Mesoporous hollow cerium oxide multifunctional composite material and preparation method thereof

Abstract

The invention belongs to the field of nano materials, and relates to a mesoporous hollow cerium oxide multifunctional composite material and a preparation method thereof. The mesoporous hollow cerium oxide multifunctional composite material comprises a nano-carrier and a load, the nano-carrier is a mesoporous hollow cerium oxide nanosphere, the load is indocyanine green, and the indocyanine green is loaded on the surface and inside of the mesoporous hollow cerium oxide nanosphere. The mesoporous hollow cerium oxide nanospheres are used as a carrier, so that the indocyanine green can be simultaneously loaded on the surfaces and the interiors of the mesoporous hollow cerium oxide nanospheres, the loading capacity of the indocyanine green is effectively improved, and the photo-thermal performance and the photodynamic performance of the composite material are fully exerted. In addition, the binding force between the indocyanine green and the mesoporous hollow cerium oxide nanospheres is enhanced by virtue of the confinement effect of the mesoporous structure of the hollow cerium oxide nanospheres, and the problems that the stability is poor and the indocyanine green is easy to fall off due to the poor binding force of the existing composite material are solved.

Description

Technical Field

[0001] The present invention relates to the technical field of nanomaterials, and in particular to a mesoporous hollow cerium oxide multifunctional composite material and a preparation method thereof. Background Art

[0002] Nano-cerium oxide (CeO2) is an excellent nano-carrier with unique Ce 3+ / Ce 4+ Reversible redox properties, high surface activity, good biocompatibility and low toxicity have attracted widespread attention in biomedical fields such as antioxidant therapy, anti-inflammatory, antibacterial and tumor therapy. Cerium oxide can mimic the catalytic activity of natural enzymes, such as peroxidase-like and superoxide dismutase (SOD-like), through its redox properties, and is therefore often called nanozymes. Compared with natural enzymes, ceria-based nanozymes have advantages such as good environmental stability, low cost and strong functional adjustability. However, traditional ceria nanozymes face problems such as small specific surface area, limited catalytic efficiency and single function in practical applications, and their application value needs to be further improved through structural and performance optimization.

[0003] Indocyanine green (ICG), a near-infrared light-absorbing dye, exhibits good photothermal conversion efficiency and reactive oxygen species generation capacity in photothermal therapy (PTT) and photodynamic therapy (PDT), and has been used in medical diagnosis and treatment.

[0004] Combining cerium oxide nanozymes with indocyanine green can produce an integrated multifunctional composite nanozyme.

[0005] The invention application with publication number CN117100858A describes a method for preparing a multifunctional cerium oxide nanozyme platform with a cascade reaction. First, hollow cerium oxide nanoparticles are prepared, and then indocyanine green is mixed with the hollow cerium oxide nanoparticles to achieve the introduction of indocyanine green. However, the loading amount of indocyanine green in this scheme is small, and the photothermal and photodynamic properties cannot be fully utilized. In addition, the binding force between indocyanine green and hollow cerium oxide in this scheme is poor, the stability of the composite nanozyme is insufficient, and indocyanine green easily falls off.

[0006] Therefore, there is a need to provide a composite material with higher loading capacity and better bonding strength. Summary of the Invention

[0007] (1) Technical issues to be resolved

[0008] In order to solve the problems of low loading amount and poor binding force of indocyanine green in composite materials in the prior art, the present invention provides a mesoporous hollow cerium oxide multifunctional composite material and a preparation method thereof.

[0009] (2) Technical solution

[0010] In order to achieve the above objectives, the main technical solutions adopted by the present invention include:

[0011] In the first aspect, the present invention provides a mesoporous hollow cerium oxide multifunctional composite material, comprising a nanocarrier and a load; the nanocarrier is a mesoporous hollow cerium oxide nanosphere, and the load is indocyanine green; indocyanine green is loaded on the surface and interior of the mesoporous hollow cerium oxide nanosphere.

[0012] In the mesoporous hollow cerium oxide multifunctional composite material as described above, preferably, the diameter of the mesoporous cerium oxide nanospheres is 100-200 nm.

[0013] In the mesoporous hollow cerium oxide multifunctional composite material as described above, preferably, the diameter of the mesoporous hollow cerium oxide nanospheres is 100-120 nm.

[0014] In a second aspect, the present invention further provides a method for preparing the above-mentioned mesoporous hollow cerium oxide multifunctional composite material, comprising the following steps:

[0015] S1: hydrothermally reacting a cerium source with a structure-directing agent to obtain a cerium oxide precursor;

[0016] S2: calcining the cerium oxide precursor to obtain mesoporous hollow cerium oxide nanospheres;

[0017] S3: Indocyanine green is loaded onto the surface and interior of mesoporous hollow cerium oxide nanospheres to obtain a mesoporous hollow cerium oxide multifunctional composite material.

[0018] In the method for preparing the mesoporous hollow cerium oxide multifunctional composite material as described above, preferably, in step S1, the cerium source is cerium nitrate hexahydrate, and the structure directing agent is acetic acid.

[0019] In the method for preparing the mesoporous hollow cerium oxide multifunctional composite material as described above, preferably, in step S1, a cerium source and a structure directing agent are added to a mixed solvent of water and ethylene glycol and mixed evenly, and then reacted at 175-185° C. for 180-220 minutes to obtain a cerium oxide precursor;

[0020] The mass ratio of the cerium source to the structure directing agent is 1:1-1.5:1, and the volume ratio of water to ethylene glycol is 0.02-0.07.

[0021] In the method for preparing the mesoporous hollow cerium oxide multifunctional composite material as described above, preferably, in step S2, the cerium oxide precursor is calcined in an air atmosphere to obtain mesoporous hollow cerium oxide nanospheres; the calcination temperature is 450-550° C., and the calcination time is 3-5 h.

[0022] The method for preparing the mesoporous hollow cerium oxide multifunctional composite material as described above, preferably, in step S3, the mesoporous hollow cerium oxide nanospheres and indocyanine green are dispersed in water, stirred in the dark for 24-36 hours, and washed and freeze-dried to obtain the mesoporous hollow cerium oxide multifunctional composite material;

[0023] The mass ratio of the mesoporous hollow cerium oxide nanospheres to indocyanine green is 3:1-5:1.

[0024] In the method for preparing the mesoporous hollow cerium oxide multifunctional composite material as described above, preferably, in step S1, an aqueous solution of a cerium source and an ethylene glycol solution of a structure directing agent are mixed, and then a hydrothermal reaction is carried out;

[0025] The concentration of the cerium source in the aqueous solution is 0.67-1 mg / mL, and the concentration of the structure-directing agent in the ethylene glycol solution is 0.022-0.033 mg / mL.

[0026] (3) Beneficial effects

[0027] The present invention uses mesoporous hollow cerium oxide nanospheres as carriers, so that indocyanine green can be simultaneously loaded onto the surface and interior of the mesoporous hollow cerium oxide nanospheres. Compared with the prior art in which indocyanine green can only be loaded onto the surface of hollow cerium oxide, the loading amount of indocyanine green in the present invention is effectively improved, and the photothermal and photodynamic properties of the composite material can be fully utilized.

[0028] The present invention also utilizes the confinement effect of the mesoporous structure of the hollow cerium oxide nanospheres to enhance the binding force between indocyanine green and the mesoporous hollow cerium oxide nanospheres, thereby overcoming the problems of poor stability and easy shedding of indocyanine green caused by poor binding force of existing composite materials. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 This is a transmission electron micrograph of the mesoporous hollow cerium oxide nanospheres prepared in Example 1;

[0030] Figure 2 This is a transmission electron micrograph of the mesoporous hollow cerium oxide nanospheres prepared in Example 2;

[0031] Figure 3 This is a transmission electron micrograph of the mesoporous hollow cerium oxide nanospheres prepared in Example 3;

[0032] Figure 4 This is the XRD curve of the mesoporous hollow cerium oxide nanospheres prepared in Example 1;

[0033] Figure 5 This is the N2 adsorption-desorption isotherm of the mesoporous hollow cerium oxide nanospheres prepared in Example 1;

[0034] Figure 6 This is the pore size distribution diagram of the mesoporous hollow cerium oxide nanospheres prepared in Example 1;

[0035] Figure 7 This is an XPS graph of the mesoporous hollow cerium oxide nanospheres prepared in Example 1;

[0036] Figure 8 This is the Zeta potential diagram of the mesoporous hollow cerium oxide nanospheres, indocyanine green and the composite material in Example 1;

[0037] Figure 9 This is a graph showing the absorbance variation over time at 652 nm of the mesoporous hollow cerium oxide nanospheres and the mesoporous hollow cerium oxide multifunctional composite material prepared in Example 1, as well as the oxide generated after the mesoporous hollow cerium oxide multifunctional composite material is immersed in TMB under 808 nm laser irradiation;

[0038] Figure 10 This is a graph showing the change in the amount of O2 produced by the mesoporous hollow cerium oxide nanospheres and the mesoporous hollow cerium oxide multifunctional composite material prepared in Example 1 under the action of H2O2 over time;

[0039] Figure 11 This is a temperature change diagram of the mesoporous hollow cerium oxide multifunctional composite material prepared in Example 1 at different concentrations under 808nm laser irradiation;

[0040] Figure 12 This is a temperature change diagram of the mesoporous hollow cerium oxide multifunctional composite material prepared in Example 1 under 808nm laser irradiation at different powers;

[0041] Figure 13 This is a graph showing the absorption spectrum change over time of the mesoporous hollow cerium oxide multifunctional composite material prepared in Example 1 when immersed in 1,3-diphenylisobenzofuran and irradiated with a 655 nm laser. DETAILED DESCRIPTION

[0042] In order to better explain the present invention and facilitate understanding, the present invention is described in detail below with reference to the accompanying drawings and specific embodiments.

[0043] Patent application publication number CN117100858A describes a method for preparing a multifunctional ceria nanozyme platform with a cascade reaction. This approach involves preparing hollow ceria nanoparticles and then mixing indocyanine green (ICG) with the hollow ceria nanoparticles to form a composite material. This approach, however, results in repulsion between ICG molecules and allows ICG to be loaded only onto the surface of the hollow ceria nanoparticles. This results in a low ICG loading capacity and prevents the full utilization of its photothermal and photodynamic properties.

[0044] Based on the above problems, the present invention provides a mesoporous hollow cerium oxide multifunctional composite material, including a nanocarrier and a load; the nanocarrier is a mesoporous hollow cerium oxide nanosphere, and the load is indocyanine green; indocyanine green is loaded on the surface and interior of the mesoporous hollow cerium oxide nanosphere.

[0045] The present invention uses mesoporous hollow cerium oxide nanospheres as carriers, so that indocyanine green can be simultaneously loaded onto the surface and interior of the mesoporous hollow cerium oxide nanospheres. Compared with the prior art in which indocyanine green can only be loaded onto the surface of hollow cerium oxide, the loading amount of indocyanine green in the present invention is effectively improved, and the photothermal and photodynamic properties of the composite material can be fully utilized.

[0046] The present invention also utilizes the confinement effect of the mesoporous structure of the hollow cerium oxide nanospheres to enhance the binding force between indocyanine green and the mesoporous hollow cerium oxide nanospheres, thereby overcoming the problems of poor stability and easy shedding of indocyanine green caused by poor binding force of existing composite materials.

[0047] The mesoporous hollow cerium oxide nanospheres of the present invention have a large specific surface area, a regular pore structure and good dispersibility, which can enhance the catalytic activity of the composite material. At the same time, the hollow structure not only reduces the density of the material, but also provides more space for drug loading and reactant exchange, as well as higher optical stability, providing possibilities for multifunctional applications in the biomedical field.

[0048] The multifunctional composite material prepared by the present invention has important applications in the biomedical field and can be used for integrated tumor diagnosis and treatment, antioxidant protection, and inflammation treatment.

[0049] The mesoporous hollow cerium oxide nanospheres of the present invention have excellent chemical reaction activity due to their rich pore structure and large specific surface area. The photothermal effect of the load indocyanine green has an enhancing effect on the peroxidase activity of the mesoporous hollow cerium oxide nanospheres, and the catalase activity and antioxidant capacity of the mesoporous hollow cerium oxide nanospheres can alleviate the hypoxic state in the tumor microenvironment. Under laser irradiation, the composite material of the present invention can achieve the effects of photothermal, photodynamic and chemical dynamics in one. This composite material with multiple functions in one can make up for the deficiency of traditional materials that can only play a single function in anti-oxidation, anti-inflammatory, antibacterial and tumor treatment. It has stability, high activity and multifunctionality, can efficiently load ICG and enhance its stability, and can significantly enhance the catalytic activity of the composite material, thereby realizing its efficient application in the fields of photothermal therapy, photodynamic therapy and antioxidant therapy.

[0050] Preferably, the diameter of the mesoporous cerium oxide nanospheres is 100-200 nm, more preferably 100-120 nm, and even more preferably 110 nm.

[0051] The present invention also provides a method for preparing the above-mentioned mesoporous hollow cerium oxide multifunctional composite material, comprising the following steps:

[0052] S1: hydrothermally reacting a cerium source with a structure-directing agent to obtain a cerium oxide precursor.

[0053] S2: calcining the cerium oxide precursor to obtain mesoporous hollow cerium oxide nanospheres.

[0054] S3: Indocyanine green is loaded onto the surface and interior of mesoporous hollow cerium oxide nanospheres to obtain a mesoporous hollow cerium oxide multifunctional composite material.

[0055] Preferably, in the above step S1, the cerium source is cerium nitrate hexahydrate, and the structure directing agent is acetic acid.

[0056] In step S1, a cerium source and a structure-directing agent can be added to a mixed solvent of water and ethylene glycol, mixed evenly, and then reacted at 175-185°C for 180-220 minutes. After the reaction, the precursor is cooled, separated, washed, and dried to obtain a cerium oxide precursor. The mass ratio of the cerium source to the structure-directing agent is 1:1-1.5:1, the volume ratio of water to ethylene glycol is 0.02-0.07, the drying temperature is 60-80°C, and the drying time is 10-14 hours.

[0057] More specifically, a cerium source can be added to water to produce an aqueous cerium source solution, and a structure-directing agent can be added to ethylene glycol to produce an ethylene glycol solution of the structure-directing agent. The two solutions are then mixed and subjected to a hydrothermal reaction. Preferably, the concentration of the cerium source in the aqueous cerium source solution is 0.67-1 mg / mL, and the concentration of the structure-directing agent in the ethylene glycol solution is 0.022-0.033 mg / mL.

[0058] In step S1, Ce 3+ Hydrolyzed in supersaturated solution and converted to NO3 - Oxidation forms a large number of cerium oxide nanocrystal precursors. Acetic acid can react with ethylene glycol through esterification, thereby enhancing the surface modification effect of these small molecules on the cerium oxide nanoscale crystal precursors. These nanocrystals are then aggregated into larger self-assembled spheres driven by the minimization of the total surface energy, and finally mesoporous hollow cerium oxide nanospheres are obtained.

[0059] In step S1, the addition of acetic acid is a key factor in enabling the cerium oxide nanospheres to form a mesoporous structure, and the mass ratio of the cerium source to the acetic acid is a key factor in enabling the cerium oxide nanospheres to form a hollow structure.

[0060] The present invention adopts a hot solvent method to prepare mesoporous hollow cerium oxide nanospheres. By optimizing the raw material ratio and accurately controlling the preparation conditions, mesoporous hollow cerium oxide nanomaterials with better performance and more ideal morphology are prepared.

[0061] Preferably, in the above step S2, the cerium oxide precursor can be calcined in an air atmosphere to obtain mesoporous hollow cerium oxide nanospheres. The calcination temperature is 450-550°C, preferably 500°C, and the calcination time is 3-5h, preferably 4h.

[0062] Preferably, in step S3, the mesoporous hollow cerium oxide nanospheres and indocyanine green are bonded via electrostatic adsorption. Specifically, the mesoporous hollow cerium oxide nanospheres and indocyanine green are dispersed in water, stirred at room temperature in the dark for 24-36 hours, washed, and freeze-dried for 22-26 hours to obtain a mesoporous hollow cerium oxide multifunctional composite material. The mass ratio of the mesoporous hollow cerium oxide nanospheres to indocyanine green is 3:1-5:1, and the concentration of the indocyanine green is 0.2-0.3 mg / mL.

[0063] In step S3, it was found through experimental investigation that the mesoporous hollow cerium oxide nanospheres prepared by the present invention are positively charged, while indocyanine green is negatively charged. The charge attraction between the positively charged mesoporous hollow cerium oxide nanospheres and the negatively charged indocyanine green is utilized to achieve efficient loading of indocyanine green on the mesoporous hollow cerium oxide.

[0064] The preparation method of the present invention is simple, low in cost, easy to scale up for production, and has good industrial application prospects.

[0065] In order to further clarify the solution of the present invention and its technical advancement, the following description is made in conjunction with specific embodiments and technical effects.

[0066] Example 1

[0067] This embodiment provides a method for preparing a mesoporous hollow cerium oxide multifunctional composite material, comprising the following steps:

[0068] S1: Dissolve cerium nitrate hexahydrate in deionized water and ultrasonicate for 5 minutes to obtain solution A. Disperse acetic acid in ethylene glycol and stir evenly to obtain solution B. The volume ratio of deionized water to ethylene glycol is 0.033, and the mass ratio of cerium nitrate hexahydrate to acetic acid is 1:1. Mix solution A and solution B, seal them, place them in an autoclave, and heat them at 180°C for 200 minutes. After the reaction is completed, cool and centrifuge to obtain a solid. After washing the solid with ethanol and deionized water, respectively, the solid is dried in a drying oven at 70°C for 12 hours to obtain a cerium oxide precursor.

[0069] S2: placing the cerium oxide precursor into a muffle furnace and calcining it in an air atmosphere at a temperature of 500° C. for 4 h to obtain mesoporous hollow cerium oxide nanospheres.

[0070] S3: Mesoporous hollow cerium oxide nanospheres and indocyanine green were added to water and stirred at room temperature in the dark for 24 hours. The mixture was centrifuged, washed with deionized water, and freeze-dried for 24 hours to obtain a mesoporous hollow cerium oxide multifunctional composite material. The mass ratio of the mesoporous hollow cerium oxide nanospheres to the indocyanine green was 4:1, and the concentration of the mesoporous hollow cerium oxide nanospheres was 4 mg / mL.

[0071] Example 2

[0072] This embodiment provides a method for preparing a mesoporous hollow cerium oxide multifunctional composite material, comprising the following steps:

[0073] S1: Dissolve cerium nitrate hexahydrate in deionized water and ultrasonicate for 5 minutes to obtain solution A. Disperse acetic acid in ethylene glycol and stir evenly to obtain solution B. The volume ratio of deionized water to ethylene glycol is 0.02, and the mass ratio of cerium nitrate hexahydrate to acetic acid is 1.5:1. Mix solution A and solution B, seal them, place them in an autoclave, and heat them at 175°C for 220 minutes. After the reaction is completed, cool and centrifuge to obtain a solid. After washing the solid with ethanol and deionized water, respectively, the solid is dried in a drying oven at 60°C for 14 hours to obtain a cerium oxide precursor.

[0074] S2: placing the cerium oxide precursor into a muffle furnace and calcining it in an air atmosphere at a temperature of 450° C. for 5 h to obtain mesoporous hollow cerium oxide nanospheres.

[0075] S3: Mesoporous hollow cerium oxide nanospheres and indocyanine green were added to water and stirred at room temperature in the dark for 22 hours. The mixture was centrifuged, washed with deionized water, and freeze-dried for 22 hours to obtain a mesoporous hollow cerium oxide multifunctional composite material. The mass ratio of the mesoporous hollow cerium oxide nanospheres to the indocyanine green was 3:1, and the concentration of the mesoporous hollow cerium oxide nanospheres was 4 mg / mL.

[0076] Example 3

[0077] This embodiment provides a method for preparing a mesoporous hollow cerium oxide multifunctional composite material, comprising the following steps:

[0078] S1: Dissolve cerium nitrate hexahydrate in deionized water and ultrasonicate for 5 minutes to obtain solution A. Disperse acetic acid in ethylene glycol and stir evenly to obtain solution B. The volume ratio of deionized water to ethylene glycol is 0.07, and the mass ratio of cerium nitrate hexahydrate to acetic acid is 1.2:1. Mix solution A and solution B, seal them, place them in an autoclave, and heat them at 185°C for 180 minutes. After the reaction is completed, cool and centrifuge to obtain a solid. After washing the solid with ethanol and deionized water, respectively, the solid is dried in a drying oven at 80°C for 10 hours to obtain a cerium oxide precursor.

[0079] S2: placing the cerium oxide precursor into a muffle furnace and calcining it in an air atmosphere at a temperature of 550° C. for 3 h to obtain mesoporous hollow cerium oxide nanospheres.

[0080] S3: Mesoporous hollow cerium oxide nanospheres and indocyanine green were added to water and stirred at room temperature in the dark for 26 hours. The mixture was centrifuged, washed with deionized water, and freeze-dried for 36 hours to obtain a mesoporous hollow cerium oxide multifunctional composite material. The mass ratio of the mesoporous hollow cerium oxide nanospheres to the indocyanine green was 5:1, and the concentration of the mesoporous hollow cerium oxide nanospheres was 4 mg / mL.

[0081] Comparative Example 1

[0082] This comparative example provides a method for preparing a cerium oxide composite material, which differs from Example 1 in that acetic acid is not added in step S1.

[0083] Comparative Example 2

[0084] This comparative example provides a method for preparing a cerium oxide composite material, comprising the following steps:

[0085] Cerium nitrate was added to water and stirred until completely dissolved. Ethylene glycol was then added. The mixture was then placed in an autoclave and reacted at 180°C for 5 hours. After centrifugation, washing, drying, and grinding, hollow cerium oxide nanoparticles were obtained. The mass-to-volume ratio of cerium nitrate to water was 1g:12.5mL, and the volume ratio of water to ethylene glycol was 1:1.

[0086] An aqueous solution of indocyanine green was added to an aqueous solution of hollow cerium oxide nanoparticles, stirred for 24 hours, and then centrifuged and washed to obtain a cerium oxide composite material, wherein the mass ratio of cerium oxide nanoparticles to indocyanine green was 50:15.

[0087] ① Morphology test:

[0088] Figure 1-Figure 3 The transmission electron microscope (TEM) images of the mesoporous hollow cerium oxide nanospheres prepared in Example 1-3 are shown. Figure 1-Figure 3The mesoporous hollow cerium oxide nanospheres all have a uniform hollow spherical morphology and a very rough surface, indicating that the nanospheres have a mesoporous structure. The diameter of the mesoporous hollow cerium oxide nanospheres is approximately 110-170 nm. Among them, the average diameters of the mesoporous hollow cerium oxide nanospheres in Examples 1-3 are 110 nm, 170 nm, and 165 nm, respectively.

[0089] The cerium oxide prepared in Comparative Example 1 only has a hollow structure, a low surface roughness, and no mesoporous structure is formed. The average particle size is about 120 nm.

[0090] The morphology of the composite material prepared in Comparative Example 2 can be referred to the invention patent application with publication number CN117100858A. It does not have a mesoporous structure, and the average diameter of the nanospheres is about 135 nm.

[0091] The researchers of the present invention have verified through experiments that if mesoporous cerium oxide and indocyanine green are combined only through physical adsorption, the adsorption amount of indocyanine green accounts for a maximum of 10wt% of the composite material. However, after testing, the mass proportion of indocyanine green in the mesoporous hollow cerium oxide multifunctional composite materials of Examples 1-3 was 15wt%, 15.4wt%, and 15.1wt%, respectively, indicating that the preparation method of the present invention can further increase the loading amount of indocyanine green. This may be because the present invention allows more indocyanine green to be loaded into the interior of the hollow mesoporous cerium oxide nanospheres.

[0092] ② Characterization of physical and chemical properties:

[0093] The physical and chemical properties of the mesoporous hollow cerium oxide nanospheres prepared in Example 1 were characterized. Figure 4 、 Figure 5 、 Figure 6 as well as Figure 7 .

[0094] Figure 4 is the XRD curve of mesoporous hollow cerium oxide nanospheres (mCeO2-H). Figure 4 In the figure, the diffraction peaks at 2θ = 28.5°, 33.1°, 47.5° and 56.3° are clearly visible, corresponding to the (111), (200), (220) and (311) crystal planes, respectively. The positions and intensities of these peaks are consistent with the standard card of cubic fluorite CeO2 (PDF#34-0394), and Figure 4 No other impurity peaks appeared in the results, indicating that the obtained mCeO2-H particles were of high purity and free of other impurities.

[0095] Figure 5 is the N2 adsorption-desorption isotherm of mesoporous hollow cerium oxide nanospheres (mCeO2-H). Figure 6The pore size distribution of mesoporous hollow cerium oxide nanospheres (mCeO2-H) is shown in Figure 2. Figure 5 as well as Figure 6 It can be seen that mCeO2-H exhibits a type IV isotherm with an H3 hysteresis loop, which is a characteristic of mesoporous materials, and its specific surface area is 144.622 m 2 / g, pore volume is 0.397cm 3 / g, pore diameter is 3.831nm.

[0096] Figure 7 is the XPS curve of mesoporous hollow cerium oxide nanospheres (mCeO2-H). Figure 7 It can be seen that the content of trivalent cerium ions in mCeO2-H is 21.52%, indicating that the mesoporous structure has a rich pore structure and a large specific surface area, as well as a high trivalent cerium ion content, and has better chemical reaction activity.

[0097] In addition, the position and intensity of the diffraction peak of mCeO2-H prepared in Example 2-3 are consistent with the standard card of cubic fluorite structure CeO2 and have no impurity peaks.

[0098] The mCeO2-H prepared in Examples 2-3 also exhibited a type IV isotherm with an H3 hysteresis loop, and their specific surface areas were 136.82 m 2 / g and 139.374m 2 / g, and the pore volume is 0.375cm 3 / g and 0.381cm 3 / g, the pore diameters are 3.906nm and 3.648nm respectively, and the contents of trivalent cerium ions in mCeO2-H are 20.81% and 21.26 respectively.

[0099] The length of the indocyanine green molecule is about 1.2-1.5 nm, and the width is about 0.5-0.7 nm, both of which are smaller than the mesopore diameter of the mesoporous cerium oxide nanospheres in Examples 1-3, indicating that the indocyanine green in Examples 1-3 is fully capable of being loaded into the nanospheres.

[0100] ③Zeta potential test:

[0101] Figure 8 Zeta potential diagram of mesoporous hollow cerium oxide nanospheres (mCeO2-H), indocyanine green (ICG) and mesoporous hollow cerium oxide composite material (mCeO2-H-ICG) prepared in Example 1. Figure 8It can be seen that the Zeta potential of mCeO2-H is 33.3 mV, the Zeta potential of ICG is -27.1 mV, and the Zeta potential of mCeO2-H-ICG is -19 mV. The potential of the mesoporous hollow cerium oxide nanospheres changed from positive to negative after loading ICG, indicating that ICG was successfully loaded on the mesoporous hollow cerium oxide nanospheres.

[0102] Similarly, the Zeta potentials of mCeO2-H prepared in Example 2 and Example 3 were detected to be 32.8 mV and 33.9 mV, respectively, and the Zeta potentials of mCeO2-H-ICG were detected to be -18.2 mV and -19.6 mV, respectively, indicating that Example 2 and Example 3 also successfully loaded ICG onto the mesoporous hollow cerium oxide nanospheres.

[0103] As can be seen from the above, the mCeO2-H prepared in Examples 1-3 has a positively charged surface, while the ICG molecule has a negatively charged surface. Since mCeO2-H and ICG have opposite electrical properties, the mCeO2-H in Examples 1-3 easily binds to ICG through electrostatic adsorption. Furthermore, the mCeO2-H prepared in Examples 1-3 has a high zeta potential, good dispersibility, and more stable nanoparticles. When complexed with ICG, more binding sites are exposed, making it easier to bind to ICG and facilitating ICG loading.

[0104] After testing, the Zeta potentials of mCeO2-H prepared in Comparative Example 1 and Comparative Example 2 were 19.27 mV and 15.34 mV, respectively. The Zeta potential was low, the dispersion was insufficient, and the binding sites that could be exposed when complexed with ICG were insufficient.

[0105] ④ Peroxidase activity test:

[0106] The 3,3',5,5'-tetramethylbenzidine (TMB) peroxidase chromogenic assay is a widely used experimental technique in biochemical research, primarily for detecting enzyme activity and protein content. This method uses TMB as a chromogenic substrate. Its principle is that TMB undergoes oxidation under the catalytic action of peroxidase, generating a blue oxidation product. The concentration of this blue product is positively correlated with enzyme activity, and thus its absorbance can be measured using a UV-visible spectrophotometer at a specific wavelength (typically 652 nm). This method can be used to evaluate the catalytic activity of mCeO2-H-ICG.

[0107] Based on the above principle, the peroxidase-like activity changes of mCeO2-H and mCeO2-H-ICG prepared in Example 1 were detected. Specifically, the mCeO2-H-ICG / mCeO2-H prepared in Example 1 was added to a HAc-NaAc buffer solution at pH = 4 at room temperature to make the concentration of mCeO2-H-ICG / mCeO2-H 50 μg / mL, and then TMB and H2O2 were added in sequence to make the concentration of TMB 1.04 mM and the concentration of H2O2 40 mM. The absorbance changes of the samples at 652 nm over time were collected by UV-vis, and the results were obtained. Figure 9 .

[0108] pass Figure 9 It can be seen that both mCeO2-H and mCeO2-H-ICG have peroxidase-like activity, and the peroxidase-like activity of mCeO2-H-ICG is stronger than that of mCeO2-H. In addition, under 808nm laser irradiation, the peroxidase-like activity of mCeO2-H-ICG is enhanced, indicating that the peroxidase activity of mCeO2-H is significantly enhanced after loading with ICG, especially under laser irradiation.

[0109] The same test was performed on the peroxidase-like activity of mCeO2-H and mCeO2-H-ICG prepared in Example 2-3 and Comparative Example 1-2, and the results are as follows:

[0110] In Examples 2-3 and Comparative Examples 1-2, both mCeO2-H and mCeO2-H-ICG have peroxidase-like activity, and the peroxidase-like activity of mCeO2-H-ICG is stronger than that of mCeO2-H.

[0111] Furthermore, the peroxidase-like activities of mCeO2-H and mCeO2-H-ICG in Examples 2 and 3 are substantially the same as those of mCeO2-H and mCeO2-H-ICG in Example 1. Under 808 nm laser irradiation, the peroxidase-like activities of mCeO2-H-ICG in Examples 2 and 3 are significantly enhanced compared to those without laser irradiation, and are substantially the same as the peroxidase activity of mCeO2-H irradiated with 808 nm laser in Example 1. The peroxidase-like activities of mCeO2-H in Comparative Examples 1 and 2 are relatively close, and the peroxidase-like activities of mCeO2-H-ICG in Comparative Examples 1 and 2 (including the peroxidase-like activity under 808 nm laser irradiation) are relatively close, with no significant difference between the two. The peroxidase-like activity of mCeO2-H in Comparative Examples 1 and 2 is close to that of mCeO2-H in Examples 1-3. The peroxidase-like activity of mCeO2-H-ICG in Examples 1-3 (including the peroxidase-like activity under 808 nm laser irradiation) is significantly higher than that of mCeO2-H-ICG in Comparative Examples 1 and 2. Figure 9 The slope in the equation indicates the activity level. The slope can be used to represent the change in absorbance per unit time, also known as the reaction rate. Figure 9 As shown, the slope of mCeO2-H+H2O2 is 2.66×10 -4 The slope of mCeO2-H-ICG+H2O2 is 6.07×10 -4 The slope of mCeO2-H-ICG+H2O2+808nm is 7.27×10 -4 .

[0112] ⑤ Type 5 catalase activity test:

[0113] The catalase-like activity changes of mCeO2-H and mCeO2-H-ICG prepared in Example 1 were detected. Specifically, the mCeO2-H-ICG / mCeO2-H prepared in Example 1 was added to a PBS buffer solution at pH = 7.4, so that the final concentrations of mCeO2-H-ICG / mCeO2-H and H2O2 were 1.5 mg / mL and 0.6% (w / v), respectively. The oxygen concentration was measured using a dissolved oxygen meter to obtain Figure 10 The activity of catalase-like enzymes can be expressed by the amount of oxygen produced within 5 minutes. Figure 10As shown in the figure, the oxygen production of mCeO2-H + H2O2 is 3.53 mg / L, and the oxygen production of mCeO2-H-ICG + H2O2 is 1.67 mg / L. The oxygen production decreases after loading ICG, which may be caused by the smaller pore size after loading ICG into the mesoporous channels.

[0114] The same test was performed on the catalase-like activity of mCeO2-H and mCeO2-H-ICG prepared in Example 2-3 and Comparative Example 1-2, and the following results were obtained:

[0115] In Examples 2-3 and Comparative Examples 1-2, mCeO2-H and mCeO2-H-ICG also have catalase-like activity.

[0116] Furthermore, the catalase-like activity of mCeO2-H and mCeO2-H-ICG in Examples 2 and 3 is substantially the same as the catalase-like activity of mCeO2-H and mCeO2-H-ICG in Example 1. The catalase-like activity of mCeO2-H in Comparative Examples 1 and 2 is relatively close, and the catalase-like activity of mCeO2-H-ICG in Comparative Examples 1 and 2 is relatively close, with no significant difference between the two. The catalase-like activity of mCeO2-H in Comparative Examples 1 and 2 is relatively close to the catalase-like activity of mCeO2-H in Examples 1-3.

[0117] ⑥Photothermal performance change test:

[0118] The mCeO2-H-ICG prepared in Example 1 was prepared into solutions with different concentrations (100, 200, 300, 400, and 500 μg / mL), and PBS solution was used as a blank control. The mCeO2-H-ICG was illuminated by an 808 nm laser (150 mW / cm 2 ) irradiate the solution for 6 minutes, 1 minute at a time, and use an infrared thermal imager to record the temperature data in the tube. Figure 11 Then, 300 μg / mL mCeO2-H-ICG solution was prepared and the cells were illuminated with 808 nm laser of different powers (0, 50, 100, 150, 200 mW / cm 2 ) were irradiated for 6 minutes, during which the temperature data inside the tube was recorded using an infrared thermal imager. Figure 12 .

[0119] pass Figure 11 as well as Figure 12 It can be seen that the temperature-raising ability of the mCeO2-H-ICG prepared in Example 1 after laser irradiation gradually increases with the increase of concentration. Among them, the temperature of the mCeO2-H-ICG solution with the same concentration under laser irradiation for the same time also increases with the increase of laser power.

[0120] As a control, the PBS solution without material was exposed to 808 nm (150 mW / cm 2 ) After 6 minutes of laser irradiation, the solution temperature only rose by less than 2°C, but the temperature of the mCeO2-H-ICG solution increased significantly to varying degrees, and with the increase of mCeO2-H-ICG concentration, the temperature-raising ability of the system after laser irradiation gradually increased. Among them, the temperature of the mCeO2-H-ICG solution with the same concentration under the same laser irradiation time also increased with the increase of laser power. As can be seen from the figure, 300μg / ml mCeO2-H-ICG at 808nm (150mW / cm 2 ) After irradiation with laser for 6 minutes, the temperature increased by 20°C, while the PBS solution as a blank control only increased by 2°C, indicating that the material has good mild photothermal properties.

[0121] The same test was performed on the changes in the photothermal properties of the mCeO2-H-ICG prepared in Examples 2-3 and Comparative Examples 1-2. As in Example 1, the temperature rise ability of the mCeO2-H-ICG prepared in Examples 2-3 after laser irradiation gradually increased with increasing concentration. The temperature rise of the mCeO2-H-ICG solution with the same concentration under the same laser irradiation time also increased with increasing laser power. Under the same conditions (same time-same concentration, same time-same power), the temperature rise of the mCeO2-H-ICG in Examples 2 and 3 over time was not significantly different from that in Example 1. The photothermal performance of the mCeO2-H-ICG in Comparative Examples 1-2 was relatively close, but significantly lower than that in Examples 1-3.

[0122] ⑦Photodynamic performance change test:

[0123] 1,3-Diphenylisobenzofuran (DPBF) to singlet oxygen ( 1 O2) has a high specificity. Based on this characteristic, LDPBF with a concentration of 15 μg / mL and mCeO2-H-ICG solution with a concentration of 30 μg / mL were irradiated with a 655 nm laser (150 mW / cm 2 ) Irradiate for different time periods and measure the absorbance at 410 nm every 30 seconds to evaluate the 1 O2 generation capacity (i.e. photodynamic performance), obtained Figure 13 .pass Figure 13 It can be seen that after mCeO2-H-ICG is mixed with DPBF, there is a significant decrease in absorption at 410nm under 655nm laser irradiation, indicating the generation of singlet oxygen, which intuitively illustrates that the mCeO2-H-ICG prepared in Example 1 has a photodynamic effect, and the effect is good.

[0124] The same test was conducted on the photodynamic performance changes of the mCeO2-H-ICG prepared in Examples 2-3 and Comparative Examples 1-2. As in Example 1, the mCeO2-H-ICG prepared in Examples 2-3, after being mixed with DPBF, also had a significant decrease in absorption at 410nm under 655nm laser irradiation, producing singlet oxygen, and had a good photodynamic effect. The photodynamic performance of the mCeO2-H-ICG prepared in Comparative Examples 1 and 2 was relatively close, but significantly lower than that of Examples 1-3. In addition, it can also be used Figure 13 The photodynamic performance was compared by comparing the decrease in absorbance per unit time. The absorbance of the mCeO2-H-ICG in Example 1 decreased by about 0.5 within 270 s, and the absorbance of the mCeO2-H-ICG in Examples 2 and 3 also decreased by about 0.5 within 270 s.

[0125] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the above embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A mesoporous hollow cerium oxide multifunctional composite material, characterized in that: The invention comprises a nano-carrier and a load; the nano-carrier is a mesoporous hollow cerium oxide nanosphere, and the load is indocyanine green; the indocyanine green is loaded on the surface and inside of the mesoporous hollow cerium oxide nanosphere.

2. The mesoporous hollow cerium oxide multifunctional composite material according to claim 1, characterized in that: The diameter of the mesoporous cerium oxide nanospheres is 100-200 nm.

3. The mesoporous hollow cerium oxide multifunctional composite material according to claim 1, characterized in that: The diameter of the mesoporous hollow cerium oxide nanospheres is 100-120 nm.

4. A method for preparing the mesoporous hollow cerium oxide multifunctional composite material according to any one of claims 1 to 3, characterized in that: The steps include: S1: hydrothermally reacting a cerium source with a structure-directing agent to obtain a cerium oxide precursor; S2: calcining the cerium oxide precursor to obtain mesoporous hollow cerium oxide nanospheres; S3: Indocyanine green is loaded onto the surface and interior of mesoporous hollow cerium oxide nanospheres to obtain a mesoporous hollow cerium oxide multifunctional composite material.

5. The method for preparing the mesoporous hollow cerium oxide multifunctional composite material according to claim 4, characterized in that: In step S1, the cerium source is cerium nitrate hexahydrate, and the structure directing agent is acetic acid.

6. The method for preparing the mesoporous hollow cerium oxide multifunctional composite material according to claim 4, characterized in that: In step S1, a cerium source and a structure directing agent are added to a mixed solvent of water and ethylene glycol and mixed evenly, and then reacted at 175-185° C. for 180-220 minutes to obtain a cerium oxide precursor; The mass ratio of the cerium source to the structure directing agent is 1:1-1.5:1, and the volume ratio of water to ethylene glycol is 0.02-0.

07.

7. The method for preparing the mesoporous hollow cerium oxide multifunctional composite material according to claim 4, characterized in that: In step S2, the cerium oxide precursor is calcined in an air atmosphere to obtain mesoporous hollow cerium oxide nanospheres; the calcination temperature is 450-550° C., and the calcination time is 3-5 hours.

8. The method for preparing the mesoporous hollow cerium oxide multifunctional composite material according to claim 4, characterized in that: In step S3, the mesoporous hollow cerium oxide nanospheres and indocyanine green are dispersed in water, stirred in the dark for 24-36 hours, and washed and freeze-dried to obtain a mesoporous hollow cerium oxide multifunctional composite material; The mass ratio of the mesoporous hollow cerium oxide nanospheres to indocyanine green is 3:1-5:

1.

9. The method for preparing the mesoporous hollow cerium oxide multifunctional composite material according to claim 4, characterized in that: In step S1, an aqueous solution of a cerium source and an ethylene glycol solution of a structure-directing agent are mixed, and then a hydrothermal reaction is performed; The concentration of the cerium source in the aqueous solution is 0.67-1 mg / mL, and the concentration of the structure-directing agent in the ethylene glycol solution is 0.022-0.033 mg / mL.

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