Method for constructing oxygen vacancies based on sub-5 nanoscale iron oxide nanoparticles and application

Abstract

The invention discloses a method for constructing oxygen vacancies based on sub-5-nanometer iron oxide nanoparticles. The method comprises the following steps: step 1, dispersing sub-5-nanometer extremely small iron oxide nanoparticles in an aqueous solution to prepare an iron oxide nanoparticle dispersion liquid; step 2, introducing inert gas into the iron oxide nanoparticle dispersion liquid prepared in the step 1; step 3, adding a reducing agent into the oxygen-removed iron oxide nanoparticle dispersion liquid prepared in the step 2; step 4, placing the ferric oxide nanoparticle dispersion liquid added with the reducing agent prepared in the step 3 in an alternating magnetic field environment, and placing the ferric oxide nanoparticle dispersion liquid in a low-temperature state at the same time; step 5, performing dialysis treatment on the iron oxide nanoparticle dispersion liquid treated in the step 4, and taking dialysate; and step 6, carrying out centrifugal collection on the dialysate prepared in the step 5, and carrying out freeze drying treatment on the separated nano-particles to obtain the sub-5 nanoscale iron oxide nano-particles rich in oxygen vacancies.

Description

Technical Field

[0001] The present application relates to the field of material surface engineering, and specifically to a method and application of constructing oxygen vacancies based on sub-5 nanometer iron oxide nanoparticles. Background Art

[0002] Iron oxide nanoparticles, due to their excellent biocompatibility and unique relaxivity, are considered ideal candidates for the development of a new generation of highly efficient and low-toxic magnetic resonance T1 contrast agents. However, due to limitations in their intrinsic electronic structure, the T1 contrast performance of current iron oxide-based contrast agents remains inferior to that of clinically used gadolinium-based contrast agents. Numerous studies have demonstrated that the T1 relaxation efficiency of nanoparticles can be effectively enhanced by regulating their interactions with water molecules. Specific strategies can be summarized into two aspects: first, by controlling the particle size to an extremely small size range below 5 nm, the specific surface area is significantly increased to facilitate sufficient contact between water molecules and surface iron ion sites; second, oxygen vacancy defects are added to the particle surface to provide stable adsorption sites for water molecules. Therefore, the preparation of sub-5 nm iron oxide nanoparticles rich in oxygen vacancies is of great significance for the further development of high-performance iron-based T1 contrast agents.

[0003] However, how to obtain sub-5 nm iron oxide nanoparticles rich in oxygen vacancies still faces certain technical challenges. From a thermodynamic point of view, when the particle size enters the sub-5 nm range, the surface compression tension is significantly enhanced, resulting in an increase in the Fe-O bond energy, which makes the oxygen vacancy formation energy increase sharply. In terms of kinetics, the strong self-purification effect caused by the extremely small size will promote the spontaneous annihilation of lattice defects, which imposes certain limitations on the stability of oxygen vacancies. Therefore, it is very difficult to directly prepare sub-5 nm iron oxide nanoparticles rich in oxygen vacancies through chemical synthesis, and certain technical means are required to rationally construct oxygen vacancies on the surface of sub-5 nm iron oxide nanoparticles.

[0004] The current mainstream methods of oxygen vacancy engineering in metal oxides include high-energy particle bombardment, high-temperature heat treatment and chemical reduction, but these technologies have fundamental limitations in their application to sub-5 nanometer iron oxide systems: high-energy particle bombardment is difficult to effectively deoxidize due to the spatial shielding effect of organic ligands on the particle surface; although high-temperature heat treatment can achieve desorption through thermal vibration of oxygen atoms, extreme temperature conditions will trigger particle sintering growth; in chemical reduction, gas-phase reducing agents (such as H2, NH3) require high-temperature activation and have poor controllability, and although liquid-phase reduction systems (such as sodium borohydride and alcohols) have the potential advantage of low-temperature treatment, they are limited by the inherent contradiction between the stability of the reducing agent and the reaction kinetics - the reaction rate is too low under low temperature conditions, and heating causes the reducing agent to quickly decompose and inactivate.

[0005] In summary, existing oxygen vacancy construction technologies are not applicable to sub-5 nanometer iron oxide nanoparticle systems, and there is an urgent need to develop new surface engineering strategies to achieve efficient construction of oxygen vacancies. Summary of the Invention

[0006] For extremely small iron oxide nanoparticle systems at the sub-5 nanometer level, the existing oxygen vacancy construction technology has significant limitations (causing particle growth, phase change, etc.), and it is urgent to develop new surface engineering methods to achieve efficient construction of oxygen vacancies.

[0007] The present application provides a method for constructing oxygen vacancies in sub-5 nanometer iron oxide nanoparticles, comprising the following steps:

[0008] Step 1: Dispersing sub-5 nanometer iron oxide nanoparticles in an aqueous solution to prepare a sub-5 nanometer iron oxide nanoparticle dispersion, wherein the Fe concentration is less than 300 mg / L;

[0009] Step 2: introducing an inert gas into the sub-5 nanometer iron oxide nanoparticle dispersion in step 1 to remove oxygen from the sub-5 nanometer iron oxide nanoparticle dispersion;

[0010] Step 3, adding a reducing agent to the oxygen-removed sub-5 nanometer iron oxide nanoparticle dispersion prepared in Step 2;

[0011] Step 4, placing the sub-5 nanometer iron oxide nanoparticle dispersion prepared in step 3 and having added a reducing agent in an alternating magnetic field environment, while keeping the sub-5 nanometer iron oxide nanoparticle dispersion in a low temperature state;

[0012] Step 5, dialyzing the iron oxide nanoparticle dispersion after the treatment in step 4 to obtain dialysate to remove excess reducing agent;

[0013] Step 6: The dialysate prepared in step 5 is collected by centrifugation, and the separated nanoparticles are freeze-dried to obtain sub-5 nanometer iron oxide nanoparticles rich in oxygen vacancies.

[0014] The present application provides sub-5 nanometer iron oxide nanoparticles rich in oxygen vacancies obtained according to the construction method.

[0015] The present application also provides the use of sub-5 nanometer iron oxide nanoparticles rich in oxygen vacancies in high-performance magnetic resonance T1 contrast agents.

[0016] Beneficial effects

[0017] In view of the limitations of traditional oxygen vacancy construction technology, this invention proposes a low-temperature reduction strategy based on alternating magnetic field induction. Magnetic iron oxide nanoparticles represented by Fe3O4 and γ-Fe2O3 can efficiently convert electromagnetic energy into thermal energy through Neel relaxation loss under the action of an alternating magnetic field. By precisely controlling the magnetic field parameters, a local thermal effect of sub-5 nm iron oxide particles can be achieved in an aqueous dispersion system, causing the surface lattice oxygen to vigorously oscillate and desorb, while synergistically activating the electronic state of the reducing agent molecules in the system, reducing the energy barrier for oxygen vacancy formation, and thus achieving precise construction of oxygen vacancies on the particle surface. A specially designed circulating water cooling system can precisely control the reaction system temperature below 10°C, effectively avoiding the problems of particle growth, phase change, and thermal decomposition and deactivation of the reducing agent caused by high temperature in traditional thermal reduction methods. The resulting beneficial effects are: (1) efficient and precise construction of oxygen vacancies on the surface of sub-5 nm iron oxide nanoparticles; (2) the process is simple and controllable with good repeatability; (3) the operating conditions are mild and do not require complex equipment; (4) the cost is low and it is easy to achieve large-scale production. This technology combines ease of operation with engineering scale-up potential, and is expected to provide a new paradigm for the construction of surface oxygen vacancies in sub-5-nanometer iron oxide nanoparticles. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 The X-ray diffraction pattern (XRD) of the product prepared in Example 1 of the present application is shown;

[0019] Figure 2 A scanning transmission electron microscope (STEM) image of the product prepared in Example 1 of the present application is shown;

[0020] Figure 3 The XAFS characterization results of the product prepared in Example 1 of the present application are shown, wherein A shows the X-ray absorption fine structure spectrum (XAFS), and B shows the fitting result of the ratio of the Fe-O bond content to the Fe-Fe bond content;

[0021] Figure 4 The T1 relaxation properties of the product prepared in Example 1 of the present application under a 3T magnetic resonance scanner are shown;

[0022] Figure 5 The X-ray diffraction pattern (XRD) of the product prepared in Example 2 of the present application is shown;

[0023] Figure 6 Scanning transmission electron microscopy (STEM) image of the product prepared in Example 2 of the present application is shown

[0024] Figure 7 The XAFS characterization results of the product prepared in Example 2 of the present application are shown, wherein A shows the X-ray absorption fine structure spectrum (XAFS), and B shows the fitting result of the ratio of the Fe-O bond content to the Fe-Fe bond content;

[0025] Figure 8 The T1 relaxation properties of the product prepared in Example 2 of the present application under a 3T magnetic resonance scanner are shown;

[0026] Figure 9 The X-ray diffraction pattern (XRD) of the product prepared in Example 3 of the present application is shown;

[0027] Figure 10 Scanning transmission electron microscopy (STEM) image of the product prepared in Example 3 of the present application is shown

[0028] Figure 11 The XAFS characterization results of the product prepared in Example 3 of the present application are shown, wherein A shows the X-ray absorption fine structure spectrum (XAFS), and B shows the fitting result of the ratio of the Fe-O bond content to the Fe-Fe bond content;

[0029] Figure 12 The T1 relaxation properties of the product prepared in Example 3 of the present application under a 3T magnetic resonance scanner are shown;

[0030] Figure 13 The X-ray diffraction pattern (XRD) of the product prepared in the comparative example of the present application is shown;

[0031] Figure 14 The scanning transmission electron microscope (STEM) image of the product prepared in the comparative example of the present application is shown

[0032] Figure 15 The XAFS characterization results of the products prepared in the comparative examples of the present application are shown, wherein A shows the X-ray absorption fine structure spectrum (XAFS), and wherein B shows the fitting result of the ratio of the content of Fe-O bonds to Fe-Fe bonds;

[0033] Figure 16 The T1 relaxation properties of the product prepared in the comparative example of the present application under a 3T magnetic resonance scanner are shown; DETAILED DESCRIPTION

[0034] The preferred embodiments of the present invention will be described in detail below with reference to the examples. It should be understood that the following examples are provided for illustrative purposes only and are not intended to limit the scope of the present invention. Those skilled in the art may make various modifications and substitutions to the present invention without departing from the purpose and spirit of the present invention.

[0035] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0036] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0037] An embodiment of the present application provides a method for constructing oxygen vacancies based on sub-5 nanometer iron oxide nanoparticles, the method comprising the following steps:

[0038] Step 1: Dispersing sub-5 nanometer iron oxide nanoparticles in an aqueous solution to prepare a sub-5 nanometer iron oxide nanoparticle dispersion, wherein the Fe concentration is less than 300 mg / L;

[0039] Step 2: introducing an inert gas into the sub-5 nanometer iron oxide nanoparticle dispersion in step 1 to remove oxygen from the sub-5 nanometer iron oxide nanoparticle dispersion;

[0040] Step 3, adding a reducing agent to the oxygen-removed sub-5 nanometer iron oxide nanoparticle dispersion prepared in Step 2;

[0041] Step 4, placing the sub-5 nanometer iron oxide nanoparticle dispersion prepared in step 3 and having added a reducing agent in an alternating magnetic field environment, while keeping the sub-5 nanometer iron oxide nanoparticle dispersion in a low temperature state;

[0042] Step 5, dialyzing the iron oxide nanoparticle dispersion after the treatment in step 4 to obtain dialysate to remove excess reducing agent;

[0043] Step 6: The dialysate prepared in step 5 is collected by centrifugation, and the separated nanoparticles are freeze-dried to obtain sub-5 nanometer iron oxide nanoparticles rich in oxygen vacancies.

[0044] In one embodiment, the step 1 of dispersing the iron oxide nanoparticles in the aqueous solution is performed by ultrasonic treatment.

[0045] In one embodiment, in step 2, the inert gas comprises nitrogen.

[0046] In one embodiment, in step 3, the reducing agent includes aqueous ammonia and sodium borohydride.

[0047] In one embodiment, in step 3, aqueous ammonia is used as the reducing agent, and the mass fraction of aqueous ammonia in the dispersion is greater than 3%.

[0048] In one embodiment, in step 3, sodium borohydride is used as a reducing agent, and the concentration of sodium borohydride in the dispersion is greater than 100 mg / mL.

[0049] In one embodiment, in step 4, in the alternating magnetic field environment, the alternating magnetic field strength is 10 kA / m-20 kA / m, and the frequency is 0.8 MHz-1.2 MHz.

[0050] In one embodiment, the low temperature state is that the temperature of the sub-5 nanometer iron oxide nanoparticle dispersion is controlled at 1° C.-10° C., and the alternating magnetic field treatment time of the sub-5 nanometer iron oxide nanoparticle dispersion is more than 20 minutes.

[0051] An embodiment of the present application provides oxygen vacancy-rich sub-5 nanometer iron oxide nanoparticles prepared according to the oxygen vacancy construction method.

[0052] One embodiment of the present application provides the use of the oxygen vacancy-rich sub-5 nanometer iron oxide nanoparticles in a high-performance magnetic resonance T1 contrast agent.

[0053] Example 1

[0054] 1) Prepare an aqueous dispersion of sub-5 nm iron oxide nanoparticles with an Fe concentration of 100 mg / L. Use a 500 W ultrasonic cell disruptor in pulse mode (2 seconds on, 1 second off) for 40 minutes in an ice bath. Characterize particle dispersion by dynamic light scattering (DLS) to ensure a PDI < 0.2.

[0055] 2) Transfer the dispersion to a three-necked flask. Insert a nitrogen tube into the main port to 1 cm below the liquid surface. Connect the side port to a bubble counter. Adjust the nitrogen flow rate to 2 bubbles per second. Continue bubbling for 20 minutes, then seal the system and let it rest for 5 minutes. Use a dissolved oxygen meter to confirm the dissolved oxygen content is < 0.3 mg / L.

[0056] 3) Under nitrogen, slowly add 25% ammonia water at a flow rate of 1 mL / min using a syringe pump while magnetically stirring (300 rpm) to ensure uniform mixing. Adjust the amount of ammonia water added to achieve a 5% ammonia concentration in the dispersion.

[0057] 4) Place the mixed solution in a low-temperature thermostat and maintain the solution temperature at 5°C using a circulating water cooling system. Set the alternating magnetic field generator to an intensity of 18 kA / m and a frequency of 1.2 MHz for 30 minutes.

[0058] 5) Place the treated solution into a 100 kDa MWCO dialysis bag, immerse in 5 L of ultrapure water, and dialyze at 4°C for 72 hours. Replace the ultrapure water every 12 hours to ensure that the final dialysate conductivity is ≤ 2 μS / cm.

[0059] 6) Centrifuge at 15,000 rpm for 30 minutes in a high-speed centrifuge. Discard the supernatant, resuspend the pellet in 5 mL of ultrapure water, and repeat the centrifugation once. Subsequently, prefreeze the nanoparticle suspension in liquid nitrogen for 10 minutes and place it in a freeze dryer (-50°C cold trap, 0.05 mbar vacuum) for 24 hours to obtain a dry product.

[0060] Example 2

[0061] 1) Prepare an aqueous dispersion of sub-5 nm iron oxide nanoparticles with an Fe concentration of 200 mg / L. Use a 500W ultrasonic cell disruptor in pulse mode (2 seconds on, 1 second off) for 30 minutes in an ice bath. Characterize particle dispersibility by dynamic light scattering (DLS) to ensure a PDI < 0.2.

[0062] 2) Transfer the dispersion to a three-necked flask. Insert a nitrogen tube into the main port to 1 cm below the liquid surface. Connect the side port to a bubble counter. Adjust the nitrogen flow rate to 3 bubbles per second. Continue bubbling for 15 minutes, then seal the system and let it rest for 5 minutes. Use a dissolved oxygen meter to confirm the dissolved oxygen content is < 0.3 mg / L.

[0063] 3) Weigh a certain amount of sodium borohydride and slowly add it to the dispersion from 2) under nitrogen to a concentration of 150 mg / mL. Ensure uniform mixing by magnetic stirring (300 rpm).

[0064] 4) Place the mixed solution in a low-temperature thermostat and maintain the solution temperature at 5°C using a circulating water cooling system. Set the alternating magnetic field generator to an intensity of 18 kA / m and a frequency of 1.2 MHz for 40 minutes.

[0065] 5) Place the treated solution into a 100 kDa MWCO dialysis bag, immerse in 5 L of ultrapure water, and dialyze at 4°C for 72 hours. Replace the ultrapure water every 12 hours to ensure that the final dialysate conductivity is ≤ 2 μS / cm.

[0066] 6) Centrifuge at 15,000 rpm for 30 minutes in a high-speed centrifuge. Discard the supernatant, resuspend the pellet in 5 mL of ultrapure water, and repeat the centrifugation once. Subsequently, prefreeze the nanoparticle suspension in liquid nitrogen for 10 minutes and place it in a freeze dryer (-50°C cold trap, 0.05 mbar vacuum) for 24 hours to obtain a dry product.

[0067] Example 3

[0068] 1) Prepare an aqueous dispersion of very small iron oxide nanoparticles with an Fe concentration of 200 mg / L. Use a 500W ultrasonic cell disruptor in pulse mode (2 seconds on, 1 second off) for 40 minutes in an ice bath. Characterize particle dispersibility by dynamic light scattering (DLS) to ensure a PDI < 0.2.

[0069] 2) Transfer the dispersion to a three-necked flask. Insert a nitrogen tube into the main port to 1 cm below the liquid surface. Connect the side port to a bubble counter. Adjust the nitrogen flow rate to 2 bubbles per second. Continue bubbling for 20 minutes, then seal the system and let it rest for 5 minutes. Use a dissolved oxygen meter to confirm the dissolved oxygen content is < 0.3 mg / L.

[0070] 3) Under nitrogen, slowly add 25% aqueous ammonia at a flow rate of 1 mL / min using a syringe pump while magnetically stirring (300 rpm) to ensure uniform mixing. Adjust the amount of aqueous ammonia added to achieve a 10% aqueous ammonia concentration in the dispersion.

[0071] 4) Place the mixed solution in a low-temperature thermostat and maintain the solution temperature at 5°C using a circulating water cooling system. Set the alternating magnetic field generator to 10 kA / m and a frequency of 0.8 MHz for 30 minutes.

[0072] 5) Place the treated solution into a 100 kDa MWCO dialysis bag, immerse in 5 L of ultrapure water, and dialyze at 4°C for 72 hours. Replace the ultrapure water every 12 hours to ensure that the final dialysate conductivity is ≤ 2 μS / cm.

[0073] 6) Centrifuge at 15,000 rpm for 30 minutes in a high-speed centrifuge. Discard the supernatant, resuspend the pellet in 5 mL of ultrapure water, and repeat the centrifugation once. Subsequently, prefreeze the nanoparticle suspension in liquid nitrogen for 10 minutes and place it in a freeze dryer (-50°C cold trap, 0.05 mbar vacuum) for 24 hours to obtain a dry product.

[0074] Comparative Example

[0075] 1) Prepare an aqueous dispersion of very small iron oxide nanoparticles with an Fe concentration of 200 mg / L. Use a 500W ultrasonic cell disruptor in pulse mode (2 seconds on, 1 second off) for 40 minutes in an ice bath. Characterize particle dispersibility by dynamic light scattering (DLS) to ensure a PDI < 0.2.

[0076] 2) Transfer the dispersion to a three-necked flask. Insert a nitrogen tube into the main port to 1 cm below the liquid surface. Connect the side port to a bubble counter. Adjust the nitrogen flow rate to 2 bubbles per second. Continue bubbling for 20 minutes, then seal the system and let it rest for 5 minutes. Use a dissolved oxygen meter to confirm the dissolved oxygen content is < 0.3 mg / L.

[0077] 3) Centrifuge the dispersion at 15,000 rpm for 30 minutes in a high-speed centrifuge. Discard the supernatant, resuspend the pellet in 5 mL of ultrapure water, and repeat the centrifugation once. Subsequently, prefreeze the nanoparticle suspension in liquid nitrogen for 10 minutes and place it in a freeze dryer (-50°C cold trap, 0.05 mbar vacuum) for 24 hours to obtain a dry product.

[0078] XRD characterization test

[0079] Based on Example 1, iron oxide nanoparticles were obtained and subjected to XRD (X-ray Diffraction) analysis. The XRD results are as follows: Figure 1 As shown, the nanoparticles maintain the spinel structure.

[0080] Based on Example 2, iron oxide nanoparticles were obtained and subjected to XRD (X-ray Diffraction) analysis. The XRD results are as follows: Figure 5 As shown, the nanoparticles maintain the spinel structure.

[0081] Based on Example 3, iron oxide nanoparticles were obtained and subjected to XRD (X-ray Diffraction) analysis. The XRD results are as follows: Figure 9 As shown, the nanoparticles maintain the spinel structure.

[0082] Based on the comparative example, iron oxide nanoparticles were obtained and subjected to XRD (X-ray Diffraction) analysis. The XRD results are as follows: Figure 13 As shown, the nanoparticles maintain the spinel structure.

[0083] The XRD characterization results show that compared with the comparative example, the crystal phase of the iron oxide nanoparticles in the three examples of the present application has not changed, and the spinel structure is maintained. This result shows that the method of the present invention can effectively avoid the phase change problem of sub-5 nanometer iron oxide nanoparticles caused by the traditional high-temperature reduction method.

[0084] Scanning transmission electron microscopy (STEM) characterization test

[0085] Iron oxide nanoparticles were obtained based on Example 1 and characterized using a scanning transmission electron microscope (STEM). Figure 2 As shown. The nanoparticle size is below 5nm.

[0086] Iron oxide nanoparticles were obtained based on Example 2 and characterized using a scanning transmission electron microscope (STEM). Figure 6 As shown. The nanoparticle size is below 5nm.

[0087] Iron oxide nanoparticles were obtained based on Example 3 and characterized using a scanning transmission electron microscope (STEM). Figure 10 As shown. The nanoparticle size is below 5nm.

[0088] Iron oxide nanoparticles were obtained based on the comparative example and characterized by scanning transmission electron microscopy (STEM). Figure 14 As shown. The nanoparticle size is below 5nm.

[0089] STEM characterization results showed that the sizes of the iron oxide nanoparticles in the three examples remained unchanged compared to the comparative examples, remaining in the sub-5 nanometer range. This result demonstrates that the method of the present invention can effectively avoid the aggregation and growth problems of sub-5 nanometer iron oxide nanoparticles caused by traditional high-temperature reduction methods.

[0090] XAFS (X-ray Absorption Fine Structure) analysis

[0091] Based on the iron oxide nanoparticles obtained in Example 1, X-ray Absorption Fine Structure (XAFS) analysis was performed on them. The X-ray absorption fine structure spectrum of the product prepared in Example 1 is as follows: Figure 3 As shown in A. The ratio of Fe-O bond to Fe-Fe bond content is 1.06, and the fitting results are as follows Figure 3 As shown in B.

[0092] Based on the iron oxide nanoparticles obtained in Example 2, X-ray Absorption Fine Structure (XAFS) analysis was performed on them. The X-ray absorption fine structure spectrum of the product prepared in Example 2 is as follows: Figure 7 As shown in A. The ratio of Fe-O bond to Fe-Fe bond content is 0.81, and the fitting results are as follows Figure 7 As shown in B.

[0093] Based on the iron oxide nanoparticles obtained in Example 3, X-ray Absorption Fine Structure (XAFS) analysis was performed on them. The X-ray absorption fine structure spectrum of the product prepared in Example 3 is as follows: Figure 11 As shown in A. The ratio of Fe-O bond to Fe-Fe bond content is 0.94, and the fitting results are as follows Figure 11 As shown in B.

[0094] Based on the comparative example, iron oxide nanoparticles were obtained. The X-ray absorption fine structure spectrum of the product prepared in the comparative example is as follows: Figure 15 As shown in A. The ratio of Fe-O bond to Fe-Fe bond content is 1.3, and the fitting results are as follows Figure 15 As shown in B.

[0095] XAFS characterization results show that the ratio of Fe-O bonds to Fe-Fe bonds in the three examples is significantly lower than that in the comparative examples, demonstrating that the method of the present invention can effectively construct oxygen vacancies on sub-5 nanometer iron oxide nanoparticles. By leveraging the spatially localized magnetocaloric effect, the present invention precisely confines the high-temperature reduction process to the nanoparticle surface. Combined with water cooling technology, this method achieves coordinated regulation of high-temperature activation of the nanoparticle surface and the overall low-temperature environment of the system.

[0096] T1 relaxation properties testing under 3T MRI scanner

[0097] Iron oxide nanoparticles were obtained based on Example 1 and characterized using a 3T magnetic resonance scanner. The T1 relaxation properties under the 3T magnetic resonance scanner were as follows: Figure 4As shown in Figure 2, the T1 relaxation rate reached 3.19.

[0098] The iron oxide nanoparticles obtained in Example 2 were characterized using a 3T magnetic resonance scanner. The T1 relaxation properties of the nanoparticles under the 3T magnetic resonance scanner were as follows: Figure 8 As shown in Figure 2, the T1 relaxation rate reached 3.55.

[0099] The iron oxide nanoparticles obtained in Example 3 have a T1 relaxation property under a 3T magnetic resonance scanner. Figure 12 As shown in Figure 2, the T1 relaxation rate reached 2.98.

[0100] Based on the comparative example, iron oxide nanoparticles were obtained, and their T1 relaxation properties under a 3T magnetic resonance scanner were as follows: Figure 16 The T1 relaxation rate was 2.03.

[0101] The results of T1 relaxation properties showed that compared with the comparative example, the T1 relaxation rates in the three embodiments were increased by 46.8%-74.9%, indicating that the method of the present invention can significantly improve the T1 angiography performance of sub-5 nanometer iron oxide nanoparticles.

[0102] The examples and characterization results of this application show that the method described in this application can effectively construct oxygen vacancies on sub-5 nanometer iron oxide nanoparticles, and the T1 relaxation rate at a field strength of 3T is increased by 46.8%-74.9%, reaching a maximum of 3.55mM -1 s -1 , can be used in magnetic resonance T1 contrast agents.

[0103] The above are only preferred embodiments of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for constructing oxygen vacancies based on sub-5 nanometer iron oxide nanoparticles, characterized in that: The method comprises the following steps: Step 1: Dispersing sub-5 nanometer iron oxide nanoparticles in an aqueous solution to prepare a sub-5 nanometer iron oxide nanoparticle dispersion, wherein the Fe concentration is less than 300 mg / L; Step 2: introducing an inert gas into the sub-5 nanometer iron oxide nanoparticle dispersion in step 1 to remove oxygen from the sub-5 nanometer iron oxide nanoparticle dispersion; Step 3, adding a reducing agent to the oxygen-removed sub-5 nanometer iron oxide nanoparticle dispersion prepared in Step 2; Step 4, placing the sub-5 nanometer iron oxide nanoparticle dispersion prepared in step 3 and having added a reducing agent in an alternating magnetic field environment, while keeping the sub-5 nanometer iron oxide nanoparticle dispersion in a low temperature state; Step 5, dialyzing the iron oxide nanoparticle dispersion after the treatment in step 4 to obtain dialysate to remove excess reducing agent; Step 6: The dialysate prepared in step 5 is collected by centrifugation, and the separated nanoparticles are freeze-dried to obtain sub-5 nanometer iron oxide nanoparticles rich in oxygen vacancies.

2. The method for constructing oxygen vacancies based on sub-5 nanometer iron oxide nanoparticles according to claim 1, characterized in that: In step 1, the iron oxide nanoparticles are dispersed in the aqueous solution by ultrasonic treatment.

3. The method for constructing oxygen vacancies based on sub-5 nanometer iron oxide nanoparticles according to claim 1, characterized in that: In step 2, the inert gas comprises nitrogen.

4. The method for constructing oxygen vacancies based on sub-5 nanometer iron oxide nanoparticles according to claim 1, characterized in that: In step 3, the reducing agent includes aqueous ammonia and sodium borohydride.

5. The method for constructing oxygen vacancies based on sub-5 nanometer iron oxide nanoparticles according to claim 4, characterized in that: In step 3, aqueous ammonia is used as a reducing agent, and the mass fraction of aqueous ammonia in the dispersion is greater than 3%.

6. The method for constructing oxygen vacancies based on sub-5 nanometer iron oxide nanoparticles according to claim 4, characterized in that: In step 3, sodium borohydride is used as a reducing agent, and the concentration of sodium borohydride in the dispersion is greater than 100 mg / mL.

7. The method for constructing oxygen vacancies based on sub-5 nanometer iron oxide nanoparticles according to claim 1, characterized in that: In step 4, in the alternating magnetic field environment, the alternating magnetic field strength is 10 kA / m-20 kA / m, and the frequency is 0.8 MHz-1.2 MHz.

8. The method for constructing oxygen vacancies based on sub-5 nanometer iron oxide nanoparticles according to claim 1, characterized in that: In step 4, the low temperature state is that the temperature of the sub-5 nanometer iron oxide nanoparticle dispersion is controlled at 1° C.-10° C., and the alternating magnetic field is used to treat the sub-5 nanometer iron oxide nanoparticle dispersion for more than 20 minutes. 9 . The method according to claim 1 , wherein the prepared iron oxide nanoparticles are sub-5 nanometers and rich in oxygen vacancies.

10. Use of the oxygen vacancy-rich sub-5 nanometer iron oxide nanoparticles according to claim 9 in a high-performance magnetic resonance T1 contrast agent.

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