Oxidation modified drug-loaded carbon nanofiber and preparation method thereof
By performing surface oxidation modification of carbon nanofibers and loading Bi3+ and pericardium lactone on it, the problems of unstable structure of existing drug carrier materials and inaccurate drug delivery are solved, and the efficient loading and accurate and controllable release of drugs are achieved, which significantly improves the inhibitory effect of cancer cells.
Patent Information
- Application Number
- CN202510453750.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-11
- Publication Date
- 2025-05-13
- Estimated Expiration
- 2045-04-11
AI Technical Summary
The existing drug carrier materials have unstable structures and are susceptible to environmental factors. They have poor drug loading stability and low utilization rate. It is difficult to achieve effective transmission and accurate release of drugs, and it is difficult to accurately deliver drugs to the lesion tissue, resulting in the accumulation of drugs in non-targeted tissues and produce unnecessary side effects.
The carbon nanofibers are treated by surface oxidation modification, Bi3+ is reduced to Bi element, and the pericardium lactone is loaded on the modified carbon nanofiber to achieve efficient loading and accurate and controlled release of the drug.
It improves the load and stability of the drug, achieves the accurate and controllable release of the drug, significantly improves the inhibitory effect of cancer cells, and reduces the burden and side effects on the human body.
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Figure CN119971080A_ABST
Abstract
Description
Technical Field
[0001] The 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 development of materials science, the use of nanomaterials as drug carriers has become a new way to solve the problem of drug delivery. At present, related research mainly focuses on the use of exosomes, liposomes, polymers, micelles, microcapsules and other materials as drug carriers. Although these materials have a certain drug loading capacity, their geometric structure is unstable and easily affected by factors such as temperature and pH value, thus affecting the storage and application effect of drugs.
[0003] In order to overcome the above problems, researchers began to explore the use of nanomaterials with better physical and chemical properties as drug carriers. Carbon nanofibers, as a new type of nanomaterial, show great potential in the field of new 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, there are still some problems that need to be solved. For example, the structure of these materials is not stable enough, they are easily affected by environmental factors, the drug loading stability is poor, the utilization rate is low, and it is difficult to achieve effective drug delivery and precise release. In addition, existing materials often cannot accurately deliver drugs to diseased tissues, resulting in drug accumulation in non-targeted tissues and unnecessary side effects. Therefore, it is particularly important to develop a new drug-carrying material that can effectively solve the above problems. 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, which can achieve an increase in the drug loading capacity and precise and controllable release, has a good cancer cell inhibition effect, and has a simple preparation process and high preparation efficiency.
[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 encapsulate 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 the bismuth element to the 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, 9:1, and further preferably (0.8-1.5):1. By modifying the carbon nanofiber surface with bismuth element, it can simultaneously trigger the photothermal-photodynamic therapy effect under a single near-infrared light irradiation. Under the irradiation of near-infrared light, the carbon nanofiber can better exert the photothermal conversion performance, and the bismuth element can convert hydrogen peroxide in the tumor cell microenvironment into reactive oxygen to achieve the photodynamic therapy effect; in addition, the loading and stability of the drug on the surface of the carbon nanofiber can be further improved.
[0010] In some technical schemes of the present invention, the mass ratio of andrographolide to carbon nanofiber is (0.01-0.1):1, specifically, 0.02:1, 0.03:1, 0.04:1, 0.05:1, 0.06:1, 0.07:1, 0.08:1, 0.09:1, and further preferred is (0.04-0.06):1. Andrographolide is a natural anti-biological drug. After being encapsulated and delivered to tumors using modified carbon nanofibers, it can induce oxidative stress to increase the autophagy induction of tumor cells and cause apoptosis of tumor cells. Due to its strong hydrophobicity, its release rate in the in vivo environment is slow, and its low toxicity to normal cells makes the treatment process have a lower burden and side effects on the human body. Encapsulating andrographolide on surface-modified carbon nanofibers avoids the loading difficulties caused by the hydrophobicity of the drug and achieves efficient encapsulation of the drug.
[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, and electrospinning is performed. The prepared fiber web is pre-oxidized at 240-260°C for 1.5-2.5 hours, and then carbonized in a carbonization furnace at 650°C-850°C for 1-3 hours. The product is ground into powder to obtain carbon nanofibers.
[0013] Step 2: oxidative modification of the carbon nanofiber surface, firstly mixing the carbon nanofiber with the oxidant, heating and stirring for 3-5 hours, centrifuging, washing with deionized water, and then freeze-drying in a vacuum to obtain oxidized carbon nanofibers;
[0014] Step 3: Bismuth modification, mixing the oxidized carbon nanofibers with bismuth nitrate pentahydrate and dispersing them in anhydrous ethanol and stirring, then adding a reducing agent and stirring for 0.5-2 minutes, centrifuging and washing with water, and then freeze-drying to obtain bismuth-modified carbon nanofibers;
[0015] Step 4: andrographolide encapsulation, add excess andrographolide into methanol, stir thoroughly and centrifuge to obtain the supernatant, then disperse the bismuth-modified carbon nanofibers in the supernatant, incubate at 24-26°C in the dark for 2-24h to prepare the oxidatively modified drug-loaded carbon nanofibers.
[0016] In some technical schemes 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, which is beneficial to the modification of bismuth and the loading of andrographolide drugs.
[0017] Furthermore, the mass concentration of the polyacrylonitrile in the solution is 2.7-16.7wt%, and the mass concentration of the polymethyl methacrylate in the solution is 0.5-5.6wt%.
[0018] In some technical solutions of the present invention, the oxidant in step 2 is a mixture of nitric acid and sulfuric acid. Further, the volume ratio of nitric acid to sulfuric acid is (2.5-4):1, and further is 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 schemes 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, 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 schemes of the present invention, the mass concentration of 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 light-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 the hydrophobicity of drugs, and improve the loading capacity and stability of drugs; and through the modification of bismuth elements, photothermal and photodynamic therapy effects can be triggered simultaneously under single near-infrared light irradiation. Under the irradiation of near-infrared light, carbon nanofibers can better exert their photothermal conversion performance to generate a large amount of heat, and the modified bismuth elements can convert hydrogen peroxide in the tumor cell microenvironment into reactive oxygen to achieve photodynamic therapy effects, thereby improving the tumor inhibition effect and reducing the requirements for light sources.
[0028] 2. Andrographolide is a natural anti-biotic drug. After being encapsulated and delivered to tumors using modified carbon nanofibers, it can induce oxidative stress to increase autophagy in tumor cells and cause apoptosis of tumor cells. Due to its strong hydrophobicity, its release rate in the in vivo environment is slow and its toxicity to normal cells is low.
[0029] The surface oxidized and modified drug-loaded carbon nanofibers provided by the present invention realize the photothermal controllable release of drugs through photothermal effect and photodynamic benefit. Near infrared is used as the switch for the photothermal controllable 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 the release. Under the condition of no 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 carbon nanofiber material modified with bismuth element and the induced oxidative stress of andrographolide produce a synergistic effect, which greatly enhances the inhibitory effect of 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 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 in the present invention in conjunction with the embodiments of the present invention. The described embodiments are part of the embodiments of the present invention, but not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work 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 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 was cooled, it was removed and ground into fine powder to obtain carbon nanofiber 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 then 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 modified 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. Centrifuge, wash with water, and freeze-dry to obtain bismuth-modified oxidized modified carbon nanofibers Bi / PCNFs-1.
[0040] 4. Encapsulation of andrographolide (AGP): Take 50 mL of methanol, add excess andrographolide, stir at room temperature in the dark for 12 hours, centrifuge and take the supernatant; disperse 50 mg of bismuth-modified oxidized carbon nanofiber Bi / PCNFs-1 in 50 mL of the obtained supernatant, incubate at room temperature in the dark for 4 hours to obtain the oxidized modified drug-loaded carbon nanofiber 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 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 was cooled, it was removed and ground into fine powder to obtain carbon nanofiber 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 then 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 modified 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. Centrifuge, wash with water, and freeze-dry to obtain bismuth-modified oxidized modified carbon nanofibers Bi / PCNFs-2.
[0045] 4. Encapsulation of andrographolide (AGP): Take 50 mL of methanol, add excess andrographolide, stir at room temperature in the dark for 12 hours, centrifuge and take the supernatant; disperse 50 mg of bismuth-modified oxidized carbon nanofiber Bi / PCNFs-1 in 50 mL of the obtained supernatant, incubate at room temperature in the dark for 4 hours to obtain the oxidized modified drug-loaded carbon nanofiber AGP@Bi / PCNFs-2.
[0046] Embodiment 3:
[0047] 1. Preparation of carbon nanofibers: 2 g of polyacrylonitrile and 0.5 g of polymethyl methacrylate were dissolved in 18 g of 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 was cooled, it was removed and ground into fine powder to obtain carbon nanofiber 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 then 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 modified 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. Centrifuge, wash with water, and freeze-dry to obtain bismuth-modified oxidized modified carbon nanofibers Bi / PCNFs-3.
[0050] 4. Encapsulation of andrographolide (AGP): Take 50 mL of methanol, add excess andrographolide, stir at room temperature in the dark for 12 hours, centrifuge and take the supernatant; disperse 50 mg of bismuth-modified oxidized carbon nanofiber Bi / PCNFs-1 in 50 mL of the obtained supernatant, incubate at room temperature in the dark for 4 hours to obtain the oxidized modified drug-loaded carbon nanofiber AGP@Bi / PCNFs-3.
[0051] Embodiment 4:
[0052] 1. Preparation of carbon nanofibers: 2 g of polyacrylonitrile and 0.5 g of polymethyl methacrylate were dissolved in 18 g of 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 was cooled, it was removed and ground into fine powder to obtain carbon nanofiber 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 then 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 modified 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. Centrifuge, wash with water, and freeze-dry to obtain bismuth-modified oxidized modified carbon nanofibers Bi / PCNFs-4.
[0055] 4. Encapsulation of andrographolide (AGP): Take 50 mL of methanol, add excess andrographolide, stir at room temperature in the dark for 4 hours, centrifuge and take the supernatant; disperse 50 mg of bismuth-modified oxidized carbon nanofiber Bi / PCNFs-1 in 50 mL of the obtained supernatant, incubate at room temperature in the dark for 4 hours to obtain the oxidized modified drug-loaded carbon nanofiber AGP@Bi / PCNFs-4.
[0056] Embodiment 5:
[0057] 1. Preparation of carbon nanofibers: 2 g of polyacrylonitrile and 0.5 g of polymethyl methacrylate were dissolved in 18 g of 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 was cooled, it was removed and ground into fine powder to obtain carbon nanofiber 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 then 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 modified 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. Centrifuge, wash with water, and freeze-dry to obtain bismuth-modified oxidized modified carbon nanofibers Bi / PCNFs-5.
[0060] 4. Encapsulation of andrographolide (AGP): Take 50 mL of methanol, add excess andrographolide, stir at room temperature in the dark for 2 hours, centrifuge and take the supernatant; disperse 50 mg of bismuth-modified oxidized carbon nanofiber Bi / PCNFs-1 in 50 mL of the obtained supernatant, incubate at room temperature in the dark for 4 hours to obtain the oxidized modified drug-loaded carbon nanofiber 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 element.
[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) Use an 808nm multimode fiber-coupled laser with adjustable power (0~5W) as the light source. The spot area is about 0.78cm2 and the power density is adjustable in the range of 0~1.5W / cm2. Prepare a 200μg / mL sample aqueous dispersion, take 0.25mL and put it into an EP tube. Place a thermocouple (accuracy ±1.0℃) in parallel with the EP tube. Irradiate the laser vertically. Be careful to avoid direct laser irradiation on the thermocouple. Use a thermometer to record the temperature data at fixed intervals.
[0068] (2) Calculation of photothermal conversion efficiency (η) Under infrared laser irradiation with a wavelength of 808 nm and a power density of 1 W / cm2, record the temperature (℃) of the sample aqueous solution as it changes with time (s). η can be calculated using the following formula:
[0069] (2-1)
[0070] Wherein, 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 the solvent, I (mW / cm2) is the laser power density, and A808 represents the absorbance of a sample aqueous solution of known concentration at 808nm.
[0071] 3. Photodynamic effect test:
[0072] (1) Add 70 µL of 6 mg / mL 1,3-diphenylbenzisofuran (DPBF) DMSO solution to 3 mL of 8 mg / mL sample aqueous dispersion. Irradiate with 808 nm NIR at 2.5 W / cm2 for 15 min and measure the change in absorbance of DPBF before and after irradiation.
[0073] (2) The photodynamic effect is expressed by the consumption rate of DPBF. The more DPBF is consumed, the higher the amount of active oxygen produced. The calculation formula is as follows:
[0074]
[0075] Among them, 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 ~ Bi / PCNFs-5 prepared in Examples 1-5 and the non-bismuth-modified oxidized carbon nanofibers OPCNFs-1 prepared in Example 1 were placed in AGP solutions of the same concentration, stirred for 24 hours in a dark place, the supernatant was removed and dissolved in a cuvette, the absorbance was measured by scanning, and the adsorption amount of AGP by Bi / PCNFs-1 ~ Bi / PCNFs-5 was calculated.
[0077] 5. Evaluation of tumor cell inhibition effect: B16F was inoculated in a 96-well plate at a density of 104 cells / well. After culturing in a 37°C incubator for 24 hours, the culture medium was removed and the cells were washed twice with PBS preheated at 37°C to remove dead cells. The culture medium containing the sample (concentration of 200 μg / mL) was added and cultured for 4 hours. After that, the cells were irradiated with a NIR 808nm laser with a power density of 1W cm-2 for 5 minutes, placed in a cell culture incubator, and cultured for another 24 hours. The culture medium was removed, washed twice with preheated PBS, and the relative cell survival rate was detected by the MTT method.
[0078] Test result description:
[0079] 1. Characterization of surface oxidation modification of carbon nanofibers: Figure 4 As shown, after being treated with bismuth nitrate, 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 the Bi element has been successfully modified onto PCNFs.
[0080] 2. Performance test results of embodiments 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 / Light and heat 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 the loading of drugs, and the modification of bismuth 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 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 with 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: it is still possible to modify the technical solutions recorded in the aforementioned embodiments, or to replace part or all of the technical features therein with equivalents; and these modifications or replacements do not make the essence of the corresponding technical solution deviate from the scope of the technical solution of the embodiments of the present invention.
Claims
1. An oxidatively modified drug-loaded carbon nanofiber, characterized in that: The carbon nanofiber has a porous structure and a BET specific surface area range of 60-150m2 / g; 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; the modified carbon nanofiber encapsulates andrographolide; the mass ratio of andrographolide to carbon nanofiber is: (0.01-0.1):
1.
2. The oxidatively modified drug-loaded carbon nanofiber according to claim 1, characterized in that: The mass ratio of the bismuth element to the carbon nanofiber is (0.5-10):
1.
3. The oxidatively modified drug-loaded carbon nanofiber according to claim 1, characterized in that: The mass ratio of andrographolide to carbon nanofiber is (0.04-0.06):
1.
4. 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, and electrospinning is performed. The prepared fiber web is pre-oxidized at 240-260°C for 1.5-2.5h, and then carbonized in a carbonization furnace at 650°C-850°C for 1-3h. The product is ground into powder to obtain carbon nanofibers. Step 2: oxidative modification of the carbon nanofiber surface, firstly mixing the carbon nanofiber with the oxidant, heating and stirring for 3-5 hours, centrifuging, washing with deionized water, and then freeze-drying in a vacuum to obtain oxidized carbon nanofibers; Step 3: Bismuth modification, mixing the oxidized carbon nanofibers with bismuth nitrate pentahydrate and dispersing them in anhydrous ethanol and stirring, then adding a reducing agent and stirring for 0.5-2 minutes, centrifuging and washing with water, and then freeze-drying to obtain bismuth-modified carbon nanofibers; Step 4: andrographolide encapsulation, add excess andrographolide into methanol, stir thoroughly and centrifuge to obtain the supernatant, then disperse the bismuth-modified carbon nanofibers in the supernatant, incubate at 24-26°C in the dark for 3-5h, to prepare the oxidatively modified drug-loaded carbon nanofibers.
5. The method for preparing oxidatively modified drug-loaded carbon nanofibers according to claim 4, characterized in that: The mass ratio of polyacrylonitrile to polymethyl methacrylate in step 1 is (0.5-30):
1.
6. The method for preparing oxidatively modified drug-loaded carbon nanofibers according to claim 4, characterized in that: In step 1, the mass concentration of polyacrylonitrile in the solution is 2.7-16.7wt%, and the mass concentration of polymethyl methacrylate in the solution is 0.5-5.6wt%.
7. The method for preparing oxidatively modified drug-loaded carbon nanofibers according to claim 4, characterized in that: The mass concentration of the carbon nanofibers in the oxidant in step 2 is 0.05-16.7 mg / mL.
8. The method for preparing oxidatively modified drug-loaded carbon nanofibers according to claim 4, characterized in that: The mass ratio of the oxidized carbon nanofibers to the bismuth nitrate pentahydrate in step 3 is (0.005-1):
1.
9. The method for preparing oxidatively modified drug-loaded carbon nanofibers according to claim 4, 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.
10. The method for preparing oxidatively modified drug-loaded carbon nanofibers according to claim 4, characterized in that: The andrographolide incubation time in step 4 is 12-48 hours away from light.