Albumin-bound manganese borate nanoparticles and application thereof in preparation of tumor treatment drugs

Abstract

The invention relates to the technical field of anti-tumor drugs, in particular to albumin-bound manganese borate nanoparticles and application thereof in preparation of tumor treatment drugs. According to the technical scheme, the nanoparticle comprises a manganese borate compound and an albumin shell, the manganese borate compound is combined with manganese ions through coordinate bonds, and the albumin shell coats the manganese borate compound to form the nanoparticle; wherein the average particle size of the nanoparticles ranges from 100 nm to 300 nm, and the mass ratio of the albumin to the manganese borate compound ranges from 10: 1 to 1000: 1. The albumin-bound manganese borate nanoparticles provided by the invention not only can synergistically enhance the inhibition effect of boric acid on tumor cells and remarkably inhibit tumor growth of tumor-bearing mice, but also can improve the proportion of tumor-infiltrating T cells, increase the level of immune killing factors and activate a tumor immune system, so that the tumor-infiltrating effect of the tumor-bearing mice is improved. And multiple effects of targeted delivery, image guidance, collaborative treatment, immune sensitization and the like are achieved, and an efficient and accurate innovative scheme is provided for tumor treatment.

Description

Technical Field

[0001] The present invention relates to the technical field of anti-tumor drugs, and particularly to albumin-bound manganese borate nanoparticles and their application in the preparation of anti-tumor drugs. Background Art

[0002] Currently, cancer remains one of the biggest problems threatening human health. As a frontier targeted cancer treatment technology, Boron Neutron Capture Therapy (BNCT) can be clinically promoted and applied due to the emergence of hospital-based neutron accelerators. Its principle is to inject a boron-containing drug into the human body, enabling it to accumulate in tumor cells, and then irradiating with a neutron beam to trigger a nuclear reaction, generating high-energy alpha particles and lithium ions to precisely destroy cancer cells, achieving cell-level targeted therapy with minimal damage to normal tissues.

[0003] The boron-containing drug is the core for its precise treatment. An ideal boron-containing drug should be dynamically monitorable and have low toxicity, be able to stay in tumor tissues for a long time, and at least uptake more than 20 μg of 10B per gram of tumor tissue (equivalent to more than 109 10B atoms in each tumor cell). In addition, the boron-containing drug in blood and normal tissues can be rapidly metabolized, and the 10B concentration ratio between tumor tissue and normal tissue (T / N) and the 10B concentration ratio between tumor tissue and blood (T / B) should be > 3. Currently, the first-generation BNCT boron drugs such as boric acid and its derivatives have a relatively high boron content (up to the theoretical value of 17.5%), but have poor specificity for tumor cells, resulting in a low boron concentration ratio between tumor and normal tissues, and it is impossible to avoid damaging normal tissues of the body, severely restricting the selectivity and treatment window of neutron irradiation. Therefore, the first batch of BNCT clinical trials ended in failure. The second-generation BNCT drug such as boronophenylalanine (BPA), although it has shown significant efficacy in clinical applications due to its tumor targeting advantage mediated by the L-type amino acid transporter (LAT1), is currently approved by the US Food and Drug Administration for the clinical treatment of cancer by BNCT. However, its boron atom content has been greatly reduced (the boron atom content is only about 3.8% (mass fraction)), resulting in that patients need to receive a large dose of injection (300 - 500 mg / kg) to reach the required boron concentration for treatment (15 - 35 μg / g), which not only increases the metabolic burden on the liver and kidneys, but may also cause systemic toxic and side reactions such as hypotension. In addition, the retention time of BPA at the tumor site is relatively short, which may be due to the effect of the anti-transport mechanism of LAT1 on intracellular BPA molecules.

[0004] Therefore, the boron drugs currently used in BNCT have problems such as low boron content, insufficient tumor targeting, and too high treatment dose, resulting in limited clinical application and failure to fully exert the anti-tumor immune effect. This application proposes albumin-bound manganese borate nanoparticles and their application in the preparation of anti-tumor drugs. Summary of the Invention

[0005] The object of the present invention is to address the problems in the background art, namely, the boron drugs used in current BNCT have low boron content, insufficient tumor targeting, and excessive treatment doses. The present invention provides albumin-bound manganese borate nanoparticles and their application in the preparation of tumor treatment drugs.

[0006] In a first aspect, the present application provides albumin-bound manganese borate nanoparticles, comprising: A manganese borate compound, which is bound to manganese ions through a coordination bond; An albumin shell, which coats the manganese borate compound to form nanoparticles; Wherein, the average particle size of the nanoparticles is 100 nm to 300 nm, and the mass ratio of albumin to the manganese borate compound is 10:1 to 1000:1.

[0007] Optionally, the albumin is selected from one or more of serum albumin, ovalbumin, lactalbumin, myoalbumin, wheat albumin, and soybean albumin, preferably human serum albumin.

[0008] Optionally, the average particle size of the nanoparticles is 150 nm to 250 nm.

[0009] Optionally, the mass ratio of albumin to the manganese borate compound is 10:1.

[0010] Optionally, the nanoparticles are prepared by a process with an ultrafiltration membrane having a molecular weight cut-off of 95 - 105 kDa and are formed by high-pressure homogenization at 2°C - 6°C for 20 - 40 minutes.

[0011] In a second aspect, the present application provides a pharmaceutical composition comprising the albumin-bound manganese borate nanoparticles according to the first aspect and a pharmaceutically acceptable excipient, and the pharmaceutical composition is an intravenous injection preparation or a freeze-dried powder injection.

[0012] In a third aspect, the present application provides the use of the albumin-bound manganese borate nanoparticles according to the first aspect in the preparation of a tumor treatment drug, and the tumors include colon cancer, triple-negative breast cancer, malignant melanoma, non-small cell lung cancer, liver cancer, renal cell carcinoma, prostate cancer, ovarian cancer, or gastric cancer.

[0013] Optionally, the albumin-bound manganese borate nanoparticles achieve tumor targeting through the following technical features: a. Enrich in tumor tissues through the albumin-mediated transmembrane transport mechanism; b. Respond to the hydrogen peroxide (H2O2) concentration gradient in the tumor microenvironment to release boric acid and manganese ions, such that the boron concentration ratio (T / N) between tumor tissue and normal tissue is ≥3.

[0014] Optionally, the manganese ions released by the nanoparticles produce an enhanced T1-weighted signal in magnetic resonance imaging (MRI) for guiding neutron beam localization.

[0015] Optionally, the nanoparticles are obtained through the following preparation steps: a. Under ice bath conditions, introduce manganese ions into the albumin solution and stir at 450 - 550 rpm for 8 - 12 minutes; b. Add the sodium tetraborate solution and continue stirring for 5 - 15 minutes; c. Perform buffer replacement and concentration through an 80 - 120 kDa ultrafiltration membrane; d. Perform high-pressure homogenization for 20 - 40 minutes to obtain the final nanoparticles.

[0016] Compared with the prior art, the present application includes at least one of the following beneficial technical effects: Manganese in the nano-system of the pharmaceutical composition of the present invention can induce enhanced MRI signals, providing guidance for pre-treatment triage and neutron beam localization.

[0017] There is a synergistic effect in the nano-system of the pharmaceutical composition of the present invention. The synergistic effect of manganese ions not only significantly enhances the damage of tumor cells induced by neutron irradiation, but also enhances the radiation-activated innate immune response.

[0018] The nano-system of the pharmaceutical composition of the present invention has good tumor cell targeting. Through the specific transmembrane transport mechanism mediated by albumin, efficient tumor cell enrichment is achieved, and then boric acid and manganese ions are precisely released in response to the H2O2 microenvironment, reducing the toxic and side effects on other normal tissues.

[0019] The nano-system of the pharmaceutical composition of the present invention shows superior anti-tumor effects in both intratumoral injection and systemic administration, and at the same time synergizes with adoptive T cell immunotherapy and immune checkpoint inhibitors, providing an innovative solution to overcome the limitations of BNCT efficacy related to tumor heterogeneity.

[0020] The albumin-bound manganese borate nanoparticles provided by the present invention can be targeted and enriched in tumor tissues through the transmembrane transport mechanism mediated by albumin, release boric acid and manganese ions in response to the hydrogen peroxide concentration gradient in the tumor microenvironment (so that the boron concentration ratio of tumor to normal tissue ≥ 3), and the released manganese ions can also guide the precise localization of neutron beams by enhancing the MRI signal; the nanoparticles can not only synergistically enhance the inhibitory effect of boric acid on tumor cells, significantly inhibit the tumor growth of tumor-bearing mice, but also increase the proportion of tumor-infiltrating T cells and up-regulate the level of immune killing factors, activating the tumor immune system, and having multiple effects such as targeted delivery, imaging guidance, synergistic treatment and immune sensitization, providing an efficient and precise innovative solution for tumor treatment. Description of the Drawings

[0021] Figure 1 It is the preparation appearance diagram of the drug composition nano - system; Figure 2 is Mn 2+ The synergistic effect diagram of boric acid inhibiting tumor cells; Figure 3 It is the release situation of the drug composition nano - system under the condition of H2O2 in vitro; Figure 4 It is the statistical result diagram of the biodistribution of the drug composition nano - system in tumor - bearing mice; Figure 5 It is the MRI tracking signal diagram of the drug composition nano - system in mice; Figure 6 It is the tumor volume diagram of each group of mice in Example 8; Figure 7 It is the statistical result diagram of the relative percentages of tumor CD3 +, CD8 +, CD11c and CD45 + T lymphocytes in each group of mice in Example 9; Figure 8 It is the statistical result diagram of the levels of INF - β and CXCL10 in the tumors of each group of mice in Example 9. Detailed implementation manners

[0022] The technical solutions of the present invention will be further described below in conjunction with the accompanying drawings and specific embodiments.

[0023] Example 1: Preparation scheme of manganese borate albumin nanoparticles Under ice - bath conditions, manganese ions were introduced into the albumin solution and stirred at a speed of 500 rpm for 10 minutes. Subsequently, sodium tetraborate solution was quickly added to the mixture and stirred for another 10 minutes. The resulting solution was concentrated and buffer replacement was carried out using a 100 kDa ultrafiltration membrane. The concentrated solution was subjected to high - pressure homogenization treatment at 4°C for 30 minutes, and finally the prepared drug composition nano - system (Albumin@MnB) was obtained. The preparation appearance is shown in Figure 1 .

[0024] Example 2: Preparation scheme of manganese borate albumin nanoparticles Under ice - bath conditions, manganese ions were introduced into the transferrin solution and stirred at a speed of 500 rpm for 10 minutes. Subsequently, sodium tetraborate solution was quickly added to the mixture and stirred for another 10 minutes. The resulting solution was concentrated and buffer replacement was carried out using a 100 kDa ultrafiltration membrane. The concentrated solution was subjected to high - pressure homogenization treatment at 4°C for 30 minutes, and finally the prepared drug composition nano - system (Albumin@MnB) was obtained.

[0025] Example 3: Preparation of manganese borate albumin nanoparticles Under ice bath conditions, manganese ions were introduced into the trastuzumab solution and stirred at 500 rpm for 10 minutes. Then, sodium tetraborate solution was quickly added to the mixture and stirred for 10 minutes. The obtained solution was concentrated and buffer exchanged using a 100 kDa ultrafiltration membrane. The concentrated solution was treated by high-pressure homogenization at 4°C for 30 minutes to finally obtain the prepared pharmaceutical composition nanosystem (Albumin@MnB).

[0026] Example 4: Mn 2+ Can synergistically enhance the inhibitory effect of boric acid on tumor cells Mn was determined by CCK-8 assay 2+ Effects on the survival rate of B16 cells treated with BNCT, see Figure 2 . B16 cells were seeded in a 96-well plate at a density of 5×10³ cells per well. B16 cells were treated with different concentrations (0, 5, 10, 20, 40, 80 and 160µM) of Mn²⁺ for 24 hours. Six replicate wells were set up for each concentration of each metal ion, and the same volume of blank solvent was used as a control group. Subsequently, the culture medium was removed, and 100µL of DMEM culture medium containing 10% CCK-8 reagent was added to each cell well. After incubation for 1 hour, the absorbance (OD value) was measured at a wavelength of 450 nm using an automatic microplate reader.

[0027] Example 5: Release of the composition under in vitro H2O2 conditions B16 cells were first treated with Alb@MnB and then exposed to H2O and different concentrations of H2O2 (1%, 0.1% and 0.01%) for 5 min, 15 min, 30 min, 60 min and 2 h, respectively. After the cells were collected, the supernatant was obtained by centrifugation and the concentration of B10 in each sample was measured. The measurement results are shown in Figure 3 .

[0028] Example 6: Biodistribution of the drug composition nanosystem in tumor-bearing mice Male Balb / c mice weighing about 18-22g were selected to establish a subcutaneous melanoma (B16) transplantation model, and the biodistribution of the nanosystem in mice was studied using ICP-MS analysis. Five days after tumor inoculation, the drug composition nanosystem (5 mg / kg) was injected into the tail vein. At 3h, 6h and 24h after administration, the mice were anesthetized with 2% sodium pentobarbital solution, and the biodistribution of the drug composition nanosystem in vivo was tracked by ICP-MS ( Figure 4). The results showed that the drug - composition nanosystem could achieve effective boron accumulation in tumor tissues, and the boron concentration ratio of tumor tissues to normal tissues exceeded 3, meeting the basic treatment threshold of BNCT.

[0029] Example 7: MRI Tracking of the Drug - Composition Nanosystem in Mice Given that divalent manganese (Mn²⁺) itself has magnetic resonance imaging (MRI) signals, after subcutaneous injection of Alb@MnB, the metabolic process of Mn²⁺ in mice can be clearly tracked by MRI. Select the mice with subcutaneous transplanted melanoma (B16) model established in Example 6. First, they received subcutaneous injection of MnCl2 and Alb@MnB with equal doses of manganese, and then were anesthetized and fixed. MRI scans were performed at 3 hours and 24 hours after injection to carefully observe the metabolic changes of Mn²⁺ in mice. The results showed that 3 hours later, the mice in the Albumin@MnB group showed stronger T1 - weighted imaging signals in the tumor area than those injected with MnCl2 ( Figure 5 ). This signal difference became more obvious at 12 hours, indicating that the drug was gradually released in the tumor through H2O2 - reactive dissociation in the tumor microenvironment.

[0030] Example 8: Evaluation of the Antitumor Efficacy of the Drug - Composition Nanosystem Using a B16 Tumor - Bearing Mouse Model Select male Balb / c mice at 6 - 7 weeks of age, with a body weight between 18 - 22 g, and establish a subcutaneous transplanted mouse melanoma (B16) model to evaluate the antitumor effect of the drug - composition nanosystem (Albumin@MnB) prepared in Example 1. Five days after tumor inoculation (the tumor size was approximately 80 mm 3 ), the mice were randomly divided into 5 groups (8 - 10 mice in each group): ① Control group: 5 mg / kg normal saline (i.v.); ② 5 mg / kg 4B (i.v.); ③ 5 mg / kg BPA (i.v.); ④ 5 mg / kg drug - composition nanosystem (i.v.), and ⑤ 5 mg / kg drug - composition nanosystem (i.t.). Neutron beam irradiation was started. The experiment lasted for 16 days. During the experiment, the tumor size was measured every other day for the first 4 days, and then every 2 days, and the data were recorded. The tumor volumes of each group of mice are shown in Figure 6 . The results showed that compared with the normal saline control group, 4B did not show a therapeutic effect, BPA showed moderate tumor inhibition but without statistical significance, while Albumin@MnB (i.v.) significantly inhibited tumor growth, and intratumoral injection of Albumin@MnB (i.t.) further enhanced the efficacy.

[0031] Example 9: Effects of the Treatment with the Drug - Composition Nanosystem on Tumor - Infiltrating T Cells The mouse tumor tissues of the control group, BPA group, and Albumin@MnB (i.v.) group in Example 8 were made into 8-μm section samples, and were fluorescently stained with anti-mouse CD3-Alexa Fluor antibody (Biolegend), anti-CD8-Alexa Fluor594 antibody (Biolegend), anti-CD11c-Alexa Fluor 488 antibody, and anti-CD45-Alexa Fluor 488 antibody (Biolegend) for the corresponding CD3 + , CD8 + , CD11c, and CD45+ T cells. The relative percentages of various infiltrating T cells in the tumor tissues of each group of mice were quantified by immunofluorescence. The results are shown in Figure 7 . The results showed that compared with the normal saline control group, both BPA and Albumin@MnB increased the recruitment of CD45 white blood cells, and the proportion of dendritic cells (CD11c-CD45) was also comparable. However, Albumin@MnB increased the infiltration of CD3 and CD8 T cells (P < 0.05 compared with normal saline), while BPA failed to increase the level of CD8 T cells.

[0032] Example 10: Effect of the drug composition nano-system treatment on the levels of immune killing factors in tumors B16 cells were seeded in 6-well culture plates at a density of 2×10 5 cells per milliliter and were treated with B, Mn, and Alb@MnB respectively. After 24 hours, the cells were collected and centrifuged. Subsequently, the concentrations of INF-β and CXCL10 in the samples were detected using mouse INF-β enzyme-linked immunosorbent assay (ELISA) kits and mouse CXCL10 ELISA kits respectively. The detection results are shown in Figure 8 . The results showed that the secretion of IFN-β and CXCL10 proteins in the tumor supernatants of the Albumin@MnB group increased, indicating that the drug composition nano-system could effectively activate the tumor immune system, significantly increasing the levels of cytotoxic killing factors of effector T cells and sensitizing the anti-tumor immune effect.

[0033] Example 11: Transcriptomic analysis of the anti-tumor effect of the drug composition nano-system First, high-quality total RNA was extracted from the NC group, B, and Albumin@MnB administration groups, and RNA quality assessment was performed. Subsequently, cDNA libraries were constructed using qualified RNA samples. These libraries were then sequenced through a high-throughput sequencing platform, generating a large amount of transcriptome sequence data. In the data analysis stage, the DESeq2 software package was used for differential expression analysis. Genes with an adjusted P-value less than 0.05 and an absolute log2 fold change greater than 1 were identified as differentially expressed genes. In addition, visualization tools such as volcano plots and box plots were also used to intuitively display the differentially expressed genes. Transcriptomic analysis revealed distinct mechanistic contrasts: conventional BNCT mainly activates pro-survival pathways (such as DNA replication, homologous recombination), while Albumin@MnB-based BNCT shifts the transcriptomic landscape towards innate immunity. Key immune pathways - including TNF / NF-κB signaling, antigen processing, and interferon response - were all significantly upregulated (P<0.001). At the same time, DNA repair genes (PARP1, XRCC1) and oxidative stress alleviating factors (TXNIP) were downregulated, indicating impaired damage resolution.

[0034] The present invention utilizes the natural biocompatibility and tumor-targeting properties of albumin (such as transmembrane transport mediated by albumin receptors highly expressed on tumor cells, EPR effect), and the nanoparticles can be enriched in the tumor site, reducing damage to normal tissues. Example 6 shows that the boron concentration ratio of tumor tissue to normal tissue ≥3, meeting the core threshold of boron neutron capture therapy (BNCT), proving its significant targeted enrichment effect. The increased concentration of hydrogen peroxide (H2O2) in the tumor microenvironment triggers the dissociation of the nanoparticles and releases boric acid and manganese ions, achieving "on-demand release", further increasing the local concentration of the drug in the tumor and reducing systemic toxicity.

[0035] It is worth noting that the released manganese ions (Mn²⁺) act as T1-weighted contrast agents, enhancing the MRI signal in the tumor region. Example 7 shows that the signal in the tumor region of the Albumin@MnB group is significantly stronger than that of free MnCl2, proving its specific enrichment and slow-release characteristics in vivo, providing real-time imaging guidance for neutron beam localization, and improving the precision of BNCT.

[0036] In the present invention, boric acid, as a key component of BNCT, generates high-energy α particles and lithium ions through neutron bombardment, selectively killing tumor cells (with a range of only a few micrometers, precisely damaging the DNA of neighboring cells). Manganese ions (Mn²⁺) can synergistically enhance the anti-tumor effect of boric acid (CCK-8 experiment in Example 4), possibly by regulating tumor cell metabolism or oxidative stress response, and sensitizing tumor cells to BNCT. Examples 9-11 confirm that the nanoparticles can significantly increase the infiltration of CD3⁺ / CD8⁺ T cells in tumors (activation of cellular immunity), up-regulate immune killing factors such as IFN-β and CXCL10 (activation of humoral immunity), and at the same time, through transcriptomic analysis, it is found that they induce the activation of innate immune pathways (such as TNF / NF-κB signaling) and inhibit the expression of DNA repair genes. This dual mechanism of "direct killing + immune activation" can synergistically enhance the anti-tumor efficacy and reduce the risks of tumor recurrence and drug resistance.

[0037] In the present invention, ultrafiltration membrane (100 kDa) buffer replacement and high-pressure homogenization treatment are adopted. The process is simple and has good repeatability, suitable for large-scale production. The average particle size of the nanoparticles is controlled within 100-300 nm (preferably 150-250 nm), with both long-circulation characteristics (avoiding rapid clearance by mononuclear macrophages) and tumor penetration ability (enriching through the gaps between vascular endothelial cells). The mass ratio range of albumin to manganese borate is wide (10:1 to 1000:1), which can flexibly adjust the shell thickness and drug loading amount to meet different tumor treatment needs.

[0038] By providing intravenous injection preparations and lyophilized powder injections, the former is suitable for systemic targeted therapy, and the latter is convenient for storage and transportation, broadening the clinical application scenarios. Example 8 shows that both intravenous injection and intratumoral injection can significantly inhibit tumor growth, especially the intratumoral injection has further enhanced efficacy, proving strong dosage form adaptability. Albumin, as a natural carrier, has low immunogenicity and high biodegradability, reducing the risk of allergic reactions. No obvious toxic reactions are mentioned in the examples, and by adjusting the mass ratio and particle size, the pharmacokinetic properties can be further optimized to improve the therapeutic window.

[0039] One of the current bottlenecks of BNCT is the insufficient enrichment efficiency of boron compounds in tumors. This scheme significantly increases the boron concentration ratio through albumin nanoparticles, providing a key technological breakthrough for the clinical application of BNCT. The present invention integrates nanomaterials science, nuclear medicine, and immunology to achieve "diagnosis-treatment-immune regulation" integration, conforming to the development trend of precision medicine and personalized treatment, and having broad technical extension space (such as combined radiotherapy and chemotherapy, immune checkpoint inhibitors). The scheme solves the problems of insufficient drug enrichment and single efficacy of traditional BNCT drugs through the multi-mechanism synergy of "targeted delivery-responsive release-imaging guidance-immune activation", and has the characteristics of scientificity, practicability, and forward-looking patent layout, providing an efficient and safe innovative strategy for tumor precision treatment.

[0040] The above specific embodiments are only 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. Albumin-bound manganese borate nanoparticles, characterized in that, Comprising: A manganese borate compound, which is combined with manganese ions through a coordination bond; An albumin shell, coating the manganese borate compound to form nanoparticles; Wherein, the average particle size of the nanoparticles is 100 nm to 300 nm, and the mass ratio of the albumin to the manganese borate compound is 10:1 to 1000:

1.

2. The albumin-binding manganese borate nanoparticles according to claim 1, characterized in that The albumin is selected from one or more of serum albumin, ovalbumin, lactalbumin, myoalbumin, wheat albumin, and soybean albumin.

3. The albumin-binding manganese borate nanoparticles according to claim 1, characterized in that, The average particle size of the nanoparticles is 150 nm to 250 nm.

4. The albumin-bound manganese borate nanoparticles according to claim 1, wherein The mass ratio of the albumin to the manganese borate compound is 10:

1.

5. The albumin-binding manganese borate nanoparticles according to claim 1, characterized in that, The nanoparticles are prepared by a process with an ultrafiltration membrane cut-off molecular weight of 95 - 105 kDa and are formed by high-pressure homogenization treatment at 2°C - 6°C for 20 - 40 minutes.

6. A pharmaceutical composition, characterized in that, Containing the albumin-bound manganese borate nanoparticles according to any one of claims 1 - 5 and a pharmaceutically acceptable excipient, and the pharmaceutical composition is an intravenous injection preparation or a freeze-dried powder injection.

7. Use of the albumin-bound manganese borate nanoparticles according to any one of claims 1-5 in the preparation of a tumor therapeutic drug, characterized in that, The tumor is selected from colon cancer, triple-negative breast cancer, malignant melanoma, non-small cell lung cancer, liver cancer, renal cell carcinoma, prostate cancer, ovarian cancer, or gastric cancer.

8. Use of the albumin-bound manganese borate nanoparticles according to claim 7 in the preparation of a tumor therapeutic agent, characterized in that, The albumin-bound manganese borate nanoparticles achieve tumor targeting through the following technical features: a. Enriched in tumor tissues through the albumin-mediated transmembrane transport mechanism; b. Responding to the hydrogen peroxide concentration gradient in the tumor microenvironment to release boric acid and manganese ions, such that the boron concentration ratio between the tumor tissue and the normal tissue is ≥3.

9. Use of the albumin-bound manganese borate nanoparticles according to claim 8 in the preparation of a tumor therapeutic agent, characterized in that, The manganese ions released by the nanoparticles produce enhanced T1-weighted signals in magnetic resonance imaging for guiding neutron beam localization.

10. Use of the albumin-bound manganese borate nanoparticles according to claim 8 in the preparation of a tumor therapeutic agent, characterized in that, The nanoparticles are obtained through the following preparation steps: a. Under ice bath conditions, introducing manganese ions into the albumin solution and stirring at 450 - 550 rpm for 8 - 12 minutes; b. Adding sodium tetraborate solution and continuing to stir for 5 - 15 minutes; c. Performing buffer replacement and concentration through an 80 - 120 kDa ultrafiltration membrane; d. Performing high-pressure homogenization treatment for 20 - 40 minutes to obtain the final nanoparticles.

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