Tadpole-shaped functional carbon nanotubes, their preparation method and applications

Abstract

The present application relates to the technical field of functional nanomaterials, and in particular to a tadpole-shaped functional carbon nanotube as well as a preparation method and application thereof.The tadpole-shaped functional carbon nanotube provided by the present application has the following characteristics: (1) the whole is a nitrogen-doped U-shaped carbon nanotube; (2) group VIII transition metal nanoparticles are encapsulated at the bottom of the U-shaped carbon nanotube to form the head of the tadpole-shaped carbon tube; and (3) a single-atom zinc is inlaid on the tadpole-shaped tail carbon tube.The tadpole-shaped functional carbon nanotube can realize the cascade of four tumor treatment methods of chemical kinetics, photodynamic kinetics, photo-thermal and chemotherapy, and achieve a beneficial effect of synergistic treatment of tumors.

Description

Technical Field

[0001] This invention relates to the field of functional nanomaterials technology, and in particular to a tadpole-shaped functional carbon nanotube, its preparation method, and its application. Background Technology

[0002] The rise and rapid development of nanomaterials has brought new ideas and hopes to the diagnosis and treatment of tumors. They not only endow traditional chemotherapy drugs with targeting properties, but also bring a wealth of treatment methods, such as photothermal therapy, photodynamic therapy, chemodynamic therapy, etc. At the same time, with the development of nanomaterial preparation and functional integration technology, the exploration of the integration of the above-mentioned multiple treatment methods in a single nanomaterial to achieve the beneficial effect of synergistic treatment has received increasing attention [Nat. Rev. Mater., 2021, 6, 766; Nat. Rev. Clin. Oncol., 2020, 17, 657; Br. J. Cancer, 2020, 123, 871].

[0003] Carbon nanotubes are a type of material composed of sp 2Hybridized carbon nanotubes, linked by carbon-carbon σ bonds to form a hexagonal honeycomb structure, form tubular carbon materials. This unique structure determines the distinctive physicochemical properties of these materials, such as: a huge aspect ratio (radial dimensions on the nanometer scale and axial dimensions on the micrometer scale), high specific surface area, high mechanical strength, abundant electrical properties, excellent thermal conductivity, and excellent chemical and thermal stability (Science of Fullerenes and Carbon Nanotubes, Academic Press, New York, 1996; Chem. Rev., 1999, 99, 1787). Therefore, since the discovery of carbon nanotubes, researchers have been focusing on their applications in the biomedical field, such as nanobiosensing and recognition, and bioreactors. In recent years, due to their high drug-carrying capacity and superhydrophobic properties, carbon nanotubes have made significant progress in the application of disease diagnosis and treatment [J. Control. Release, 2015, 210, 230–245; ACS Appl. NanoMater., 2022, 5, 13685–13696; J. Mater. Chem. B, 2022, 10, 9944]. Furthermore, the potential application value of these nanomaterials in photothermal therapy and photodynamic therapy has been confirmed [Chem. Mater., 2023, 35, 4751-4760; ACS Nano]. [2009, 3, 3707], gradually transforming towards clinical application, and successively developing various functionalized carbon nanotube materials [CN200710037418.X, CN200710158315.9, CN201110003490.7, CN201310031811.3, CN201210001297.4, CN201711369639.7, CN202211074076.X, CN201110372002.X, CN201580043053.4, CN201110377663.1, etc.]. However, due to limitations in carbon nanotube preparation methods and functional integration technology, currently available carbon nanotubes for cancer treatment cannot functionally achieve the cascade of four treatment methods: photodynamic therapy, photothermal therapy, chemokinetics, and chemotherapy. Therefore, their synergistic therapeutic benefits in cancer treatment are limited. Summary of the Invention

[0004] The purpose of this invention is to solve the technical problem that carbon nanotubes used in cancer treatment are unable to achieve the cascade of four treatment methods: photodynamic therapy, photothermal therapy, chemokinetics and chemotherapy. The invention provides a tadpole-shaped functional carbon nanotube, its preparation method and application.

[0005] In this invention, the tadpole-shaped functional carbon nanotubes are mainly composed of the following chemical elements: C, Group VIII transition metal elements, Zn, and N; the morphological structure is a "U"-shaped nitrogen-doped carbon nanotube, with the head being a Group VIII transition metal nanoparticle encapsulated at the bottom of the "U" shape, and the tail being a nitrogen-doped carbon nanotube embedded with a single atom of zinc.

[0006] The objective of this invention can be achieved through the following technical solutions:

[0007] This invention provides a tadpole-shaped functional carbon nanotube. The carbon nanotube has a "U"-shaped structure and its main chemical components include: C, group VIII transition metal elements, Zn, and N. The tadpole-shaped tail is a nitrogen-doped carbon nanotube embedded with a single atom of zinc. The nitrogen-doped carbon nanotube is "U"-shaped and has a single atom of zinc embedded on it. The tadpole-shaped head is a group VIII transition metal nanoparticle encapsulated at the bottom of the "U".

[0008] In one embodiment of the present invention, the nitrogen atoms in the nitrogen-doped carbon nanotubes are pyridine nitrogen, pyrrole nitrogen, graphitic nitrogen, or nitrogen oxide, and the molar mass ratio of carbon to nitrogen is in the range of 50 to 60.

[0009] Since nitrogen-doped carbon nanotubes are embedded with single-atom zinc, nitrogen-doped carbon nanotubes with embedded single-atom zinc can be represented as Zn-NC. x state.

[0010] In one embodiment of the present invention, the aspect ratio of the "U"-shaped nitrogen-doped carbon nanotubes is in the range of 3 to 12, and the diameter is in the range of 50 to 80 nm, with I... D / I G The numerical values ​​used to measure the structural integrity of graphitized materials range from 1.2 to 0.8.

[0011] In one embodiment of the present invention, the size of the group VIII transition metal nanoparticles is in the range of 10 to 30 nm, the group VIII transition metal is selected from one of Fe, Co, Ni or an alloy of Fe and Co or an alloy of Fe and Ni, and the molar mass ratio of the group VIII transition metal element to carbon is in the range of 1:(5 to 20).

[0012] In one embodiment of the invention, single-atom zinc is uniformly embedded in nitrogen-doped carbon nanotubes, via Zn-NC x The force is anchored, and the molar mass ratio of carbon to zinc is in the range of 100 to 150.

[0013] This invention further provides a method for preparing the tadpole-shaped functional carbon nanotubes, comprising the following steps:

[0014] Step 1: Disperse zinc nitrate and acetylacetone salt in methanol solution by ultrasonication. After a period of time, add a certain amount of imidazole compound to the mixed solution. After stirring and reacting, obtain uniform precursor nanoparticles, i.e. nanoparticles containing acetylacetone salt.

[0015] Step 2: The acetylacetone salt is thermally reduced to a metal nanocatalyst using a high-temperature pyrolysis method, and then ZIF-8 is catalyzed to form carbon nanotubes. Specifically, the precursor nanoparticles are placed in a tube furnace and calcined at a certain temperature under an inert atmosphere for a period of time. After cooling to room temperature, they are ground, dispersed in a solution by ultrasonication, differential centrifugation, magnetic separation, and vacuum drying to obtain the tadpole-shaped functional carbon nanotubes.

[0016] In the above technical solution, imidazole compounds are used as the main raw material for "U"-shaped nitrogen-doped carbon nanotubes, acetylacetone salts are used as the raw material for group VIII transition metal nanoparticles, zinc nitrate is used as the raw material for single-atom zinc, and methanol is used as the solvent.

[0017] In one embodiment of the present invention, the acetylacetone salt is selected from one or a combination of two of acetylacetone iron, acetylacetone cobalt, or acetylacetone nickel, and the imidazole compound is selected from any one of 2-methylimidazole, 2-formaldehyde imidazole, 2-bromoimidazole, 4-formic acid imidazole, or 4,5-dimethylimidazole.

[0018] In one embodiment of the present invention, the molar ratio of imidazole compound, acetylacetone salt, zinc nitrate and methanol is (15-30):(0-3):6:8.3, preferably (15-30):(0-1):6:8.3, in which case the acetylacetone salt is uniformly encapsulated in a molecular cage.

[0019] In one embodiment of the present invention, in step one, the crystallinity and size of the prepared nanoproduct can be achieved by changing the stirring time, reaction temperature, or amount of imidazole compound. Extending the stirring time, increasing the reaction temperature, and increasing the amount of imidazole compound can yield nanoparticle precursors with uniform size. The stirring reaction conditions are: a stirring time of 20–28 h and a reaction temperature of 40–60 °C.

[0020] In one embodiment of the present invention, in step two, the calcination temperature is between 500 and 900°C. If the temperature is below 500°C, the relevant nano-metal compounds do not reach the degree of crystallization. If the temperature is above 900°C, the metal nanoparticles will severely aggregate and reach the boiling point of zinc, and then volatilize and disappear. The optimal calcination temperature is 600 to 800°C.

[0021] In one embodiment of the present invention, in step two, the inert atmosphere can be any gas that does not have oxidizing, reducing or reacting properties with materials, wherein high-purity nitrogen or argon is preferred, with high-purity nitrogen being the most economical.

[0022] In one embodiment of the present invention, in step two, the calcination time is between 1 and 3 hours, preferably 2 hours, and the gas flow rate is between 50 and 150 mL / min. –1 Between, at 90 mL·min –1 Preferably, the heating rate is 1–5 °C·min. –1 Between, at 2℃·min –1 Better.

[0023] The present invention further provides the application of the tadpole-shaped functional carbon nanotubes in the preparation of nanomaterials that kill tumor cells.

[0024] Specifically, the tadpole-shaped functional carbon nanotubes can serve as a nanomaterial for chemically kinetic killing of tumor cells. More specifically, the Group VIII transition metal nanoparticles at the head of the tadpole-shaped functional carbon nanotubes catalyze tumor cell death through a nano-Fenton-like reaction.

[0025] The tadpole-shaped functional carbon nanotubes can be used as a nanomaterial for photodynamic killing of tumor cells. Specifically, the tail of the tadpole-shaped functional carbon nanotubes is embedded with nitrogen-doped carbon nanotubes containing single-atom zinc, which have photosensitizing effects and can produce biotoxic singlet oxygen and other reactive oxygen substances, which can kill tumor cells at specific sites.

[0026] The tadpole-shaped functional carbon nanotubes can be used as a nanomaterial for photothermal killing of tumor cells. Specifically, the tadpole-shaped functional carbon nanotubes have excellent photothermal conversion efficiency and can generate high temperatures locally, causing tumor cells to undergo pyroptosis.

[0027] This invention further provides applications of the tadpole-shaped functional carbon nanotubes, specifically their use in the preparation of nanomaterials for delivering anticancer drugs. Specifically, the tadpole-shaped functional carbon nanotubes possess a large external surface area and an open tubular structure, enabling them to load small molecule chemotherapeutic drugs. Utilizing the high permeability and retention effect of tumors, targeted drug delivery and treatment of tumor cells can be achieved.

[0028] The tadpole-shaped functional carbon nanotubes provided by this invention integrate four treatment methods: photodynamic therapy, photothermal therapy, chemokinetic therapy, and chemotherapy drug delivery, achieving a beneficial effect of synergistic treatment of tumors.

[0029] The tadpole-shaped functional carbon nanotubes provided by this invention exhibit photothermal properties where temperature changes are influenced by the concentration of carbon nanotubes and the irradiation time. These tadpole-shaped functional carbon nanotubes possess excellent photothermal conversion efficiency and can reach localized high temperatures of 50°C to 65°C, thus meeting the requirements for thermotherapy.

[0030] The tadpole-shaped functional carbon nanotubes provided by this invention exhibit the following chemical kinetic properties: the Group VIII transition metal nanoparticles at the head of the tadpole-shaped functional carbon nanotubes can undergo a Fenton-like reaction with hydrogen peroxide, generating a large amount of ROS that induces cell apoptosis. When further laser irradiation is introduced, the increased temperature significantly improves the Fenton-like catalytic efficiency, as evidenced by the near disappearance of the characteristic absorption peak of methylene blue.

[0031] The tadpole-shaped functional carbon nanotubes provided by this invention exhibit photodynamic properties where the tadpole-shaped functional carbon nanotubes are embedded with single-atom zinc, exhibiting photosensitivity and generating biotoxic singlet oxygen and other reactive oxygen species, capable of selectively killing tumor cells. The singlet oxygen yield is positively correlated with time and temperature, with the characteristic absorption peak intensity of 1,3-diphenylisobenzofuran (DPBF) gradually decreasing. When hydrogen peroxide is further introduced, providing a large amount of oxygen, the singlet oxygen yield significantly increases, manifested as the almost disappearance of the characteristic absorption peak of DPBF.

[0032] The tadpole-shaped functional carbon nanotubes provided by this invention exhibit superior chemotherapy drug delivery performance. These nanotubes possess a large external surface area and an open tubular structure, enabling them to load small molecule chemotherapy drugs. Utilizing the high permeability and retention effect of tumors, targeted drug delivery and treatment of tumor cells can be achieved. Taking the antitumor drug doxorubicin as an example, the material provided by this invention can load 200–300 mg / g, and under the influence of acidity, temperature, and gas propulsion, the drug release rate can reach over 50% within 10 hours.

[0033] The tadpole-shaped functional carbon nanotubes provided by this invention exhibit high biocompatibility and synergistic tumor-killing ability both in vivo and in vitro.

[0034] Compared with the prior art, the technical solution of the present invention has the following advantages and beneficial effects:

[0035] (1) This invention provides a tadpole-shaped functional carbon nanotube, which for the first time integrates and cascades four tumor treatment methods: photodynamic therapy, photothermal therapy, chemokinetics and chemotherapy, and has obvious beneficial effects of synergistic treatment.

[0036] (2) The present invention provides a tadpole-shaped functional carbon nanotube, the head of which is a group VIII metal nanoparticle wrapped in a graphitized carbon layer, and the carbon nanotube is a nitrogen-doped carbon nanotube with a single atom of zinc embedded on it. Therefore, it has obvious advantages in biological safety compared with the nanomaterials of common photothermal therapy, photodynamic therapy and chemidynamic therapy.

[0037] (3) The present invention provides a tadpole-shaped functional carbon nanotube. The raw materials are inexpensive and readily available imidazole, zinc nitrate and acetylacetone salt. The preparation process is simple and the product is easy to separate. Compared with other types of functional carbon nanotubes, the cost is lower and it is easier to commercialize. Attached Figure Description

[0038] Figure 1 The images show transmission electron microscopy (TEM) and dynamic light scattering (DLS) images of the tadpole-shaped functional carbon nanotubes prepared in Example 1. The size is approximately 200–800 nm.

[0039] Figure 2 Transmission electron microscopy (TEM) images and dynamic light scattering patterns of the tadpole-shaped functional carbon nanotubes prepared in Example 2. The size is approximately 200–600 nm.

[0040] Figure 3 Transmission electron microscopy (TEM) images and dynamic light scattering patterns of the tadpole-shaped functional carbon nanotubes prepared in Example 3. The size is approximately 300–600 nm.

[0041] Figure 4 High-resolution transmission electron microscopy (TEM) image and X-ray powder diffraction (PXRD) pattern of the tadpole-shaped functional carbon nanotubes prepared in Example 1.

[0042] Figure 5 An experiment to evaluate the photothermal properties of the tadpole-shaped functional carbon nanotubes prepared in Example 1.

[0043] Figure 6 An experiment was conducted to evaluate the Fenton-like catalytic performance of the tadpole-shaped functional carbon nanotubes prepared in Example 1.

[0044] Figure 7 The photodynamic performance evaluation experiment of the tadpole-shaped functional carbon nanotubes prepared in Example 1.

[0045] Figure 8 The chemotherapy drug delivery evaluation experiment of the tadpole-shaped functional carbon nanotubes prepared in Example 1 showed that the drug loading content and release amount met the requirements of clinical treatment and research.

[0046] Figure 9 The cytotoxicity of different concentrations of tadpole-shaped functional carbon nanotubes prepared in Example 1 after co-incubation with melanoma cells for 12 hours.

[0047] Figure 10The tadpole-shaped functional carbon nanotubes prepared in Example 1 were co-incubated with melanoma cells after being treated in different ways for 12 hours to detect cytotoxicity.

[0048] Figure 11 The image shows a laser confocal image of tadpole-shaped functional carbon nanotubes prepared in Example 1 after being co-incubated with melanoma cells in different ways for 12 hours.

[0049] Figure 12 The curves show the weight changes of C57BL / 6 female mice carrying melanoma treated in different ways during the treatment period.

[0050] Figure 13 The curves show the changes in tumor volume in C57BL / 6 female mice carrying melanoma treated in different ways during the treatment period.

[0051] Figure 14 Optical photographs of tumors in female C57BL / 6 mice carrying melanoma after different treatments.

[0052] Figure 15 Images of stained sections of tissue from C57BL / 6 female mice carrying melanoma after different treatments. Detailed Implementation

[0053] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments.

[0054] Example 1

[0055] Preparation of tadpole-shaped functional carbon nanotubes: 1790 mg Zn(NO3)·6H2O and 212 mg ferric acetylacetone were dissolved in 240 mL anhydrous methanol and sonicated for 10 minutes. Then, 1478 mg 2-methylimidazole was added to the above mixture, and the mixture was heated and stirred at 50 °C for 24 hours. After cooling to room temperature, the product was repeatedly washed with methanol by centrifugation and collected, then dried at 60 °C to obtain an orange dry solid powder. 100 mg of the orange product was then placed in a tube furnace and heated to 800 °C at a nitrogen atmosphere at a rate of 2 °C / min. After holding for 2 hours, the mixture was rapidly cooled to room temperature, then ground, centrifuged at 5000 rpm for 5 minutes, magnetically separated, and vacuum dried at 60 °C to obtain tadpole-shaped functional carbon nanotubes, i.e., Figure 1 As shown.

[0056] Example 2

[0057] Preparation of tadpole-shaped functional carbon nanotubes: 1790 mg Zn(NO3)·6H2O, 106 mg iron acetylacetone, and 78 mg cobalt acetylacetone were dissolved in 240 mL anhydrous methanol and sonicated for 10 minutes. Then, 1478 mg 2-methylimidazole was added to the above mixture, and the mixture was heated and stirred at 50 °C for 24 hours. After cooling to room temperature, the product was repeatedly washed with methanol by centrifugation and collected, then dried at 60 °C to obtain an orange dry solid powder. 100 mg of the orange product was then placed in a tube furnace and heated to 800 °C at a nitrogen atmosphere at a rate of 2 °C / min. After holding for 2 hours, the mixture was rapidly cooled to room temperature, then ground, centrifuged at 5000 rpm for 5 minutes, magnetically separated, and vacuum dried at 60 °C to obtain tadpole-shaped functional carbon nanotubes, i.e., Figure 2 As shown.

[0058] Example 3

[0059] Preparation of iron-based nanoparticles: 1790 mg Zn(NO3)·6H2O, 106 mg iron acetylacetone, and 77 mg nickel acetylacetone were dissolved in 240 mL anhydrous methanol and sonicated for 10 minutes. Then, 1478 mg 2-methylimidazole was added to the above mixture, and the mixture was heated and stirred at 50 °C for 24 hours. After cooling to room temperature, the product was repeatedly washed with methanol by centrifugation and collected. It was then dried at 60 °C to obtain an orange dry solid powder. Next, 100 mg of the orange product was placed in a tube furnace and heated to 800 °C at a nitrogen atmosphere at a rate of 2 °C / min. After holding for 2 hours, it was rapidly cooled to room temperature, then ground, centrifuged at 5000 rpm for 5 minutes, magnetically separated, and vacuum dried at 60 °C to obtain tadpole-shaped functional carbon nanotubes, i.e. Figure 3 As shown.

[0060] Example 4

[0061] Photothermal performance testing of tadpole-shaped functional carbon nanotubes (Fe@CNT-Zn) obtained in Example 1: Tadpole-shaped functional carbon nanotubes were prepared into aqueous solutions of different mass concentrations, and the solutions were tested using an 808nm laser (1W / cm²). 2 Irradiation lasted 10 minutes, during which a FLIRE53 infrared thermal imager collected real-time temperature changes and thermal images. The results are shown below. Figure 5 .

[0062] Example 5

[0063] Chemical kinetics test of the tadpole-shaped functional carbon nanotubes (Fe@CNT-Zn) obtained in Example 1: 100 μg of tadpole-shaped functional carbon nanotubes were dispersed in mixed solutions of methylene blue (10 mg / L, 3 mL) at pH 7.4 and pH 5.5 with different concentrations of hydrogen peroxide. After reacting in the dark for 1 hour, the mixture was centrifuged, and the supernatant was collected. To evaluate the effect of the high temperature generated by photothermal stimulation on the catalytic performance, an 808 nm laser (1 W / cm²) was used during the reaction. 2 Irradiation was performed for 10 minutes. After the reaction was complete, the supernatant was collected by centrifugation. The UV-Vis spectrum of the supernatant was then measured to reflect the degradation of methylene blue. The results are shown below. Figure 6 .

[0064] Example 6

[0065] Photodynamic performance testing of tadpole-shaped functional carbon nanotubes (Fe@CNT-Zn) obtained in Example 1: 300 μL of tadpole-shaped functional carbon nanotube solution (1 mg / mL) was dispersed in DMSO solution of DPBF (2 mL, 10 mM). Then, an 808 nm laser (1 W / cm²) was used. 2 Irradiation was performed for 0, 5, 10, 15, and 20 minutes. DPBF in the supernatant was then measured using a UV-Vis spectrophotometer. Additionally, the reaction temperature was maintained at 25°C to assess the effect of high temperature on photodynamics. Hydrogen peroxide was added to the reaction system under laser irradiation to evaluate the enhancing effect of chemical kinetics on photodynamics; the results are shown below. Figure 7 .

[0066] Example 7

[0067] Drug loading and release performance tests of tadpole-shaped functional carbon nanotubes obtained in Example 1:

[0068] (1) Drug loading experiment of the tadpole-shaped functional carbon nanotubes obtained in Example 1:

[0069] 10 mg of tadpole-shaped functional carbon nanotubes were dispersed in 2 mL of DOX (1 mg / mL). -1 In a solution, stir for approximately 12 hours at room temperature in the dark. Then, wash three times with PBS and centrifuge, collecting the supernatant and washings. The concentration of DOX in the collected solution is determined using a UV-Vis spectrophotometer. Repeat the above steps several times until adsorption equilibrium is reached.

[0070] (2) Drug sustained-release experiment of the tadpole-shaped functional carbon nanotubes obtained in Example 1:

[0071] Two mg of DOX-loaded tadpole-shaped functionalized carbon nanotubes (Fe@CNT-Zn / DOX) were dispersed in 30 mL of PBS solutions at different pH values ​​(7.4 and 5.5). For the laser group, 808 nm near-infrared laser (1 W / cm²) was used at selected times. 2 Irradiate for 10 minutes; for the hydrogen peroxide group, add a certain amount of hydrogen peroxide to the above mixed solution. Take 3 mL of the above solution at regular intervals, centrifuge to obtain the supernatant, and determine the DOX content in the supernatant using a UV-Vis spectrophotometer. Calculate the DOX release percentage using the DOX standard curve. Results are shown in [Figure number missing]. Figure 8 .

[0072] Example 8

[0073] The cytotoxicity test of the tadpole-shaped functional carbon nanotubes obtained in Example 1 was performed using the CCK-8 assay, as follows: B16 cells were digested with trypsin and seeded in 96-well plates. The plates were incubated at 37°C with 5% CO2 for 12 hours. Different concentrations of the tadpole-shaped functional carbon nanotubes (Fe@CNT-Zn) from Example 1 were then added, and incubation continued for another 12 hours. Then, 10 μL of CCK-8 medium dilution was added to each well, and the plates were returned to a 37°C incubator for approximately 2 hours. Viable cells were stained with CCK-8, and the OD value at 450 nm in each well was measured using a microplate reader (TECAN, Infinite M200, Germany). Cell viability was calculated using the following formula: Cell viability (%) = (Average absorbance of experimental group / Average absorbance of control group) × 100%. Figure 9 As shown.

[0074] Example 9

[0075] The in vitro synergistic therapy evaluation of the tadpole-shaped functional carbon nanotubes obtained in Example 1 was conducted using the CCK-8 assay, as follows: B16 cells were digested with trypsin, seeded in 96-well plates, and incubated at 37°C and 5% CO2 for 12 hours. Different concentrations of tadpole-shaped functional carbon nanotubes (Fe@CNT-Zn / DOX) were then added and incubated for 6 hours. For the laser group, 808 nm near-infrared laser (1 W / cm²) was used at selected times. 2 Irradiate for 5 minutes; for the hydrogen peroxide group, add 100 μM hydrogen peroxide to the above mixed solution. After different treatments, continue incubation for 6 hours, then add 10 μL of CCK-8 medium dilution to each well, and return the plate to a 37°C incubator for about 2 hours. Viable cells will be stained with CCK-8, and the OD value of each well at 450 nm will be measured using a microplate reader (TECAN, Infinite M200, Germany). Cell viability will be calculated according to the following formula: Cell viability (%) = (Average absorbance of experimental group / Average absorbance of control group) × 100%, i.e. Figure 10As shown.

[0076] Example 10

[0077] B16 cells were digested with trypsin, seeded in 6-well plates, and incubated at 37°C under 5% CO2 for 12 h. 50 μg / mL –1 The DOX-loaded sample from Example 1 was dispersed in fresh culture medium, and tadpole-shaped functional carbon nanotubes were added and incubated for 6 hours. For the laser group, an 808 nm near-infrared laser (1 W / cm²) was used at selected times. 2 Irradiate for 5 minutes; for the hydrogen peroxide group, add 100 μM hydrogen peroxide to the above mixed solution. After different treatments, continue incubation for 6 hours, wash cells three times with PBS, and add 1 mL of fresh culture medium. Then stain with Calcein-AM and PI dye. After staining, wash cells twice with PBS solution. Image the stained cells using an Olympus FluoView FV1000 confocal microscope. Figure 11 As shown.

[0078] Example 11

[0079] Twenty female C57BL / 6 mice bearing a melanoma cell model were randomly divided into five groups: I) PBS group, II) Fe@CNT-Zn group, III) Fe@CNT-Zn / DOX group, IV) Fe@CNT-Zn+Laser group, and V) Fe@CNT-Zn / DOX+Laser group. Each mouse was administered medication via intratumoral injection of 200 μL of PBS, Fe@CNT-Zn, or Fe@CNT-Zn / DOX solution at a concentration of 10 mg / kg. Two hours after administration, the tumor sites in the laser groups were irradiated with an 808 nm near-infrared laser for 5 minutes. During the 14-day treatment cycle, the mice's body weight and tumor volume were recorded daily. Results are shown below. Figure 12 and 13 .

[0080] Example 12

[0081] After treatment, the mice were euthanized, the tumors in each mouse were removed, and optical photographs were recorded. The results are shown below. Figure 14 Simultaneously, tumor masses and major organs (heart, liver, spleen, lung, and kidney) were collected for histological sections, then stained with standard Sudan Red and eosin, and finally subjected to histological analysis. The results are shown below. Figure 15 .

[0082] The above description of the embodiments is provided to enable those skilled in the art to understand and use the invention. It will be apparent to those skilled in the art that various modifications can be made to these embodiments, and the general principles described herein can be applied to other embodiments without inventive effort. Therefore, the present invention is not limited to the above embodiments, and any improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the invention should be within the protection scope of the present invention.

Claims

1. A method for preparing tadpole-like functionalized carbon nanotubes, characterized by, It comprises the following steps: Step one: ultrasonic dispersion of zinc nitrate and acetylacetone salt in methanol solution, after a period of time, a certain amount of imidazole compound is added to the mixed solution, and a uniform precursor nanoparticle is obtained after stirring reaction, that is, a nanoparticle containing acetylacetone salt; Step two: the precursor nanoparticle is placed in a tube furnace, calcined at a certain temperature under inert atmosphere for a period of time, cooled to room temperature, then ground, dispersed in solution, ultrasonic, differential centrifugation, magnetic separation, vacuum drying, and the tadpole-shaped functional carbon nanotube is obtained; The acetylacetone salt is selected from one or a combination of two of acetylacetone iron, acetylacetone cobalt or acetylacetone nickel.

2. The method for preparing tadpole-shaped functional carbon nanotubes according to claim 1, characterized in that, The imidazole compound is selected from any one of 2-methyl imidazole, 2-formaldehyde imidazole, 2-bromine imidazole, 4-formic acid imidazole or 4, 5-dimethyl imidazole; The molar ratio of imidazole compound, acetylacetone salt, zinc nitrate and methanol is (15-30):(0-3):6:8.

3.

3. The method for preparing tadpole-shaped functional carbon nanotubes according to claim 1, characterized in that, The stirring reaction conditions are as follows: in step one, the stirring reaction time is 20-28 h, and the reaction temperature is 40-60 °C; In step two, the temperature of the calcination is between 500 and 900 °C, the calcination time is between 1 and 3 hours, the gas flow is between 50 and 150 mL·min –1 , and the heating rate is between 1 and 5 °C·min –1 .

4. A tadpole-like functionalized carbon nanotube, characterized by, Prepared by the method of any one of claims 1-3, having a "U" type structure, and mainly composed of chemical elements including C, a group VIII transition metal element, Zn, and N, wherein the tadpole-shaped tail is a nitrogen-doped carbon nanotube inlaid with single-atom zinc, the nitrogen-doped carbon nanotube is a "U" type nitrogen-doped carbon nanotube, single-atom zinc is inlaid on the nitrogen-doped carbon nanotube, and the tadpole-shaped head is a group VIII transition metal nanoparticle encapsulated at the bottom of the "U" type nitrogen-doped carbon nanotube.

5. The tadpole-like functionalized carbon nanotube according to claim 4, wherein In the nitrogen-doped carbon nanotube, the doped nitrogen atoms are pyridine nitrogen, pyrrole nitrogen, graphite nitrogen or oxidized nitrogen, and the molar mass ratio of carbon to nitrogen is in the range of 50-60.

6. The tadpole-like functionalized carbon nanotube according to claim 4, wherein The aspect ratio of the "U" type nitrogen-doped carbon nanotube is in the range of 3 ~ 12, and the diameter is in the range of 50 ~ 80 nm, and the length is in the range of 1 ~ 5 μm. I D / I G The value of the structure integrity of the graphitized material measured by the Raman spectrum is in the range of 1.2 ~ 0.

8.

7. The tadpole-like functionalized carbon nanotube according to claim 4, wherein the functional group is a group represented by the following formula (1) : -C≡C- (1). The size of the group VIII transition metal nanoparticle is in the range of 10-30 nm, and the group VIII transition metal is selected from one of Fe, Co and Ni, or an alloy of Fe and Co, an alloy of Fe and Ni, and the molar mass ratio of the group VIII transition metal element to carbon is in the range of 1:(5-20).

8. The tadpole-like functionalized carbon nanotube according to claim 4, wherein Single-atom zinc is uniformly embedded in nitrogen-doped carbon nanotubes, through Zn-NC x The force is anchored, and the molar mass ratio of carbon to zinc is in the range of 100 to 150.

9. Use of the tadpole-like functionalized carbon nanotubes according to any one of claims 4 to 8, characterized in that, The tadpole-shaped functional carbon nanotube is used in the preparation of a nanomaterial for killing tumor cells.

10. Use of the tadpole-like functionalized carbon nanotubes according to any one of claims 4 to 8, characterized in that, The tadpole-shaped functional carbon nanotube is used in the preparation of a nanomaterial for delivering anticancer drugs.

Images