Green chemical method for preparing water-soluble nano metal oxide and application

Abstract

The invention belongs to the field of pharmacy and materials, and relates to a green chemical method for preparing a water-soluble nano metal oxide and application, the method comprises the following steps: firstly, forming a eutectic compound by using sugar and a complexing agent, then reacting with metal ions and alkali in an aqueous solution, and preparing the water-soluble nano metal oxide in one step by using the eutectic compound as a stabilizer. The aqueous solution of the nano metal oxide can be kept stable, is uniform and clear and does not generate aggregation and precipitation, and the synthesis process can be used for preparing various water-soluble metal oxides, has the characteristics of simple preparation process, no use of organic solvents, greenness, environmental protection and low toxicity, and is suitable for industrial mass production.

Description

Technical Field

[0001] This invention belongs to the fields of pharmacy and materials, and specifically relates to a method for preparing water-soluble nano-metal oxides. Background Technology

[0002] Nanoscale metal oxides, due to their unique optical, electrical, magnetic, and catalytic properties, show broad application prospects in energy, environment, biomedicine, and electronic devices. Particularly in the biomedical field, nanoscale metal oxides, due to their unique size effect, can exhibit antibacterial, anticancer, drug delivery, and bioimaging functions, possessing significant research value. However, in practical applications, nanoscale metal oxides suffer from poor water solubility, low biocompatibility, and high surface energy, making them prone to aggregation and leading to decreased stability, severely limiting their application in the biomedical field.

[0003] Currently, the main methods for improving the water solubility of nano-metal oxides include surface modification, copolymerization, and encapsulation. For example, modifying the surface of nanoparticles with hydrophilic groups such as hydroxyl (-OH), amino (-NH2), carboxyl (-COOH), or thiol (-SH) groups can improve their dispersibility in water. Additionally, the aggregation of nanoparticles can be inhibited by adding surfactants or dispersants. However, these methods are usually cumbersome, and the introduced organic reagents may be toxic to organisms, hindering biomedical applications. Alternatively, polymers can be used to disperse and stabilize metal oxides, but polymers (such as polyethylene glycol (PEG) and dextran) may activate the complement system or induce IgE-mediated hypersensitivity reactions, manifesting as anaphylactic shock, red man syndrome, etc. Severe allergic reactions have been reported in clinical trials of PEG-containing mRNA vaccines and drug formulations. Therefore, there is currently a lack of a universal preparation method that can simultaneously meet the requirements of controllable particle size, good water solubility, high biocompatibility, simple process, and no use of organic solvents. This greatly limits the development and application of nano-metal oxides in the biomedical field.

[0004] Metallic elements such as calcium, iron, zinc, sodium, potassium, magnesium, copper, manganese, cobalt, and vanadium play crucial roles in the human body. Nanoscale metal oxides not only retain the bioactivity of these elements but may also possess new functions due to the nanoscale effect, such as enhanced drug loading capacity, targeted delivery, and fluorescent labeling. Therefore, developing a universal method for preparing water-soluble nanoscale metal oxides applicable to various metal ions is of great significance for promoting their application in the biomedical field.

[0005] Water-soluble metal oxides that have been extensively studied include manganese oxide, zinc oxide, silver oxide, and gadolinium oxide. Among these, water-soluble zinc oxide nanoparticles are prepared by co-precipitation in an ethanol solution of KOH and zinc acetate, followed by surface modification with 3-aminopropyltriethoxysilane (APTES). However, APTES is toxic, affecting the biosafety of the material and limiting its application in the biomedical field. Water-soluble silver oxide is often prepared by co-precipitation of sodium dodecyl sulfate, sucrose esters, trisodium citrate, oleylamine, chitosan, PEG, and plant extracts in a mixture of silver nitrate and alkali. However, it is generally unstable in air and cannot be stored for long periods.

[0006] Currently, the preparation of water-soluble nano-metal oxides is complex, often involving either toxic precursors (esters or metal alkoxides) or the extensive use of organic solvents. To achieve highly transparent, uniformly dispersed, and stable aqueous solutions, it is necessary not only to control the size of nanoparticles during the nucleation reaction but also to modulate surface-modified functional groups to achieve transparent dispersion. Carbohydrate molecules, due to their abundant hydroxyl functional groups, possess excellent water solubility, biocompatibility, and stability, and have been widely used for regulating the nucleation and growth of nanoparticles. However, current methods for preparing nano-metal oxides based on carbohydrate molecules still suffer from poor water solubility, the use of organic solvents, and insufficient long-term stability. Therefore, there is an urgent need to develop a green, safe, versatile, and highly stable strategy for the synthesis of water-soluble nano-metal oxides. Summary of the Invention

[0007] To address the problems of poor water solubility, complex preparation processes, and high toxicity of nano-metal oxides, this invention proposes a green chemistry method utilizing intermolecular hydrogen bonds. This method involves forming a eutectic compound between a sugar and a coordinating agent, using this eutectic compound as a stabilizer to prepare water-soluble nano-metal oxides. Compared to traditional nano-metal oxide preparation processes, this method solves the problems of poor dispersibility of nano-metal oxides in water, the large-scale use of organic solvents, and complex preparation processes.

[0008] The technical solution of this invention is implemented as follows: This application provides a green chemical method for preparing water-soluble nano-metal oxides, the steps of which are as follows: (1) Mix sugar (proton donor) and ligand (proton acceptor) and react them to form a eutectic compound by using intermolecular hydrogen bonds; (2) Dissolve the eutectic compound, metal ion solution and alkali in water, purify after reaction, dry, and the resulting powder is water-soluble nano metal oxide.

[0009] Preferably, in step (1) above, the sugar is a monosaccharide, oligosaccharide, or polysaccharide, and the ligand is any one of ethylenediamine, citric acid, sodium citrate, acetylacetone, and EDTA; in step (2), the metal ion is Gd. 3+ Cu 2+ Ag + Zn 2+ Mn 4+ and Mg 2+ Any one of them, where the base is sodium hydroxide or potassium hydroxide.

[0010] Preferably, in step (1) above, the molar ratio of sugar to ligand, calculated as a single glucose unit, is 1:0.1-10, the reaction temperature is 50-100℃, and the reaction time is 6-24 h.

[0011] Preferably, in step (2) above, the mass of metal ions reacted with each gram of eutectic compound is 0.05-1 g, the reaction temperature is 25-240℃, and the reaction time is 2-24h.

[0012] The specific steps are as follows: (1) The sugar and the ligand are reacted at a molar ratio of 1:0.1-10 at 50-100℃ until a eutectic compound is formed. The mixture is then purified and dried to obtain the product. Then, the product is dissolved in water with metal ions and an alkali (sodium hydroxide, potassium hydroxide or ammonia). The mixture is reacted at 25-240℃ for 2-24 h. The product is purified and dried to obtain the powder, which is the water-soluble nano metal oxide. (2) When it is necessary to improve the crystallinity of nano metal oxides, the powder obtained in step (1) can be further heat-treated, purified and dried to obtain water-soluble nano metal oxides with better crystallinity.

[0013] Preferably, the above-mentioned further heat treatment is selected from any of the following: ① Heat the powder in air, nitrogen, or vacuum at 25-240℃ for 0.1-48 h; ② Dissolve the powder in water and perform a hydrothermal reaction at 110-240℃ for 1-48 hours.

[0014] Secondly, the water-soluble nano-metal oxides prepared by the above-mentioned green chemical method for preparing water-soluble nano-metal oxides.

[0015] Thirdly, the application of the aforementioned water-soluble nano-metal oxides is selected from at least one of the following applications: a. Preparation of medical image enhancement reagents; b. As a drug carrier; c. As a magnetothermal therapy product; d. Preparation of fluorescent labels; e. Preparation of antibacterial materials; f. Preparation of zinc supplements.

[0016] Preferably, the above-mentioned medical image enhancement agents include those used as magnetic resonance imaging (MRI) contrast agents or CT contrast agents.

[0017] If the metal ion is Gd 3+ or Mn 4+ The resulting nano-gadolinium oxide or nano-manganese oxide can be used as a contrast agent for nuclear magnetic resonance or CT, a drug carrier, magnetothermal therapy, etc. If the metal ion is Zn 2+ The resulting nano zinc oxide can be used as a fluorescent labeling agent, antibacterial agent, zinc supplement, etc. If the metal ion is Ag + The resulting nano-silver oxide can be used as a fluorescent labeling material, antibacterial material, etc. If the metal ion is Cu 2+ The resulting nano-copper oxide can be used as an antibacterial material or a copper supplement.

[0018] The present invention has the following beneficial effects: 1. This application is the first to use eutectic compounds, metal ions and alkali as raw materials. By adjusting the reaction temperature, time and composition of the eutectic compounds, water-soluble nano-metal oxides of different metals can be prepared in one step without complicated post-processing, without the use of organic solvents, without environmental pollution, and suitable for large-scale industrial production.

[0019] 2. The preparation method described in this application is simple, involves few steps, and is easy to operate. Various nano-metal oxides were successfully prepared. In vitro cytotoxicity experiments showed that the proliferation rate of HK-2 and HepG2 cells remained above 85% under different concentrations of Gd₂O₃NPs-220, indicating relatively low cytotoxicity. It exhibits good blood compatibility, without producing acute or long-term toxicity, making it suitable for in vivo magnetic resonance imaging (MRI). It also has the potential to be used as a contrast agent for T1 MRI. The ultra-small particle size (1.33 nm) of the nano-gadolinium oxide allows for direct glomerular filtration, significantly reducing the risk of gadolinium deposition in the brain. The ultra-small size not only improves particle stability and dispersibility, enabling uniform dispersion in aqueous media and avoiding aggregation, but also ensures stability during in vivo circulation. Furthermore, the uniform particle size distribution indicates that the hydrothermal synthesis method used in this experiment has good controllability and can prepare nanoparticles with uniform particle size. Attached Figure Description

[0020] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0021] Figure 1 The diagram shows the eutectic compound of sodium citrate and glucose.

[0022] Figure 2 Images of water-soluble gadolinium oxide nanoparticles; where A is the sunlight image, B is the fluorescence image (365 nm), and C is the fluorescence image after dialysis of the aqueous solution (365 nm).

[0023] Figure 3 Images of water-soluble nano-copper oxide; where A represents the morphology after dialysis and B represents the diluted aqueous solution state.

[0024] Figure 4 Fluorescence images (365 nm) of water-soluble silver nanoparticles after drying under different reaction conditions.

[0025] Figure 5 Images of water-soluble zinc oxide nanoparticles; where A is the aqueous solution under sunlight irradiation, and B is the solid fluorescence image (365 nm) after drying.

[0026] Figure 6 Images of water-soluble nano-manganese oxide are shown; where A is the aqueous solution under sunlight, B is the fluorescence image (365 nm), C is the solid image under sunlight, and D is the solid fluorescence image (365 nm).

[0027] Figure 7 Image of water-soluble nano-magnesium oxide.

[0028] Figure 8 Images of water-soluble gadolinium oxide nanoparticles; where A is the sunlight image and B is the fluorescence image (365 nm).

[0029] Figure 9 Images of water-soluble gadolinium oxide nanoparticles; where A is the sunlight image and B is the fluorescence image (365 nm).

[0030] Figure 10 Infrared spectra of sodium citrate, glucose, and eutectic compounds.

[0031] Figure 11 The image shows the 1H NMR spectrum of a eutectic compound of sodium citrate and glucose.

[0032] Figure 12 This is a transmission electron microscope image of the sample from Example 1.

[0033] Figure 13 The hysteresis curve is shown for the sample in Example 1.

[0034] Figure 14 The XPS plot (a) of the sample from Example 1 and the fitting curve (b) of gadolinium are shown.

[0035] Figure 15 The curves for 1 / T1 (a), 1 / T2 (b) and gadolinium concentration of the sample in Example 1 under an electric field strength of 7.0T are shown.

[0036] Figure 16 This is an in vivo MRI image of the mouse sample from Example 1.

[0037] Figure 17 This is a transmission electron microscope (TEM) image of the sample from Example 11.

[0038] Figure 18 The infrared spectra are of β-CD, trisodium citrate, and a mixture thereof.

[0039] Figure 19 The infrared spectrum of the sample in Example 11 is shown.

[0040] Figure 20 This is a thermogravimetric curve of β-CD.

[0041] Figure 21 Thermogravimetric curve of trisodium citrate dihydrate.

[0042] Figure 22 The thermogravimetric curve of the sample in Example 11 is shown.

[0043] Figure 23 XRD patterns of β-CD and trisodium citrate dihydrate.

[0044] Figure 24 The image shown is the XRD pattern of the sample from Example 11.

[0045] Figure 25 XPS image of sample 11 in Example 11.

[0046] Figure 26 This is the hysteresis curve diagram for Example 11.

[0047] Figure 27 The curves for 1 / T1 versus gadolinium concentration are shown under an electric field strength of 7.0T.

[0048] Figure 28 The effect of reaction time.

[0049] Figure 29 The XPS spectrum is from Example 12.

[0050] Figure 30 This is a transmission electron microscope image of Example 12.

[0051] Figure 31 The infrared spectrum of Example 12 is shown.

[0052] Figure 32 This is a thermogravimetric diagram of Example 12.

[0053] Figure 33 This is the XRD pattern of Example 12.

[0054] Figure 34 This is the hysteresis curve diagram for Example 12.

[0055] Figure 35 This is a stability test of the aqueous solution of the sample in Example 12.

[0056] Figure 36 For MTT test.

[0057] Figure 37 This is a hemolysis test.

[0058] Figure 38 The curves of 1 / T1(a), 1 / T2(b) and gadolinium concentration for sample 12 under an electric field strength of 7.0T are shown.

[0059] Figure 39 The image shows an in vitro T1-weighted MRI image of the sample from Example 12.

[0060] Figure 40 This is an in vivo magnetic resonance imaging (MRI) image of a mouse in Example 12. Detailed Implementation

[0061] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0062] Unless otherwise specified, the experimental methods used in the following experimental examples are conventional methods; the materials and reagents used are commercially available unless otherwise specified.

[0063] Example 1 The method for preparing water-soluble nano-metal oxides using green chemistry in this embodiment includes the following steps: First, glucose and trisodium citrate dihydrate (molar ratio 1:1) were reacted at 70°C for 24 h. The resulting eutectic compound after purification was as follows: Figure 1The sample exhibits a certain degree of viscosity and can be drawn into threads. A melting point apparatus determined the initial melting point of this eutectic compound to be 63.4℃, the final melting point to be 66.8℃, and the melting range to be 3.4℃. These values ​​are significantly lower than the melting points of glucose (146℃) and trisodium citrate dihydrate (323.5℃), confirming the formation of the eutectic compound.

[0064] 0.6 g of the dried white powder of the obtained eutectic compound was dissolved in 20 mL of water, and GdCl3 (0.05 mol / L) was added. After dissolution, sodium hydroxide (0.15 mol / L) was added, and the reaction was carried out at 70 °C for 4 h. The colorless aqueous solution after the reaction was purified and dried. The resulting white sample was further heat-treated by dissolving 0.2 g of the white sample in 10 mL of water and placing it in a 25 mL reaction vessel. The reaction was carried out at 220 °C for 6 h. The resulting white powder solid showed blue fluorescence under a 365 nm UV lamp. Figure 2 As shown.

[0065] Example 2 The method for preparing water-soluble nano-metal oxides using green chemistry in this embodiment includes the following steps: β-cyclodextrin (calculated as glucose units) was reacted with sodium citrate (molar ratio 2:1) at 70℃ for 12 h. After purification, the resulting eutectic compound was dissolved by stirring, and CuCl2 was added. After dissolution, sodium hydroxide (molar ratio Cu:NaOH = 1:2) was added, and the reaction was carried out at 70℃ for 2 h. The mass ratio of the eutectic compound to CuCl2 in the reaction solution was (1:1). After the reaction, the aqueous solution was purified and dried, and then vacuum-treated at 120℃ for 6 h. The resulting brownish-red powder was water-soluble nano-copper oxide. Figure 3 As shown.

[0066] Example 3 The method for preparing water-soluble nano-metal oxides using green chemistry in this embodiment includes the following steps: Glucose and sodium citrate (molar ratio 2:1) were reacted at 70℃ for 24 h. After purification, the resulting eutectic compound was dissolved by stirring, and silver nitrate was added. After dissolution, sodium hydroxide (molar ratio Ag:NaOH = 1:1) was added, and the reaction was carried out at 70℃ for 2 h. The mass ratio of the eutectic compound to silver nitrate in the reaction solution was (1:0.4). After the reaction, the aqueous solution was purified and dried, and the resulting brownish-red powder was water-soluble nano-silver oxide, which fluoresced green under a 356 nm UV lamp. Figure 4 As shown in Figure A.

[0067] Example 4 The method for preparing water-soluble nano-metal oxides using green chemistry in this embodiment includes the following steps: Glucose and sodium citrate (molar ratio 1:1) were reacted at 70℃ for 24 h. After purification, the resulting eutectic compound was dissolved by stirring, and silver nitrate was added. After dissolution, sodium hydroxide was added to adjust the pH to 8.5, and the reaction was carried out at 70℃ for 2 h. The mass ratio of the eutectic compound to silver nitrate in the reaction solution was (1:0.6). After the reaction, the aqueous solution was purified and dried, and the resulting brownish-red powder was water-soluble nano-silver oxide, which fluoresced yellow under a 356 nm UV lamp. Figure 4 As shown in B.

[0068] Example 5 The method for preparing water-soluble nano-metal oxides using green chemistry in this embodiment includes the following steps: Glucose and sodium citrate (molar ratio 0.6:1) were reacted at 70℃ for 24 h. After purification, the resulting eutectic compound was dissolved by stirring, and silver nitrate was added. After dissolution, sodium hydroxide was added to adjust the pH to 9.5, and the reaction was carried out at 70℃ for 2 h. The mass ratio of the eutectic compound to silver nitrate in the reaction solution was (1:0.8). After the reaction, the aqueous solution was purified and dried, and the resulting brownish-red powder was water-soluble nano-silver oxide, which fluoresced orange under a 356 nm UV lamp. Figure 4 As shown in C.

[0069] Example 6 The method for preparing water-soluble nano-metal oxides using green chemistry in this embodiment includes the following steps: Water-soluble starch (converted to glucose units) and sodium citrate (molar ratio 1:0.6) were reacted at 70℃ for 24 h. After purification, the resulting eutectic compound was dissolved by stirring, and ZnCl2 was added. After dissolution, 3 mol / L sodium hydroxide was added to adjust the pH to 8.5, and the reaction was carried out at 70℃ for 6 h. The mass ratio of the eutectic compound to ZnCl2 in the reaction solution was (2.4:1). After the reaction, the aqueous solution was purified and dried, and then vacuum-treated at 110℃ for 10 h. The resulting white powder was water-soluble nano-zinc oxide, which fluoresced blue under a 356 nm UV lamp. Figure 5 As shown.

[0070] Example 7 The method for preparing water-soluble nano-metal oxides using green chemistry in this embodiment includes the following steps: Glucose and sodium citrate (molar ratio 1:1) were reacted at 70℃ for 16 h. After purification, the resulting eutectic compound was dissolved by stirring, and MnCl2 was added. After dissolution, sodium hydroxide (molar ratio Mn:NaOH = 1:4) was added, and the reaction was carried out at 70℃ for 6 h. The mass ratio of the eutectic compound to MnCl2 in the reaction solution was (3.2:1). After the reaction, the aqueous solution was purified and dried, and the resulting light brownish-yellow powder was water-soluble nano-manganese oxide, which fluoresced blue under a 356 nm UV lamp. Figure 6 As shown.

[0071] Example 8 The method for preparing water-soluble nano-metal oxides using green chemistry in this embodiment includes the following steps: Glucose and sodium citrate (molar ratio 1:1) were reacted at 70℃ for 16 h. After purification, the resulting eutectic compound was dissolved by stirring, and MgCl2 was added. After dissolution, 3 mol / L sodium hydroxide was added to adjust the pH to 10, and the reaction was carried out at 70℃ for 6 h. The mass ratio of the eutectic compound to MgCl2 in the reaction solution was (3:1). After the reaction, the aqueous solution was purified and dried, and then vacuum-treated at 110℃ for 8 h. The resulting white powder was water-soluble nano-magnesium oxide, which fluoresced blue under a 356 nm UV lamp. Figure 7 As shown.

[0072] Example 9 The method for preparing water-soluble nano-metal oxides using green chemistry in this embodiment includes the following steps: Glucose and sodium citrate (molar ratio 10:1) were reacted at 70℃ for 16 h. After purification, the resulting eutectic compound was dissolved by stirring, and GdCl3 was added. After dissolution, ammonia water was added, with a molar ratio of GdCl3 to ammonia water of 1:3. The reaction was carried out at 70℃ for 4 h. The mass ratio of the eutectic compound to GdCl3 in the reaction solution was (3:1). After the reaction, the aqueous solution was purified and dried. The resulting white powder was prepared into a 20 mg / mL aqueous solution and reacted in a reaction vessel at 160℃ for 6 h. The purified and dried white powder was the water-soluble nano-gadolinium oxide, which emitted a weak blue fluorescence under a 356 nm UV lamp. Figure 8 As shown.

[0073] Example 10 The method for preparing water-soluble nano-metal oxides using green chemistry in this embodiment includes the following steps: Glucose and EDTA (molar ratio 1:10) were reacted at 70℃ for 16 h. The resulting eutectic compound was purified, dissolved by stirring, and then GdCl3 was added. After dissolution, potassium hydroxide was added to adjust the pH to 10.5, and the reaction was carried out at 70℃ for 2 h. The mass ratio of the eutectic compound to GdCl3 in the reaction solution was (3:1). The resulting white powder was prepared into a 20 mg / mL aqueous solution and reacted at 240℃ for 2 h. After the reaction, the aqueous solution was purified and dried. The resulting white powder was water-soluble gadolinium oxide nanoparticles, which emitted a very weak blue fluorescence under a 356 nm UV lamp. Figure 9 As shown.

[0074] Example 11 The method for preparing water-soluble nano-metal oxides using green chemistry in this embodiment includes the following steps: β-Cyclodextrin (converted to glucose units) was reacted with sodium citrate (molar ratio 4:1) at 70°C for 24 hours. After purification, a eutectic compound was obtained. This compound was dissolved by stirring, and GdCl3 was added. After dissolution, sodium hydroxide was added. The molar ratio of GdCl3 to sodium hydroxide in the reaction solution was 1:3, and the mass ratio of the eutectic compound to GdCl3 was (0.7:1). The reaction was stirred at 70°C for 4 hours. The resulting colorless and transparent solution was purified and dried to obtain a white powder, which is water-soluble nano-gadolinium oxide.

[0075] Example 12 The method for preparing water-soluble nano-metal oxides using green chemistry in this embodiment includes the following steps: β-Cyclodextrin (converted to glucose units) was reacted with sodium citrate (molar ratio 4:1) at 70°C for 24 hours. After purification, a eutectic compound was obtained. This compound was dissolved by stirring, and GdCl3 was added. After dissolution, sodium hydroxide was added. The molar ratio of GdCl3 to sodium hydroxide in the reaction solution was 1:3, and the mass ratio of the eutectic compound to GdCl3 was (0.7:1). The reaction was stirred at 70°C for 4 hours. The resulting colorless and transparent solution was purified and dried to obtain a white powder sample. 0.2 g of the white sample was dissolved in 10 mL of water and reacted in a reactor at 220°C for 6 hours. The resulting colorless and transparent solution was purified and dried, yielding the water-soluble nano-gadolinium oxide.

[0076] Example 13 The method for preparing water-soluble nano-metal oxides using green chemistry in this embodiment includes the following steps: Glucose and sodium citrate (molar ratio 10:1) were reacted at 100℃ for 6 h. After purification, the resulting eutectic compound was stirred and dissolved, and GdCl3 was added. After dissolution, ammonia water was added, with a molar ratio of GdCl3 to ammonia water of 1:3. The reaction was carried out at 25℃ for 24 h. The mass ratio of the eutectic compound to GdCl3 in the reaction solution was (3:1). After the reaction was completed, the aqueous solution was purified and dried. The resulting white powder was prepared into a 20 mg / mL aqueous solution and reacted in a reaction vessel at 160℃ for 6 h. The purified and dried white powder was the water-soluble nano-gadolinium oxide.

[0077] Example 14 The method for preparing water-soluble nano-metal oxides using green chemistry in this embodiment includes the following steps: Glucose and sodium citrate (molar ratio 10:1) were reacted at 50℃ for 24 h. After purification, the resulting eutectic compound was dissolved by stirring and then GdCl3 was added. After dissolution, ammonia water was added, with a molar ratio of GdCl3 to ammonia water of 1:3. The reaction was carried out at 240℃ for 2 h. The mass ratio of the eutectic compound to GdCl3 in the reaction solution was (1:0.05). After the reaction was completed, the aqueous solution was purified and dried. The resulting white powder was prepared into a 20 mg / mL aqueous solution and reacted in a reaction vessel at 160℃ for 6 h. The purified and dried white powder was the water-soluble nano-gadolinium oxide.

[0078] Example of implementation effect 1 The water-soluble gadolinium oxide nanoparticles prepared in Example 1 were characterized and their performance was tested.

[0079] 1. Characterization results of water-soluble nano-gadolinium oxide Figure 10 The infrared spectra of glucose, trisodium citrate dihydrate, and the eutectic compound formed by their reaction are shown. The results indicate that the hydroxyl stretching vibration peak of the eutectic compound is significantly higher than that of glucose at 3390 cm⁻¹. -1 The peak at 3456 cm⁻¹ becomes broader due to intermolecular hydrogen bonding and shifts to lower wavenumbers due to intermolecular association. In trisodium citrate dihydrate, the peak at 3456 cm⁻¹ is... -1 The peak at 3269 cm⁻¹ is attributed to the OH stretching vibration of the water of crystallization. -1 The peaks at [value missing] are generated by the OH stretching vibration inherent in the sodium citrate molecule. These two peaks are masked in eutectic compounds by the broad hydroxyl peaks. Upon hydrogen bonding, the OH stretching vibration energy level distribution broadens, especially in the 3200-3600 cm⁻¹ range. -1 The region exhibits a significantly broad peak, which may mask other signals. In trisodium citrate dihydrate, the peak is at 1589 cm⁻¹. -1 and 1439 cm -1 The bimodal characteristic of the antisymmetric and symmetric stretching vibrations of the carboxylate group, together forming the peak at 1630 cm⁻¹, is observed. -1 This is due to the bending vibration of the water of crystallization (HOH). In the eutectic compound formed by glucose and trisodium citrate dihydrate, the characteristic bimodal shift of the carboxylate salt to 1579 cm⁻¹. -1 and 1410 cm -1 Furthermore, the peak shape broadens significantly. (RCOO) - The carboxylate ion readily forms polymers (such as dimers or chain structures) through hydrogen bonds, leading to a dispersed distribution of the OH vibrational energy levels. This significantly broadens the peaks of both antisymmetric and symmetric stretching vibrations, forming a strong hydrogen bond network structure. Simultaneously, the carboxylate ion exhibits charge delocalization (ionic resonance), enhancing the dipole moment change of its CO stretching vibration. This facilitates vibrational coupling with adjacent groups (such as the OH group of water molecules), resulting in broadening or shifting of the bimodal peaks. Figure 11 The 1H NMR spectrum of the eutectic compound clearly shows that the quartet of the methylene group in sodium citrate at chemical shift 2.5 transforms into a large, blunt peak, indicating the formation of a complex hydrogen-bonded structure similar to that of the eutectic solvent. Figure 12 Transmission electron microscopy revealed that the water-soluble gadolinium oxide was uniformly dispersed with an average particle size of approximately 1.39 nm. It can dissolve rapidly and uniformly in water to form a colorless, clear, and transparent solution, and remains stable in a strong magnetic field without agglomeration. Figure 13 Hysteresis curve analysis results indicate that the prepared gadolinium oxide nanoparticles are weakly paramagnetic, exhibiting a magnetic field strength of 1.35 emu / g in a 30000 Oe magnetic field. Figure 14 The XPS spectrum shows that the sample contains gadolinium, indicating the presence of gadolinium oxide. ICP analysis showed that the gadolinium content in the sample was 18.85%.

[0080] 2. MRI test results of water-soluble nano-gadolinium oxide The gadolinium oxide nanoparticles measured in a 7.05T magnetic field had an r1 value of 11.69, approximately four times that of the clinically commonly used contrast agent Gd-DTPA (r1=2.91), and an r2 value of 12.45, resulting in an r2 / r1 ratio of 1.1. This is beneficial for achieving high-contrast T1 imaging. Figure 15 As shown. In vivo imaging results indicated that a dose of 0.05 mmol Gd / kg (half the human clinical dose) significantly improved abdominal vascular imaging in mice at 10 minutes and 30 minutes post-administration. Abdominal vascular imaging at 1 hour post-administration was almost identical to that before administration. Figure 16 As shown, this may be due to the small particle size of the nanoparticles, about 1-2 nm, which allows them to be rapidly excreted by the kidneys.

[0081] Example 2 of implementation results The water-soluble gadolinium nanoparticles prepared in Example 11 were characterized and their performance was tested.

[0082] 1. Characterization results of water-soluble nano-gadolinium oxide The reaction time at 70℃ was investigated, and it was found that even after 24 hours, the solution remained colorless. This is because β-CD is relatively stable within this range of sodium hydroxide dosage and does not react with sodium hydroxide. The Gd₂O₃ solid powder prepared under the 70℃ reaction conditions all exhibited weak fluorescence under 365 nm excitation, and the fluorescence intensity slightly increased with increasing β-CD addition. This may be because gadolinium oxide has a wide band gap (approximately 5.4 eV), and its ultra-small particle size (≤10 nm) enhances the quantum confinement effect, resulting in weak blue-green light emission under UV excitation. Transmission electron microscopy results are as follows: Figure 17As shown, the microstructure of the samples is approximately spherical, with an average particle size of about 1.07 nm and a lattice spacing of about 0.31 nm, consistent with the 222 crystal plane of Gd₂O₃. Fourier transform infrared spectroscopy results ( Figure 18 The results show that a large number of -OH stretching vibrations in β-CD occur due to intermolecular hydrogen bonds at 3390 cm⁻¹. -1 A broad, blunt peak is observed at 3456 cm⁻¹. In trisodium citrate dihydrate, this peak is... -1 The peak at 3269 cm⁻¹ is attributed to the OH stretching vibration of the water of crystallization. -1 The peak at 1589 cm⁻¹ represents the stretching vibration of OH groups in the molecular skeleton, which shifts to lower wavenumbers due to intermolecular association; -1 and 1439 cm -1 The bimodal characteristic of carboxylates, 1630 cm⁻¹ -1 This is the bending vibration of the water of crystallization (HOH). The infrared spectrum of the mixture of β-CD and trisodium citrate dihydrate shows that its peak positions are almost a superposition of the infrared spectra of the two. In the sample ( Figure 19 A broad, blunt peak appears at 3383 cm⁻¹ -1 At this point, a redshift occurs compared to β-CD, further demonstrating the formation of more intermolecular hydrogen bonds; the characteristic doublet of carboxylate redshifts to 1589 cm⁻¹ in the sample. -1 and 1421 cm -1 The infrared spectrum of the mixture showed a significant change compared to that of the other two substances, indicating the formation of a new substance. Thermogravimetric results showed that β-CD ( Figure 20 During the low-temperature dehydration stage (room temperature to 150℃), the TG curve shows a continuous downward slope, while the DTG curve exhibits a broad, gentle peak at 50-100℃, with an initial mass loss of approximately 13-15%, corresponding to the removal of adsorbed water and water of crystallization. In the structural water release stage (150-250℃), the TG curve shows a slow downward slope without sharp weight loss steps (weight loss rate approximately 3-5%), corresponding to the removal of bound water within the β-CD cavity and the breaking of intermolecular hydrogen bonds. The 300-500℃ stage is the main decomposition stage, where glycosidic bond breakage leads to severe weight loss, with a weight loss rate >70%, and the DTG peak temperature is approximately 335℃. (Note: The last sentence appears to be incomplete and possibly refers to a product called trisodium citrate dihydrate.) Figure 21 Significant weight loss occurred around 150℃, corresponding to the removal of two water of crystallization molecules, with a mass loss of approximately 12%, consistent with the theoretical weight loss rate of approximately 12.2%. The substance began to slowly decompose at approximately 250℃, with the carboxyl group breaking down at high temperatures to generate sodium carbonate, carbon dioxide, and carbonaceous residues. (Sample (...)) Figure 22The thermogravimetric curves of β-CD and trisodium citrate dihydrate differed significantly from those of gadolinium oxide (GA). Before 100℃, it lost adsorbed water, resulting in a loss of approximately 12%; in the 250-350℃ range, the organic layer fractured, leading to a rapid mass decrease of 12%; the rapid mass loss at 700℃ was due to the reduction reaction between residual carbon generated from the earlier pyrolysis and nano-gadolinium oxide at high temperatures. Due to its high specific surface area, nano-gadolinium oxide significantly reduced the carbothermic reduction activation energy, resulting in a reaction temperature lower than that of the bulk material. The final residues were gadolinium oxide and sodium carbonate. β-cyclodextrin, due to its cyclic heptaglucose unit structure, showed significant differences in XRD patterns (…). Figure 23 The sample exhibits a cluster of crystalline peaks, with all peaks of trisodium citrate being sharp and symmetrical, indicating its high crystallinity. Figure 24 Due to the high content of β-cyclodextrin, the XPS diagram shows a peak group similar to that of β-cyclodextrin, but the peak intensities are very weak and their positions have changed significantly, confirming the formation of a new phase. Figure 25 The presence of gadolinium can be confirmed. The broad peak at 535.9 eV in the O 1s spectrum is caused by residual water of crystallization, which is consistent with the OH peak with water of crystallization in the infrared spectrum, and is also consistent with the residual Na modified by trisodium citrate. + It is possible that the KLL Auger peaks (534-536 eV, broad peak > 3.0 eV) are superimposed together. The 531.3 eV peak comes from the hydroxyl group of β-cyclodextrin or the carboxyl group of sodium citrate, which is the binding energy of C=O. The 533.1 eV peak comes from the binding energy of CO. Figure 26Hysteresis curve analysis showed that the prepared gadolinium oxide nanoparticles were weakly paramagnetic, exhibiting zero coercivity, no hysteresis, and zero remanence. In a 30,000 Oe magnetic field, the magnetism was only 0.22 emu / g, indicating that the relatively low reaction temperature of 70℃ might have led to incomplete crystal growth or the presence of disordered regions, resulting in almost no magnetism. The colloidal stability of the sample in pure water was monitored using dynamic light scattering (DLS) technology. The hydrodynamic size of the sample began to increase rapidly on day 7, and by day 14, the solution began to show slight turbidity. This may be due to incomplete crystal growth or the presence of disordered regions in the gadolinium oxide, which facilitates the detachment of gadolinium ions from the crystal lattice and their entry into the solution. Simultaneously, crystal defects or disordered lattice arrangement increased the specific surface area, exposing more active sites and accelerating hydrolysis and ion dissolution. The disordered structure hindered the directional crystallization of hydration products, tending to form amorphous gadolinium hydrate precipitates (such as Gd(OH)3·nH2O). Water molecules easily penetrate crystal defect regions, inducing localized expansion stress, leading to lattice collapse or particle breakage, and accelerating the overall material decomposition. This causes the solution to become turbid. Furthermore, the sample's zeta potential is -25.7 mV, indicating poor colloidal stability and weak electrostatic repulsion between particles, making it prone to aggregation and precipitation. Dialysis of the sample aqueous solution in a dialysis bag for 48 hours, followed by inductively coupled plasma (ICP) detection, revealed gadolinium ion leakage from the dialysis bag, with a leakage rate of 3.27%, further demonstrating the poor stability of the nano-gadolinium oxide prepared at 70℃.

[0083] 2. MRI test results of water-soluble gadolinium oxide composite materials like Figure 27 As shown, the r1 value of this nano-Gd2O3 was measured to be 3.29, which is slightly higher than that of commercially available Gd-DTPA contrast agents.

[0084] Example of implementation effect 3 The water-soluble gadolinium nanoparticles prepared in Example 12 were characterized and their performance was tested.

[0085] 1. Characterization results of water-soluble nano-gadolinium oxide The reaction time at 220℃ was investigated. Within 6 hours of reaction at 220℃, the solution remained colorless, clear, and transparent. This is because at 70℃, sodium citrate and β-cyclodextrin formed numerous intermolecular hydrogen bonds. The hydrogen bond network enhances the thermal stability of the molecular aggregate, thus inhibiting the carbonization reaction of organic matter at such high temperatures. As the reaction time increased to 7 hours, the solution turned into a white suspension, presumably due to the conversion of gadolinium oxide into gadolinium hydroxide precipitate at high temperature. After 8 hours, carbonization of the organic matter began, and the solution gradually turned yellow. By 9 hours, carbonization was significant, and the solution turned dark brown. This was because the carbonization of the organic matter reduced the functional groups such as hydroxyl groups on the surface of the nanoparticles, leading to the emergence of layering. After 10 hours, the layering phenomenon became even more pronounced. Figure 28As shown, the Gd₂O₃ solid powder prepared at a reaction temperature of 220℃ exhibits weak fluorescence under 365 nm excitation, and the fluorescence intensity is slightly enhanced compared to the reaction at 70℃. This may be because in the high-temperature, high-pressure, and closed reactor at 220℃, the gadolinium oxide nanoparticles undergo a dissolution-recrystallization process, forming gadolinium oxide with high crystallinity, fewer lattice defects, and a more uniform particle size distribution, which helps to improve the intrinsic fluorescence intensity. Furthermore, if gadolinium chloride, sodium hydroxide, sodium citrate, and β-cyclodextrin are placed directly in the reactor in the same proportion and reacted at 220℃, the solution turns brownish-brown within 3 hours. This is because a hydrogen-bonded network structure has not yet formed in the solution system, leading to the carbonization of a large amount of free organic matter. XPS diagram ( Figure 29 The presence of gadolinium was confirmed. The broad peak at 535.6 eV in the O 1s spectrum originated from residual water of crystallization, possibly related to the modification of residual Na by trisodium citrate. + The generated KLL Auger peaks superimposed. The peak at 531.2 eV is attributed to the hydroxyl group of β-cyclodextrin or the carboxyl group of sodium citrate, i.e., the binding energy of C=O, while the peak at 532.8 eV originates from the binding energy of CO. Under high-temperature conditions in a closed reactor environment, the newly generated carbon dots have strong reducing properties, reducing some C=O to CO, thus making the intensity of the CO peak in this sample significantly higher than that in the sample of Example 11. The transmission electron microscopy results are as follows: Figure 30 As shown, the sample exhibits an approximately spherical microstructure with an average particle size of about 1.33 nm and a lattice spacing of about 0.31 nm, consistent with the 222 crystal plane of Gd₂O₃. According to Ostwald's ripening and hard agglomeration theory, the solubility of small-diameter particles increases sharply at 220℃, inducing dissolution and deposition of small particles onto the surface of larger particles, leading to an increase in average particle size. Simultaneously, the dielectric constant of water decreases significantly at 220℃ (approaching the level of organic solvents), weakening the double-layer repulsion and exacerbating particle agglomeration. When the temperature exceeds 150℃, the ripening rate increases exponentially, with the particle size increase being particularly significant at 220℃. However, after further heating at 220℃, the particle size of gadolinium oxide did not increase significantly, demonstrating that the outer organic layer possesses high-temperature resistance. Its stable structure effectively inhibits the particle size growth of nanoparticles at 220℃, verifying that β-CD and sodium citrate constructed a stable multi-hydrogen bond structure during the preparation process. Fourier transform infrared spectroscopy results (…) Figure 31 The data shows that a broad, blunt peak appears at 3372 cm⁻¹ in the sample. -1 At this point, a significant red shift occurs compared to β-CD, further demonstrating the formation of more intermolecular hydrogen bonds; the characteristic doublet of carboxylate salts redshifts to 1577 cm⁻¹ in the sample. -1 and 1404 cm -1 The infrared spectrum of the mixture phase changed significantly compared to the other phase, indicating the formation of a new substance. Thermogravimetric results ( Figure 32The XRD pattern showed that the thermogravimetric curve of the sample differed significantly from that of β-CD and trisodium citrate dihydrate, and was similar to that of the sample in Example 11. Before 100°C, the sample lost adsorbed water, a loss of approximately 12%; in the 250-350°C range, the organic layer fractured, leading to a rapid mass decrease of 12%; the rapid mass loss at 700°C was due to the reduction reaction between residual carbon generated from the previous pyrolysis and nano-gadolinium oxide at high temperatures. The XRD pattern is shown below. Figure 33 As shown, the β-cyclodextrin structure was destroyed after the sample was reacted at high temperature. At the same time, the gadolinium oxide particle size was only 1-2 nm, so no peaks appeared and it was in an amorphous state. Figure 34 Hysteresis curve analysis showed that the prepared gadolinium oxide nanoparticles exhibited weak paramagnetism, i.e., zero coercivity, no hysteresis, and zero remanence, with a magnetic field strength of 2.27 emu / g in a 30,000 Oe magnetic field. This is significantly higher than the 0.22 emu / g magnetic field of the sample in Example 11, indicating that the high-temperature reaction resulted in a more regular arrangement of gadolinium oxide molecules and improved crystallinity, thus leading to better magnetic properties. The colloidal stability of the sample in pure water was monitored for 60 days. Figure 35 As shown, the sample aqueous solution remained clear and transparent for at least 60 days. DLS results showed that the hydrodynamic dimensions of the sample were relatively stable. The sample's zeta potential was -30.4 mV; the high absolute zeta potential value indicates good colloidal stability and that the nanoparticles are unlikely to aggregate. Dialysis of the sample aqueous solution in a dialysis bag for 48 hours and ICP analysis showed no leakage of gadolinium ions from the dialysis bag. This lack of leakage is likely due to the low gadolinium content in the nanoparticles, which, after high temperature, form stable nanonuclei, and the citrate and β-cyclodextrin form a protective outer layer, further effectively preventing gadolinium release.

[0086] 2. MRI test results of water-soluble gadolinium oxide composite materials 2.1 Cytotoxicity Because gadolinium-based contrast agents are primarily nephrotoxic in clinical settings, to assess the effects of samples on the kidneys and liver, standard MTT assays were performed in vitro using HK-2 (normal cells) and HepG2 (tumor cells). In the experiment, HK-2 and HepG2 cells were incubated for 24 hours at different concentrations of Gd₂O₃NPs-220 (0, 25, 50, 100, 200, 300, 400, 500, 750, 1000 mg / L). Figure 36 As shown, even at the highest concentration of 1000 mg / L, the cell proliferation rate remained above 85%, indicating that the drug has relatively low cytotoxicity.

[0087] 2.2 Hemolytic test Assessing blood compatibility is crucial because the contrast agent comes into immediate contact with blood components after intravenous injection. After incubating the sample with red blood cells for 2 hours, the absorbance was assessed visually and measured at 540 nm. Figure 37 The results showed that even at a high concentration of 3.5 mg / mL, the hemolysis rate of Gd2O3NPs-220 was comparable to that of physiological saline, which confirms its excellent blood compatibility.

[0088] 2.3 Acute toxicity test Acute toxicity results showed that even when the tail vein dose was 20 times the imaging dose, i.e. 1 mmol / kg, no animal deaths were observed, nor were obvious toxic reactions such as drowsiness, tremors, convulsions, or abnormal behavior observed.

[0089] 2.4 Single-dose toxicity test On days 1, 7, and 14 after administration, no significant changes were observed in liver function-related parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBILC), direct bilirubin (DBILC), gamma-glutamyl transferase (GGT-L); kidney function-related parameters (urea (UREA), uric acid (UA), creatinine (CRE2); or total protein (TP), albumin (ALB), alkaline phosphatase (ALP04), lactate dehydrogenase (LDH-L), and creatine kinase (CK). There were no significant differences in weight changes between the experimental and control groups. These results indicate that the sample does not cause long-term toxicity in vivo and is therefore suitable for further in vivo magnetic resonance imaging (MRI).

[0090] 2.5 In vitro magnetic resonance imaging The high-temperature environment lowers the diffusion barrier of Gd atoms, leading to the formation of dense aggregates through surface atomic bonding after atomic collisions. This compact structure endows the nanoparticles with a higher r1 value. Simultaneously, this ultrasmall nanostructure exposes more paramagnetic gadolinium ion surface sites, significantly increasing the longitudinal relaxation rate (r1 value) and reducing the r2 / r1 ratio. Its r1 value can reach 8.43 at 7T. Figure 38 As shown, it is approximately four times more potent than commercially available Gd-DTPA contrast agents, with an r2 / r1 ratio of 1.2, close to 1, which is beneficial for achieving high-contrast imaging at T1. Figure 39 As shown, the T1-weighted image gradually brightens with increasing gadolinium concentration, exhibiting significant bright contrast, indicating that this sample has the potential to be used as a contrast agent for T1 magnetic resonance imaging.

[0091] 2.6 Intravenous magnetic resonance imaging In mice, administration via tail vein at a dose of 0.05 mmol / kg resulted in significantly enhanced effects, even at lower doses. Figure 40As shown, due to the sample's high r1 value, 10 minutes after injection, not only the major abdominal blood vessels but also many small vessels, even microvessels as small as 0.21 mm in diameter, were clearly visible. High-resolution imaging of microvessels is crucial for the diagnosis and treatment of small vessel diseases. After 30 minutes, the imaging effect of the abdominal veins significantly decreased, indicating rapid clearance from the body. The imaging time window was short, with optimal imaging results lasting no more than 0.5 hours. This may be because the sample's ultra-small particle size (1.33 nm) allows for direct clearance via glomerular filtration, significantly reducing the risk of gadolinium deposition in the brain.

[0092] The nanoscale size gives it a significant advantage in the field of MRI contrast enhancement. Compared with traditional contrast agents, its ultra-small size not only helps to improve the stability and dispersibility of the particles, allowing them to be uniformly dispersed in aqueous media and avoiding aggregation, but also ensures stability during in vivo circulation. Simultaneously, the uniform particle size distribution also indicates that the hydrothermal synthesis method used in this experiment has good controllability and can prepare nanoparticles with uniform particle size.

[0093] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing water-soluble nano-metal oxides using green chemistry, characterized in that, The steps are as follows: (1) Reaction of sugar and ligand to form eutectic compounds; (2) Dissolve the eutectic compound, metal ion solution and alkali in water, purify after reaction, dry, and the resulting powder is water-soluble nano metal oxide.

2. The method for preparing water-soluble nano-metal oxides using green chemistry according to claim 1, characterized in that: In step (1), the sugar is a monosaccharide, oligosaccharide, or water-soluble polysaccharide, and the ligand is any one of ethylenediamine, citric acid, sodium citrate, acetylacetone, and EDTA; in step (2), the metal ion is Gd. 3+ Cu 2+ Ag + Zn 2+ Mn 4+ and Mg 2+ Any one of the following, wherein the base is sodium hydroxide, potassium hydroxide, or ammonia.

3. The method for preparing water-soluble nano-metal oxides using green chemistry according to claim 2, characterized in that: In step (1), the molar ratio of sugar to ligand, calculated as a single glucose unit, is 1:0.1-10, the reaction temperature is 50-100℃, and the reaction time is 6-24 h.

4. The method for preparing water-soluble nano-metal oxides using green chemistry according to claim 3, characterized in that: In step (2), the mass of metal ions reacted with each gram of eutectic compound is 0.05-1 g, the reaction temperature is 25-240℃, and the reaction time is 2-24 h.

5. The method for preparing water-soluble nano-metal oxides using green chemistry according to claim 4, characterized in that: When it is necessary to improve the crystallinity of nano-metal oxides, the powder obtained in step (2) can be further heat-treated, purified and dried to obtain water-soluble nano-metal oxides with better crystallinity.

6. The method for preparing water-soluble nano-metal oxides using green chemistry according to claim 5, characterized in that, The further heat treatment is selected from any of the following: ① Heat the powder in air, nitrogen, or vacuum at 25-240℃ for 0.1-48 h; ② Dissolve the powder in water and perform a hydrothermal reaction at 110-240℃ for 1-48 hours.

7. Water-soluble nano-metal oxides prepared by the method according to any one of claims 1-6.

8. The application of the water-soluble nano-metal oxide according to claim 7, characterized in that, Selected from at least one of the following applications: a. Preparation of medical image enhancement reagents; b. As a drug carrier; c. As a magnetothermal therapy product; d. Preparation of fluorescent labels; e. Preparation of antibacterial materials; f. Preparation of zinc and copper supplements.

9. The application according to claim 8, characterized in that: The medical image enhancement agents include those used as magnetic resonance imaging (MRI) contrast agents or CT contrast agents.

10. The application according to claim 9, characterized in that, Specific applications are as follows: When the metal ion is Gd 3+ or Mn 4+ The prepared water-soluble nano-gadolinium oxide or nano-manganese oxide can be used as a magnetic resonance imaging contrast agent, CT contrast agent, drug carrier or magnetothermal therapy product; When the metal ion is Zn 2+ The prepared water-soluble nano-zinc oxide can be used to prepare fluorescent labels, antibacterial materials, or zinc supplements. When the metal ion is Ag + The prepared water-soluble nano-silver oxide can be used to prepare fluorescent labels or antibacterial materials; When the metal ion is Cu 2+ The prepared water-soluble nano-copper oxide can be used to prepare antibacterial materials or copper supplements.

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