Paclitaxel / molybdenum boride nanomaterials, methods of making and uses thereof

By combining paclitaxel with molybdenum boride nanosheets, the problems of biocompatibility and low photothermal conversion efficiency of photothermal nanomaterials in lung cancer treatment were solved, achieving synergistic effects of chemotherapy and photothermal therapy, significantly inhibiting lung cancer cell growth and reducing drug resistance.

CN119838008BActive Publication Date: 2025-12-09WEST CHINA HOSPITAL SICHUAN UNIV
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Patent Information

Application Number
CN202411873025.2
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2024-12-18
Publication Date
2025-12-09
Estimated Expiration
2044-12-18

AI Technical Summary

Technical Problem

Existing photothermal nanomaterials for lung cancer treatment suffer from poor biocompatibility, low photothermal conversion efficiency, poor chemical stability, and cumbersome preparation, leading to inconsistent efficacy of chemotherapy drugs and increased risk of drug resistance.

Method used

A complex of paclitaxel and stable molybdenum boride nanosheets was used, and the molybdenum boride nanosheets were encapsulated with soybean phospholipids to improve their biocompatibility and drug loading rate, and the near-infrared photothermal effect was used to enhance the chemotherapy effect.

Benefits of technology

It achieves a synergistic effect between chemotherapy drugs and photothermal therapy, significantly induces cancer cell apoptosis, inhibits tumor growth, reduces the risk of drug resistance, and provides a new option for the treatment of lung cancer.

✦ Generated by Eureka AI based on patent content.

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Abstract

The application belongs to the technical field of medicine, and particularly relates to paclitaxel / molybdenum boride nanomaterial and a preparation method and application thereof. 4 / 3 B 2‑x Nanosheet material, the material improves the stability of Mo 4 / 3 B 2‑x Nanosheet by introducing soybean phospholipid, has the characteristics of simple preparation, high drug loading rate and high photo-thermal conversion efficiency. After the nanomaterial loads paclitaxel, as a dual-functional nanodrug for chemotherapy and photo-thermal therapy, when used for lung adenocarcinoma cells, the apoptosis of cancer cells is induced, and the induction effect is better than that of Taxol and Mo 4 / 3 B 2‑x +IR alone. When the nanodrug is applied to a mouse lung cancer model, the growth of the tumor is significantly inhibited, and the inhibition effect is better than that of Taxol and Mo 4 / 3 B 2‑x +IR alone. The results show that the Taxol / Mo 4 / 3 B 2‑x Nanosheet has a synergistic effect when used for lung cancer treatment.
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Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of medicine, and particularly relates to paclitaxel / molybdenum boride nanomaterials, a preparation method therefor, and use thereof. BACKGROUND

[0002] Lung cancer has become the leading cause of cancer death worldwide. Therefore, the development of effective lung cancer treatment methods has attracted much attention in recent years. Treatment methods for lung cancer include surgery, radiotherapy, chemotherapy, and targeted therapy. Among these treatment methods, targeted therapy is widely used because it can specifically attack cancer cells and reduce damage to healthy cells. However, although targeted therapy aims to precisely eliminate cancer cells, its efficacy sometimes shows inconsistency and can lead to the emergence of drug resistance. In view of these challenges, it is particularly important to develop new medical technologies and promote diagnostic and analytical technologies for lung cancer.

[0003] Among the treatment methods for lung cancer, drug therapy is most widely used, such as paclitaxel (Taxol) and doxorubicin. These drugs have good targeting effects, are technically mature and stable, but long-term use can lead to drug resistance and a series of side effects. In order to reduce the risk of drug resistance, researchers in the field combine chemotherapy drugs with photothermal nanomaterials. The heat generated by photothermal materials increases the sensitivity of tumor cells to chemotherapy drugs, reducing the dose of chemotherapy drugs; the precise drug delivery and controlled release of photothermal nanomaterials reduce the toxic side effects of chemotherapy drugs, reduce treatment interruptions due to side effects, and further reduce the risk of developing drug resistance; and, furthermore, photothermal materials and chemotherapy drugs have a synergistic effect, which can more effectively kill tumor cells and reduce the survival chances of drug-resistant cells.

[0004] However, there are many choices of photothermal nanomaterials, and when used for cancer treatment, it is necessary to select materials with good biocompatibility, high loading rate, and high photothermal conversion efficiency; and when applied to living organisms, there are high requirements for the absorption light of photothermal nanomaterials, which need to have strong tissue penetration, low autofluorescence, and matching of the resonance frequency with biological molecules, etc. Therefore, there are great challenges in the selection of photothermal nanomaterials.

[0005] Studies have shown that different kinds of inorganic nanomaterials have been developed and used for photothermal therapy, such as noble metals (Au, Ag, Pt, etc.), transition metal compounds (such as Ti-, Mn-, Cu-, Si-based compounds, etc.), and metal-organic framework materials, etc. However, some of the nanomaterials have the disadvantages of poor chemical stability, low photothermal conversion efficiency, high cost or high toxicity, etc., which greatly hinder their practical application. Molybdenum-based nanomaterials (Mo-NMs), including molybdenum chalcogenides, molybdenum oxides, molybdenum-based polyoxometalates and molybdenum-based nanocomposites, have unique advantages: (1) excellent biocompatibility and low cytotoxicity; (2) high specific surface area; (3) strong absorption in the near-infrared window can effectively reduce the absorption of light by biological tissues. However, molybdenum-based nanomaterials have the problems of poor chemical stability, complicated preparation, and lower photothermal conversion rate than noble metals.

[0006] Therefore, it is necessary to explore a kind of molybdenum-based nanomaterial-chemotherapy drug composite material with stable properties, simple preparation and high photothermal conversion rate, so as to realize the better synergistic effect of chemotherapy drugs and nanomaterials in cancer treatment. SUMMARY

[0007] In view of the defects of the prior art, the present application provides paclitaxel / molybdenum boride nanomaterials, a preparation method and uses thereof, aiming to realize the better synergistic effect of paclitaxel and molybdenum boride nanosheets in lung cancer treatment.

[0008] The present application provides a kind of stable molybdenum boride material, the chemical formula of the molybdenum boride is Mo 4 / 3 B 2-x Wherein x represents the number of missing molybdenum atoms, x is 0-0.5; the surface of the molybdenum boride is wrapped with soybean phospholipid.

[0009] Preferably, the molybdenum boride is prepared by a method comprising the following steps:

[0010] Step 1, a three-dimensional molybdenum boride material is exfoliated into a two-dimensional molybdenum boride nanomaterial;

[0011] Step 2, the two-dimensional molybdenum boride nanomaterial is mixed with soybean phospholipid, rotary evaporation is performed, and the precipitate is obtained;

[0012] The mass ratio of the soybean phospholipid to the two-dimensional molybdenum boride in step 2 is 1-2.2:1.

[0013] Preferably, the rotary evaporation in step 2 is performed at 55-65℃ for 0.5-1h.

[0014] The present application provides a kind of bifunctional nanomaterial, the bifunctional nanomaterial comprises chemotherapy drug and the stable molybdenum boride material of any one of the above; the mass ratio of the chemotherapy drug to the stable molybdenum boride material is 0.4-8:4.

[0015] Preferably, the chemotherapy drug is selected from paclitaxel, doxorubicin, epirubicin, cisplatin, carboplatin, bleomycin, oxaliplatin, entinostat, repotrectinib, repotrectinib.

[0016] Preferably, it is prepared by mixing the chemotherapy drug with the molybdenum boride material, centrifuging, and taking the precipitate.

[0017] Preferably, the mixing is stirring in the dark for 5-10h.

[0018] The application provides a preparation method of the bifunctional nanomaterial of any one of the above, comprising the following steps: mixing a chemotherapy drug with the molybdenum boride material, centrifuging, and taking the precipitate.

[0019] The application provides the use of the bifunctional nanomaterial of any one of the above in the preparation of a drug for treating cancer.

[0020] Preferably, the drug needs to be treated under the irradiation of light when treating cancer, the light is near-infrared light of 800-808nm, the irradiation time is 2-5 minutes, and the power is 1-2W / cm 2 ;

[0021] And / or, the cancer is lung cancer.

[0022] And / or, when the drug is used for cancer cells, the concentration of the bifunctional nanomaterial is 0.9-1.1mg / mL.

[0023] And / or, when the drug is used for mice, the dose of the bifunctional nanomaterial is 0.09-0.11mg per mouse.

[0024] The application prepares a Taxol / Mo 4 / 3 B 2-x nanosheet material, which improves the stability of Mo 4 / 3 B 2-x nanosheets by introducing soybean phospholipids, and has the characteristics of simple preparation, high drug loading rate, and high photothermal conversion efficiency. Figure 1 As shown in the figure, after loading paclitaxel, the nanomaterial serves as a bifunctional nanodrug for chemotherapy and photothermal therapy, and significantly induces apoptosis of cancer cells when applied to human lung adenocarcinoma cells, and the induction effect is better than the sum of Taxol and Mo 4 / 3 B 2-x +IR. Especially at a drug concentration of 1mg / mL, good biological safety is ensured, and good synergistic treatment effect is also obtained. When the nanodrug is applied to a mouse lung cancer model, the growth of the tumor is significantly inhibited, and the inhibition effect is also better than the sum of Taxol and Mo 4 / 3 B2-x +IR. The results show that Taxol / Mo 4 / 3 B 2-x The nanosheet material achieves good synergistic effect when applied to lung cancer treatment. Therefore, the paclitaxel / molybdenum boride system utilizes the targeted treatment activity of the drug to compensate for the defects of the poor targeting of the nanomaterial itself, and the photothermal effect of molybdenum boride compensates for the deficiency of single drug treatment, so as to achieve good synergistic effect. The present application proves that the paclitaxel / molybdenum boride nanodrug has an effective remission effect on lung cancer, and provides a new choice for the clinical treatment of lung cancer.

[0025] Obviously, according to the above content of the present application, according to the ordinary technical knowledge and conventional means in the art, other various forms of modifications, replacements or changes can be made without departing from the above basic technical idea of the present application.

[0026] The above content of the present application will be further described in detail through the specific embodiments below. However, this should not be understood as limiting the scope of the above subject matter of the present application to the following examples. Any technology realized based on the above content of the present application belongs to the scope of the present application. BRIEF DESCRIPTION OF DRAWINGS

[0027] Figure 1 Taxol / Mo 4 / 3 B 2-x Research roadmap of bifunctional nanodrug;

[0028] Figure 2 Taxol / Mo 4 / 3 B 2-x Material characterization chart; (a) is a transmission electron microscope picture; (b) is a UV-visible absorption spectrum chart of Taxol / Mo 4 / 3 B 2-x with different concentrations of Taxol; (c) is a chart of the change of Taxol / Mo 4 / 3 B 2-x with irradiation time and temperature;

[0029] Figure 3 Apoptosis experiment result chart of A549 cells induced by different concentrations of Taxol / Mo 4 / 3 B 2-x Apoptosis experiment result chart of A549 cells induced by different concentrations of Taxol / Mo

[0030] Figure 4 Apoptosis experiment result chart of A549 cells induced by different drugs;

[0031] Figure 5 Result chart of the change of tumor volume after lung cancer mice are treated by different drugs;

[0032] Figure 6 Results of water-soluble metabolomics and lipidomics changes induced after paclitaxel / molybdenum boride bifunctional drug treatment of lung cancer mice. DETAILED DESCRIPTION

[0033] In the following examples and experimental examples, reagents and materials not specifically mentioned are commercially available.

[0034] Paclitaxel (Taxol) was purchased from Selleck, molybdenum boride (Mo 4 / 3 B 2-x ) was purchased from Foshan Xinyan Nanometer Material Technology Co., Ltd., mice were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., and soybean phospholipids were purchased from Yuan Ye Biotechnology Co., Ltd.

[0035] Example 1 Mo 4 / 3 B 2-x nanoplate loaded paclitaxel (Taxol / Mo 4 / 3 B 2-x ) nanodrug and a preparation method thereof

[0036] The Taxol / Mo 4 / 3 B 2-x of this example was prepared by the following method:

[0037] 1. Preparation of two-dimensional molybdenum boride Mo 4 / 3 B 2-x nanoplate

[0038] 1 g of molybdenum boride was dispersed in 25 mL of a 20% mass percentage tetrabutylammonium hydroxide (TBAOH) aqueous solution, and was magnetically stirred at room temperature for 24 hours. Then, the supernatant was removed by centrifugation (4500 rpm, 10 minutes, 22°C). The resulting precipitate was treated with a 0.22 μm filter, and the precipitate was further freeze-dried to obtain a dry powder. The dry powder was stored in a sealed bottle and stored in the dark.

[0039] 2. Modification of two-dimensional molybdenum boride Mo 4 / 3 B 2-x nanoplate

[0040] The two-dimensional molybdenum boride Mo 4 / 3 B 2-x nanoplate was modified with soybean phospholipids. The specific steps were as follows: 500 mg of Mo 4 / 3B 2-x nanoplate was mixed with 1 g of soybean phospholipids and dispersed in 300 mL of chloroform, and was rotary evaporated at 60°C for 1 h. The precipitate was collected to obtain modified Mo 4 / 3B 2-x nanoplate. This modification ensured that Mo 4 / 3 B 2-xThe effective dispersion and convenient transportation of the nanosheet in blood vessels and the large surface area provided for the loading of Taxol.

[0041] 3、Taxol / Mo 4 / 3 B 2-x Preparation

[0042] The modified two-dimensional molybdenum boride Mo 4 / 3 B 2-x nanosheet is dissolved in PBS (10 mM, pH = 7) to prepare a Mo 4 / 3B 2-x nanosheet solution of 2 mg / mL. Taxol is dissolved in water to prepare a Taxol solution of 1 mg / mL.

[0043] Take 2.0 mL of the Mo 4 / 3 B 2-x nanosheet solution (2 mg / mL) and mix with 4.0 mL of the Taxol solution (1 mg / mL) and stir overnight in the dark. Centrifuge, collect the precipitate, resuspend with PBS; centrifuge again and collect the precipitate. The obtained Taxol / Mo 4 / 3 B 2-x dispersion in PBS and store at 4°C in the dark.

[0044] In other embodiments, the concentration of the added Taxol solution can also be 0.1-2 mg / mL.

[0045] The technical solutions of the present application are further described below through experiments. The two-dimensional molybdenum boride Mo 4 / 3 B 2-x nanosheet and Taxol / Mo 4 / 3 B 2-x in the following experimental examples are both prepared by the method of Example 1.

[0046] Experimental Example 1 Characterization of Taxol / Mo 4 / 3 B 2-x

[0047] I. Experimental Methods

[0048] 1. Characterization of morphology and size

[0049] Determined by transmission electron microscopy (TEM).

[0050] 2. Characterization of Taxol loading

[0051] Taxol / Mo 4 / 3 B 2-x ​, the concentration of Taxol solution added is 0.015 mg / mL, 0.075 mg / mL, 0.15 mg / mL, 0.225 mg / mL, and 0.45 mg / mL, respectively. Therefore, the concentration of Taxol in the mixed solution is 0.01 mg / mL, 0.05 mg / mL, 0.10 mg / mL, 0.15 mg / mL, and 0.30 mg / mL, respectively. The prepared Taxol / Mo 4 / 3 B 2-x The ultraviolet-visible spectrophotometer is used to determine the ultraviolet-visible absorption spectrum.

[0052] 3. Photothermal effect determination

[0053] The water, 0.0625 mg / mL, 0.125 mg / mL, 0.25 mg / mL, 0.5 mg / mL, and 1 mg / mL Taxol / Mo 4 / 3B 2-x Solutions are respectively taken, and the solutions are irradiated with 808 nm near-infrared light (NIR) (the power is 1.5 W / cm 2 The thermal imager is used to determine the temperature rise of the solution with irradiation time.

[0054] II. Experimental results

[0055] 1. Morphology size

[0056] The TEM result is shown in Figure 2 (a). The Taxol / Mo 4 / 3 B 2-x Prepared by the application is a two-dimensional sheet structure, and the size is 500-600 nm.

[0057] 2. Drug loading condition

[0058] The ultraviolet-visible absorption spectrum result is shown in Figure 2 (b). With the increase of the concentration of Taxol, the absorption peak signal of Taxol / Mo 4 / 3 B 2-x Prepared by the application is obviously increased at 240 nm, which indicates that the Mo 4 / 3 B 2-x Nanosheet has a high drug loading rate.

[0059] 3. Photothermal effect

[0060] The photothermal effect result is shown in Figure 2(c) as shown: when the concentration of nanomaterials is greater than 0.125 mg / mL, the solution temperature is obviously improved with the increase of the concentration of nanomaterials and the extension of irradiation time. When the concentration is 1 mg / mL, the temperature is rapidly increased with the extension of irradiation time, and 50 DEG C can be reached when irradiated for 300 s. The results show that the Taxol / Mo 4 / 3 B 2-x has high photo-thermal conversion efficiency.

[0061] The above results show that the Taxol / Mo 4 / 3 B 2-x has two-dimensional nanosheet structure, high drug loading rate and high photo-thermal conversion efficiency.

[0062] Experimental Example 2 Taxol / Mo 4 / 3 B 2-x Nanodrug for A549 cell-based therapeutic effect

[0063] I. Experimental method

[0064] 1. Cell culture

[0065] A549 cells were cultured in DMEM containing 10% FBS and 1% penicillin-streptomycin solution in a humidified incubator at 37 DEG C and 5% CO2. The culture medium was replaced every two days to maintain cell viability, and other conditions remained unchanged. The cells were subcultured with 0.25% trypsin.

[0066] 2. Cell toxicity experiment

[0067] A549 cells were incubated with different concentrations of Taxol / Mo 4 / 3 B 2-x for 24 h, and then apoptosis experiments were performed, respectively, and cell toxicity was determined by apoptosis rate.

[0068] The concentration of Taxol / Mo 4 / 3 B 2-x was set to 0 mg / mL, 0.25 mg / mL, 0.5 mg / mL, 1 mg / mL, 2 mg / mL and 3 mg / mL, respectively.

[0069] 3. Experimental grouping

[0070] This experimental example is divided into six groups, namely control (Control) group, Taxol group (1 mg / mL Taxol), Taxol+IR group (1 mg / mL Taxol plus 808 nm NIR irradiation), Mo 4 / 3 B 2-x group (1 mg / mL Mo 4 / 3 B 2-x), Mo 4 / 3 B 2-x + IR group (1 mg / mL Mo 4 / 3 B 2-x with 808 nm NIR irradiation), Taxol / Mo 4 / 3 B 2-x + IR group (1 mg / mL Taxol / Mo 4 / 3 B 2-x with 808 nm NIR irradiation). The irradiation power of NIR was 1.5 W / cm 2 , and the irradiation time was 5 minutes.

[0071] Before treatment, A549 cells were washed with PBS, and then 1 mL of 0.25% trypsin was added to resuspend the cells in fresh culture medium at a density of 5x10 5 cells / mL. Then, 2 ml of A549 cells were evenly dispersed and equally divided into 6 parts, and inoculated into each well of a 6-well plate. The adherent A549 cells were then exposed to the drugs and irradiation conditions of each group, and irradiation was performed after 4 hours of drug addition. The control group was treated with the same volume of PBS without irradiation. After 24 hours of drug incubation with the cells, apoptosis testing was performed.

[0072] 4. Cell apoptosis experiment

[0073] Cell apoptosis was measured by Annexin V and propidium iodide (PI) double staining (4A Biotech, China). A549 cells were incubated with 5 μL of Annexin V-FITC at room temperature for 5 minutes in the dark, and then mixed with 10 μL of PI. The apoptosis rate was determined by flow cytometry analysis (Annexin V / FITC, Ex / Em: 488 nm / 525 nm; PI, Ex / Em: 561 nm / 575 nm).

[0074] II. Experimental results

[0075] 1. Cell toxicity

[0076] The results of the cell toxicity experiment are shown in Table 1: Table 1 Figure 3 The concentration of Taxol / Mo 4 / 3 B 2-x was 0-1 mg / mL, and the apoptosis rate of the cells was very low, while the concentration of Taxol / Mo 4 / 3 B 2-x was greater than or equal to 2 mg / mL, and the number of apoptotic cells increased. Therefore, when the concentration of Taxol / Mo 4 / 3 B 2-x was 1 mg / mL, the cell toxicity was low, and the biological safety was good.

[0077] 2. Cell apoptosis

[0078] The apoptosis results of each experimental group are shown in Table 1. Figure 4 As shown in Table 1, the apoptosis rates of the Taxol group and the Taxol+IR group are relatively low, being 6.22% and 3.48% respectively; the apoptosis rates of the Mo 4 / 3 B 2-x group and the Mo 4 / 3 B 2-x +IR group are also relatively low, being 2.94% and 15.98% respectively. It is shown that, under the conditions of the present experimental example, the apoptosis is less when the cells are treated by Taxol or Mo 4 / 3 B 2-x +IR. However, in the Taxol / Mo 4 / 3 B 2-x +IR group, the apoptosis rate is obviously increased, being 46.33%, and the apoptosis rate result is higher than the sum of the Taxol group and the Mo 4 / 3B 2-x +IR group.

[0079] The results show that the Taxol / Mo 4 / 3 B 2-x prepared by the present application can induce cell apoptosis, especially at the concentration of 1 mg / mL, which has good biological safety and realizes the synergistic effect of Taxol chemotherapy and Mo 4 / 3 B 2-x photothermal therapy.

[0080] Experimental Example 3: Treatment effect of Taxol / Mo 4 / 3 B 2-x nanomedicine on a mouse-based lung cancer model

[0081] 1. Establishment of lung cancer model and experimental grouping

[0082] BALB / c-nu nude mice were randomly divided into a control group, a Taxol group, a Mo 4 / 3 B 2-x group, a Taxol+IR group, a Mo 4 / 3 B 2-x +IR group, and a Taxol / Mo 4 / 3 B 2-x +IR group, a total of 6 groups, 6 mice in each group. Among them, except for the control group, the mice in the other groups were respectively injected with 100 μL of A549 cells with a concentration of 2×10 5 / mL subcutaneously at the right back position to establish a tumor model, and the mice in the control group were injected with 100 μL of PBS subcutaneously at the same position.

[0083] The control group was only given normal diet and boiled water; the Taxol group and the Mo 4 / 3 B 2-xTaxol and Mo were injected into the tail vein of the mice in the Taxol+IR group and the Mo+IR group, respectively 4 / 3 B 2-x Normal diet and white water were given at the same time; Taxol / Mo+IR group 4 / 3 B 2-x Taxol and Mo were injected into the tail vein of the mice in the Taxol+IR group and the Mo+IR group, respectively 4 / 3 B 2-x Normal diet and white water were given at the same time; Taxol / Mo+IR group 4 / 3 B 2-x Taxol / Mo were injected into the tail vein of the mice in the Taxol+IR group and the Mo+IR group, respectively 4 / 3 B 2-x Normal diet and white water were given at the same time; Taxol / Mo+IR group 2 The treatment time was 15 days, and the drug injection volume was 100 μL, the drug concentration was 1 mg / mL, and the light irradiation time was 4 h after each drug injection. The specific operation of near-infrared light irradiation was as follows: the tumor-bearing mice under general anesthesia were exposed to infrared laser (wavelength: 808 nm) with a power density of 1.5 W / cm 2 for 5 minutes. Using the FLIR One Pro camera (USA), the highest temperature and real-time thermal image were captured and recorded at the tumor site by infrared thermal detector.

[0084] The specific operation of near-infrared light irradiation was as follows: the tumor-bearing mice under general anesthesia were exposed to infrared laser (wavelength: 808 nm) with a power density of 1.5 W / cm 2 for 5 minutes. Using the FLIR One Pro camera (USA), the highest temperature and real-time thermal image were captured and recorded at the tumor site by infrared thermal detector.

[0085] 2. Measurement of tumor volume

[0086] During the treatment, the tumor volume was measured once a day. The length and width of the tumor were measured using a vernier caliper. The tumor volume was calculated by the following formula:

[0087]

[0088] where a represents the maximum length of the tumor (mm), and b represents the minimum width of the tumor (mm).

[0089] 3. Metabolomics analysis

[0090] Mice were general anesthetized, and blood samples were collected using blood collection tubes containing ethylenediaminetetraacetic acid (EDTA). After collection, the samples were centrifuged (2000 rpm, 10 min, 8 °C), and the supernatant was collected as plasma. 50 μl of plasma was mixed with 250 μl of methanol (CH3OH) and incubated at -20 °C for 20 min. Subsequently, the mixture was shaken at 1500 rpm for 30 sec at 4 °C. After centrifugation (13000 rpm, 15 min, 4 °C), 150 μl of the supernatant was vacuum dried for 2 h. The dried water-soluble sample was redissolved in 500 μl of HILIC solution (10 mM ammonium acetate, 30% water / 70% acetonitrile + 0.2% acetic acid) and analyzed by LC-MS / MS. Metabolomics analysis was performed using an LC-MS / MS system with an AB Sciex triple quadrupole 6500 mass spectrometer and a Nexera LC-30A UPLC system (AB Sciex, Framingham, MA) in multiple reaction monitoring (MRM) mode.

[0091] II. Experimental Results

[0092] 1. Tumor suppression

[0093] Tumor growth status as follows Figure 5 As shown: Under the experimental conditions of this example, the tumor size in the Taxol group continued to grow rapidly, and Taxol had no significant inhibitory effect on tumor growth; Mo 4 / 3 B 2-x In the +IR group, tumor growth slowed after 10 days of treatment, and the tumors shrank after 12 days, indicating that Mo... 4 / 3 B 2-x The photothermal effect can inhibit tumor growth; Taxol / Mo 4 / 3B 2-x In the +IR group, tumor growth ceased after 10 days of treatment, tumor volume significantly decreased after 10 days, and complete tumor elimination occurred on day 15. These results demonstrate that, after day 15 of treatment, the Taxol / Mo prepared in this invention... 4 / 3 B 2-x It exhibits excellent synergistic therapeutic effects, and its tumor-inhibiting effect is superior to that of the Taxol group and Mo. 4 / 3 B 2-x +The sum of the IR groups.

[0094] 2. Results of metabolomics analysis

[0095] The results of metabolomics analysis are as follows Figure 6 As shown: Metabolomics studies revealed significant changes in amino acid and lipid metabolism, indicating that Taxol / Mo 4 / 3 B 2-x It regulates the homeostasis of amino acid and lipid metabolism.

[0096] The above results show that the Taxol / Mo 4 / 3 B 2-x The synergistic effect of chemotherapy and photothermal therapy can be achieved, the growth of mouse tumor is effectively inhibited, and the homeostasis of amino acid and lipid metabolism is regulated.

[0097] As can be seen from the above examples and experimental examples, the Taxol / Mo 4 / 3 B 2-x Nanosheet material is prepared, the stability of the Mo 4 / 3 B 2-x Nanosheet is improved, and the nanomaterial has the characteristics of simple preparation, high drug loading rate and high photothermal conversion efficiency. When the nanomaterial is applied to human lung adenocarcinoma cells, the apoptosis of the cancer cells is significantly induced, and the induction effect is better than that of Taxol and Mo 4 / 3 B 2-x +IR. Especially at a drug concentration of 1 mg / mL, good biological safety is ensured, and good synergistic treatment effect is also obtained. When the nanomaterial is applied to a mouse lung cancer model, the growth of the tumor is significantly inhibited, and the inhibition effect is also better than that of Taxol and Mo 4 / 3 B 2-x +IR. The results show that the Taxol / Mo 4 / 3 B 2-x Nanosheet material achieves a very good synergistic effect when applied to lung cancer treatment. The present application proves that the paclitaxel / molybdenum boride nanodrug has an effective remission effect on lung cancer, and provides a new choice for the clinical treatment of lung cancer.

Claims

1. A bifunctional nanomaterial, characterized in that: The bifunctional nanomaterial comprises a chemotherapy drug and molybdenum boride; the mass ratio of the chemotherapy drug to the molybdenum boride is 0.4-8:

4. The chemotherapy drug is paclitaxel; the chemical formula of the molybdenum boride is Mo. 4 / 3 B 2-x , where x represents the number of missing boron atoms, and x takes a value of 0-0.5; the surface of the molybdenum boride is coated with soybean lecithin.

2. The bifunctional nanomaterial according to claim 1, characterized in that: The molybdenum boride material is prepared by a method comprising the following steps: Step 1: Two-dimensional molybdenum boride nanomaterials are exfoliated from the three-dimensional molybdenum boride material; Step 2: Mix the two-dimensional molybdenum boride nanomaterials with soybean lecithin, rotary evaporate, and collect the precipitate to obtain the final product. The mass ratio of soybean phospholipids to two-dimensional molybdenum boride in step 2 is 1-2.2:

1.

3. The bifunctional nanomaterial according to claim 2, characterized in that: The rotary evaporation described in step 2 is carried out at 55-65°C for 0.5-1 h.

4. The bifunctional nanomaterial according to claim 1, characterized in that: The material is prepared by the following steps: mixing the chemotherapy drug with the molybdenum boride material, centrifuging, and collecting the precipitate.

5. The bifunctional nanomaterial according to claim 4, characterized in that: The mixing process involves stirring in the dark for 5-10 hours.

6. A method for preparing the bifunctional nanomaterial according to any one of claims 1-5, characterized in that, The process includes the following steps: mixing the chemotherapy drug with the molybdenum boride material, centrifuging, and collecting the precipitate to obtain the final product.

7. Use of the bifunctional nanomaterial according to any one of claims 1-5 in the preparation of a medicament for treating cancer.

8. The use according to claim 7, characterized in that: The drug is used to treat cancer under light irradiation, specifically near-infrared light of 800-808 nm, for 2-5 minutes at a power of 1-2 W / cm². 2 ; And / or, the cancer is lung cancer; And / or, when the drug is used on cancer cells, the concentration of the bifunctional nanomaterial is 0.9-1.1 mg / mL; And / or, when the drug is used on mice, the dose of the bifunctional nanomaterial is 0.09-0.11 mg / mouse.

Citation Information

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