A hydrophilic cerium nanoparticle, a dispersion thereof, and a preparation method and application thereof

Abstract

The present application provides a kind of hydrophilic cerium oxide nanoparticles and its dispersion liquid.Hydrophilic cerium oxide nanoparticles include cerium oxide nanoparticles core and the hydrophilic polymer compound coated on its surface, and cerium element in cerium oxide nanoparticles exists in two valence states of Ce 3+ And Ce 4+ . The hydrophilic polymer compound is coated on the surface of cerium oxide nanoparticles, which can improve its dispersibility and stability in aqueous system.The present application also provides a preparation method of hydrophilic cerium oxide nanoparticles, which can be carried out in aqueous system under normal temperature and pressure, and has mild process and simple operation.The obtained hydrophilic cerium oxide nanoparticles have good free radical scavenging capacity, dispersion stability and oxidative stress regulation activity, can form stable dispersion liquid in water system, and show good antioxidant and tissue protection effect in cell and animal oxidative stress model.The present application also provides the application of hydrophilic cerium oxide nanoparticles or its dispersion liquid in antioxidant, oxidative stress regulation and related preparations.

Description

Technical Field

[0001] This invention relates to the field of nanomaterial preparation technology, and in particular to a green preparation method for hydrophilic cerium nanoparticles (CeNPs) suitable for the food, cosmetics or pharmaceutical fields, and the aqueous dispersion formed therefrom. Background Technology

[0002] Reactive oxygen species (ROS) are a class of reactive molecules produced during redox metabolism in the body, playing important roles in cell signaling regulation, inflammatory responses, and tissue damage. Excessive ROS levels in the body can easily trigger oxidative stress, which is closely related to the development of various diseases such as chronic inflammation, skin aging, neurodegenerative diseases, and tumors. Therefore, scavenging excess ROS and maintaining redox homeostasis has become an important research direction in the fields of anti-aging and the prevention and treatment of related diseases. Traditional small-molecule antioxidants, such as vitamin C and glutathione, while possessing certain free radical scavenging effects, generally suffer from problems such as easy oxidative inactivation, poor stability, and low bioavailability, thus limiting their practical applications.

[0003] In recent years, nanomaterials have been widely used in fields such as anti-oxidation, anti-inflammation, targeted therapy, and imaging due to their strong structural designability, ease of surface modification, and diverse functions. Among them, cerium-based nanomaterials are a class of inorganic nanomaterials with broad research value, showing good application potential in scavenging reactive oxygen species and regulating the microenvironment under oxidative stress. Studies have shown that cerium-based nanomaterials possess various enzyme-like activities, such as superoxide dismutase (SOD) and catalase (CAT), enabling sustained free radical scavenging and making them one of the important representatives of "nanozymes".

[0004] However, most current methods for synthesizing cerium nanoparticles use industrial-grade raw materials, which have significant shortcomings in terms of structural controllability, biocompatibility, and dispersion stability. They are prone to aggregation in aqueous phases, affecting the uniform dispersion of particles and the effective exposed surface area, thus leading to a decrease in enzyme-like activity. Furthermore, the poor stability of the dispersion system limits their further application in physiological environments. In addition, reports indicate that the synthesis of most nanomaterials requires harsh conditions such as high-temperature calcination, strong acids, or organic solvents, making the process complex. The resulting products often fail to meet the purity, safety, and application suitability requirements of food, cosmetics, or pharmaceutical fields.

[0005] In product applications requiring direct contact with the skin or digestive system, particularly in the development of cosmetics, sunscreens, or oral formulations, the biocompatibility, safety, and green preparation process of materials are crucial considerations. Most existing inorganic nanomaterials still face limitations in terms of raw material sourcing, preparation processes, and product safety, failing to fully meet the requirements of cosmetics, food, and pharmaceutical industries regarding raw material quality, safety evaluation, and application standards. Therefore, there is an urgent need to develop a hydrophilic cerium nanomaterial that can be prepared in a green aqueous system at room temperature and pressure, without high-temperature calcination and avoiding organic solvent contamination. This material should possess good water dispersibility, storage stability, and controllable particle size, and preferably be prepared using raw materials that meet food-grade, cosmetic-grade, or pharmaceutical standards, thereby expanding its application potential in areas such as free radical scavenging, skin protection, and functional formulations. Summary of the Invention

[0006] In view of the above-mentioned technical problems existing in the prior art, the primary objective of the present invention is to provide a hydrophilic cerium nanoparticle or an aqueous dispersion thereof. The hydrophilic cerium nanoparticle has good dispersibility, high storage stability and biocompatibility, and possesses the ability to continuously scavenge reactive oxygen species.

[0007] Another objective of this invention is to provide a green method for preparing the aforementioned hydrophilic cerium nanoparticles. This method can be carried out under mild conditions, without the need for high-temperature and high-pressure treatment or the use of toxic or harmful reagents. It features simple process, environmental friendliness, and suitability for large-scale preparation, and can meet the application needs of cosmetics, food, and pharmaceutical fields.

[0008] Another object of the present invention is to provide applications of the hydrophilic cerium nanoparticles or their aqueous dispersions. The hydrophilic cerium nanoparticles or their aqueous dispersions can be applied in fields such as free radical scavenging, skin protection, inflammation relief, anti-aging, skin whitening, wound repair, and oxidative stress regulation.

[0009] The above-mentioned objective of this invention is achieved through the following technical solution:

[0010] In a first aspect, the present invention provides hydrophilic cerium nanoparticles, comprising a cerium oxide nanoparticle core and a hydrophilic polymer compound coating the surface of the cerium oxide nanoparticles; wherein the cerium element in the cerium oxide nanoparticles includes Ce. 3+ and Ce 4+ Two valence states; the hydrophilic polymer compound binds to the cerium oxide nanoparticles through surface coating or adsorption to improve its dispersibility and storage stability in aqueous dispersions.

[0011] The hydrophilic cerium nanoparticles of this invention are nanoscale particles, and their morphology can be spherical, near-spherical, or cubic. By adjusting the type of hydrophilic polymer compound and the preparation conditions, the particle size and morphology of the obtained hydrophilic cerium nanoparticles can be controlled, and the particle size is 5-600 nm.

[0012] The hydrophilic cerium nanoparticles of this invention can form a stable dispersion in pure water or a hydrophilic system, exhibiting good dispersibility, redispersibility, and storage stability. Therefore, this invention also provides a cerium nanoparticle dispersion, wherein the dispersion is a dispersion system formed by dispersing the hydrophilic cerium nanoparticles of this invention in water or a hydrophilic solvent, and the concentration of the hydrophilic cerium nanoparticles is 0.01–2 mg / mL. The dispersion shows no significant aggregation after prolonged standing at room temperature.

[0013] These hydrophilic cerium nanoparticles possess a multivalent structure, in which cerium is denoted by Ce. 3+ and Ce 4+ The coexistence of two oxidation states gives it a catalytic cycling ability similar to that of natural enzymes; meanwhile, Ce 3+ and Ce 4+ The coexistence of these components is beneficial for endowing cerium nanoparticles with good antioxidant activity. Furthermore, the hydrophilic cerium nanoparticles of this invention are coated with a hydrophilic polymer compound. This hydrophilic polymer compound can act on the surface of the cerium nanoparticles through adsorption, electrostatic interaction, hydrogen bonding, coordination, or combinations thereof, forming a stable hydrophilic coating layer or hydration layer on the particle surface. This structural feature effectively inhibits the aggregation of cerium nanoparticles during preparation, dispersion, and storage, reducing instability caused by interparticle attraction, thereby improving its dispersibility, dispersion stability, and storage stability in aqueous systems. This makes it less prone to significant precipitation in conventional aqueous systems and better meets the requirements for dispersion performance and system stability in daily use or product development. On the other hand, the hydrophilic coating layer also helps improve the effective contact and interaction efficiency of cerium nanoparticles in oxidative stress environments, thus helping to maintain or improve their free radical scavenging ability.

[0014] The hydrophilic polymer compound described in this invention is a naturally derived polymer or a hydrophilic polymer material with good biocompatibility, which can be used as a coating agent, stabilizer, or dispersant on the surface of the cerium nanoparticles. The hydrophilic polymer compound may be selected from one or more of polysaccharides, aminopolysaccharides, polyamino acids, cellulose polymers, and their derivatives, including but not limited to pectin, chitosan, sodium alginate, polyglutamic acid, hyaluronic acid, maltodextrin, dextran, carboxymethyl cellulose, and hydroxypropyl methyl cellulose.

[0015] In a second aspect, the present invention provides a method for preparing the hydrophilic cerium nanoparticles described in the first aspect, comprising the following steps:

[0016] 1) Add a hydrophilic polymer to a cerium solution with a cerium ion concentration of 0.5-3.0 mmol / 100 mL, control the mass ratio of cerium ions to hydrophilic polymer in the solution to be 5-30:1, stir to fully dissolve or uniformly disperse it to obtain a mixed solution;

[0017] 2) Add a regulator to the mixed liquid obtained in step 1) to control the molar ratio of cerium ions to regulator to be 5-20:1, and continue stirring to make the reaction system more homogeneous and obtain a multivalent cerium solution;

[0018] 3) Add an alkaline solution to the multivalent cerium solution obtained in step 2), and control the molar ratio of the alkali to the cerium ions in the alkaline solution to be 2-8:1, to initiate the hydrolysis, polymerization, nucleation and growth reactions of cerium species, and gradually form hydrophilic nano-cerium particles;

[0019] 4) After the reaction in step 3) is completed, continue stirring for 3-24 hours to further stabilize the resulting particle structure;

[0020] 5) After the reaction is complete, the resulting system is separated and purified to obtain the hydrophilic cerium nanoparticles or their aqueous dispersion. The separation and purification process includes one or more of centrifugation, washing, redispersion, and drying.

[0021] In the preferred preparation method of the present invention, 1) the concentration of cerium ions in the cerium solution is 0.8-2 mmol / 100 mL.

[0022] In the preferred preparation method of the present invention, 1) the mass ratio of cerium ions to hydrophilic polymer materials in the solution is 8-20:1.

[0023] In a preferred preparation method of the present invention, 1) the cerium solution contains a soluble cerium salt, which is one or more of cerium nitrate hexahydrate, cerium ammonium nitrate, cerium chloride, or cerium acetate. More preferably, the soluble cerium salt is cerium nitrate hexahydrate, cerium ammonium nitrate, or cerium chloride.

[0024] In the preparation method of the present invention, 1) the hydrophilic polymer compound is a naturally sourced polymer or a hydrophilic polymer material with good biocompatibility, which may be selected from one or more of polysaccharides, aminopolysaccharides, polyamino acids, cellulose polymers and their derivatives, including but not limited to pectin, chitosan, sodium alginate, polyglutamic acid, hyaluronic acid, maltodextrin, dextran, carboxymethyl cellulose and hydroxypropyl methyl cellulose; in a further preferred embodiment, the hydrophilic polymer material is one or more of sodium alginate, pectin, maltodextrin or hyaluronic acid.

[0025] In the preparation method of this invention, 2) the regulator is a reducing agent, which can be selected from one or more of the following: naturally derived small molecules, biocompatible small molecules, or other molecules with strong reducing properties, including but not limited to ascorbic acid, glutathione, L-cysteine, N-acetylcysteine, α-lipoic acid, dihydrolipoic acid, polyphenolic small molecules, reducing sugar small molecules and their derivatives. The regulator is used to regulate the reaction rate, nucleation and growth process, and is beneficial for controlling the surface valence distribution, particle size, morphology and dispersion stability of the obtained cerium nanoparticles. After the regulator is added, the reaction process can be monitored by combining solution color changes, reaction time or product characterization results. Preferably, the regulator is one or more of ascorbic acid, glutathione, or α-lipoic acid.

[0026] In the preparation method of this invention, the alkaline solution in step 3) contains an inorganic or organic base that can promote the hydrolysis, polymerization, nucleation, and growth of cerium species. The base contained in the alkaline solution includes, but is not limited to, one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, trisodium phosphate, disodium hydrogen phosphate, ammonia, and tris(hydroxymethyl)aminomethane. Preferably, the alkaline solution is one or more of sodium hydroxide, sodium carbonate, sodium bicarbonate, potassium hydroxide, or tris(hydroxymethyl)aminomethane. More preferably, the alkaline solution is a solution of sodium hydroxide, sodium carbonate, and potassium hydroxide. Preferably, the alkaline solution is slowly added to the reaction system under continuous stirring.

[0027] In the preparation method of this invention, 3) after adding the alkaline solution, the pH of the reaction system is adjusted to 8-12. Preferably, the pH of the reaction system is adjusted to 10-12.

[0028] In a preferred embodiment of the present invention, the method for preparing the hydrophilic cerium nanoparticles comprises the following steps:

[0029] (1) Under normal temperature and pressure conditions, cerium nitrate hexahydrate is dissolved in deionized water to form a cerium precursor solution; the concentration of cerium ions is controlled within the range of 1.0-2.0 mmol / 100 mL of reaction system.

[0030] (2) Add a hydrophilic polymer compound to the cerium precursor solution obtained in (1) above, and stir thoroughly to dissolve or disperse it evenly to obtain a mixture; the hydrophilic polymer compound is preferably sodium alginate, or may be selected from one or more of pectin, chitosan, polyglutamic acid, hyaluronic acid, maltodextrin, etc.; the mass ratio of cerium ions to hydrophilic polymer compound is 5-30:1, preferably 8-20:1.

[0031] (3) Add a regulator to the mixture obtained in (2) above and continue stirring to make the reaction system more uniform; the regulator is preferably ascorbic acid, or it can be selected from one or more of the reducing regulatory molecules such as glutathione, cysteine, acetylcysteine, and lipoic acid; the molar ratio of cerium ions to regulator is 5-20:1, preferably 8-15:1.

[0032] (4) Under continuous stirring, an alkaline solution is slowly added dropwise to the reaction solution obtained in (3) above to adjust the pH of the reaction system to 8-12, preferably 10-12, thereby initiating the hydrolysis, polymerization, nucleation and growth of cerium species, and gradually generating hydrophilic nano-cerium particles; the alkaline solution is preferably a sodium hydroxide solution, or may be selected from one or more of potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, trisodium phosphate, disodium hydrogen phosphate, ammonia, and tris(hydroxymethyl)aminomethane; the alkaline solution is preferably added slowly under continuous stirring to avoid excessive local alkaline concentration causing particle aggregation.

[0033] (5) After the above (4) reaction is completed, continue stirring for 6-24 hours, preferably 10-18 hours, to promote further stabilization of the particle structure.

[0034] (6) After the reaction is completed, the resulting system is separated and purified to obtain hydrophilic cerium nanoparticles or their aqueous dispersion; the separation and purification process includes one or more of centrifugation, washing, redispersion, and drying. The drying method can be selected from freeze drying, spray drying, vacuum drying, or spray freeze drying. Preferably, freeze drying is used for laboratory preparation; more preferably, spray drying is used for large-scale production.

[0035] Thirdly, the present invention provides the application of the hydrophilic cerium nanoparticles or dispersion thereof described in the first aspect, or the hydrophilic cerium nanoparticles or dispersion thereof prepared by the method described in the second aspect, in the preparation of functional preparations with antioxidant, oxidative stress regulation, anti-inflammatory, anti-aging, and tissue protection properties.

[0036] In the applications described in this invention, the hydrophilic cerium nanoparticles or their dispersion can be used to prepare compositions, carrier systems, or formulations with functions such as antioxidation, anti-inflammation, soothing, barrier protection, tissue repair promotion, and oxidative stress regulation. The compositions, carrier systems, or formulations can be cosmetics, food additives, functional foods, medical antioxidants, medical excipients, topical preparations, or other related products.

[0037] In the applications described in this invention, the hydrophilic cerium nanoparticles or their dispersions can be used to remove reactive oxygen species from the skin, cells, tissues, or in vivo environment. These reactive oxygen species include, but are not limited to, superoxide anions, hydrogen peroxide, hydroxyl radicals, and other oxidizing reactive molecules, thereby reducing oxidative damage and maintaining redox homeostasis.

[0038] In the applications described in this invention, the hydrophilic cerium nanoparticles or their dispersion can be used to alleviate oxidative stress caused by ultraviolet radiation, environmental pollutants, irritating chemicals, inflammatory reactions, or other external factors, to stabilize the local microenvironment, reduce the level of oxidative damage, and promote the recovery of cell, tissue, or skin condition.

[0039] In the applications described in this invention, the hydrophilic cerium nanoparticles or their dispersion can be used to regulate skin barrier-related functions, including improving skin's antioxidant capacity, improving skin barrier status, maintaining skin hydration, reducing sensitivity and irritation, improving skin tolerance, and promoting skin homeostasis.

[0040] In the applications described in this invention, the hydrophilic cerium nanoparticles or their dispersion can be used for anti-inflammatory, anti-aging, skin regeneration promotion, wound repair promotion, tissue repair promotion, reduction of oxidative damage-related degeneration, reduction of chronic inflammation-related damage, and improvement of oxidative stress-related physiological imbalance.

[0041] In the applications described in this invention, the hydrophilic cerium nanoparticles or their dispersion can also be used to enhance the antioxidant defense capacity of cells, promote the scavenging of intracellular reactive oxygen species, maintain the redox balance of cells, and reduce mitochondrial functional damage, cell damage, or tissue damage caused by oxidative stress.

[0042] In the applications described in this invention, the hydrophilic cerium nanoparticles or their dispersions can be used to prepare daily chemical preparations, medical preparations, or functional supplements with antioxidant, anti-inflammatory, soothing, barrier protection, tissue repair promotion, or anti-aging functions. The daily chemical preparations include, but are not limited to, serums, sprays, lotions, creams, gels, ointments, sunscreens, masks, and personal care products; the food additives or functional foods include, but are not limited to, beverage additives, solid beverages, capsules, tablets, powders, or other nutritional supplements; the medical antioxidant preparations include, but are not limited to, topical antioxidant preparations, wound care preparations, inflammation relief preparations, radiation damage relief preparations, eye care preparations, oral care preparations, mucosal protection preparations, postoperative repair preparations, and other preparations related to free radical scavenging or oxidative stress regulation. In some embodiments, the hydrophilic cerium nanoparticles or their dispersions can also be used to prepare adjunctive intervention preparations for oxidative damage-related diseases.

[0043] In a further preferred application of the present invention, the hydrophilic cerium nanoparticles or their dispersion exist in an aqueous dispersion system and can be further compounded with pharmaceutically acceptable excipients, cosmetically acceptable excipients, food-acceptable excipients, or other functional components to form a formulation system suitable for different application scenarios.

[0044] The hydrophilic cerium nanoparticles described in this invention exhibit good dispersibility and stability, and possess enzyme-like activity related to reactive oxygen species scavenging. The cerium element in these hydrophilic cerium nanoparticles exists in both trivalent and tetravalent valence states, and the coating layer formed by the hydrophilic polymer compound helps maintain the dispersion of the particles in the aqueous system and facilitates their antioxidant and oxidative stress regulation effects.

[0045] The hydrophilic cerium nanoparticles described in this invention can form a stable dispersion in an aqueous system. In some embodiments, the hydrophilic cerium nanoparticles can form a stable dispersion in the concentration range of 0.01-2 mg / mL; at a concentration of 1 mg / mL, no obvious precipitation occurs after prolonged standing at room temperature, exhibiting good dispersion stability and storage stability.

[0046] In some embodiments, the hydrophilic cerium nanoparticles of the present invention exhibit significant free radical scavenging ability and antioxidant activity, and show superoxide dismutase (SOD)-like activity and catalase (CAT)-like activity, indicating that they can be used for applications related to reactive oxygen species scavenging and oxidative stress regulation.

[0047] In some embodiments, the hydrophilic cerium nanoparticles of the present invention can be used to prepare antioxidants, anti-inflammatory agents, anti-aging agents, skin protectants, wound repair agents, functional skin care agents, functional food additives, or medical antioxidants.

[0048] Compared with the prior art, the present invention has the following beneficial effects:

[0049] 1. The hydrophilic cerium nanoparticles of this invention are formed using soluble cerium salts as precursors in the presence of hydrophilic polymers through an alkaline solution. The resulting hydrophilic cerium nanoparticles are nanoscale particles with a controllable particle size of 5-600 nm, and can be spherical, near-spherical, or cubic in shape, exhibiting good dispersibility and storage stability. These hydrophilic cerium nanoparticles can form a stable dispersion in an aqueous system, showing no significant aggregation after 30 days at room temperature at a concentration of 1 mg / mL, making them suitable for the development of liquid formulations, functional materials, and related product systems.

[0050] 2. The preparation process of the hydrophilic cerium nanoparticles described in this invention does not require high temperature, high pressure, or calcination treatment, nor does it require the use of organic solvents. It can be completed in an aqueous system under normal temperature and pressure conditions. The process conditions are mild, the operation is simple, and it has good green preparation characteristics and scale-up potential. This method is suitable for preparing hydrophilic cerium nanoparticles with high dispersibility and good biocompatibility, which is beneficial for their application in cosmetics, food additives, functional foods, and medical antioxidants.

[0051] 3. The cerium nanoparticles of the present invention are coated with a hydrophilic polymer compound, such as one or more of sodium alginate, pectin, chitosan, polyglutamic acid, hyaluronic acid, and maltodextrin. The hydrophilic polymer compound can form a stable coating layer on the surface of the cerium nanoparticles, which helps to inhibit particle aggregation during preparation, storage, and application, and improves their dispersibility, stability, and application suitability in aqueous systems, physiological environments, or complex formulation systems.

[0052] 4. In the cerium nanoparticles of this invention, cerium exists in both trivalent and tetravalent valence states. Combined with a hydrophilic polymer coating, this facilitates the particles' enzyme-like activity related to reactive oxygen species (ROS) scavenging. The hydrophilic cerium nanoparticles can scavenge reactive oxygen species such as superoxide anions, hydrogen peroxide, and hydroxyl radicals, and exhibit superoxide dismutase-like and catalase-like activities. This helps to reduce oxidative stress damage, alleviate inflammatory responses, maintain the homeostasis of the skin or tissue microenvironment, and has potential applications in antioxidation, anti-inflammation, anti-aging, barrier protection, and tissue repair.

[0053] 5. Compared to the problems of traditional cerium nanomaterials being prone to aggregation and having poor dispersion stability, the hydrophilic cerium nanoparticles of this invention can be obtained as solid products after freeze-drying, vacuum drying, spray drying, or spray freeze-drying, and can be redispersed in water or hydrophilic systems when needed, facilitating product storage, transportation, and subsequent processing. Freeze-drying is preferred for laboratory preparation, while spray drying is preferred for large-scale production.

[0054] 6. The preparation process provided by this invention is simple, with a clear reaction path, a wide range of raw material sources, and low preparation cost, making it suitable for laboratory preparation and large-scale production. This method not only helps improve the quality stability, dispersibility, and application adaptability of hydrophilic cerium nanoparticles, but also provides a new technical approach for the green manufacturing, functional development, and industrial application of nano-antioxidant materials. Attached Figure Description

[0055] Figure 1 This is a transmission electron microscope image of the hydrophilic cerium nanoparticles prepared in Example 1.

[0056] Figure 2 This demonstrates the particle size distribution of the hydrophilic cerium nanoparticles prepared in Example 1 as detected by dynamic light scattering.

[0057] Figure 3 This demonstrates the stability of the hydrophilic cerium nanoparticles prepared in Example 1.

[0058] Figure 4 This is a transmission electron microscope image of the hydrophilic cerium nanoparticles prepared in Example 2.

[0059] Figure 5 This demonstrates the particle size distribution and stability (no significant change in particle size) of the hydrophilic cerium nanoparticles prepared in Example 2 as measured by dynamic light scattering.

[0060] Figure 6 This is a transmission electron microscope image of the unprotected cerium nanoparticles prepared in Comparative Example 1.

[0061] Figure 7 This demonstrates the particle size distribution of the nano-cerium particles prepared in Comparative Example 1 as detected by dynamic light scattering.

[0062] Figure 8 This demonstrates the SOD-like activity of solutions with different concentrations in Experiment Example 4.

[0063] Figure 9 This demonstrates the CAT-like activity of Experiment 4 in solutions of different concentrations.

[0064] Figure 10 This reflects the results of using the DCFH-DA probe in Experiment 5 to detect the ROS fluorescence intensity of normal cells, cells with inflammation combined with oxidative stress, and cells with inflammation combined with oxidative stress treated with cerium nanoparticles in Examples 1 and 2.

[0065] Figure 11This reflects the quantitative analysis results of the ROS fluorescence intensity of normal cells, cells with inflammation combined with oxidative stress, and cells with inflammation combined with oxidative stress treated with cerium nanoparticles in Examples 1 and 2, as detected by the DCFH-DA probe in Experiment Example 5.

[0066] Figure 12 This demonstrates the results of reactive oxygen species scavenging in Experiment 5, which was achieved by using flow cytometry to detect the scavenging of normal cells, cells with inflammation combined with oxidative stress, and cells with inflammation combined with oxidative stress treated with cerium nanoparticles as described in Examples 1 and 2.

[0067] Figure 13 This demonstrates the quantitative results of reactive oxygen species scavenging in Experiment 5, which were obtained by flow cytometry from normal cells, cells with inflammation combined with oxidative stress, and cells with inflammation combined with oxidative stress treated with cerium nanoparticles in Examples 1 and 2.

[0068] Figure 14 These are pathological slices of liver tissue after different drugs were administered to the inflammatory injury model in Experiment Example 6. Detailed Implementation

[0069] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to specific embodiments and accompanying drawings. It should be understood that the following embodiments are for illustrative purposes only and are not intended to limit the scope of protection of this invention. All equivalent substitutions, improvements, and variations made within the spirit and principles of this invention should be included within the scope of protection of this invention. Other embodiments made by those skilled in the art based on the disclosed embodiments of this invention without departing from the concept of this invention are all within the scope of protection of this invention.

[0070] In this invention, the surface of the hydrophilic cerium nanoparticles is coated with a hydrophilic polymeric protective agent. The hydrophilic polymeric protective agent can be a naturally derived polymer or a hydrophilic polymer material with good biocompatibility, such as one or more of sodium alginate, pectin, chitosan, hyaluronic acid, polyglutamic acid, maltodextrin, and their derivatives. This coating layer helps stabilize the dispersion of cerium oxide nanoparticles in an aqueous system, inhibiting particle aggregation and sedimentation, and also helps maintain their antioxidant activity and oxidative stress regulation-related activities.

[0071] In some embodiments, the hydrophilic cerium oxide nanoparticles are nanoscale particles with a controllable particle size of 5-600 nm, and their morphology can be spherical, near-spherical, or cubic. The hydrophilic cerium oxide nanoparticles can form a stable dispersion in an aqueous system. At a concentration of 1 mg / mL, the dispersion showed no significant aggregation after being left at room temperature for 30 days, exhibiting good dispersion and storage stability.

[0072] This invention also provides a green aqueous phase preparation method for the aforementioned hydrophilic cerium oxide nanoparticles. The method can be carried out under ambient temperature and pressure conditions, using a soluble cerium salt precursor as the cerium source, and forming hydrophilic cerium oxide nanoparticles under the combined action of a hydrophilic polymeric protective agent, a regulator, and an alkaline solution. The soluble cerium salt precursor can be one or more of cerium nitrate hexahydrate, cerium ammonium nitrate, cerium chloride, cerium acetate, or other soluble cerium salts. The regulator can be one or more of ascorbic acid, glutathione, cysteine, acetylcysteine, lipoic acid, or other reducing regulatory molecules. The alkaline solution can be one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, trisodium phosphate, disodium hydrogen phosphate, ammonia, and tris(hydroxymethyl)aminomethane.

[0073] The hydrophilic cerium oxide nanoparticles described in this invention can be used for antioxidant, anti-inflammatory, anti-aging, skin repair promotion, wound healing promotion, barrier protection and oxidative stress regulation and other related applications. They can also be used to prepare skin care preparations, health supplement preparations, medical excipients, topical preparations, functional food additives and other related products.

[0074] To further illustrate the present invention, the following examples provide a detailed description of the hydrophilic cerium oxide nanoparticles, their preparation method, and applications. Unless otherwise specified, the reagents and materials used in the following examples are commercially available.

[0075] Example 1. Preparation of hydrophilic cerium oxide nanoparticles (CeNPs@Alg) coated with sodium alginate

[0076] Cerium nitrate hexahydrate was dissolved in deionized water under normal temperature and pressure conditions to form a cerium precursor solution. The concentration of cerium ions was 1.5 mmol / 100 mL.

[0077] Sodium alginate was added to the above cerium precursor solution and stirred until fully dissolved or uniformly dispersed to obtain a mixture. The mass ratio of cerium ions to sodium alginate was 8:1. In this embodiment, sodium alginate is used as a hydrophilic polymeric protective agent to regulate the particle formation process and improve the dispersibility and stability of the obtained cerium oxide nanoparticles in an aqueous system.

[0078] Subsequently, a regulator was added to the above mixture, and stirring continued to further homogenize the reaction system. The molar ratio of cerium ions to ascorbic acid was 10:1. In this embodiment, ascorbic acid is used as a regulator to adjust the reaction rate, nucleation and growth process, and is beneficial for controlling the surface valence state distribution, particle size and morphology of the obtained cerium oxide nanoparticles.

[0079] Under continuous stirring, an alkaline solution is slowly added dropwise to the above reaction solution to adjust the pH of the reaction system to 12, so as to promote the hydrolysis, polymerization, nucleation and growth of cerium species, and gradually form hydrophilic cerium oxide nanoparticles coated with sodium alginate. The alkaline solution is preferably a sodium hydroxide solution.

[0080] After the reaction is complete, stirring is continued for 12 hours to further stabilize the particle structure. The reaction system is then centrifuged and washed 2-3 times with deionized water to remove unreacted substances, small molecule impurities, and free protective agents. The obtained product can be directly retained as an aqueous dispersion, or further processed by freeze-drying, vacuum drying, spray drying, or spray-freeze drying to obtain a powdered product. Freeze-drying is preferred for laboratory preparation, while spray drying is preferred for large-scale production.

[0081] The resulting sodium alginate-coated hydrophilic cerium oxide nanoparticles exhibit good water dispersibility and storage stability, and can be used for subsequent characterization and functional evaluation.

[0082] Figure 1 This is a transmission electron microscope image of a CeNPs@Alg aqueous dispersion. (See image.) Figure 1 As shown, the cerium nanoparticles (CeNPs) prepared in this embodiment are cubic or spherical, uniform in size and basically evenly distributed, with an average particle size of approximately 5 nm. The hydrated particle size is approximately 30 nm (see [reference]). Figure 2 The test results showed that the particle size did not change significantly after 30 days of standing (see [reference]). Figure 3 The test results showed that the colloid had good stability.

[0083] Example 2 Preparation of pectin-coated hydrophilic cerium oxide nanoparticles (CeNPs@Pec)

[0084] The preparation method of this embodiment is basically the same as that of Example 1. The difference is that the hydrophilic polymeric protective agent used in this embodiment is pectin, the cerium salt precursor used is cerium ammonium nitrate, and the alkaline solution used is sodium bicarbonate solution.

[0085] Under normal temperature and pressure conditions, cerium ammonium nitrate was dissolved in ultrapure water to prepare a cerium precursor solution, wherein the cerium ion concentration was 1.2 mmol / 100 mL.

[0086] Pectin was added to the above cerium precursor solution and stirred until fully dissolved or uniformly dispersed to obtain a mixture. The mass ratio of cerium ions to pectin was 8:1. In this embodiment, pectin is used as a hydrophilic polymeric protective agent to regulate the particle formation process and improve the dispersibility and stability of the obtained cerium oxide nanoparticles in an aqueous system.

[0087] Subsequently, a regulator was added to the above mixture, and stirring continued to further homogenize the reaction system. The regulator was ascorbic acid, and the molar ratio of cerium ions to ascorbic acid was 8:1. In this embodiment, ascorbic acid is used as a regulator to adjust the reaction rate, nucleation and growth process, and is beneficial for controlling the surface valence state distribution, particle size and morphology of the obtained cerium oxide nanoparticles.

[0088] Under continuous stirring, an alkaline solution is slowly added dropwise to the above reaction solution to adjust the pH of the reaction system to 8-9, so as to promote the hydrolysis, polymerization, nucleation and growth of cerium species, and gradually form pectin-coated hydrophilic cerium oxide nanoparticles. The alkaline solution is preferably a sodium bicarbonate solution.

[0089] After the reaction is complete, stirring is continued for 6 hours to further stabilize the particle structure. The reaction system is then centrifuged and washed 2-3 times with deionized water to remove unreacted substances, small molecule impurities, and free protective agents. The obtained product can be directly retained as an aqueous dispersion, or further processed by freeze-drying, vacuum drying, spray drying, or spray-freeze drying to obtain a powdered product. Freeze-drying is preferred for laboratory preparation, while spray drying is preferred for large-scale production.

[0090] Compared with Example 1, this example uses pectin as a protective agent and employs a relatively low to medium range of protective and regulating agent dosages to provide another type of hydrophilic coating system for investigating the effects of different types of protective agents and dosage conditions on particle size, surface potential, dispersibility, stability, and biological function.

[0091] The CeNPs@Pec prepared in this embodiment were dispersed in an aqueous solution, and their microstructure was observed. Figure 4 This is a transmission electron microscope image of the aqueous dispersion. (Example:) Figure 4 As shown, the cerium nanoparticles obtained in this embodiment are spherically distributed with an average particle size of approximately 80 nm. The hydrated particle size is approximately 160 nm (see [reference]). Figure 5 The test results showed that the particle size did not change much after standing for 5 days, indicating that the colloidal stability was good.

[0092] Comparative Example 1. Preparation of Cerium Oxide Nanoparticles (CeNPs) without Protecting Agent

[0093] Under ambient temperature and pressure, cerium nitrate hexahydrate was dissolved in deionized water to form a cerium precursor solution. The concentration of cerium ions was 1.5 mmol / 100 mL. A regulator was then added to the cerium precursor solution, and stirring continued to further homogenize the reaction system. The molar ratio of cerium ions to ascorbic acid was 10:1. Under continuous stirring, an alkaline solution was slowly added dropwise to the reaction solution to adjust the pH to 12, promoting the hydrolysis, polymerization, nucleation, and growth of cerium species, gradually forming unprotected cerium oxide nanoparticles. The alkaline solution was preferably a sodium hydroxide solution. After the reaction was complete, stirring continued for 12 h. The reaction system was then centrifuged and washed 2-3 times with deionized water. The obtained product could be directly retained as an aqueous dispersion or further dried to obtain a powder product.

[0094] Because sodium alginate, pectin, or other hydrophilic polymeric protective agents were not added in this comparative example, the resulting cerium oxide nanoparticles were more prone to aggregation. Figure 6 As shown, the particle size is non-uniform, averaging approximately 150 nm. Due to aggregation, the hydrated particle size exceeds 1000 nm (see [reference]). Figure 7 The test results (as shown in the comparative example) indicate that the nano-cerium particles prepared in this study agglomerated. Under these conditions, they exhibited poor particle size uniformity, water dispersibility, resolubility, and storage stability, and can serve as an important control for evaluating the protective agent's effect.

[0095] Experimental Example 1. Transmission Electron Microscopy Characterization of Hydrophilic Cerium Oxide Nanoparticles

[0096] The samples obtained in Examples 1, 2, and Comparative Example 1 were dispersed in deionized water to prepare dispersions of suitable concentrations. These dispersions were then dropped onto a copper grid, dried, and observed using a transmission electron microscope (TEM). The morphology, particle size distribution, and aggregation state of the particles were analyzed using TEM images.

[0097] The results showed that Example 1 (see Figure 1 ) and Example 2 (see Figure 4 The obtained hydrophilic cerium oxide nanoparticles all exhibited good dispersion and relatively regular particle morphology, while Comparative Example 1 (see...) Figure 6 The unprotected sample was more prone to particle aggregation and morphological inhomogeneity. A comparison of transmission electron microscopy results from Examples 1, 2, and 1 (Comparative Example 1) demonstrates that both sodium alginate and pectin protectants are beneficial in improving the microstructure and dispersion of cerium oxide nanoparticles.

[0098] Experimental Example 2: Dynamic light scattering particle size characterization of hydrophilic cerium oxide nanoparticles

[0099] The hydrated particle size and polydispersity index of the samples prepared in Examples 1, 2, and Comparative Example 1 were determined using dynamic light scattering. After ultrasonic dispersion, each sample was placed in a dynamic light scattering instrument for testing, and its average particle size and particle size distribution characteristics were recorded.

[0100] The results showed that Example 1 (see Figure 2 ) and Example 2 (see Figure 5 The resulting hydrophilic cerium oxide nanoparticles have a smaller average particle size and a relatively concentrated particle size distribution, while Comparative Example 1 (see Figure 7 The untreated sample had a larger particle size. These results indicate that adding sodium alginate or pectin as a hydrophilic polymeric protective agent improves the controllability of cerium oxide nanoparticle size and enhances their dispersion in aqueous systems.

[0101] Experimental Example 3: Evaluation of the Dispersion Stability of Hydrophilic Cerium Oxide Nanoparticles

[0102] The cerium oxide nanoparticles obtained in Examples 1, 2, and Comparative Example 1 were prepared into aqueous dispersions of the same concentration, preferably 1 mg / mL, and stored at room temperature. The appearance changes of the samples were observed at preset time points, and the particle size changes and aggregation were detected to evaluate their dispersion stability and storage stability.

[0103] The results showed that the samples obtained in Examples 1 and 2 both exhibited good stable dispersion in aqueous systems. Specifically, at a concentration of 1 mg / mL, the sodium alginate-coated hydrophilic cerium oxide nanoparticles obtained in Example 1 showed no significant aggregation after 30 days at room temperature (see...). Figure 3 The pectin-coated sample obtained in Example 2 also showed good dispersion stability (see Example 2). Figure 5 In contrast, the sample in Comparative Example 1 was more prone to sedimentation, flocculation, or significant particle size increase. These results indicate that the introduction of a hydrophilic polymeric protective agent is beneficial for improving the long-term dispersion and storage stability of cerium oxide nanoparticles.

[0104] Experimental Example 4. Evaluation of the enzyme-like activity of the hydrophilic cerium oxide nanoparticles obtained in Example 1.

[0105] The superoxide dismutase (SOD)-like and catalase (CAT)-like activities of the samples obtained in Example 1 were measured using appropriate detection methods. A normal control group (corresponding to a CeNPs@Alg concentration of 0 μg / mL in the figure) and multiple treatment groups from Example 1 (corresponding to CeNPs@Alg concentrations of 40 μg / mL, 80 μg / mL, 120 μg / mL, 160 μg / mL, 200 μg / mL, and 1000 μg / mL in the figure, respectively) were set up to compare the changes in relevant enzyme-like activity indicators under different conditions. The SOD-like activity was tested using the nitroblue tetrazolium (NBT) colorimetric method. As the CeNPs@Alg concentration increased, the reduction effect of superoxide anion on NBT decreased, and the absorbance at 560 nm decreased (see Figure 1). Figure 8 This indicates that the CeNPs@Alg nanoparticles obtained in Example 1 exhibit SOD-like activity.

[0106] The CAT-like enzyme activity of CeNPs@Alg nanoparticles was observed using a yield method, such as... Figure 9 As shown, hydrogen peroxide treated with CeNPs@Alg nanoparticles produced obvious bubbles, indicating that the CeNPs@Alg nanoparticles obtained in Example 1 exhibit CAT-like activity and can catalyze the production of oxygen from hydrogen peroxide.

[0107] In summary, the results indicate that the sample obtained in Example 1 has an enzyme-like activity basis in terms of reactive oxygen species scavenging and oxidative stress regulation.

[0108] Experimental Example 5. The effect of hydrophilic cerium oxide nanoparticles on the scavenging of intracellular reactive oxygen species.

[0109] RAW264.7 cells were selected as a model and incubated with sodium alginate-coated hydrophilic cerium oxide nanoparticles prepared in Example 1 for 12 hours. Then, 100 μM hydrogen peroxide was added to stimulate the cells for 1 hour, forming the experimental group. Simultaneously, a no-stimulation group (normal group), a hydrogen peroxide stimulation control group (PBS), and a cerium ion control group (CeNPs@Alg and CeNPs@Pec) were set up. The intracellular reactive oxygen species (ROS) levels in each group were detected using the DCFH-DA probe.

[0110] The results are as follows Figure 10 As shown. By Figure 10 It can be seen that, compared with the normal group and the PBS group, the intracellular DCFH-DA fluorescence intensity was significantly reduced after pretreatment with CeNPs@Alg obtained in Example 1 and CeNPs@Pec obtained in Example 2, indicating that reactive oxygen species induced by inflammation and oxidative stress were effectively cleared. Figure 11Quantitative results showed that, compared with the normal group and the PBS group, the levels of reactive oxygen species (ROS) decreased significantly after treatment with the hydrophilic cerium oxide nanoparticles (CeNPs@Alg and CeNPs@Pec) obtained in Examples 1 and 2. These results indicate that the hydrophilic cerium oxide nanoparticles described in this invention can effectively reduce intracellular ROS levels and alleviate hydrogen peroxide-induced oxidative stress damage.

[0111] Meanwhile, flow cytometry analysis was further performed on the cell models of inflammation combined with oxidative stress after treatment in Examples 1 and 2. The results are as follows: Figure 12 and Figure 13 As shown, compared with the PBS group, the FITC fluorescence signal of the CeNPs@Alg group obtained in Example 1 and the CeNPs@Pec group obtained in Example 2 was significantly reduced, approaching the level of the unstimulated normal group, further demonstrating that the hydrophilic cerium oxide nanoparticles obtained in Example 1 and Example 2 have good intracellular reactive oxygen species scavenging ability.

[0112] Experimental Example 6. Evaluation of the effect of hydrophilic cerium oxide nanoparticles on alleviating oxidative stress damage in vivo.

[0113] An acute systemic oxidative stress model was induced in female BALB / c mice by intraperitoneal injection of lipopolysaccharide. After modeling, the mice were randomly divided into a model control group (PBS) and a treatment group (Example 1). In some embodiments, different dose groups can be further set up as needed, such as a low-dose group (1 mg / kg), a medium-dose group (5 mg / kg), and a high-dose group (10 mg / kg). The treatment group (Example 1) was treated with hydrophilic cerium oxide nanoparticles (CeNPs@Alg) coated with sodium alginate prepared in Example 1, and the administration route could be a single tail vein injection.

[0114] After treatment, serum and tissue samples were collected from mice to assess relevant antioxidant indicators, and histopathological observations were performed on the liver and kidneys. Histopathological changes in liver and kidney tissues were observed after HE staining. Figure 14 The results showed that, compared with the model control group (PBS), the pathological damage to liver and kidney tissues in each dose of the Example 1 treatment group was significantly reduced. The model control group (PBS) showed significant tissue edema, inflammatory infiltration, and cell damage, while the Example 1 treatment group, especially under higher doses (5 mg / kg and 10 mg / kg), showed more significant improvement in tissue structure, suggesting that the hydrophilic cerium oxide nanoparticles obtained in Example 1 have the effect of alleviating oxidative stress damage and protecting tissues in vivo.

[0115] Experimental Example 7: Evaluation of the biosafety and blood biochemical parameters of hydrophilic cerium oxide nanoparticles

[0116] A normal control group, a model control group, and a treatment group (Example 1) were established. The normal control group received no treatment; the model control group was treated with lipopolysaccharide; and the treatment group (Example 1) received lipopolysaccharide treatment plus hydrophilic cerium oxide nanoparticles coated with sodium alginate obtained in Example 1.

[0117] After processing, animal blood samples were collected, and blood biochemical indicators were tested and analyzed. These biochemical indicators included, but were not limited to, alanine aminotransferase, aspartate aminotransferase, creatinine, and blood urea nitrogen, to comprehensively evaluate the biosafety of the sample from Example 1 and its effect on alleviating liver and kidney damage. The test results are shown in Tables 1-4 below:

[0118] Table 1. Alanine aminotransferase

[0119]

[0120] Table 2. Aspartate aminotransferases

[0121]

[0122] Table 3. Creatinine content

[0123]

[0124] Table 4. Urea content

[0125]

[0126] The above test results indicate that, compared with the model control group, some blood biochemical indicators in the treatment group of Example 1 were improved, suggesting that the hydrophilic cerium oxide nanoparticles coated with sodium alginate obtained in Example 1 can alleviate lipopolysaccharide-induced liver and kidney function damage to a certain extent. Furthermore, combined with histopathological results, it is evident that the sample of Example 1 has good biocompatibility and a certain degree of in vivo protective effect.

[0127] In summary, the hydrophilic cerium oxide nanoparticles described in this invention exhibit excellent reactive oxygen species (ROS) scavenging, cytoprotective, and tissue-protective effects in cellular and animal oxidative stress models. In particular, the sodium alginate-coated hydrophilic cerium oxide nanoparticles show promising application potential in reducing intracellular ROS levels, alleviating inflammation and oxidative stress damage, improving liver and kidney-related biochemical indicators, and reducing tissue pathological damage. This suggests that they can be used as antioxidant and oxidative stress regulation materials in the development of skincare, functional formulations, and medical antioxidant systems.

Claims

1. A hydrophilic cerium nanoparticle, characterized in that: The hydrophilic cerium nanoparticles comprise a cerium oxide nanoparticle core and a hydrophilic polymer compound coating the surface of the cerium oxide nanoparticles; the cerium element in the cerium oxide nanoparticles is represented by Ce. 3+ and Ce 4+ Two valence states coexist; the hydrophilic polymer compound is coated on the surface of the cerium oxide nanoparticles to improve their dispersibility and stability in the aqueous system.

2. The hydrophilic cerium nanoparticles as described in claim 1, characterized in that: The hydrophilic cerium nanoparticles are spherical, near-spherical, or cubic in shape, with a particle size of 5-600 nm; preferably, the particle size is 10-300 nm.

3. The hydrophilic cerium nanoparticles as described in claim 1, characterized in that: The hydrophilic polymer compound is selected from any one or a mixture of two or more of the following: pectin, chitosan, sodium alginate, polyglutamic acid, hyaluronic acid, maltodextrin, dextran, carboxymethyl cellulose, and hydroxypropyl methyl cellulose.

4. A dispersion of cerium nanoparticles, characterized in that: The dispersion is a dispersion of hydrophilic cerium nanoparticles as described in any one of claims 1-3 in water or a hydrophilic solvent; the concentration of the hydrophilic cerium nanoparticles is 0.01-2 mg / mL; preferably 0.5-1.5 mg / mL; more preferably 1 mg / mL.

5. A method for preparing hydrophilic cerium nanoparticles according to any one of claims 1-3, characterized in that, Includes the following steps: 1) Add a hydrophilic polymer to a cerium solution with a cerium ion concentration of 0.5-3.0 mmol / 100 mL, and control the mass ratio of cerium ions to hydrophilic polymer in the solution to be 2-30:

1. Stir to dissolve or disperse evenly to obtain a mixed solution. 2) Add a regulator to the mixture obtained in 1) to control the molar ratio of cerium ions to regulator in the mixture to be 3-20:1, and continue stirring to make the reaction system more homogeneous; 3) Add alkali to the reaction solution obtained in 2) and adjust the pH of the solution to 8-12, preferably to 10-12, to initiate the hydrolysis, polymerization and nucleation reaction of Ce species, and obtain the hydrophilic cerium nanoparticles.

6. The method as described in claim 5, characterized in that: 1) The concentration of cerium ions in the cerium solution is 0.8-2.0 mmol / 100 mL, more preferably 1.0-1.8 mmol / 100 mL.

7. The method as described in claim 5, characterized in that: 1) The mass ratio of cerium ions to hydrophilic polymer materials is 2.5-20:

1.

8. The method as described in claim 5, characterized in that: 1) The cerium solution is an aqueous solution prepared from any one or more of cerium nitrate hexahydrate, cerium ammonium nitrate, cerium chloride trihydrate, and cerium acetate; preferably, it is an aqueous solution prepared from cerium nitrate hexahydrate, cerium ammonium nitrate, or cerium chloride trihydrate.

9. The method as described in claim 5, characterized in that: 1) The hydrophilic polymer material is selected from any one or a mixture of two or more of pectin, chitosan, sodium alginate, polyglutamic acid, hyaluronic acid, maltodextrin, dextran, carboxymethyl cellulose, and hydroxypropyl methyl cellulose; in a preferred embodiment, 1) the hydrophilic polymer material is any one of sodium alginate, pectin, chitosan, polyglutamic acid, or hyaluronic acid.

10. The method as described in claim 5, characterized in that: 2) The regulator is selected from any one or a mixture of two or more of ascorbic acid, glutathione, L-cysteine, N-acetylcysteine, α-lipoic acid, and dihydrolipoic acid; in a preferred embodiment, the regulator is ascorbic acid, glutathione, or α-lipoic acid.

11. The method as described in claim 5, characterized in that: 3) The alkali is selected from any one or a mixture of two or more of sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, trisodium phosphate, disodium hydrogen phosphate, ammonia, and tris(hydroxymethyl)aminomethane; in a preferred embodiment, the alkali in 3) is a sodium hydroxide solution, and the addition method is slow dropwise addition under continuous stirring.

12. The method as described in claim 5, characterized in that: Step 3) After adding the alkali, the molar ratio of the alkali to cerium ions is 2-8:1; preferably 3-6:

1.

13. The method as described in claim 5, characterized in that: After step 3), continue stirring and reacting for 6-24 hours; preferably 10-18 hours.

14. The method as described in claim 5, characterized in that: Step 3) After the reaction is completed, the obtained product is subjected to one or more of the following treatments: centrifugation, washing, redispersing and drying, to obtain the hydrophilic cerium nanoparticles or their dispersion.

15. The method as described in claim 14, characterized in that: The drying method is selected from freeze drying, vacuum drying, spray drying or spray freeze drying; preferably, freeze drying is used for laboratory preparation and spray drying is used for large-scale production.

16. The hydrophilic cerium nanoparticles according to any one of claims 1-3, the dispersion according to claim 4, or the hydrophilic cerium nanoparticles prepared by the method according to any one of claims 5-15, are used in anti-oxidation or oxidative stress regulation, or in the preparation of anti-inflammatory, anti-aging, tissue protection, skin barrier protection, or wound repair promotion products.

17. The application as described in claim 16, characterized in that: The hydrophilic cerium nanoparticles according to any one of claims 1-3, or the dispersion according to claim 4, or the hydrophilic cerium nanoparticles prepared by the method according to any one of claims 5-15, are prepared into a bioactive carrier system; the bioactive carrier system is any one of cosmetics, food additives, functional foods, medical antioxidants, topical preparations, or medical excipients.

18. The application as described in claim 17, characterized in that: The cosmetics include serums, sprays, lotions, creams, gels, ointments, sunscreens, masks, or personal care products; the food additives or functional foods include beverage additives, solid beverages, capsules, tablets, or powders; the medical antioxidants include topical antioxidants, wound care preparations, inflammation relief preparations, radiation damage relief preparations, eye care preparations, oral care preparations, mucosal protectants, or postoperative repair preparations.

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