Titanium carbide nanocomposite drug-loaded material, and preparation method and application thereof

Abstract

The application relates to the fields of material chemistry and biomedical engineering, and particularly relates to a titanium carbide nanocomposite drug-loaded material and a preparation method and application thereof; the titanium carbide nanocomposite drug-loaded material is prepared by taking two-dimensional sheet structure titanium carbide as a drug carrier, loading glucose oxidase and nano-magnetic four-oxide three-iron; the preparation method is that titanium carbide is dissolved, glucose oxidase is added, four-oxide three-iron is added after being uniformly dispersed, and the titanium carbide nanocomposite drug-loaded material is obtained; wherein the titanium carbide is prepared by taking MAX-Ti3AlC2 as a reaction raw material and adding hydrofluoric acid, and the four-oxide three-iron is prepared by adopting a coprecipitation method. The preparation method has the advantages of mild reaction condition, easy operation, no by-product, high yield and the like. The prepared titanium carbide nanocomposite drug-loaded material has good cell compatibility, photothermal conversion and anticancer activity, has no obvious toxic side effects on organisms, and has a good application prospect in the field of cancer treatment drugs.

Description

Technical Field

[0001] This invention relates to the fields of materials chemistry and biomedical engineering, specifically to a titanium carbide nanocomposite drug-carrying material, its preparation method, and its application. Background Technology

[0002] The rapid proliferation of cancer cells requires a large amount of nutrients, and utilizing glucose metabolism for tumor diagnosis and treatment has been a hot research topic in recent years. Glucose oxidase (GOx)-mediated starvation therapy is considered a promising strategy, which can effectively catalyze glucose oxidation, deprive cancer cells of their energy supply, and reduce their sensitivity to treatment. However, single-drug therapy targeting glucose metabolism often fails to kill tumor cells (see Y. Zhang, S. Feng, G. Hu, et al. Advanced Functional Materials 2021, 32.). Therefore, leveraging the ability of nanomaterials to accumulate at lesion sites to load drugs onto nanoplatforms and construct a nanomaterial drug delivery platform, combined with other treatment methods, is of great significance for achieving efficient cancer treatment.

[0003] Titanium carbide (Ti3C2) is an emerging two-dimensional material formed by etching the precursor MAX phase into two-dimensional sheet-like structures. It exhibits strong absorption and excellent tissue penetration in the near-infrared (NIR) region, making it suitable as a photothermal medium for tumor therapy. Furthermore, due to its two-dimensional sheet-like structure, titanium carbide can effectively load GOx, making it an effective tool for combining photothermal therapy and starvation therapy to kill cancer cells.

[0004] GOx is a natural oxidoreductase that specifically and efficiently catalyzes the oxidation of glucose to gluconic acid and hydrogen peroxide. GOx can selectively deplete glucose within tumor cells, thereby cutting off the tumor's energy supply and achieving starvation therapy. However, in the tumor environment, the self-regulation of tumor cells and the oxygen supply from capillaries (see M. Wu, Q. Zhang, Y. Fang, et al. J Colloid Interface Sci 2021, 586, 20-29.) limit cellular starvation therapy, making it impossible to kill cancer cells.

[0005] Ferric oxide (Fe3O4) nanoparticles possess excellent photothermal properties, making them suitable as a medium for photothermal therapy and as a drug in chemokinetic therapy. They release ferrous ions in acidic tumor media. Fenton agents such as Fe(II), Cu(II), and Mn(II) can convert hydrogen peroxide in situ into hydroxyl radicals toxic to cancer cells, while also enhancing the catalytic efficiency of GOx by consuming hydrogen peroxide products (see Y. Yao, Y. Xu, X. Zhao, et al. Chemical Engineering Journal 2023, 451.). Due to the excellent magnetic targeting and biocompatibility of Fe3O4 nanomaterials, modifying Fe3O4 nanoparticles onto carriers can achieve sustained drug release and magnetically targeted drug delivery. However, achieving uniform and efficient loading of Fe3O4 particles on Ti3C2 is difficult, limiting its application in the biological field. Currently, there are no publicly reported technologies using Ti3C2 and Fe3O4 particles as composite nanocarriers to achieve targeted drug delivery to tumor cells under an external magnetic field, and to achieve synergistic treatment of starvation therapy and photothermal therapy. Summary of the Invention

[0006] To address the shortcomings and deficiencies of existing technologies, the first objective of this invention is to provide a titanium carbide nanocomposite drug-carrying material. This material uses Ti3C2 as a carrier to load GOx and Fe3O4 nanoparticles, thereby improving the water solubility and stability of the carrier and exhibiting excellent biocompatibility.

[0007] The second objective of this invention is to provide a method for preparing the above-mentioned titanium carbide nanocomposite drug-carrying material, which has the advantages of mild reaction conditions, easy operation, no by-products, and high yield.

[0008] The third objective of this invention is to provide the application of the above-mentioned titanium carbide nanocomposite drug-carrying material, which has good cell compatibility, photothermal conversion and anticancer activity, no obvious toxic side effects on organisms, and has good application prospects in the field of cancer treatment drugs.

[0009] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0010] A titanium carbide nanocomposite drug-carrying material, wherein the titanium carbide nanocomposite drug-carrying material uses Ti3C2 as a drug carrier and loads GOx and Fe3O4.

[0011] Furthermore, the Ti3C2 has a two-dimensional sheet-like structure; the Fe3O4 has a particle size of 20-30 nm.

[0012] The preparation method of the above-mentioned titanium carbide nanocomposite drug-carrying material comprises the following steps:

[0013] (1) Using MAX-Ti3AlC2 as the reactant, hydrofluoric acid was added to prepare Ti3C2;

[0014] (2) Using ferric chloride hexahydrate (FeCl3·6H2O) and ferrous sulfate heptahydrate (FeSO4·7H2O) as reaction raw materials, sodium hydroxide (NaOH) solution and trisodium citrate were added, and Fe3O4 was prepared by co-precipitation method;

[0015] (3) Dissolve the titanium carbide prepared in step (1) in deionized water, add GOx, dissolve, add Fe3O4 prepared in step (2), and obtain the titanium carbide nanocomposite drug-carrying material.

[0016] Further, in step (3), the mass-to-volume ratio of Ti3C2, GOx, Fe3O4 and deionized water is 3.2-4 mg: 0.02 mg: 0.2-0.4 mg: 2-10 mL;

[0017] The method by which Ti3C2 is dissolved in deionized water is ultrasonic treatment;

[0018] After adding GOx, it is necessary to dissolve and stir it for 12 hours.

[0019] After adding the Fe3O4 prepared in step (2), it is necessary to dissolve, stir, centrifuge, and wash.

[0020] Furthermore, the dissolution method is ultrasonic treatment, the stirring time is 12 h, the centrifugation conditions are 10000 rpm for 8 min, the washing is three times with deionized water, and the washing is followed by freeze drying.

[0021] Further, in step (1), the Ti3C2 is prepared using the following steps:

[0022] (1) Dissolve 0.5-1 g MAX-Ti3AlC2 in 5 mL of deionized water, sonicate for 15 min, add 15-20 mL of hydrofluoric acid, stir at room temperature for 48-72 h, centrifuge to obtain the precipitate;

[0023] (2) Add 20-30 mL of deionized water to the precipitate obtained in step (1), sonicate for 20 min, centrifuge, and obtain the precipitate;

[0024] (3) Repeat step (2) until the pH of the supernatant is 7.4;

[0025] (4) Add 20-30 mL of dimethyl sulfoxide (DMSO) to the precipitate obtained in step (3), stir at room temperature for 24 h, sonicate for 1 h, and centrifuge to obtain the precipitate;

[0026] (5) Add 30 mL of deionized water to the precipitate obtained in step (4), wash, and centrifuge;

[0027] (6) Repeat step (5) three times, and then freeze-dry to obtain the Ti3C2.

[0028] Further, in step (1), the centrifugation conditions are 4000 rpm and 10 min; in step (2), the centrifugation conditions are 6000 rpm and 10 min; in step (4), the centrifugation conditions are 10000 rpm and 10 min; in step (5), the centrifugation conditions are 10000 rpm and 10 min, and the centrifugation is performed three times.

[0029] Further, in step (2), the Fe3O4 is prepared using the following steps:

[0030] (1) Dissolve 0.541-0.811 g FeCl3·6H2O and 0.278-0.556 g FeSO4·7H2O in 50-80 mL of ultrapure water, stir under nitrogen, add NaOH until the pH of the solution is 9-10, stir for 2.5-3.5 min to obtain the solution;

[0031] (2) The solution obtained in step (1) is subjected to magnetic separation, washed, and then subjected to magnetic separation again to obtain a precipitate;

[0032] (3) Disperse the precipitate obtained in step (3) in 25-40 mL of deionized water, add 0.092-0.184 g of sodium citrate, stir for 1-2 h, then perform magnetic separation and freeze-dry to obtain the Fe3O4.

[0033] Further, in step (1), the stirring speed is 650 rpm; in step (2), the washing is first washing with distilled water and then washing twice with nitric acid.

[0034] The above-mentioned titanium carbide nanocomposite drug-carrying material can be used to prepare drugs for treating cancer.

[0035] Furthermore, the drug is one or more of the following: paclitaxel, camptothecin, doxorubicin, vincristine, cisplatin, carboplatin, methotrexate, daunorubicin, interleukin, interferon, growth factor, and tumor necrosis factor.

[0036] Furthermore, the cancer is one or more of the following: stomach cancer, ovarian cancer, breast cancer, liver cancer, and bladder cancer. By changing the types of active pharmaceutical ingredients contained in the drug carrier, it can be used to prepare therapeutic drugs for a variety of diseases. Beneficial effects

[0037] (1) The titanium carbide nanocomposite drug carrier prepared by the present invention has good cell compatibility, excellent photothermal conversion performance and anticancer activity, and has no obvious toxic side effects on organisms. It has good application prospects in the fields of drug carrier and cancer treatment.

[0038] (2) This invention uses commercially available MAX-Ti3AlC2 as raw material to prepare Ti3C2. The preparation of the carrier can be completed by simple etching and stripping. The reaction conditions are mild, easy to operate, have no by-products, and have a high yield, which can realize large-scale production. Ti3C2 has poor water solubility as a carrier. Surface modification with water-soluble GOx and nano Fe3O4 can significantly improve its water solubility and stability. Both Ti3C2 and Fe3O4 have excellent photothermal properties. Under the irradiation of external near-infrared light, they can effectively convert light into local heat, thereby damaging tumor tissue. The Fenton effect of nano Fe3O4 can convert hydrogen peroxide in cells into hydroxyl radicals, thereby improving the catalytic efficiency of GOx. Nano Fe3O4 has excellent magnetic targeting and biocompatibility. Modifying Fe3O4 particles on the carrier can realize drug sustained release and magnetic targeted drug delivery.

[0039] (3) This invention overcomes the shortcomings of single starvation therapy by using Ti3C2 with excellent photothermal properties as a drug carrier, combining photothermal therapy with starvation therapy, which greatly improves the mortality rate of tumor cells. The Fenton effect generated by divalent ferrous ions in nano Fe3O4 produces harmful reactive oxygen species in the tumor microenvironment, further promoting cancer cell death, and can achieve targeted drug delivery and sustained drug release in vivo under the action of an external magnetic field. Attached Figure Description

[0040] Figure 1 Transmission electron microscopy image of Ti3C2+GOx+Fe3O4 prepared in Example 1;

[0041] Figure 2 The infrared spectra of Ti3C2, Fe3O4 and Ti3C2+GOx+Fe3O4 prepared in Example 1 are shown.

[0042] Figure 3 The UV spectrum of Ti3C2+GOx+Fe3O4 prepared in Example 1;

[0043] Figure 4 The dispersion diagram of Ti3C2 prepared in Example 1 in deionized water;

[0044] Figure 5 The dispersion diagram of Fe3O4 and Ti3C2+GOx+Fe3O4 prepared in Example 1 in deionized water;

[0045] Figure 6 Photothermal data statistics of Ti3C2, Fe3O4 and Ti3C2+GOx+Fe3O4 prepared in Example 1;

[0046] Figure 7 A statistical graph showing the cell viability of HeLa cells cultured in Ti3C2 at different concentrations prepared in Example 1;

[0047] Figure 8 A statistical graph showing the cell viability of HeLa cells after culturing Ti3C2+GOx+Fe3O4 prepared in Example 1 and Ti3C2+GOx prepared in Comparative Example 1 for 24 h.

[0048] Figure 9 The graph shows the cell viability of HeLa cells after 24 h of culture with GOx, Ti3C2+GOx+Fe3O4 prepared in Example 1, and Ti3C2+GOx+Fe3O4 under near-infrared light irradiation. Detailed Implementation

[0049] To provide a more detailed description of the present invention, the following specific implementation examples are given, but are only used to illustrate the present invention and make the steps clearer, and are not intended to limit the scope of application of the present invention. Example 1

[0050] (1) Preparation of Ti3C2: Add 5 mL of deionized water to a polytetrafluoroethylene beaker, dissolve 1 g of MAX-Ti3AlC2 in the deionized water and sonicate for 15 min, then slowly add 20 mL of hydrofluoric acid to the beaker and stir at room temperature for 72 h. Centrifuge the reaction liquid obtained after stirring (4000 rpm, centrifugation time 10 min), discard the supernatant strong acid product after centrifugation, add 30 mL of deionized water to the precipitate in the centrifuge tube and mix well, sonicate for 20 min and centrifuge (6000 rpm, 10 min), repeat several times until the pH of the solution in the centrifuge tube is about 7.4. Add 30 mL of DMSO to the washed centrifuge tube and mix well. Transfer the mixture to a beaker and stir continuously at room temperature for 24 h. Then sonicate for 1 h. Centrifuge the sonicated reaction solution (10,000 rpm, 10 min). Add 30 mL of deionized water and mix well. Repeat the washing and centrifugation (10,000 rpm, 10 min) three times. The precipitate obtained is Ti3C2. Freeze-dry to obtain solid Ti3C2.

[0051] (2) Synthesis of Fe3O4: 0.541 g FeCl3·6H2O and 0.278 g FeSO4·7H2O were dissolved in 50 mL of ultrapure water and stirred (650 rpm) under nitrogen protection. NaOH solution was then added to adjust the pH to 9, and stirring continued for 3 min to obtain a clear black solution. The solution was magnetically separated and washed with distilled water, then washed twice with nitric acid, and then magnetically separated again. The precipitate was dispersed in 25 mL of deionized water. 0.092 g of trisodium citrate was added to the system, and stirring was performed for 1 h. The prepared nanoparticles were then magnetically separated and freeze-dried. The particle size of the prepared Fe3O4 was approximately 20 nm.

[0052] (3) Combination of Ti3C2, GOx and Fe3O4: 3.2 mg of Ti3C2 prepared in step (1) was weighed and dissolved in 2 mL of deionized water and sonicated. Then, 0.02 mg of GOx was added and completely dissolved, and the mixture was stirred for 12 h. Then, 0.32 mg of Fe3O4 prepared in step (2) was added to the solution, and the mixture was sonicated for 10 min and completely dissolved, and then stirred for 12 h. The resulting mixed solution was centrifuged at high speed (10000 rpm, 8 min), and the supernatant was removed. The solution was washed with deionized water, and the process was repeated three times. The titanium carbide nanocomposite drug-carrying material, namely Ti3C2+GOx+Fe3O4, was obtained by freeze drying.

[0053] Figure 1 The image shows a transmission electron microscope (TEM) image of the titanium carbide nanocomposite drug-carrying material Ti3C2+GOx+Fe3O4 prepared in Example 1. The results show that the prepared Ti3C2+GOx+Fe3O4 has a two-dimensional sheet-like Ti3C2 surface coated with chain-like GOx, with Fe3O4 nanoparticles adsorbed on the outermost layer. The size of Ti3C2+GOx+Fe3O4 is approximately 600 nm. When the material is targeted and injected into the cancerous site and enters the cancer cells, the outermost Fe3O4 nanoparticles decompose in the acidic cellular environment, subsequently releasing GOx and exerting its effect. Simultaneously, under near-infrared light irradiation, the temperature around the cells increases, and photothermal therapy and starvation therapy synergistically promote apoptosis of cancer cells.

[0054] An effective drug loading process can be achieved through Figure 2 and Figure 3 The infrared and ultraviolet spectra were verified. Example 2

[0055] (1) Preparation of Ti3C2: Add 5 mL of deionized water to a polytetrafluoroethylene beaker, dissolve 0.5 g of MAX-Ti3AlC2 in the deionized water and sonicate for 15 min, then slowly add 15 mL of hydrofluoric acid to the beaker and stir at room temperature for 72 h. Centrifuge the reaction liquid obtained after stirring (4000 rpm, centrifugation time 10 min), discard the supernatant strong acid product after centrifugation, add 20 mL of deionized water to the precipitate in the centrifuge tube and mix well, sonicate for 20 min and centrifuge (6000 rpm, 10 min), repeat several times until the pH of the solution in the centrifuge tube is about 7.4. Add 20 mL of DMSO to the washed centrifuge tube and mix well. Transfer the mixture to a beaker and stir continuously at room temperature for 24 h. Then sonicate for 1 h. Centrifuge the sonicated reaction solution at 10,000 rpm for 10 min. Add 30 mL of deionized water and mix well. Repeat the washing and centrifugation (10,000 rpm for 10 min) three times. The precipitate obtained is Ti3C2. Freeze-dry to obtain solid Ti3C2.

[0056] (2) Synthesis of Fe3O4: 0.541 g FeCl3·6H2O and 0.278 g FeSO4·7H2O were dissolved in 50 mL of ultrapure water and stirred (650 rpm) under nitrogen protection. Then, NaOH solution was added to adjust the pH of the solution to 9, and stirring was continued for 3 min to obtain a black and clear solution. The solution was magnetically separated and washed with distilled water, then washed twice with nitric acid, and then magnetically separated again. The precipitate was dispersed in 25 mL of deionized water. 0.092 g of trisodium citrate was added to the system and stirred for 1 h. The prepared nanoparticles were then magnetically separated and freeze-dried.

[0057] (3) Combination of Ti3C2, GOx and Fe3O4: 4 mg of Ti3C2 prepared in step (1) was weighed and dissolved in 10 mL of deionized water and sonicated. Then, 0.02 mg of GOx was added and completely dissolved, and the mixture was stirred for 12 h. Subsequently, 0.4 mg of Fe3O4 prepared in step (2) was added to the solution, and the mixture was sonicated for 10 min and completely dissolved, and then stirred for 12 h. The resulting mixed solution was centrifuged at high speed (10000 rpm, 8 min), and the supernatant was removed. The solution was washed with deionized water, and the process was repeated three times. The titanium carbide nanocomposite drug-carrying material, namely Ti3C2+GOx+Fe3O4, was obtained by freeze-drying. Example 3

[0058] (1) Preparation of Ti3C2: 5 mL of deionized water was added to a polytetrafluoroethylene beaker. 0.5 g of MAX-Ti3AlC2 was dissolved in the deionized water and sonicated for 15 min. Then, 15 mL of hydrofluoric acid was slowly added dropwise to the beaker, and the mixture was stirred at room temperature for 48 h. The reaction liquid obtained after stirring was centrifuged (4000 rpm, 10 min). After centrifugation, the supernatant strong acid product was discarded. 20 mL of deionized water was added to the precipitate in the centrifuge tube and mixed thoroughly. The mixture was sonicated for 20 min and centrifuged (6000 rpm, 10 min). This process was repeated several times until the pH of the solution in the centrifuge tube was about 7.4. 20 mL of DMSO was added to the washed centrifuge tube and mixed thoroughly. The mixture was then transferred to a beaker and stirred continuously at room temperature for 24 h. Then, sonicate for 1 h, centrifuge the sonicated reaction solution (10,000 rpm, 10 min), add 30 mL of deionized water and mix well, repeat washing and centrifugation (10,000 rpm, 10 min) three times, and the obtained precipitate is Ti3C2, which is freeze-dried to obtain solid Ti3C2.

[0059] (2) Synthesis of Fe3O4: 0.811 g FeCl3·6H2O and 0.556 g FeSO4·7H2O were dissolved in 80 mL of ultrapure water and stirred (650 rpm) under nitrogen protection. Then, NaOH solution was added to adjust the pH of the solution to 10, and stirring was continued for 2.5 min to obtain a black and clear solution. The solution was magnetically separated and washed with distilled water, then washed twice with nitric acid, and then magnetically separated again. The precipitate was dispersed in 40 mL of deionized water. 0.184 g of trisodium citrate was added to the system and stirred for 1 h. The prepared nanoparticles were magnetically separated and freeze-dried to obtain solid Fe3O4.

[0060] (3) Combination of Ti3C2, GOx and Fe3O4: 3.2 mg of Ti3C2 prepared in step (1) was weighed and dissolved in 2 mL of deionized water and sonicated. Then, 0.02 mg of GOx was added and completely dissolved, and the mixture was stirred for 12 h. Then, 0.32 mg of Fe3O4 prepared in step (2) was added to the solution and sonicated for 20 min until completely dissolved, and the mixture was stirred for 12 h. The resulting mixed solution was centrifuged at high speed (10000 rpm, 8 min), and the supernatant was removed. The solution was washed with deionized water, and the process was repeated three times. The titanium carbide nanocomposite drug-carrying material, namely Ti3C2+GOx+Fe3O4, was obtained by freeze drying. Example 4

[0061] (1) Preparation of Ti3C2: Add 5 mL of deionized water to a polytetrafluoroethylene beaker, dissolve 1 g of MAX-Ti3AlC2 in the deionized water and sonicate for 15 min, then slowly add 20 mL of hydrofluoric acid to the beaker and stir at room temperature for 72 h. Centrifuge the reaction liquid obtained after stirring (4000 rpm, centrifugation time 10 min), discard the supernatant strong acid product after centrifugation, add 30 mL of deionized water to the precipitate in the centrifuge tube and mix well, sonicate for 20 min and centrifuge (6000 rpm, 10 min), repeat several times until the pH of the solution in the centrifuge tube is about 7.4. Add 30 mL of DMSO to the washed centrifuge tube and mix well. Transfer the mixture to a beaker and stir continuously at room temperature for 24 h. Then sonicate for 1 h. Centrifuge the sonicated reaction solution (10,000 rpm, 10 min). Add 30 mL of deionized water and mix well. Repeat the washing and centrifugation (10,000 rpm, 10 min) three times. The precipitate obtained is Ti3C2. Freeze-dry to obtain solid Ti3C2.

[0062] (2) Synthesis of Fe3O4: 0.811 g FeCl3·6H2O and 0.556 g FeSO4·7H2O were dissolved in 80 mL of ultrapure water and stirred (650 rpm) under nitrogen protection. Then, NaOH solution was added to adjust the pH of the solution to 10, and stirring was continued for 2.5 min to obtain a black and clear solution. The solution was magnetically separated and washed with distilled water, then washed twice with nitric acid, and then magnetically separated again. The precipitate was dispersed in 40 mL of deionized water. 0.184 g of trisodium citrate was added to the system and stirred for 2 h. The prepared nanoparticles were magnetically separated and freeze-dried to obtain solid Fe3O4.

[0063] (3) Combination of Ti3C2, GOx and Fe3O4: 4 mg of Ti3C2 prepared in step (1) was weighed and dissolved in 2 mL of deionized water and sonicated. Then, 0.02 mg of GOx was added and completely dissolved, and the mixture was stirred for 12 h. Subsequently, 0.2 mg of Fe3O4 solid prepared in step (2) was added to the solution, and the mixture was sonicated and completely dissolved, and then stirred for 12 h. The resulting mixed solution was centrifuged at high speed (10000 rpm, 8 min), and the supernatant was removed. The solution was washed with deionized water, and the process was repeated three times. The titanium carbide nanocomposite drug-carrying material, namely Ti3C2+GOx+Fe3O4, was obtained by freeze-drying. Example 5

[0064] (1) Preparation of Ti3C2: Add 5 mL of deionized water to a polytetrafluoroethylene beaker, dissolve 1 g of MAX-Ti3AlC2 in the deionized water and sonicate for 15 min, then slowly add 20 mL of hydrofluoric acid to the beaker and stir at room temperature for 72 h. Centrifuge the reaction liquid obtained after stirring (4000 rpm, centrifugation time 10 min), discard the supernatant strong acid product after centrifugation, add 30 mL of deionized water to the precipitate in the centrifuge tube and mix well, sonicate for 20 min and centrifuge (6000 rpm, 10 min), repeat several times until the pH of the solution in the centrifuge tube is about 7.4. Add 30 mL of DMSO to the washed centrifuge tube and mix well. Transfer the mixture to a beaker and stir continuously at room temperature for 24 h. Then sonicate for 1 h. Centrifuge the sonicated reaction solution (10,000 rpm, 10 min). Add 30 mL of deionized water and mix well. Repeat the washing and centrifugation (10,000 rpm, 10 min) three times. The precipitate obtained is Ti3C2. Freeze-dry to obtain solid Ti3C2.

[0065] (2) Synthesis of Fe3O4: 0.811 g FeCl3·6H2O and 0.556 g FeSO4·7H2O were dissolved in 80 mL of ultrapure water and stirred (650 rpm) under nitrogen protection. Then, NaOH solution was added to adjust the pH of the solution to 10, and stirring was continued for 3.5 min to obtain a black and clear solution. The solution was magnetically separated and washed with distilled water, then washed twice with nitric acid, and then magnetically separated again. The precipitate was dispersed in 40 mL of deionized water. 0.184 g of trisodium citrate was added to the system and stirred for 2 h. The prepared nanoparticles were magnetically separated and freeze-dried to obtain solid Fe3O4 with a particle size of about 30 nm.

[0066] (3) Combination of Ti3C2, GOx and Fe3O4: 4 mg of Ti3C2 prepared in step (1) was weighed and dissolved in 2 mL of deionized water and sonicated. Then, 0.02 mg of GOx was added and completely dissolved, and the mixture was stirred for 12 h. Subsequently, 0.2 mg of Fe3O4 solid prepared in step (2) was added to the solution, and the mixture was sonicated and completely dissolved, and then stirred for 12 h. The resulting mixed solution was centrifuged at high speed (10000 rpm, 8 min), and the supernatant was removed. The solution was washed with deionized water, and the process was repeated three times. The titanium carbide nanocomposite drug-carrying material, namely Ti3C2+GOx+Fe3O4, was obtained by freeze-drying.

[0067] Comparative Example 1

[0068] (1) Preparation of Ti3C2: Add 5 mL of deionized water to a polytetrafluoroethylene beaker, dissolve 1 g of MAX-Ti3AlC2 in the deionized water and sonicate for 15 min, then slowly add 20 mL of hydrofluoric acid to the beaker and stir at room temperature for 72 h. Centrifuge the reaction liquid obtained after stirring (4000 rpm, centrifugation time 10 min), discard the supernatant strong acid product after centrifugation, add 30 mL of deionized water to the precipitate in the centrifuge tube and mix well, sonicate for 20 min and centrifuge (6000 rpm, 10 min), repeat several times until the pH of the solution in the centrifuge tube is about 7.4. Add 30 mL of DMSO to the washed centrifuge tube and mix well. Transfer the mixture to a beaker and stir continuously at room temperature for 24 h. Then sonicate for 1 h. Centrifuge the sonicated reaction solution (10,000 rpm, 10 min). Add 30 mL of deionized water and mix well. Repeat the washing and centrifugation (10,000 rpm, 10 min) three times. The precipitate obtained is Ti3C2. Freeze-dry to obtain solid Ti3C2.

[0069] (2) Ti3C2 loaded with GOx yields Ti3C2+GOx

[0070] Weigh 3.2 mg of Ti3C2 prepared in step (1), dissolve it in 2 mL of deionized water, and sonicate it. Then add 0.02 mg of GOx and dissolve it completely. Stir continuously for 12 h. After centrifugation at high speed (10000 rpm, 8 min), remove the supernatant, wash with deionized water, and repeat three times. Obtain Ti3C2+GOx by freeze drying.

[0071] Comparative Example 2

[0072] (1) Preparation of Ti3C2: 10 mL of hydrofluoric acid was added to a polytetrafluoroethylene beaker, and 0.5 g of MAX-Ti3AlC2 was slowly added to the beaker. The mixture was stirred at room temperature for 72 h. The reaction liquid obtained after stirring was centrifuged (4000 rpm, 15 min). After centrifugation, the supernatant strong acid product was discarded. 20 mL of deionized water was added to the precipitate in the centrifuge tube and mixed evenly. The mixture was centrifuged again (6000 rpm, 15 min) until the pH of the solution in the centrifuge tube was about 7.4. 20 mL of DMSO was added to the washed centrifuge tube and mixed evenly. The mixture was transferred to a beaker and stirred continuously at room temperature for 24 h. The reaction solution after stirring was centrifuged (10000 rpm, 10 min). 20 mL of deionized water was added and mixed evenly. The washing and centrifugation were repeated three times (10000 rpm, 10 min). The precipitate obtained was Ti3C2. Solid Ti3C2 was obtained by freeze-drying.

[0073] (2) Synthesis of Fe3O4: 0.811 g FeCl3·6H2O and 0.556 g FeSO4·7H2O were dissolved in 80 mL of ultrapure water and stirred (650 rpm) under nitrogen protection. Then NaOH solution was added to adjust the pH of the solution to 10 and stirring was continued for 2.5 min to obtain a black and clear solution. The solution was magnetically separated and washed with distilled water, then washed twice with nitric acid, and then magnetically separated again. The precipitate was dispersed in 40 mL of deionized water. The prepared nanoparticles were magnetically separated and freeze-dried to obtain solid Fe3O4.

[0074] (3) Combination of Ti3C2, GOx and Fe3O4: 4 mg of Ti3C2 prepared in step (1) was weighed and dissolved in 2 mL of deionized water and sonicated. Then, 0.02 mg of GOx was added and completely dissolved, and the mixture was stirred for 12 h. Then, 0.2 mg of Fe3O4 solid prepared in step (2) was added to the solution and completely dissolved, and the mixture was stirred for 12 h. The resulting mixed solution was centrifuged at high speed (10000 rpm, 8 min), and the supernatant was removed. The solution was washed with deionized water, and the process was repeated three times. Titanium carbide nanocomposite drug-carrying material, Ti3C2+GOx+Fe3O4 solid, was obtained by freeze drying.

[0075] Performance testing

[0076] 1. Dispersibility determination

[0077] The dispersion of 2 mg Ti3C2 solid dissolved in 4 mL of deionized water and sonicated for 10 min is shown in the following image. Figure 4 As shown, the solution has an uneven color and obvious sedimentation.

[0078] Dissolve 2 mg each of GOx, Fe3O4, and Ti3C2+GOx+Fe3O4 solids in 4 mL of deionized water. The dispersion images after sonication for 10 min are shown below. Figure 5 As shown, pure GOx and Fe3O4 have good water solubility and stability, and the dispersibility of Ti3C2 in water is significantly improved after modification with GOx and Fe3O4.

[0079] Photothermal properties measurement

[0080] Solutions of Ti3C2, Fe3O4, and Ti3C2+GOx+Fe3O4 with the same concentration were prepared and sonicated for 15 min. 1 mL of each solution was added to a glass tube, sonicated for 3 min, and then cooled to room temperature. A temperature sensor was fixed to the bottom of the glass tube, connected to a thermocouple, and an 808 nm near-infrared laser emitter was used. The power was adjusted to 1.8 W / cm² by controlling the current. 2Then the irradiation began, and the timer started when the temperature rose to 25 ℃, recording the temperature every 30 seconds.

[0081] like Figure 6 The figure shows a power of 1.8 W / cm. 2 Under 808 nm infrared light irradiation, the temperature of ultrapure water remained almost unchanged, while the temperature of 800 µg / mL Ti3C2 and Fe3O4 could rise to 60 °C after 5 min. The temperature of Ti3C2+GOx+Fe3O4 of the same concentration could rise to 65 °C, indicating that the prepared Ti3C2+GOx+Fe3O4 has good near-infrared absorption and photothermal properties.

[0082] 3. Cytotoxicity assay

[0083] The Ti3C2 carrier prepared in Example 1 was configured into solutions of different concentrations for cytotoxicity testing, and the results are as follows: Figure 7 As shown, the survival rate of HeLa cells did not change significantly after being cultured with different concentrations of Ti3C2 for 24 h, indicating that the cytotoxicity of Ti3C2 was negligible.

[0084] 4. Anticancer activity assay

[0085] Cytotoxicity tests were performed on Ti3C2+GOx solutions prepared in Comparative Example 1 and Ti3C2+GOx+Fe3O4 solutions prepared in Example 1, using the same drug gradient concentrations. The results are as follows: Figure 8 As shown, the cell survival rate of Ti3C2+GOx was lower than that of Ti3C2+GOx+Fe3O4. This is because the photothermal therapy and Fenton effect of Fe3O4 reduced the survival rate of cancer cells.

[0086] HeLa cells were seeded in 96-well plates using Ti3C2 co-loaded with GOX and Fe3O4. After 24 hours, parallel controls were established using pure GOX, Ti3C2+GOx+Fe3O4 loaded with the same concentration of GOX, and Ti3C2+GOx+Fe3O4+808 nm laser. Cell viability was assessed after 24 hours. Results are shown below. Figure 9 As shown, compared with starvation therapy with pure GOx, the introduction of Ti3C2 and Fe3O4 can significantly reduce the survival rate of cancer cells, indicating that photothermal therapy can achieve a good synergistic effect with starvation therapy.

[0087] The above description merely illustrates several embodiments of the present invention and should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make modifications, substitutions, and improvements without departing from the concept and scope of the present invention, and these all fall within the protection scope of the present invention. Therefore, the patent protection scope of the present invention should be determined by the described claims.

Claims

1. A titanium carbide nanocomposite drug-loaded material, characterized in that, The titanium carbide nanocomposite drug-loaded material takes titanium carbide as a drug carrier, and loads glucose oxidase and ferroferric oxide; The surface of the two-dimensional sheet-shaped Ti3C2 of the titanium carbide nanocomposite drug-loaded material is wrapped by the chain-shaped GOx, and the Fe3O4 nanoparticles are adsorbed in the outermost layer. The titanium carbide nanocomposite drug-loaded material is prepared by the following method: (1) taking MAX-Ti3AlC2 as a reaction raw material, adding hydrofluoric acid to prepare titanium carbide; (2) taking FeCl3·6H2O and FeSO4·7H2O as reaction raw materials, adding NaOH solution and trisodium citrate, and adopting a coprecipitation method to prepare ferroferric oxide; (3) dissolving the titanium carbide prepared in step (1) in deionized water, adding glucose oxidase, and adding the ferroferric oxide prepared in step (2) to obtain the titanium carbide nanocomposite drug-loaded material; the mass-volume ratio of the titanium carbide, glucose oxidase, ferroferric oxide and deionized water is 3.2-4 mg:0.02 mg:0.2-0.4 mg:2-10 mL; after adding the glucose oxidase, dissolution, stirring and stirring for 12 h are further needed; after adding the ferroferric oxide prepared in step (2), dissolution, stirring, centrifugation and washing are further needed.

2. The titanium carbide nanocomposite drug-loaded material of claim 1, wherein, The structure of the titanium carbide is a two-dimensional sheet structure; the particle size of the ferroferric oxide is 20-30 nm.

3. The titanium carbide nanocomposite drug-loaded material according to claim 1, in step (3), the titanium carbide is dissolved in deionized water by ultrasonic treatment; after adding the ferroferric oxide prepared in step (2), the dissolution is performed by ultrasonic treatment, the stirring time is 12 h; the centrifugation condition is 10000 rpm for 8 min, and the washing is performed by using deionized water for three times, and the freezing drying is further needed after the washing.

4. The titanium carbide nanocomposite drug-loaded material of claim 1, wherein, In step (1), the titanium carbide is prepared by the following steps: (1) dissolving 0.5-1 g of MAX-Ti3AlC2 in 5 mL of deionized water, ultrasonic treating for 15 min, adding 15-20 mL of hydrofluoric acid, stirring at room temperature for 48-72 h, centrifuging to obtain a precipitate; (2) adding deionized water to the precipitate obtained in step (1), ultrasonic treating, and centrifuging to obtain a precipitate; (3) adding 20-30 mL of dimethyl sulfoxide to the precipitate obtained in step (2), stirring at room temperature for 24 h, ultrasonic treating for 1 h, and centrifuging to obtain a precipitate; (4) adding 30 mL of deionized water to the precipitate obtained in step (3), washing, and centrifuging; (5) repeating step (4) three times, and then freezing and drying to obtain the titanium carbide.

5. The titanium carbide nanocomposite drug-loaded material according to claim 4, wherein In step (1), the centrifugation condition is 4000 rpm for 10 min; in step (2), the pH of the supernatant after centrifugation is 7.4, and the centrifugation condition is 6000 rpm for 10 min; in step (4), the centrifugation condition is 10000 rpm for 10 min; in step (5), the centrifugation condition is 10000 rpm for 10 min, and the centrifugation is performed three times.

6. The titanium carbide nanocomposite drug-loaded material of claim 1, wherein, In step (2), the ferroferric oxide is prepared by the following steps: (1) 0.541-0.811 g FeCl3·6H2O and 0.278-0.556 g FeSO4·7H2O are dissolved in 50-80 mL ultrapure water, stirred under nitrogen, and NaOH is added until the pH of the solution is 9-10, and stirred for 2.5-3.5 min to obtain a solution; (2) the solution obtained in step (1) is subjected to magnetic separation, washed, and then subjected to magnetic separation to obtain a precipitate; (3) the precipitate obtained in step (2) is dispersed in 25-40 mL deionized water, 0.092-0.184 g sodium citrate is added, stirred for 1-2 h, subjected to magnetic separation, and freeze-dried to obtain the ferroferric oxide.

7. The titanium carbide nanocomposite drug-loaded material of claim 6, wherein, In step (1), the stirring speed is 650 rpm; in step (2), the washing is first with distilled water, and then with nitric acid twice.

8. Use of the titanium carbide nanocomposite drug-loaded material according to any one of claims 1 to 7, characterized in that, The titanium carbide nanocomposite drug-loaded material can be used for preparing a drug for treating cancer.

9. Use according to claim 8, characterized in that, The drug is one or several of paclitaxel, camptothecin, doxorubicin, vinblastine, cisplatin, carboplatin, methotrexate, daunorubicin, interleukin, interferon, growth factor, and tumor necrosis factor; The cancer is one or several of gastric cancer, ovarian cancer, breast cancer, liver cancer, and bladder cancer.

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