilled in the art can make various alternative improvements and combinations to the above specific embodiments.

Claims

1. A composition of albumin and mercapto dodecaborane, characterized in that, Comprising: Albumin, which is covalently coupled with mercaptododecaborane through the cysteine thiol group at position 34 to construct a nucleation site, and further loads mercaptododecaborane on the protein at a fixed point through the nucleation effect; The thiol group of the mercaptododecaborane is bound to the thiol group of cysteine 34 of albumin through a disulfide bond, wherein the disulfide bond stably exists in the physiological environment and is reversibly cleaved in the acidic microenvironment of tumors for targeted release of mercaptododecaborane.

2. The composition of albumin and mercaptododecaborane according to claim 1, wherein The pH of the physiological environment is 7.3 - 7.5, and the pH of the acidic microenvironment of tumors is 6.5 - 7.

0.

3. The composition of albumin and mercaptododecaborane according to claim 1, wherein The albumin is selected from any one or more of the following: human serum albumin, ovalbumin, lactalbumin, myoalbumin, wheat albumin, soybean albumin.

4. A composition of albumin and mercaptododecaborane according to claim 1, characterized in that The mass ratio of the albumin to the mercaptododecaborane is 1:1 to 1000:

1.

5. A composition of albumin and mercaptododecaborane according to claim 1, wherein the composition further comprises a pharmaceutically acceptable excipient, and the excipient is selected from one or more of a stabilizer, a buffer, a preservative, and an osmotic pressure regulator.

6. The composition of albumin and mercaptododecaborane according to claim 1, wherein The preparation form of the composition is an intravenous injection or a freeze-dried powder injection.

7. A drug, characterized in that, Comprising the composition of albumin-mercaptododecaborane according to any one of claims 1 - 6, and a pharmaceutically acceptable carrier.

8. Use of the drug according to claim 7 in the preparation of a tumor therapeutic drug, characterized in that, The tumor treatment is boron neutron capture therapy, and the tumor is any one of colon cancer, triple-negative breast cancer, malignant melanoma, non-small cell lung cancer, liver cancer, renal cell carcinoma, prostate cancer, ovarian cancer, gastric cancer.

9. Use of the drug according to claim 8 in the preparation of a tumor therapeutic drug, characterized in that, After the drug is intravenously injected, the ratio of boron concentration in tumor tissue to boron concentration in normal tissue T / N ≥ 3:

1.

10. Use of the drug according to claim 8 in the preparation of a tumor therapeutic drug, characterized in that, The drug is released in the acidic microenvironment of tumors through a pH-responsive release mechanism 10 B, for killing tumor cells.

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