Preparation method and application of cerium oxide / carbon composite material
By preparing nanorod-shaped CeOx/C materials using a solvothermal method, the stability and catalytic efficiency of cerium oxide and carbon nanozymes in complex physiological environments were solved, enabling efficient ROS scavenging and fluorescence imaging-guided inflammatory therapy.
Patent Information
- Application Number
- CN202511717958.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-11-21
- Publication Date
- 2026-02-10
AI Technical Summary
Existing cerium oxide nanozymes exhibit low catalytic efficiency in complex physiological environments, are prone to aggregation, have poor stability and bioavailability, and lack fluorescence properties, limiting their application in integrated diagnosis and treatment. Carbon nanozymes have low catalytic activity and are difficult to control in terms of morphology and size. Existing CeOx/C composite materials have irregular structures, resulting in limited improvement in enzyme activity.
Nanorod-shaped CeOx/C was prepared by reacting 3-aminophenylboronic acid and hydrogen peroxide dissolved in acetone with cerium chloride solution via a solvothermal method. The composite material with uniform size was obtained by combining dialysis and freeze-drying processes.
The prepared CeOx/C material possesses highly efficient CAT/SOD-like enzyme activity and near-infrared II fluorescence properties, enabling efficient ROS clearance and NIR-IIFL imaging-guided inflammatory therapy.
Smart Images
Figure CN121489979A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of nanobiomedical material preparation technology, specifically relating to a method for preparing cerium oxide / carbon composite materials and their applications. Background Technology
[0002] Reactive oxygen species (ROS) play a crucial role in the development and progression of various inflammatory diseases. Effective scavenging of excess ROS (such as hydroxyl radicals (·OH) and superoxide anions (·O2) is essential. - Nanozymes have become an important strategy for treating diseases such as arthritis, colitis, and neuroinflammation. In recent years, nanozymes with catalase-like (CAT) and superoxide dismutase (SOD) activities have been regarded as good alternatives to natural enzymes due to their high stability, low cost, and scalability.
[0003] Cerium oxide (CeO) x Nanomaterials due to their Ce 3+ / Ce 4+ The reversible conversion between CeO₂ and CeO₂ exhibits excellent oxidoreductase activity, showing great potential in the field of ROS scavenging. However, CeO₂ alone... x Nanozymes still face some challenges: First, their enzyme activity is often limited in complex physiological environments, and their catalytic efficiency needs further improvement; second, traditional CeO₂... x Nanoparticles are prone to aggregation, which leads to a decrease in their stability and bioavailability. Furthermore, the lack of inherent fluorescence properties makes it difficult to track their distribution and metabolic processes in vivo in real time and without damage, thus limiting their application in integrated diagnosis and treatment.
[0004] Carbon (C) nanomaterials are another promising candidate for nanozymes, possessing good stability, biocompatibility, tunable fluorescence, and ease of functionalization. However, single-carbon-based nanozymes typically exhibit low catalytic activity, and controlling their morphology and size remains a significant challenge. If CeO₂ is used... x While effective composites with carbon materials hold promise for improving performance, there are currently few reports on this topic, and the resulting CeO₂... x / C composite materials often exhibit irregular or amorphous structures, resulting in poor dimensional uniformity, limited enhancement of enzyme activity, and lack of fluorescence properties. Furthermore, existing preparation processes are complex, require stringent conditions, and have low reproducibility, hindering their mass production and clinical translation.
[0005] Therefore, there is an urgent need to develop a novel composite nanozyme (CeO₂) that is easy to prepare, uniform in size, and possesses both highly efficient multiple enzyme activity and inherent fluorescence properties. x / C), to promote the integrated application of diagnosis and treatment of inflammation-related diseases. Summary of the Invention
[0006] The purpose of this invention is to provide a method for preparing cerium oxide / carbon composite materials and their applications. This preparation method is simple, reproducible, and suitable for large-scale production. The cerium oxide / carbon composite material prepared by this method is a novel composite nanozyme with multiple enzyme activities and fluorescence properties. The obtained nanorod-shaped CeO₂... x / C not only has uniform size and regular shape, but also exhibits characteristics that surpass those of a single CeO x The material, or C, exhibits CAT / SOD-like enzyme activity and excellent near-infrared II fluorescence (NIR-IIFL) characteristics, enabling efficient ROS clearance and NIR-IIFL imaging-guided inflammation treatment.
[0007] The present invention adopts the following solution: A method for preparing a cerium oxide / carbon composite material includes the following steps: S1. Dissolve 3-aminophenylboronic acid and 30% hydrogen peroxide in acetone solution, disperse evenly by ultrasonication, and stir for 10-30 min to obtain a homogenized solution. S2. Add a 1-12M cerium chloride solution to the homogenized solution obtained in step S1, and stir at room temperature for 10-30 minutes until the solution is clear to obtain a homogenized mixed solution. S3. Transfer the homogenized mixed solution obtained in step S2 to a high-pressure reactor and carry out a one-step solvothermal reaction at 180-240℃ for 12-24h. S4. After the reaction is complete, let the reaction system cool naturally to room temperature, remove the acetone solvent by rotary evaporation at 60-70℃, and then redissolve it with anhydrous ethanol to obtain a homogenized ethanol dispersion. S5. Place the ethanol dispersion obtained in step S4 into a dialysis bag with a molecular cutoff of 1000 Da and dialyze it in deionized water for 24 hours to remove small molecule impurities. S6. Freeze-dry the solution after dialysis in step S5 to obtain the CeO₂. x / C.
[0008] Further, the mass ratio of 3-aminophenylboronic acid to hydrogen peroxide in step S1 is 1:50.
[0009] Further, the mass ratio of cerium chloride to 3-aminophenylboronic acid in step S2 is 5-25%.
[0010] Furthermore, CeO prepared by the method x / C is a rod-shaped structure with uniform dimensions, ranging in length from 30-40 nm and in diameter from 15-25 nm.
[0011] Application of a cerium oxide / carbon composite material in the preparation of ROS-clearing and NIR-IIFL imaging-guided inflammatory therapeutic drugs.
[0012] The beneficial effects of this invention are as follows: 1. The preparation method is simple, has good repeatability, and can be used for large-scale production.
[0013] 2. The cerium oxide / carbon composite material prepared by this method is a novel composite nanozyme with multiple enzyme activities and fluorescence properties. The obtained nanorod-shaped CeO₂... x / C not only has uniform size and regular shape, but also exhibits characteristics that surpass those of a single CeO x The material, or C, exhibits CAT / SOD-like enzyme activity and excellent near-infrared II fluorescence (NIR-IIFL) characteristics, enabling efficient ROS clearance and NIR-IIFL imaging-guided inflammatory therapy. Attached Figure Description
[0014] Figure 1 CeO synthesized in Example 1 of this invention x TEM image of / C.
[0015] Figure 2 CeO synthesized in Example 1 of this invention x XRD pattern of / C.
[0016] Figure 3 CeO synthesized in Example 1 of this invention x UV absorption spectrum of / C.
[0017] Figure 4 CeO synthesized in Example 1 of this invention x XPS spectra of / C.
[0018] Figure 5 CeO synthesized in Example 1 of this invention x Zeta potential diagram of / C.
[0019] Figure 6 CeO synthesized in Example 1 of this invention x Total antioxidant capacity of / C.
[0020] Figure 7 CeO synthesized in Example 1 of this invention x The fluorescence emission spectrum of / C.
[0021] Figure 8 CeO synthesized according to Example 1 of the present invention x Hydroxyl radical scavenging diagram of / C.
[0022] Figure 9CeO synthesized in Example 1 of this invention x Superoxide anion scavenging diagram of / C.
[0023] Figure 10 CeO synthesized in Example 1 of this invention x / C NIR-IIFL images of the lesion site before and after intra-articular injection into the ankle joint. Detailed Implementation
[0024] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0025] Example 1 S1. Dissolve 3-aminophenylboronic acid and 30% hydrogen peroxide in acetone solution, disperse evenly by ultrasonication, and stir for 15 min to obtain a homogenized solution; the mass ratio of 3-aminophenylboronic acid to hydrogen peroxide is 1:50. S2. Add a 10M cerium chloride solution to the homogenized solution obtained in step S1, and stir at room temperature for 15 minutes until the solution is clear, to obtain a homogenized mixed solution; the mass ratio of cerium chloride to 3-aminophenylboronic acid is 5%. S3. Transfer the homogenized mixed solution obtained in step S2 to a high-pressure reactor and carry out a one-step solvothermal reaction at 240°C for 24 hours. S4. After the reaction is complete, the reaction system is allowed to cool naturally to room temperature. The acetone solvent is removed by rotary evaporation at 65°C, and then the product is redissolved with anhydrous ethanol to obtain a homogenized ethanol dispersion. S5. Place the ethanol dispersion obtained in step S4 into a dialysis bag with a molecular cutoff of 1000 Da and dialyze it in deionized water for 24 hours to remove small molecule impurities. S6. Freeze-dry the solution after dialysis in step S5 to obtain the CeO₂. x / C.
[0026] Example 2 S1. Dissolve 3-aminophenylboronic acid and 30% hydrogen peroxide in acetone solution, disperse evenly by ultrasonication, and stir for 15 min to obtain a homogenized solution; the mass ratio of 3-aminophenylboronic acid to hydrogen peroxide is 1:50. S2. Add a 2M cerium chloride solution to the homogenized solution obtained in step S1, and stir at room temperature for 15 minutes until the solution is clear, to obtain a homogenized mixed solution; the mass ratio of cerium chloride to 3-aminophenylboronic acid is 10%; S3. Transfer the homogenized mixed solution obtained in step S2 to a high-pressure reactor and carry out a one-step solvothermal reaction at 230°C for 12 hours. S4. After the reaction is complete, the reaction system is allowed to cool naturally to room temperature. The acetone solvent is removed by rotary evaporation at 65°C, and then the product is redissolved with anhydrous ethanol to obtain a homogenized ethanol dispersion. S5. Place the ethanol dispersion obtained in step S4 into a dialysis bag with a molecular cutoff of 1000 Da and dialyze it in deionized water for 24 hours to remove small molecule impurities. S6. Freeze-dry the solution after dialysis in step S5 to obtain the CeO₂. x / C.
[0027] Example 3 S1. Dissolve 3-aminophenylboronic acid and 30% hydrogen peroxide in acetone solution, disperse evenly by ultrasonication, and stir for 15 min to obtain a homogenized solution; the mass ratio of 3-aminophenylboronic acid to hydrogen peroxide is 1:50. S2. Add an 8M cerium chloride solution to the homogenized solution obtained in step S1, and stir at room temperature for 10 minutes until the solution is clear, thus obtaining a homogenized mixed solution; the mass ratio of cerium chloride to 3-aminophenylboronic acid is 15%. S3. Transfer the homogenized mixed solution obtained in step S2 to a high-pressure reactor and carry out a one-step solvothermal reaction at 220°C for 18 hours. S4. After the reaction is complete, the reaction system is allowed to cool naturally to room temperature. The acetone solvent is removed by rotary evaporation at 60°C, and then the product is redissolved with anhydrous ethanol to obtain a homogenized ethanol dispersion. S5. Place the ethanol dispersion obtained in step S4 into a dialysis bag with a molecular cutoff of 1000 Da and dialyze it in deionized water for 24 hours to remove small molecule impurities. S6. Freeze-dry the solution after dialysis in step S5 to obtain the CeO₂. x / C.
[0028] Example 4 S1. Dissolve 3-aminophenylboronic acid and 30% hydrogen peroxide in acetone solution, disperse evenly by ultrasonication, and stir for 10 min to obtain a homogenized solution; the mass ratio of 3-aminophenylboronic acid to hydrogen peroxide is 1:50. S2. Add a 1M cerium chloride solution to the homogenized solution obtained in step S1, and stir at room temperature for 15 minutes until the solution is clear, to obtain a homogenized mixed solution; the mass ratio of cerium chloride to 3-aminophenylboronic acid is 20%. S3. Transfer the homogenized mixed solution obtained in step S2 to a high-pressure reactor and carry out a one-step solvothermal reaction at 210°C for 24 hours. S4. After the reaction is complete, the reaction system is allowed to cool naturally to room temperature. The acetone solvent is removed by rotary evaporation at 65°C, and then the product is redissolved with anhydrous ethanol to obtain a homogenized ethanol dispersion. S5. Place the ethanol dispersion obtained in step S4 into a dialysis bag with a molecular cutoff of 1000 Da and dialyze it in deionized water for 24 hours to remove small molecule impurities. S6. Freeze-dry the solution after dialysis in step S5 to obtain the CeO₂. x / C.
[0029] Example 5 S1. Dissolve 3-aminophenylboronic acid and 30% hydrogen peroxide in acetone solution, disperse evenly by ultrasonication, and stir for 20 min to obtain a homogenized solution; the mass ratio of 3-aminophenylboronic acid to hydrogen peroxide is 1:50. S2. Add a 6M cerium chloride solution to the homogenized solution obtained in step S1, and stir at room temperature for 10 minutes until the solution is clear, to obtain a homogenized mixed solution; the mass ratio of cerium chloride to 3-aminophenylboronic acid is 25%. S3. Transfer the homogenized mixed solution obtained in step S2 to a high-pressure reactor and carry out a one-step solvothermal reaction at 200°C for 24 hours. S4. After the reaction is complete, the reaction system is allowed to cool naturally to room temperature. The acetone solvent is removed by rotary evaporation at 60°C, and then the product is redissolved with anhydrous ethanol to obtain a homogenized ethanol dispersion. S5. Place the ethanol dispersion obtained in step S4 into a dialysis bag with a molecular cutoff of 1000 Da and dialyze it in deionized water for 24 hours to remove small molecule impurities. S6. Freeze-dry the solution after dialysis in step S5 to obtain the CeO₂. x / C.
[0030] Example 6 S1. Dissolve 3-aminophenylboronic acid and 30% hydrogen peroxide in acetone solution, disperse evenly by ultrasonication, and stir for 10 min to obtain a homogenized solution; the mass ratio of 3-aminophenylboronic acid to hydrogen peroxide is 1:50. S2. Add a 10M cerium chloride solution to the homogenized solution obtained in step S1, and stir at room temperature for 25 minutes until the solution is clear, to obtain a homogenized mixed solution; the mass ratio of cerium chloride to 3-aminophenylboronic acid is 20%. S3. Transfer the homogenized mixed solution obtained in step S2 to a high-pressure reactor and carry out a one-step solvothermal reaction at 180°C for 24 hours. S4. After the reaction is complete, the reaction system is allowed to cool naturally to room temperature. The acetone solvent is removed by rotary evaporation at 65°C, and then the product is redissolved with anhydrous ethanol to obtain a homogenized ethanol dispersion. S5. Place the ethanol dispersion obtained in step S4 into a dialysis bag with a molecular cutoff of 1000 Da and dialyze it in deionized water for 24 hours to remove small molecule impurities. S6. Freeze-dry the solution after dialysis in step S5 to obtain the CeO₂. x / C.
[0031] Figure 1 CeO synthesized in Example 1 of this invention x TEM image of / C. The image shows the synthesized CeO₂. x The morphology of / C is uniform, with a nanorod-like morphology and an average size of 30-40 nm.
[0032] Figure 2 CeO synthesized in Example 1 of this invention x The typical XRD pattern of / C was obtained. X-ray diffraction analysis of the obtained product showed that the diffraction peak positions were consistent with those in the standard cards (49-1163 and 49-1164), confirming the successful preparation of CeO by this method. x A complex with C.
[0033] Figure 3 CeO prepared in Example 1 of this invention x The UV-Vis-NIR absorption spectra of / C were used to characterize its excitation properties as a fluorescent imaging agent. For example... Figure 3 As shown, this material exhibits strong absorption in the 200-1100nm range.
[0034] Figure 4 CeO synthesized in Example 1 of this invention x The XPS full spectrum of / C was obtained. Characteristic peaks for five elements—carbon, oxygen, cerium, nitrogen, and boron—were clearly observed in the spectrum, confirming nitrogen and boron co-doping of CeO. x The successful preparation of / C provides an important compositional basis for the synergistic enhancement of enzyme-like activity and fluorescence properties of the material.
[0035] Figure 5CeO synthesized in Example 1 of this invention x The Zeta potential of / C is shown in the figure. As can be seen from the figure, the average Zeta potential is -33.62mV. This value is significantly higher than the conventional threshold for colloidal stability (absolute value >30mV), indicating that the material surface has a strong negative charge and there is a strong electrostatic repulsion between the nanoparticles, which can effectively prevent agglomeration and thus form a uniform and stable dispersion system in aqueous solution.
[0036] Figure 6 CeO synthesized in Example 1 of this invention x The ABTS radical scavenging assay of / C was performed to evaluate its total antioxidant activity. The CeO₂ prepared in Example 1 was used... x / C was prepared into solutions of different concentrations (0.25, 0.5, 1, 2 mg / mL) for testing. For example... Figure 6 As shown, the ABTS radical scavenging ability of this material exhibits a significant concentration-dependent effect. At higher concentrations, its scavenging rate reaches as high as 81.17%. This result indicates that CeO₂… x / C has a highly efficient free radical scavenging ability.
[0037] Figure 7 CeO synthesized in Example 1 of this invention x The fluorescence emission spectrum of / C. Under 808nm laser excitation, it exhibits a strong and stable fluorescence signal in the range of 900-1200nm, with the maximum emission peak at ~960nm.
[0038] Figure 8 CeO synthesized in Example 1 of this invention x ESR results for •OH at / C. The experiment used DMPO as a spin trapping agent to generate •OH in situ via the Fenton reaction system. (Example: ...) Figure 8 As shown, CeO x / C exhibits a significant concentration-dependent effect on the scavenging ability of •OH. This effect is further enhanced by the addition of CeO synthesized in Example 1. x After / C, the characteristic 1:2:2:1 quartet signal intensity of the DMPO-•OH adduct was quenched by approximately 85%. This result directly proves that CeO x / C can efficiently and dose-dependently remove •OH.
[0039] Figure 9 To evaluate the CeO synthesized in Example 1 of this invention x / C against O2 - The scavenging ability was assessed, and the activity of superoxide dismutase (SOD) was detected. The CeO2 prepared in Example 1 was used... x / C was prepared into solutions of different concentrations for testing. For example... Figure 9As shown, it is also a concentration-dependent free radical scavenger. At a concentration of 200 µg / mL, it has a significant effect on •O2. - The removal rate was as high as 78%.
[0040] Figure 10 CeO synthesized in Example 1 of this invention x Fluorescence imaging of / C. CeO x / C was dissolved in PBS and administered via intra-articular injection into the ankle joint. Prior to injection, no fluorescence was observed at the mouse ankle joint; however, immediately after injection, the joint site exhibited a strong NIR-II fluorescence signal, contrasting sharply with the surrounding tissues and the contralateral ankle joint. This result directly confirms the effectiveness of the CeO synthesized in this invention. x / C maintains excellent NIR-II fluorescence properties in vivo, and is expected to be further used in the integrated diagnosis and treatment of inflammation-related diseases.
[0041] The above description only illustrates the preferred embodiments of the present invention. However, the present invention is not limited to the above embodiments. Within the scope of knowledge possessed by those skilled in the art, various changes can be made without departing from the spirit of the present invention, and all such changes should be included within the protection scope of the present invention.
Claims
1. A method for preparing a cerium oxide / carbon composite material, characterized in that: Includes the following steps: S1. Dissolve 3-aminophenylboronic acid and 30% hydrogen peroxide in acetone solution, disperse evenly by ultrasonication, and stir for 10-30 min to obtain a homogenized solution. S2. Add a 1-12M cerium chloride solution to the homogenized solution obtained in step S1, and stir at room temperature for 10-30 minutes until the solution is clear to obtain a homogenized mixed solution. S3. Transfer the homogenized mixed solution obtained in step S2 to a high-pressure reactor and carry out a one-step solvothermal reaction at 180-240℃ for 12-24h. S4. After the reaction is complete, let the reaction system cool naturally to room temperature, remove the acetone solvent by rotary evaporation at 60-70℃, and then redissolve it with anhydrous ethanol to obtain a homogenized ethanol dispersion. S5. Place the ethanol dispersion obtained in step S4 into a dialysis bag with a molecular cutoff of 1000 Da and dialyze it in deionized water for 24 hours to remove small molecule impurities. S6. Freeze-dry the solution after dialysis in step S5 to obtain the CeO₂. x / C.
2. The method for preparing a cerium oxide / carbon composite material according to claim 1, characterized in that: The mass ratio of 3-aminophenylboronic acid to hydrogen peroxide in step S1 is 1:
50.
3. The method for preparing a cerium oxide / carbon composite material according to claim 1, characterized in that: The mass ratio of cerium chloride to 3-aminophenylboronic acid in step S2 is 5-25%.
4. A cerium oxide / carbon composite material prepared by the preparation method of claim 1 has a rod-shaped structure with uniform size, a length ranging from 30 to 40 nm, and a diameter ranging from 15 to 25 nm.
5. The use of the cerium oxide / carbon composite material as described in claim 4 in the preparation of ROS scavenging and NIR-IIFL imaging-guided inflammatory therapeutic agents.