Oxidatively modified drug-loaded carbon nanofiber and preparation method thereof

Abstract

The present invention provides an oxidatively modified drug-loaded carbon nanofiber and a preparation method thereof. The carbon nanofiber has a porous structure and its surface is modified with bismuth and loaded with andrographolide. The preparation method comprises at least the following steps: first, dissolving polyacrylonitrile and polymethyl methacrylate in N,N-dimethylformamide to obtain a polymer solution, performing electrostatic spinning, and then carbonizing the obtained carbon nanofiber in a carbonization furnace; then, oxidatively modifying and bismuth-modifying the surface of the obtained carbon nanofiber; and finally, loading andrographolide to prepare the oxidatively modified drug-loaded carbon nanofiber. The fiber can achieve increased drug loading and precise, controlled release, has a good cancer cell inhibition effect, and has a simple preparation process and high production efficiency.

Description

Technical Field

[0001] The present invention relates to the technical field of carbon nanofiber preparation, and in particular to an oxidatively modified drug-loaded carbon nanofiber and a preparation method thereof. Background Art

[0002] With the advancement of materials science, the use of nanomaterials as drug carriers has become a new approach to addressing drug delivery issues. Currently, research focuses on using materials such as exosomes, liposomes, polymers, micelles, and microcapsules as drug carriers. While these materials have a certain drug-loading capacity, their geometric structures are unstable and easily affected by factors such as temperature and pH, which can affect drug storage and application.

[0003] To overcome these problems, researchers have begun exploring the use of nanomaterials with improved physical and chemical properties as drug carriers. Carbon nanofibers, as a new type of nanomaterial, have shown great potential in the field of novel nanobiomaterials due to their high controllability of geometric dimensions, high chemical stability, and good biocompatibility.

[0004] Although some existing drug carrier materials have achieved certain application results, some urgent challenges remain. For example, these materials suffer from structural instability, are susceptible to environmental influences, have poor drug-carrying stability, and have low utilization rates, making it difficult to achieve effective drug delivery and precise release. Furthermore, existing materials often fail to precisely deliver drugs to diseased tissues, leading to drug accumulation in non-targeted tissues and unwanted side effects. Therefore, the development of new drug-carrying materials that can effectively address these challenges is crucial. Summary of the Invention

[0005] In order to solve the above technical problems, the present invention provides a drug-loaded carbon nanofiber modified by surface oxidation, in which Bi3+ is reduced to Bi element and loaded on the oxidized carbon nanofiber, and then andrographolide is loaded on the carbon nanofiber. This can achieve an increase in drug loading and precise and controllable release, with good cancer cell inhibition effect, and the preparation process is simple and the preparation efficiency is high.

[0006] To achieve the above object, the present invention provides an oxidatively modified drug-loaded carbon nanofiber, wherein the carbon nanofiber has a porous structure and a BET specific surface area range of 60-150 m2 / g;

[0007] The surface of the carbon nanofiber is modified with bismuth element, and the mass ratio of the bismuth element to the carbon nanofiber is (0.3-90):1;

[0008] The modified carbon nanofibers contain andrographolide, and the mass ratio of the andrographolide to the carbon nanofibers is (0.01-0.1):1.

[0009] In some technical solutions of the present invention, the mass ratio of bismuth to carbon nanofiber is (0.5-10):1, specifically 1:1, 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 4.5:1, 5:1, 6:1, 7:1, 8:1, and 9:1, with a further preferred ratio of (0.8-1.5):1. Bismuth modification of the carbon nanofiber surface enables simultaneous photothermal and photodynamic therapy under single near-infrared light irradiation. Under near-infrared light irradiation, the carbon nanofiber can effectively exert its photothermal conversion properties, and the bismuth can convert hydrogen peroxide in the tumor cell microenvironment into reactive oxygen species, thereby achieving a photodynamic therapy effect. Furthermore, the drug loading and stability on the carbon nanofiber surface can be further improved.

[0010] In some technical solutions of the present invention, the mass ratio of andrographolide to carbon nanofibers is (0.01-0.1):1. Specifically, ratios include 0.02:1, 0.03:1, 0.04:1, 0.05:1, 0.06:1, 0.07:1, 0.08:1, and 0.09:1, with a more preferred ratio of (0.04-0.06):1. Andrographolide is a natural antibiotic. When encapsulated and delivered to tumors using modified carbon nanofibers, it can induce oxidative stress and increase autophagy in tumor cells, leading to apoptosis. Due to its strong hydrophobicity, its release rate in the body is slow, and its low toxicity to normal cells results in a treatment with minimal burden and side effects. Encapsulating andrographolide on surface-modified carbon nanofibers avoids the loading difficulties associated with the drug's hydrophobicity, achieving efficient drug encapsulation.

[0011] The present invention also provides a method for preparing oxidatively modified drug-loaded carbon nanofibers, which comprises at least the following steps:

[0012] Step 1: Synthesis of carbon nanofibers: polyacrylonitrile and polymethyl methacrylate are dissolved in N,N-dimethylformamide to obtain a polymer solution, which is then electrospun. The prepared fiber web is pre-oxidized at 240-260°C for 1.5-2.5 hours, then carbonized in a carbonization furnace at 650-850°C for 1-3 hours, and the product is ground into powder to obtain carbon nanofibers.

[0013] Step 2: oxidative modification of the carbon nanofiber surface, first mixing the carbon nanofiber with an oxidant, heating and stirring for 3-5 hours, centrifuging, and then washing with deionized water, and then freeze-drying in a vacuum to obtain oxidized carbon nanofibers;

[0014] Step 3: Bismuth modification: the oxidized carbon nanofibers and bismuth nitrate pentahydrate are mixed and dispersed in anhydrous ethanol and stirred, and then a reducing agent is added and stirred for 0.5-2 minutes. The mixture is centrifuged, washed with water, and freeze-dried to obtain bismuth-modified carbon nanofibers.

[0015] Step 4: andrographolide encapsulation, add excess andrographolide to methanol, stir thoroughly and centrifuge to obtain the supernatant, then disperse the bismuth-modified carbon nanofibers in the supernatant, incubate in the dark at 24-26°C for 2-24 hours to prepare the oxidatively modified drug-loaded carbon nanofibers.

[0016] In some technical solutions of the present invention, the mass ratio of polyacrylonitrile to polymethyl methacrylate in step 1 is (0.5-30):1. When the mass ratio of polyacrylonitrile to polymethyl methacrylate is within this range, the BET specific surface area of ​​the prepared carbon nanofibers can be within the desired range, thereby facilitating bismuth modification and andrographolide drug loading.

[0017] Furthermore, the mass concentration of the polyacrylonitrile in the solution is 2.7-16.7 wt %, and the mass concentration of the polymethyl methacrylate in the solution is 0.5-5.6 wt %.

[0018] In some technical solutions of the present invention, the oxidant in step 2 is a mixture of nitric acid and sulfuric acid. Furthermore, the volume ratio of the nitric acid to the sulfuric acid is (2.5-4):1, and further preferably 3:1.

[0019] In some technical solutions of the present invention, the mass concentration of the carbon nanofibers in the oxidant in step 2 is 0.05-16.7 mg / mL, and further the mass concentration is 4-6 mg / mL.

[0020] In some technical solutions of the present invention, the mass ratio of the oxidized carbon nanofibers to bismuth nitrate pentahydrate in step 3 is (0.005-1):1, specifically 0.01:1, 0.1:1, 0.2:1, 0.25:1, 0.3:1, 0.35:1, 0.4:1, 0.45:1, 0.5:1, 0.55:1, 0.6:1, 0.65:1, 0.7:1, 0.75:1, 0.8:1, 0.85:1, 0.9:1, and 0.95:1, and further preferably (0.3-0.5):1.

[0021] In some technical solutions of the present invention, the mass concentration of the oxidized carbon nanofibers in anhydrous ethanol in step 3 is 0.1-5 mg / mL.

[0022] In some technical solutions of the present invention, the mass concentration of the bismuth nitrate pentahydrate in anhydrous ethanol in step 3 is 5-20 mg / mL.

[0023] In some technical solutions of the present invention, the reducing agent in step 3 is sodium borohydride. Furthermore, the mass concentration of the sodium borohydride added is 0.015-0.080 mg / mL.

[0024] In some technical solutions of the present invention, the carbon nanofibers are dispersed in the supernatant in step 4 at a concentration of 0.1-5 mg / mL.

[0025] In some technical solutions of the present invention, the dark-proof incubation time of andrographolide in step 4 is preferably 12-48 hours. When the incubation time reaches 12 hours, it can ensure that andrographolide is fully loaded in the carbon nanofibers.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] 1. The porous structure and surface modification of carbon nanofibers avoid the loading difficulties caused by drug hydrophobicity, improving drug loading and stability. Furthermore, through bismuth modification, they can simultaneously trigger photothermal and photodynamic therapy effects under single near-infrared light irradiation. Under near-infrared light irradiation, carbon nanofibers can effectively exert their photothermal conversion properties to generate a large amount of heat. The modified bismuth element can convert hydrogen peroxide in the tumor cell microenvironment into reactive oxygen species, achieving a photodynamic therapy effect, thereby enhancing tumor suppression and reducing light source requirements.

[0028] 2. Andrographolide is a natural antibiotic. When encapsulated and delivered to tumors using modified carbon nanofibers, it can induce oxidative stress and increase autophagy in tumor cells, leading to apoptosis. Due to its strong hydrophobicity, its release rate in vivo is slow and its toxicity to normal cells is low.

[0029] The surface-oxidation-modified drug-loaded carbon nanofibers provided by the present invention achieve photothermal controlled release of drugs through photothermal effect and photodynamic benefit. Near-infrared is used as the switch for photothermal controlled release of drugs. The photothermal effect under near-infrared light irradiation provides a higher ambient temperature, which accelerates the mobility of drug molecules and accelerates release. Under conditions without near-infrared light irradiation, the drug release rate returns to a lower level after the temperature drops. At the same time, the photodynamic therapy effect of the bismuth-modified carbon nanofiber material and the oxidative stress-induced effect of andrographolide produce a synergistic effect, greatly enhancing the inhibitory effect on tumor cells. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0031] Figure 1 Schematic diagram of the preparation process of the oxidatively modified drug-loaded carbon nanofibers of the present invention;

[0032] Figure 2 This is a transmission electron microscope (TEM) image of the carbon nanofiber PCNFs-1 prepared in an embodiment of the present invention;

[0033] Figure 3 This is a transmission electron microscope (TEM) image of the bismuth-modified carbon nanofibers Bi / PCNFs-1 oxidized and modified carbon nanofibers prepared in Example 1 of the present invention;

[0034] Figure 4 This is the XPS test spectrum of the bismuth-modified carbon nanofibers Bi / PCNFs-1 oxidized and modified carbon nanofibers prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0035] The following is a clear and complete description of the technical solutions of the present invention in conjunction with the embodiments of the present invention. The embodiments described are part of the embodiments of the present invention, but not all of them. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention without making creative efforts are within the scope of protection of the present invention.

[0036] Example 1

[0037] 1. Preparation of carbon nanofibers: 2 g of polyacrylonitrile and 0.5 g of polymethyl methacrylate were dissolved in 18 g of dimethylformamide (DMF), stirred at 60°C for 24 h, and then electrospun to obtain a fiber mesh. The fiber mesh was pre-oxidized at 250°C for 2 h and then carbonized in a carbonization furnace at 650°C-850°C for 2 h. After the carbonization furnace cooled, the mesh was removed and ground into a fine powder to obtain carbon nanofibers PCNFs-1.

[0038] 2. Surface oxidation modification of carbon nanofibers: 50 mg of carbon nanofiber C1 was added to 10 mL of oxidant (the oxidant was a mixture of 7.5 mL of nitric acid and 2.5 mL of sulfuric acid), stirred at 70°C for 4 h, and the product was centrifuged, washed with deionized water, and freeze-dried to obtain oxidatively modified carbon nanofibers OPCNFs-1.

[0039] 3. Bismuth modification of carbon nanofibers: Weigh 150 mg of oxidized carbon nanofibers (OC) and 156 mg of bismuth nitrate pentahydrate, disperse them in 10 mL of ethanol and stir overnight. Then, add 0.016 mmol of sodium borohydride and stir for 1 min. After centrifugation, wash with water, and freeze-dry, bismuth-modified oxidized carbon nanofibers (Bi / PCNFs-1) were obtained.

[0040] 4. Encapsulation of Andrographolide (AGP): Add an excess of andrographolide to 50 mL of methanol, stir in the dark at room temperature for 12 hours, and centrifuge to obtain the supernatant. Disperse 50 mg of bismuth-modified oxidized carbon nanofibers Bi / PCNFs-1 in 50 mL of the resulting supernatant and incubate in the dark at room temperature for 4 hours to obtain the oxidized drug-loaded carbon nanofibers AGP@Bi / PCNFs-1.

[0041] Example 2

[0042] 1. Preparation of carbon nanofibers: 2 g of polyacrylonitrile and 0.5 g of polymethyl methacrylate were dissolved in 18 g of dimethylformamide (DMF), stirred at 60°C for 24 h, and then electrospun to obtain a fiber mesh. The fiber mesh was pre-oxidized at 250°C for 2 h and then carbonized in a carbonization furnace at 650°C-850°C for 2 h. After the carbonization furnace cooled, the mesh was removed and ground into a fine powder to obtain carbon nanofibers PCNFs-1.

[0043] 2. Surface oxidation modification of carbon nanofibers: 50 mg of carbon nanofiber C1 was added to 10 mL of oxidant (the oxidant was a mixture of 7.5 mL of nitric acid and 2.5 mL of sulfuric acid), stirred at 70°C for 4 h, and the product was centrifuged, washed with deionized water, and freeze-dried to obtain oxidatively modified carbon nanofibers OPCNFs-1.

[0044] 3. Bismuth modification of carbon nanofibers: Weigh 150 mg of oxidized carbon nanofibers (OC) and 104 mg of bismuth nitrate pentahydrate, disperse them in 10 mL of ethanol and stir overnight. Then, add 0.01 mmol of sodium borohydride and stir for 1 min. After centrifugation, wash with water, and freeze-dry, bismuth-modified oxidized carbon nanofibers (Bi / PCNFs-2) were obtained.

[0045] 4. Encapsulation of Andrographolide (AGP): Add an excess of andrographolide to 50 mL of methanol, stir in the dark at room temperature for 12 hours, and centrifuge to obtain the supernatant. Disperse 50 mg of bismuth-modified oxidized carbon nanofibers Bi / PCNFs-1 in 50 mL of the resulting supernatant and incubate in the dark at room temperature for 4 hours to obtain the oxidized drug-loaded carbon nanofibers AGP@Bi / PCNFs-2.

[0046] Example 3:

[0047] 1. Preparation of carbon nanofibers: 2 g of polyacrylonitrile and 0.5 g of polymethyl methacrylate were dissolved in 18 g of dimethylformamide (DMF), stirred at 60°C for 24 h, and then electrospun to obtain a fiber mesh. The fiber mesh was pre-oxidized at 250°C for 2 h and then carbonized in a carbonization furnace at 650°C-850°C for 2 h. After the carbonization furnace cooled, the mesh was removed and ground into a fine powder to obtain carbon nanofibers PCNFs-1.

[0048] 2. Surface oxidation modification of carbon nanofibers: 50 mg of carbon nanofiber C1 was added to 10 mL of oxidant (the oxidant was a mixture of 7.5 mL of nitric acid and 2.5 mL of sulfuric acid), stirred at 70°C for 4 h, and the product was centrifuged, washed with deionized water, and freeze-dried to obtain oxidatively modified carbon nanofibers OPCNFs-1.

[0049] 3. Bismuth modification of carbon nanofibers: Weigh 150 mg of oxidized carbon nanofibers (OC) and 52 mg of bismuth nitrate pentahydrate, disperse them in 10 mL of ethanol and stir overnight. Then, add 0.005 mmol of sodium borohydride and stir for 1 min. After centrifugation, wash with water, and freeze-dry, bismuth-modified oxidized carbon nanofibers (Bi / PCNFs-3) were obtained.

[0050] 4. Encapsulation of Andrographolide (AGP): Add an excess of andrographolide to 50 mL of methanol, stir in the dark at room temperature for 12 hours, and centrifuge to obtain the supernatant. Disperse 50 mg of bismuth-modified oxidized carbon nanofibers Bi / PCNFs-1 in 50 mL of the resulting supernatant and incubate in the dark at room temperature for 4 hours to obtain the oxidized drug-loaded carbon nanofibers AGP@Bi / PCNFs-3.

[0051] Example 4:

[0052] 1. Preparation of carbon nanofibers: 2 g of polyacrylonitrile and 0.5 g of polymethyl methacrylate were dissolved in 18 g of dimethylformamide (DMF), stirred at 60°C for 24 h, and then electrospun to obtain a fiber mesh. The fiber mesh was pre-oxidized at 250°C for 2 h and then carbonized in a carbonization furnace at 650°C-850°C for 2 h. After the carbonization furnace cooled, the mesh was removed and ground into a fine powder to obtain carbon nanofibers PCNFs-1.

[0053] 2. Surface oxidation modification of carbon nanofibers: 50 mg of carbon nanofiber C1 was added to 10 mL of oxidant (the oxidant was a mixture of 7.5 mL of nitric acid and 2.5 mL of sulfuric acid), stirred at 70°C for 4 h, and the product was centrifuged, washed with deionized water, and freeze-dried to obtain oxidatively modified carbon nanofibers OPCNFs-1.

[0054] 3. Bismuth modification of carbon nanofibers: Weigh 150 mg of oxidized carbon nanofibers (OC) and 156 mg of bismuth nitrate pentahydrate, disperse them in 10 mL of ethanol and stir overnight. Then, add 0.016 mmol of sodium borohydride and stir for 1 min. After centrifugation, wash with water, and freeze-dry, bismuth-modified oxidized carbon nanofibers (Bi / PCNFs-4) were obtained.

[0055] 4. Encapsulation of Andrographolide (AGP): Add an excess of andrographolide to 50 mL of methanol, stir in the dark at room temperature for 4 hours, and centrifuge to obtain the supernatant. Disperse 50 mg of bismuth-modified oxidized carbon nanofibers Bi / PCNFs-1 in 50 mL of the resulting supernatant and incubate in the dark at room temperature for 4 hours to obtain the oxidized drug-loaded carbon nanofibers AGP@Bi / PCNFs-4.

[0056] Example 5:

[0057] 1. Preparation of carbon nanofibers: 2 g of polyacrylonitrile and 0.5 g of polymethyl methacrylate were dissolved in 18 g of dimethylformamide (DMF), stirred at 60°C for 24 h, and then electrospun to obtain a fiber mesh. The fiber mesh was pre-oxidized at 250°C for 2 h and then carbonized in a carbonization furnace at 650°C-850°C for 2 h. After the carbonization furnace cooled, the mesh was removed and ground into a fine powder to obtain carbon nanofibers PCNFs-1.

[0058] 2. Surface oxidation modification of carbon nanofibers: 50 mg of carbon nanofiber C1 was added to 10 mL of oxidant (the oxidant was a mixture of 7.5 mL of nitric acid and 2.5 mL of sulfuric acid), stirred at 70°C for 4 h, and the product was centrifuged, washed with deionized water, and freeze-dried to obtain oxidatively modified carbon nanofibers OPCNFs-1.

[0059] 3. Bismuth modification of carbon nanofibers: Weigh 150 mg of oxidized carbon nanofibers (OC) and 156 mg of bismuth nitrate pentahydrate, disperse them in 10 mL of ethanol and stir overnight. Then, add 0.016 mmol of sodium borohydride and stir for 1 min. After centrifugation, wash with water, and freeze-dry, bismuth-modified oxidized carbon nanofibers (Bi / PCNFs-5) were obtained.

[0060] 4. Encapsulation of Andrographolide (AGP): Add an excess of andrographolide to 50 mL of methanol, stir in the dark at room temperature for 2 hours, and centrifuge to obtain the supernatant. Disperse 50 mg of bismuth-modified oxidized carbon nanofibers Bi / PCNFs-1 in 50 mL of the resulting supernatant and incubate in the dark at room temperature for 4 hours to obtain the oxidized drug-loaded carbon nanofibers AGP@Bi / PCNFs-5.

[0061] Comparative Example 1: The only difference from Example 1 is that no polymethyl methacrylate is added during the preparation process.

[0062] Comparative Example 2: The only difference from Example 1 is that the carbon nanofibers are not modified with bismuth elements.

[0063] Comparative Example 3: The only difference from Example 1 is that andrographolide is not encapsulated.

[0064] Performance testing and characterization:

[0065] 1. Characterization of surface oxidation modification of carbon nanofibers: X-ray photoelectron spectroscopy (XPS) was used to analyze the prepared carbon nanofiber samples to analyze the element content and valence state on the fiber surface.

[0066] 2. Photothermal effect test:

[0067] (1) An 808 nm multimode fiber-coupled laser with adjustable power (0-5 W) was used as the light source. The spot area was approximately 0.78 cm2 and the power density was adjustable in the range of 0-1.5 W / cm2. A 200 μg / mL aqueous dispersion of the sample was prepared. 0.25 mL was taken and placed in an EP tube. A thermocouple (accuracy ±1.0 °C) was placed parallel to the EP tube. The laser was irradiated vertically. Care was taken to avoid direct laser irradiation of the thermocouple. At the same time, a thermometer was used to record the temperature data at fixed intervals.

[0068] (2) Calculation of photothermal conversion efficiency (η) Under irradiation with an infrared laser of 808 nm at a power density of 1 W / cm2, the temperature (°C) of the sample aqueous solution is recorded as it changes with time (s). η can be calculated using the following formula:

[0069] (2-1)

[0070] Where h (mW / (m2·℃)) is the heat transfer coefficient, S (m2) is the surface area of ​​the EP tube, T (℃) is the equilibrium temperature, Tsur (℃) is the ambient temperature, Q (mW) is the power absorbed by the quartz dish and solvent, I (mW / cm2) is the laser power density, and A808 represents the absorbance of a sample aqueous solution of known concentration at 808 nm.

[0071] 3. Photodynamic effect test:

[0072] (1) 70 μL of 6 mg / mL 1,3-diphenylbenzisofuran (DPBF) DMSO solution was added to 3 mL of 8 mg / mL sample aqueous dispersion. The solution was irradiated with 808 nm NIR at 2.5 W / cm2 for 15 min, and the absorbance change of DPBF before and after irradiation was measured.

[0073] (2) The photodynamic effect is expressed by the consumption rate of DPBF. The higher the DPBF consumption, the higher the amount of active oxygen produced. The calculation formula is as follows:

[0074]

[0075] Wherein, AInitial and AEventual are the initial absorbance and final absorbance of 1 mL of supernatant taken from the sample solution at 410 nm, respectively.

[0076] 4. Drug loading test: 50 mg of each of the bismuth-modified oxidized carbon nanofibers Bi / PCNFs-1 to Bi / PCNFs-5 prepared in Examples 1-5 and the non-bismuth-modified oxidized carbon nanofiber OPCNFs-1 prepared in Example 1 were placed in an AGP solution of the same concentration, stirred in the dark for 24 h, and the supernatant was removed and dissolved in a cuvette. The absorbance was scanned and measured, and the amount of AGP adsorbed by Bi / PCNFs-1 to Bi / PCNFs-5 was calculated.

[0077] 5. Evaluation of Tumor Cell Inhibitory Effect: B16F cells were seeded at a density of 10⁴ cells / well in a 96-well plate and cultured in a 37°C incubator for 24 hours. The culture medium was removed and the cells were washed twice with 37°C preheated PBS to remove dead cells. Culture medium containing the sample (at a concentration of 200 μg / mL) was added and incubated for 4 hours. The cells were then irradiated with an 808nm NIR laser at a power density of 1 W cm⁻² for 5 minutes and placed in a cell culture incubator for another 24 hours. The culture medium was removed and the cells were washed twice with preheated PBS. Relative cell viability was determined by the MTT assay.

[0078] Test result description:

[0079] 1. Characterization of carbon nanofiber surface oxidation modification: Figure 4 As shown, after bismuth nitrate treatment, the characteristic peaks of Bi 4f5 / 2 and Bi 4f7 / 2 can be clearly detected in the XPS spectrum of PCNFs in Example 1, indicating that Bi has been successfully modified onto PCNFs.

[0080] 2. Performance test results of examples and comparative examples:

[0081] Example Example 1 Example 2 Example 3 Example 4 Example 5 Comparative Example 1 Comparative Example 2 Comparative Example 3 Drug loading / mg·g-1 54.6 55.1 55.4 42.5 31.7 24.8 54.9 / Photothermal performance / ℃ 52.4 50.8 47.8 51.8 51.5 45.4 43.6 50.5 Photothermal conversion rate / % 19.56 18.96 17.98 19.49 19.38 17.08 16.40 19.00 DPBF consumption rate / % 68.45 52.73 28.27 66.16 64.32 55.91 3.53 62.64 B16F inhibition rate / % 73.46 68.42 61.74 64.75 59.16 37.67 32.71 44.63 .

[0082] It can be seen from the drug loading test results of Examples 1-5 and Comparative Examples 1 and 2 that the porous structure of the carbon nanofibers is conducive to drug loading, and the bismuth modification has no significant effect on the drug loading; it can be seen from the photodynamic and photothermal effect test results of the Examples and Comparative Examples that the DPBF consumption of the bismuth-modified oxidized carbon nanofibers can reach up to 68.45%, and the photothermal conversion rate can reach 19.56%, which is significantly improved compared with the oxidized carbon nanofibers without bismuth modification. In addition, the inhibition rate of tumor cell B16F of the bismuth-modified oxidized carbon nanofibers after loading with andrographolide can reach 73.46%, which is significantly improved compared with the inhibition rate of 32.71% of the drug-loaded oxidized carbon nanofibers without bismuth modification (Comparative Example 2) and the inhibition rate of 44.63% of the bismuth-modified oxidized carbon nanofibers without drug loading (Comparative Example 3).

[0083] Finally, a few points should be explained: Although the present invention has been described in detail above using general descriptions and specific embodiments, on the basis of the present invention, the above embodiments are only used to illustrate the technical solution of the present invention, rather than to limit it; although the present invention has been described in detail with reference to the aforementioned embodiments, ordinary technicians in this field should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents; and these modifications or replacements do not cause the essence of the corresponding technical solution to deviate from the scope of the technical solution of the embodiments of the present invention.

Claims

1. A method for preparing oxidatively modified drug-loaded carbon nanofibers, characterized in that: At least the following steps are included: Step 1: Synthesis of carbon nanofibers: Polyacrylonitrile and polymethyl methacrylate are dissolved in N,N-dimethylformamide to obtain a polymer solution, which is then electrospun. The prepared fiber web is pre-oxidized at 240-260°C for 1.5-2.5 hours, then carbonized in a carbonization furnace at 650-850°C for 1-3 hours, and the product is ground into powder to obtain carbon nanofibers. Step 2: oxidative modification of the carbon nanofiber surface, first mixing the carbon nanofiber with an oxidant, heating and stirring for 3-5 hours, centrifuging, and then washing with deionized water, and then freeze-drying in a vacuum to obtain oxidized carbon nanofibers; Step 3: Bismuth modification: the oxidized carbon nanofibers and bismuth nitrate pentahydrate are mixed and dispersed in anhydrous ethanol and stirred, and then a reducing agent is added and stirred for 0.5-2 minutes. The mixture is centrifuged, washed with water, and freeze-dried to obtain bismuth-modified carbon nanofibers. Step 4: andrographolide encapsulation, add excess andrographolide to methanol, stir thoroughly and centrifuge to obtain the supernatant, then disperse the bismuth-modified carbon nanofibers in the supernatant, incubate in the dark at 24-26°C for 3-5h to prepare the oxidatively modified drug-loaded carbon nanofibers.

2. The method for preparing oxidatively modified drug-loaded carbon nanofibers according to claim 1, characterized in that: The mass ratio of polyacrylonitrile to polymethyl methacrylate in step 1 is (0.5-30):

1.

3. The method for preparing oxidatively modified drug-loaded carbon nanofibers according to claim 1, characterized in that: In step 1, the mass concentration of the polyacrylonitrile in the solution is 2.7-16.7 wt %, and the mass concentration of the polymethyl methacrylate in the solution is 0.5-5.6 wt %.

4. The method for preparing oxidatively modified drug-loaded carbon nanofibers according to claim 1, characterized in that: The mass concentration of the carbon nanofibers in the oxidant in step 2 is 0.05-16.7 mg / mL.

5. The method for preparing oxidatively modified drug-loaded carbon nanofibers according to claim 1, characterized in that: The mass ratio of the oxidized carbon nanofibers to the bismuth nitrate pentahydrate in step 3 is (0.005-1):

1.

6. The method for preparing oxidatively modified drug-loaded carbon nanofibers according to claim 1, characterized in that: The reducing agent in step 3 is sodium borohydride, and the mass concentration of the added sodium borohydride is 0.015-0.080 mg / mL.

7. The method for preparing oxidatively modified drug-loaded carbon nanofibers according to claim 1, characterized in that: The andrographolide incubation time in step 4 is 12-48 hours in the dark.

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