Preparation method of ZnFe2O4 aerogel for photo-thermal treatment of glioma
By preparing PEG and FA-functionalized ZnFe2O4 aerogel, the problems of poor tumor aggregation ability and high irradiation density of existing photothermal materials in glioma treatment were solved, achieving efficient and low-side-effect glioma treatment and improving the accuracy and safety of treatment.
Patent Information
- Application Number
- CN202511654266.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-11-12
- Publication Date
- 2026-01-02
AI Technical Summary
Existing photothermal materials for treating gliomas suffer from poor tumor aggregation ability and high irradiation density, leading to severe damage to normal tissues. They also lack targeting and biocompatibility.
By preparing ZnFe2O4 aerogels functionalized with PEG and FA, their photothermal conversion properties are utilized to generate heat under near-infrared light irradiation to kill glioma cells. Furthermore, the biocompatibility and targeting properties are improved through CO2 supercritical drying and high-temperature heat treatment processes.
This approach achieves highly efficient and low-side-effect treatment of gliomas, improving the accuracy and safety of treatment while reducing damage to normal cells.
Abstract
Description
Technical Field
[0001] This invention belongs to the field of aerogel material preparation technology, and relates to a ZnFe2O4 aerogel material with targeting function and good photothermal properties and its preparation method. It combines functional modification to improve the biocompatibility and targeting of ZnFe2O4 aerogel. The invention utilizes CO2 supercritical drying and high-temperature heat treatment processes to prepare ZnFe2O4 aerogel for precise photothermal treatment of glioma. Background Technology
[0002] In recent years, gliomas have accounted for nearly 80% of primary malignant brain tumors, and cancer has become a leading cause of death worldwide. Compared with traditional therapies such as chemotherapy, radiotherapy, and surgery, photothermal therapy, as an emerging neurotumor treatment, has shown unparalleled advantages in the treatment and prognosis of glioma tumors and has received widespread attention.
[0003] Aerogels are nanoporous materials composed of nanoparticles, possessing unique properties such as high specific surface area, high porosity, and ultra-low packing density, attracting widespread attention in fields such as thermal insulation, adsorption, catalysis, and sensing. Their high specific surface area and highly interconnected pores expose more reactive sites, enabling efficient absorption of light energy and its conversion into heat energy. Furthermore, the porous structure of aerogels can load targeted molecules or drugs, improving the accuracy of treatment. Therefore, aerogels are ideal photothermal materials for glioma treatment. Firstly, research by Zhu et al. (International Journal of Environmental Research and Public Health, 2022, 19, 17.) showed that ZnFe2O4 possesses good photochemical stability, high porosity, and a narrow band gap (1.9 eV), making it a good candidate for photocatalysts. Especially in the near-infrared light (808 nm) range, ZnFe2O4 nanomaterials can rapidly heat up, thereby achieving effective thermotherapy of tumors. Studies by Huang et al. (Ceramics Iternational, 2022, 48, 30) have shown that ZnFe2O4 aerogel is a photocatalyst with a high specific surface area, which can increase the number of active sites and promote photothermal conversion. Despite numerous efforts in the research of novel molecular structures and photothermal materials over the past few decades, PTA (photothermal photocatalyst) can cause severe damage to normal tissues due to its poor tumor aggregation ability and high irradiation density. The preparation of targeted photothermal agents offers an attractive strategy to overcome these problems and enhance cancer treatment. Therefore, this invention utilizes PEG and FA functionalization to modify ZnFe2O4, improving its biocompatibility and targeting properties, and preparing a porous ZnFe2O4 aerogel with excellent photothermal effects, which is also an ideal material for treating gliomas. Summary of the Invention
[0004] The purpose of this invention is to provide a method for preparing ZnFe2O4 aerogel for photothermal therapy of gliomas. By preparing ZnFe2O4 aerogel, its photothermal conversion properties are utilized to generate heat under near-infrared light irradiation, thereby killing glioma cells. Multifunctional modification with PEG and FA enhances the biocompatibility and targeting properties of the ZnFe2O4 aerogel. This method aims to provide a novel, highly effective, and low-side-effect strategy for glioma treatment.
[0005] The technical solution of this invention is: a method for preparing ZnFe2O4 aerogel for photothermal therapy of gliomas, the specific steps of which are as follows:
[0006] (1) Dissolve a certain amount of zinc source and iron source in deionized water and stir to form a uniform mixed solution;
[0007] (2) After stirring and mixing evenly, add ethanol solution and continue stirring for 20-30 minutes;
[0008] (3) After the solution in step (2) is stirred, add the cross-linking agent to gel, quickly transfer it to the mold and seal it. After standing at room temperature, demold it.
[0009] (4) The ZnFe2O4 precursor obtained in step (3) is subjected to solvent replacement and aging at a temperature of 50-80℃ for 4-6 days.
[0010] (5) The ZnFe2O4 precursor aged in step (4) is subjected to supercritical drying.
[0011] (6) Dissolve the ZnFe2O4 precursor that has been supercritically dried in step (5) in deionized water, add PEG, EDC and NHS first, stir evenly, then add FA, stir for 30-40 min, so that it can be fully adsorbed on the surface of ZnFe2O4 nanoparticles.
[0012] (7) The modified ZnFe2O4 precursor in step (6) is placed in a muffle furnace and heat-treated at 200-550℃ for 2-5 hours to finally obtain the target ZnFe2O4 aerogel.
[0013] In step (1), the molar ratio of zinc source, iron source and deionized water is 1:(2~2.5):(100~125); in step (2), the amount of ethanol added is the volume ratio of ethanol to deionized water as (0.5~1):1.
[0014] The preferred zinc source in step (1) is ZnCl2, Zn(NO3)2 or Zn(CH3COO)2; the preferred iron source is FeCl3, Fe(NO3)3 or Fe(CH3COO)3.
[0015] The preferred crosslinking agent in step (3) is one of 1,2-epoxypropane, glutaraldehyde or epichlorohydrin; wherein the molar ratio of zinc source to crosslinking agent is 1:(10-12).
[0016] The preferred step (3) is to allow the solvent to stand for 24 to 36 hours; the solvent replacement frequency in step (4) is once every 6 to 12 hours.
[0017] The preferred solvent used for solvent replacement in step (4) is ethanol, acetone or tert-butanol.
[0018] The preferred supercritical drying process in step (5) is supercritical carbon dioxide drying, with carbon dioxide as the drying medium, a reaction temperature of 40-80°C, a pressure of 8-12 MPa in the high-pressure reactor, a gas release rate of 1-4 L / min, and a drying time of 8-12 h.
[0019] In preferred step (6), PEG and FA are used for functional modification, and EDC and NHS are used as coupling agents. The molar ratio of PEG, FA, EDC and NHS is 1:(1~1.2):(2~2.2):(2~2.2), and the molar ratio of PEG to ZnFe2O4 precursor is 1:(5~10).
[0020] The preferred heating rate in step (7) is 2.5 to 5 °C / min.
[0021] This invention also provides a ZnFe2O4 aerogel prepared by the above-described method. The aerogel is characterized by being a three-dimensional porous network structure composed of interconnected zinc ferrite nanoparticles, and the specific surface area of the prepared aerogel is 150 m². 2 / g~200m 2 / g, the pore size distribution is concentrated in the mesoporous range of 20nm to 40nm; the aerogel has a photothermal effect under near-infrared light irradiation at a wavelength of 808nm, and its photothermal conversion efficiency is not less than 60%.
[0022] Beneficial effects:
[0023] The method of the present invention and the ZnFe2O4 aerogel material prepared by the method for photothermal therapy of gliomas have the following characteristics:
[0024] (1): ZnFe2O4 aerogel modified with PEG and FA integrates multiple functions such as targeting, magnetothermal therapy, and photothermal therapy. It can serve as a comprehensive treatment platform to improve treatment efficacy and reduce damage to normal cells.
[0025] (2): The ZnFe2O4 aerogel prepared by this method has high porosity and specific surface area, which can provide more active sites to promote photothermal conversion.
[0026] (3): The ZnFe2O4 aerogel prepared in this method is simple to process, and its photothermal conversion ability is in line with the strategic position of prioritizing the protection of people's health. Detailed Implementation
[0027] Example 1
[0028] ZnCl2, FeCl3, and deionized water were mixed in a molar ratio of 1:2:100, with ZnCl2 at 0.01 mol. The mixture was stirred at room temperature for 30 min until a homogeneous solution was formed. Then, 9 mL of ethanol solution was added, and stirring continued for 20 min. 7 mL of 1,2-epoxypropane was added to induce gelation, and the mixture was then transferred to a mold and sealed. After standing at room temperature for 24 h, the mixture was demolded. The resulting ZnFe2O4 precursor was immersed in ethanol and placed in a 50 °C oven for solvent replacement and aging. The oven was dried for 6 days, with the ethanol being replaced every 6 hours. Subsequently, supercritical CO2 drying was performed at a reaction temperature of 40 °C, a pressure of 8 MPa in a high-pressure reactor, a gas release rate of 1 L / min, and a drying time of 8 h.
[0029] The obtained precursor was then dissolved in 15 mL of deionized water, and PEG, EDC, and NHS were added. After stirring until homogeneous, FA was added, with the molar ratio of PEG, FA, EDC, NHS, and precursor being 1:1:2:2:5, to obtain the modified ZnFe2O4 aerogel. The modified ZnFe2O4 aerogel was then heat-treated in a muffle furnace at 200℃ for 5 h at a heating rate of 2.5℃ / min, finally yielding the target ZnFe2O4 aerogel with a specific surface area of 150 m². 2 / g, with an aperture of 20nm and a photothermal conversion efficiency of 62.3%.
[0030] Example 2
[0031] ZnCl2, FeCl3, and deionized water were mixed in a molar ratio of 1:2:110, with 0.01 mol of ZnCl2. The mixture was stirred at room temperature for 35 min until a homogeneous solution was formed. Then, 10 mL of ethanol solution was added, and stirring was continued for 22 min. 18 mL of glutaraldehyde was added to induce gelation, and the mixture was then transferred to a mold and sealed. After standing at room temperature for 26 h, the mixture was demolded. The resulting ZnFe2O4 precursor was immersed in ethanol and placed in a 60 °C oven for solvent replacement and aging. The oven was dried for 5 days, with the ethanol being replaced every 8 hours. Subsequently, supercritical CO2 drying was performed at a reaction temperature of 50 °C, a pressure of 9 MPa in a high-pressure reactor, a gas release rate of 2 L / min, and a drying time of 9 h.
[0032] The obtained precursor was then dissolved in 15 mL of deionized water, and PEG, EDC, and NHS were added. After stirring until homogeneous, FA was added. The molar ratio of PEG, FA, EDC, NHS, and the precursor was 1:1.2:2:2:5, resulting in the modified ZnFe2O4 aerogel. The modified ZnFe2O4 precursor was then heat-treated in a muffle furnace at 300 °C for 4.5 h at a heating rate of 3 °C / min to finally obtain the target ZnFe2O4 aerogel with a specific surface area of 160 m². 2 / g, with an aperture of 28nm and a photothermal conversion efficiency of 63.8%.
[0033] Example 3
[0034] Zn(NO3)2, Fe(NO3)3, and deionized water were mixed in a molar ratio of 1:2.2:115, with Zn(NO3)2 being 0.01 mol. The mixture was stirred at room temperature for 40 min until a homogeneous solution was formed. Then, 12 mL of ethanol solution was added, and stirring continued for 25 min. 8 mL of 1,2-epoxypropane was added to induce gelation, and the mixture was transferred to a mold and sealed. After standing at room temperature for 28 h, the mixture was demolded. The resulting ZnFe2O4 aerogel was immersed in acetone and placed in a 60 °C oven for solvent replacement and aging. The oven was dried for 5 days, with the acetone being replaced every 10 hours. Subsequently, supercritical CO2 drying was performed at a reaction temperature of 55 °C, a pressure of 10 MPa in a high-pressure reactor, a gas release rate of 3 L / min, and a drying time of 10 h.
[0035] The obtained precursor was then dissolved in 18 mL of deionized water, and PEG, EDC, and NHS were added. After stirring until homogeneous, FA was added. The molar ratio of PEG, FA, EDC, NHS, and the precursor was 1:1.2:2:2:6, resulting in the modified ZnFe2O4 aerogel. The modified ZnFe2O4 aerogel was then heat-treated in a muffle furnace at 400℃ for 4 h at a heating rate of 3.5℃ / min, finally yielding the target ZnFe2O4 aerogel with a specific surface area of 170 m². 2 / g, with an aperture of 30nm and a photothermal conversion efficiency of 65.2%.
[0036] Example 4
[0037] Zn(NO3)2, Fe(NO3)3, and deionized water were mixed in a molar ratio of 1:2.3:120, with Zn(NO3)2 being 0.01 mol. The mixture was stirred at room temperature for 40 min until a homogeneous solution was formed. Then, 15 mL of ethanol solution was added, and stirring continued for 28 min. 8 mL of epichlorohydrin was added to induce gelation, and the mixture was then transferred to a mold and sealed. After standing at room temperature for 30 h, the mixture was demolded. The resulting ZnFe2O4 aerogel was immersed in tert-butanol and placed in a 65 °C oven for solvent replacement and aging. The oven was dried for 5 days, with the tert-butanol being replaced every 6 hours. Subsequently, supercritical CO2 drying was performed at a reaction temperature of 60 °C, a pressure of 10 MPa in a high-pressure reactor, a gas release rate of 3 L / min, and a drying time of 10 h.
[0038] The obtained precursor was then dissolved in 20 mL of deionized water, and PEG, EDC, and NHS were added. After stirring until homogeneous, FA was added. The molar ratio of PEG, FA, EDC, NHS, and the precursor was 1:1.2:2:2.2:8, resulting in the modified ZnFe2O4 aerogel. The modified ZnFe2O4 aerogel was then heat-treated in a muffle furnace at 450 °C for 3.5 h at a heating rate of 4 °C / min, finally yielding the target ZnFe2O4 aerogel with a specific surface area of 180 m². 2 / g, with an aperture of 35nm and a photothermal conversion efficiency of 66%.
[0039] Example 5
[0040] Zn(CH3COO)2, Fe(CH3COO)3, and deionized water were mixed in a molar ratio of 1:2.5:120, with Zn(CH3COO)2 being 0.01 mol. The mixture was stirred at room temperature for 45 min until a homogeneous solution was formed. Then, 18 mL of ethanol solution was added, and stirring continued for 30 min. 10 mL of epichlorohydrin was added to induce gelation, and the mixture was then transferred to a mold and sealed. After standing at room temperature for 32 h, the mixture was demolded. The resulting ZnFe2O4 aerogel was immersed in ethanol and placed in a 70 °C oven for solvent replacement and aging. The oven was dried for 4 days, with the ethanol being replaced every 12 hours. Subsequently, supercritical CO2 drying was performed at a reaction temperature of 70 °C, a pressure of 11 MPa in a high-pressure reactor, a gas release rate of 4 L / min, and a drying time of 11 h.
[0041] The obtained precursor was then dissolved in 20 mL of deionized water, and PEG, EDC, and NHS were added. After stirring until homogeneous, FA was added. The molar ratio of PEG, FA, EDC, NHS, and the precursor was 1:1.2:2:2.2:10, resulting in the modified ZnFe2O4 aerogel. The modified ZnFe2O4 aerogel was then heat-treated in a muffle furnace at 500 °C for 3 h at a heating rate of 4.5 °C / min, finally yielding the target ZnFe2O4 aerogel with a specific surface area of 190 m². 2 / g, with an aperture of 38nm and a photothermal conversion efficiency of 67.2%.
[0042] Example 6
[0043] Zn(CH3COO)2, Fe(CH3COO)3, and deionized water were mixed in a molar ratio of 1:1.8:125, with Zn(CH3COO)2 being 0.01 mol. The mixture was stirred at room temperature for 35 min until a homogeneous solution was formed. Then, 20 mL of ethanol solution was added, and stirring continued for 30 min. 10 mL of 1,2-epoxypropane was added to induce gelation, and the mixture was transferred to a mold and sealed. After standing at room temperature for 36 h, the mixture was demolded. The resulting ZnFe2O4 aerogel was immersed in ethanol and placed in an 80 °C oven for solvent replacement and aging. The oven was dried for 4 days, with the ethanol being replaced every 10 hours. Subsequently, supercritical CO2 drying was performed at a reaction temperature of 80 °C, a pressure of 12 MPa in a high-pressure reactor, a gas release rate of 4 L / min, and a drying time of 12 h.
[0044] The obtained precursor was then dissolved in 22 mL of deionized water, and PEG, EDC, and NHS were added. After stirring until homogeneous, FA was added. The molar ratio of PEG, FA, EDC, NHS, and precursor was 1:1.2:2.2:2.2:10, resulting in the modified ZnFe2O4 aerogel. The modified ZnFe2O4 aerogel was then heat-treated in a muffle furnace at 550 °C for 2 h at a heating rate of 5 °C / min, finally yielding the target ZnFe2O4 aerogel with a specific surface area of 200 m². 2 / g, with an aperture of 40nm and a photothermal conversion efficiency of 68%.
Claims
1. A method for preparing ZnFe2O4 aerogel for photothermal therapy of gliomas, the specific steps of which are as follows: (1) Dissolve a certain amount of zinc source and iron source in deionized water and stir to form a uniform mixed solution; (2) After stirring and mixing evenly, add ethanol solution and continue stirring for 20-30 minutes; (3) After the solution in step (2) is stirred, add the cross-linking agent to gel, transfer it to the mold and seal it. After standing, demold it. (4) The ZnFe2O4 precursor obtained in step (3) is subjected to solvent replacement and aging at a temperature of 50-80℃ for 4-6 days. (5) The ZnFe2O4 precursor aged in step (4) is subjected to supercritical drying. (6) Dissolve the ZnFe2O4 precursor that has been supercritically dried in step (5) in deionized water, add PEG, EDC and NHS first, stir evenly, then add FA, stir for 30-40 min, so that it can be fully adsorbed on the surface of ZnFe2O4 nanoparticles. (7) The modified ZnFe2O4 precursor in step (6) is heat-treated at 200-550℃ for 2-5 hours to finally obtain the target ZnFe2O4 aerogel. in, The molar ratio of zinc source, iron source and deionized water in step (1) is 1:(2~2.5):(100~125).
2. The preparation method according to claim 1, characterized in that... In step (1), the zinc source is ZnCl2, Zn(NO3)2 or Zn(CH3COO)2; the iron source is FeCl3, Fe(NO3)3 or Fe(CH3COO)3.
3. The preparation method according to claim 1, characterized in that... In step (2), the amount of ethanol added is such that the volume ratio of ethanol to deionized water is (0.5~1):
1.
4. The preparation method according to claim 1, characterized in that... The crosslinking agent in step (3) is one of 1,2-epoxypropane, glutaraldehyde or epichlorohydrin; the molar ratio of zinc source to crosslinking agent is 1:(10-12); the standing time in step (3) is 24-36h; the solvent replacement frequency in step (4) is once every 6-12 hours.
5. The preparation method according to claim 1, characterized in that... The solvent used for solvent replacement in step (4) is ethanol, acetone or tert-butanol.
6. The preparation method according to claim 1, characterized in that... The supercritical drying process in step (5) is supercritical carbon dioxide drying, with carbon dioxide as the drying medium, a reaction temperature of 40-80℃, a pressure of 8-12MPa in the high-pressure reactor, an venting rate of 1-4L / min, and a drying time of 8-12h.
7. The preparation method according to claim 1, characterized in that... In step (6), the molar ratio of PEG, FA, EDC and NHS is 1:(1~1.2):(2~2.2):(2~2.2); the molar ratio of PEG to ZnFe2O4 precursor is 1:(5~10).
8. The preparation method according to claim 1, characterized in that... The heating rate in step (7) is 2.5 to 5 °C / min.
9. ZnFe2O4 aerogel prepared according to the preparation method described in claims 1 to 8.
10. The ZnFe2O4 aerogel according to claim 9, characterized in that... The aerogel is a three-dimensional porous network structure composed of interconnected zinc ferrite nanoparticles, and the specific surface area of the prepared aerogel is 150 m². 2 / g~200m 2 / g, the pore size distribution is concentrated in the mesoporous range of 20nm to 40nm; the aerogel has a photothermal effect under near-infrared light irradiation at a wavelength of 808nm, and its photothermal conversion efficiency is not less than 60%.