Water-soluble manganese-doped titanium dioxide nanorods, and preparation method and application thereof

Abstract

The application relates to a water-soluble manganese-doped titanium dioxide nanorod and a preparation method and application thereof, and belongs to the technical field of nanometer material preparation; the preparation method of the water-soluble manganese-doped titanium dioxide nanorod comprises the following steps: titanium tetrachloride is added into oleic acid to prepare a titanium oleate compound precursor; then manganese oleate is dissolved in oleic acid, and the above-mentioned titanium oleate compound precursor is added after ultrasonic treatment, and the compound precursor of titanium oleate and manganese oleate is obtained by continuing ultrasonic treatment; the compound precursor of titanium oleate is taken, a mixed system of oleylamine, oleic acid and octadecene is added, the compound precursor of titanium oleate and manganese oleate is injected, oil-soluble manganese-doped titanium dioxide nanorods are obtained, and then water-soluble surface modification is carried out through sodium citrate, so that the water-soluble manganese-doped titanium dioxide nanorods are obtained. The nanorod prepared by the application can be used as an excellent T1 magnetic resonance molecular imaging contrast agent, and has important application value and wide application prospect in the biomedical imaging field such as tumor detection and blood vessel imaging.

Description

Technical Field

[0001] This invention relates to a water-soluble manganese-doped titanium dioxide nanorod, its preparation method, and its application, belonging to the field of nanomaterial preparation technology. Background Technology

[0002] T1-weighted magnetic resonance imaging (MRI) is currently widely used in clinical practice. Gadolinium chelate-based T1-weighted contrast agents dominate the market, such as Gd-DTPA (Magenovic). However, gadolinium-based contrast agents still have many problems, such as nephrotoxicity, easy deposition, and low longitudinal relaxation rate r1. Iron oxide-based contrast agents also have some limitations for MRI, namely, they are prone to artifacts and dark signals. Due to the biological properties, high paramagnetism, and biocompatibility of manganese-based contrast agents, they have been studied as an alternative to gadolinium-based contrast agents and have important clinical significance.

[0003] The journal *Chemical Industry and Engineering Progress* (Vol. 29, No. 6, 2010, pp. 1071-1074, 1079) reported the synthesis of 12 nm Mn-doped TiO2 nanoparticles. The method involved dissolving tetrabutyl titanate (TNB) in anhydrous ethanol, using MnSO4·H2O and MnC2O4·4H2O as manganese sources, and adding a certain amount of manganese source while vigorously stirring until the solution was completely transparent. Then, a certain amount of distilled water and ethanol were added. After standing for 24 hours, the mixture was transferred to a high-temperature, high-pressure reactor at 180°C and reacted for 12 hours. The mixture was then washed and dried at 110°C to obtain the final Mn-doped TiO2 nanoparticles. However, this two-step process for preparing Mn-doped TiO2 nanoparticles is cumbersome and complex, with a long reaction time and significant solvent waste. The application is as a visible-light-responsive Mn-TiO2 photocatalyst, not in the field of in vivo imaging.

[0004] The American journal *ACS Applied Materials & Interfaces* (2023, Vol. 15, pp. 20800-20810) reported the preparation of Rk1@MHT sonosensitive agents using manganese-doped hollow titanium dioxide (MHT) loaded with Rk1 to enhance the sonodynamic therapeutic effect on tumors. Simultaneously, manganese doping endowed the nanoprobe with T1-weighted MRI functionality (its relaxation ratio was r2 / r1 = 1.41). Although this research has applications in the field of magnetic resonance imaging, its primary purpose is still focused on tumor treatment; therefore, its r1 value is only 6.44 mM. -1 s -1 The longitudinal molar relaxation rate r1 is relatively low, only 2-3 mM higher than that of the clinically used commercial T1 type magnetic resonance imaging contrast agent Gd-DTPA. -1s -1 Furthermore, the synthesis process is quite complicated.

[0005] In summary, existing TiO2-based T1-type nano-magnetic resonance contrast agents either have complex nanoparticle synthesis processes and waste a lot of solvent, making them unsuitable for widespread use; or their longitudinal molar relaxation rate r1 is not significantly improved compared to the clinically used commercial T1-type magnetic resonance contrast agent Gd-DTPA. Summary of the Invention

[0006] This invention provides a water-soluble manganese-doped titanium dioxide nanorod, its preparation method, and its application to solve the technical problems existing in the prior art as described above.

[0007] One objective of this invention is to provide a method for preparing water-soluble manganese-doped titanium dioxide nanorods, comprising the following steps:

[0008] a. Add titanium tetrachloride to oleic acid, stir evenly, and then keep warm at room temperature to 100℃ for 20 min to 48 h to obtain the titanium oleate complex precursor;

[0009] b. Add manganese oleate to oleic acid, sonicate to dissolve it, then add the titanium oleate complex precursor prepared in step a, and sonicate to obtain the titanium oleate and manganese oleate complex precursor.

[0010] c. Add the titanium oleate complex precursor prepared in step a to a mixture of oleylamine, oleic acid and octadecene, stir evenly, then heat to 100~150℃ and keep warm for 0.5~2h to remove water, and heat to 240~320℃ under nitrogen protection to obtain the reaction solution.

[0011] d. At 240~320℃, the titanium oleate and manganese oleate composite precursor prepared in step b is rapidly injected into the reaction solution prepared in step c, and the temperature is maintained for 0.2~2h. Then, it is naturally cooled to room temperature to obtain oil-soluble manganese-doped titanium dioxide nanorods.

[0012] e. Use sodium citrate to perform water-soluble surface modification on the oil-soluble manganese-doped titanium dioxide nanorods prepared in step d, thereby obtaining the water-soluble manganese-doped titanium dioxide nanorods.

[0013] Based on the above technical solution, the present invention can be further improved as follows:

[0014] Furthermore, in step a, the mass ratio of titanium tetrachloride to oleic acid is 0.05~1 g / mL.

[0015] Further, in step b, the ratio of the composite precursor of manganese oleate, oleic acid and titanium oleate is 0.1~5g:0.5mL:0.5~2mL.

[0016] Further, in step c, the volume ratio of the titanium oleate complex precursor, oleic acid, oleylamine and octadecene is 0.5~2:0.5~2:10:10~20.

[0017] Furthermore, in step d, the volume ratio of the titanium oleate and manganese oleate composite precursor to the reaction solution is 1~5:20.

[0018] Furthermore, step e specifically includes the following steps:

[0019] e1. Weigh oil-soluble manganese-doped titanium dioxide nanorods into a container, add cyclohexane, disperse evenly, and obtain solution E;

[0020] e2. Add sodium citrate to the flask, then add water and disperse evenly to obtain solution F;

[0021] e3. Add solution E and ethanol to solution F, and reflux and stir at 20~80℃ for 2~24h to obtain reaction solution G;

[0022] e4. After cooling the reaction solution G to room temperature, centrifuge with excess acetone, disperse the resulting precipitate in water and freeze-dry it to obtain a solid that is then dispersed in water to obtain the water-soluble manganese-doped titanium dioxide nanorods.

[0023] Further, in step e1, the ratio of oil-soluble manganese-doped titanium dioxide nanorods to cyclohexane is 2~20 mg: 5~20 mL; in step e2, the ratio of sodium citrate to water is 2~500 mg: 5~20 mL; in step e3, the volume ratio of solution E, solution F, and ethanol is 1~2: 1~2: 1~2.

[0024] The second objective of this invention is to provide a water-soluble manganese-doped titanium dioxide nanorod prepared by the preparation method described above.

[0025] Furthermore, the longitudinal molar relaxation rate r1 of the water-soluble manganese-doped titanium dioxide nanorods is 50.7~69.46 mM. -1 S -1 .

[0026] Furthermore, the matrix material of the water-soluble manganese-doped titanium dioxide nanorods is TiO2.

[0027] Furthermore, the water-soluble manganese-doped titanium dioxide nanorods have a length of 20-23 nm and a width of 3-6 nm.

[0028] The third objective of this invention is to provide an application of the water-soluble manganese-doped titanium dioxide nanorods described above in the field of nuclear magnetic resonance.

[0029] Furthermore, the water-soluble manganese-doped titanium dioxide nanorods are used as a contrast agent for T1-type magnetic resonance imaging.

[0030] The technical solution provided by this invention has the following advantages compared with the prior art:

[0031] 1. The surface modification method for manganese-doped titanium dioxide nanorods provided by this invention is simple and easy to implement. It can obtain nanomaterials with excellent water solubility and dispersibility through simple operations such as stirring, centrifugation, and rotary evaporation. The method for preparing water-soluble rod-shaped manganese-doped titanium dioxide nanorods provides a method for directly preparing oil-soluble rod-shaped manganese-doped titanium dioxide nanorods by rapidly injecting a titanium oleate and manganese oleate composite precursor at high temperature. After surface modification with sodium citrate, these oil-soluble nanorods can yield a T1-type magnetic resonance imaging agent with excellent water solubility.

[0032] 2. The surface modification method for manganese-doped titanium dioxide nanorods of the present invention enables the nanomaterials to maintain excellent water solubility and dispersibility and good biocompatibility after being made into lyophilized powder; and the nanomaterials can maintain excellent longitudinal molar relaxation rate r1 under a 0.5T magnetic field, with an r1 value ranging from 50.7 to 69.46 mM. -1 S -1 Its performance is stable.

[0033] 3. The water-soluble manganese-doped titanium dioxide nanorods prepared by this invention have low toxicity and no other polluting impurities are generated during the preparation process, making them environmentally friendly and highly biosafe.

[0034] 4. The water-soluble manganese-doped titanium dioxide nanorods modified by this invention have uniform and controllable size, with a length of approximately 20-23 nm and a width of approximately 3-6 nm. Combined with their excellent water solubility, good biocompatibility, and low cytotoxicity, these nanorods can serve as a high-performance T1 magnetic resonance molecular imaging contrast agent, and have important application value and broad application prospects in biomedical imaging fields such as tumor detection and vascular imaging. Attached Figure Description

[0035] Figure 1 This is a transmission electron microscope (TEM) image of oil-soluble manganese-doped titanium dioxide nanorods prepared in Example 1 dispersed in cyclohexane.

[0036] Figure 2 This is a transmission electron microscope (TEM) image of the oil-soluble manganese-doped titanium dioxide nanorods prepared in Example 1.

[0037] Figure 3 The image shows a comparison of the longitudinal molar relaxation rate r1 between the oil-soluble manganese-doped titanium dioxide nanorods prepared in Example 1 and Gd-DTPA.

[0038] Figure 4 Transmission electron microscopy (TEM) image of oil-soluble manganese-doped titanium dioxide nanocrystals dispersed in cyclohexane, as prepared in Comparative Example 1.

[0039] Figure 5 This is a transmission electron microscope (TEM) image of oil-soluble manganese-doped titanium dioxide nanocrystals dispersed in cyclohexane, prepared as in Comparative Example 2.

[0040] Figure 6 This is a transmission electron microscope (TEM) image of oil-soluble manganese-doped titanium dioxide nanocrystals dispersed in cyclohexane, prepared as in Comparative Example 3. Detailed Implementation

[0041] The principles and features of the present invention are described below with reference to examples. The examples are only used to explain the present invention and are not intended to limit the scope of the present invention.

[0042] Example 1

[0043] A method for preparing water-soluble manganese-doped titanium dioxide nanorods includes the following steps:

[0044] a. Add titanium tetrachloride to oleic acid, stir evenly, and then keep warm at room temperature for 24 hours to obtain a black opaque solution A. Cool the solution A naturally to room temperature to obtain the titanium oleate complex precursor.

[0045] Wherein: the mass ratio of titanium tetrachloride to the volume ratio of oleic acid is 0.2 g / mL;

[0046] b. Add manganese oleate to oleic acid, sonicate to dissolve it, then add the titanium oleate complex precursor, and sonicate to obtain a black opaque solution B, which is the titanium oleate and manganese oleate complex precursor.

[0047] The ratio of the mass of manganese oleate, the volume of oleic acid, and the volume of the titanium oleate composite precursor is 0.1 g : 0.5 mL : 0.5 mL.

[0048] c. Add the titanium oleate complex precursor to a mixture of oleylamine, oleic acid and octadecene, stir until homogeneous, then heat to 100°C and hold for 0.5 h to remove water, and heat to 280°C under nitrogen protection to obtain reaction solution C.

[0049] The volume ratio of the titanium oleate complex precursor, oleic acid, oleylamine and octadecene is 0.5:0.5:10:10.

[0050] d. At 280℃, the titanium oleate and manganese oleate composite precursor prepared in step b is injected into the reaction solution C prepared in step c within 5 seconds, and the temperature is maintained for 1 hour to obtain solution D. Then, it is naturally cooled to room temperature to obtain oil-soluble manganese-doped titanium dioxide nanorods.

[0051] Wherein: the volume ratio of the titanium oleate and manganese oleate complex precursor to reaction solution C is 1:20;

[0052] e. Water-soluble surface modification of the oil-soluble manganese-doped titanium dioxide nanorods prepared in step d is performed using sodium citrate. The specific steps are as follows:

[0053] e1. Weigh oil-soluble manganese-doped titanium dioxide nanorods into a beaker, add cyclohexane, disperse evenly, and obtain solution E;

[0054] The mass ratio of oil-soluble manganese-doped titanium dioxide nanorods to the volume of cyclohexane is 10 mg: 10 mL.

[0055] e2. Add sodium citrate to the flask, then add water and disperse evenly to obtain solution F;

[0056] Wherein: the mass ratio of sodium citrate to water volume is 500 mg: 20 mL;

[0057] e3. Add solution E and ethanol to solution F, and reflux and stir at 60°C for 24 h to obtain reaction solution G;

[0058] The volume ratio of solution E, solution F, and ethanol is 1:2:1.

[0059] e4. After cooling the reaction solution G to room temperature, centrifuge with excess acetone (10000 rpm, 10 min) to remove water from the reaction solution G. Disperse the resulting precipitate in water and freeze-dry (-80℃, 24 h) to obtain a solid that is then redispersed in water (solid:water = 5 mg:1 mL). This completes the surface modification of the oil-soluble manganese-doped titanium dioxide nanorods and yields the water-soluble manganese-doped titanium dioxide nanorods.

[0060] Figure 1 The image shows a transmission electron microscope (TEM) image of the oil-soluble manganese-doped titanium dioxide nanomaterials prepared in Example 1 dispersed in cyclohexane (characterized using a JEOL JEM-1400 TEM). As can be seen from the image, the oil-soluble manganese-doped titanium dioxide nanomaterials prepared in Example 1 have a diameter of approximately 20 nm and a width of approximately 4 nm.

[0061] Figure 2 The image shows a transmission electron microscope (TEM) image of the water-soluble manganese-doped titanium dioxide nanorods prepared in Example 1 (characterized using a JEOL JEM-1400 TEM). As can be seen from the image, the water-soluble manganese-doped titanium dioxide nanorods prepared in Example 1 exhibit excellent dispersibility in aqueous solution. The nanoparticles have a length of approximately 20 nm and a width of approximately 4 nm. This is consistent with the TEM image of the material before modification. Figure 1There was no significant difference in appearance, and no obvious aggregation occurred.

[0062] Figure 3 This is a comparison of the longitudinal molar relaxation rate (r1) of water-soluble manganese-doped titanium dioxide nanorods after surface modification with oil-soluble manganese-doped titanium dioxide nanorods prepared in Example 1, and the commercially available T1-type contrast agent Gd-DTPA. The figure shows that the longitudinal molar relaxation rate (r1) of the water-soluble manganese-doped titanium dioxide nanorods prepared in Example 1 reaches 69.46 mM at 0.5 T. -1 S -1 It is 14.68 times more potent than the commercially available T1 contrast agent Gd-DTPA, and has great potential for clinical application.

[0063] Example 2

[0064] A method for preparing water-soluble manganese-doped titanium dioxide nanorods includes the following steps:

[0065] a. Add titanium tetrachloride to oleic acid, stir evenly, and then keep warm at 80°C for 20 min to obtain a black opaque solution A. Cool the solution A naturally to room temperature to obtain the titanium oleate complex precursor.

[0066] The mass ratio of titanium tetrachloride to oleic acid volume is 0.05 g / mL.

[0067] b. Add manganese oleate to oleic acid, sonicate to dissolve it, then add the titanium oleate complex precursor, and sonicate to obtain a black opaque solution B, which is the titanium oleate and manganese oleate complex precursor.

[0068] The ratio of the mass of manganese oleate, the volume of oleic acid, and the volume of the titanium oleate composite precursor is 0.2 g: 0.5 mL: 1 mL.

[0069] c. Add the titanium oleate complex precursor to a mixture of oleylamine, oleic acid and octadecene, stir until homogeneous, then heat to 100°C and hold for 0.5 h to remove water, and heat to 300°C under nitrogen protection to obtain reaction solution C.

[0070] The volume ratio of the titanium oleate complex precursor, oleic acid, oleylamine and octadecene is 1:2:10:10.

[0071] d. At 300℃, the titanium oleate and manganese oleate composite precursor prepared in step b is injected into the reaction solution C prepared in step c within 5 seconds, and the temperature is maintained for 0.5h to obtain solution D. Then, it is naturally cooled to room temperature to obtain oil-soluble manganese-doped titanium dioxide nanorods.

[0072] Wherein: the volume ratio of the titanium oleate and manganese oleate complex precursor to reaction solution C is 1:20;

[0073] e. Water-soluble surface modification of the oil-soluble manganese-doped titanium dioxide nanorods prepared in step d is performed using sodium citrate. The specific steps are as follows:

[0074] e1. Weigh oil-soluble manganese-doped titanium dioxide nanorods into a beaker, add cyclohexane, disperse evenly, and obtain solution E;

[0075] The mass ratio of oil-soluble manganese-doped titanium dioxide nanorods to the volume of cyclohexane was 5 mg: 10 mL.

[0076] e2. Add sodium citrate to the flask, then add water and disperse evenly to obtain solution F;

[0077] Wherein: the mass ratio of sodium citrate to water volume is 100 mg: 20 mL;

[0078] e3. Add solution E and ethanol to solution F, and reflux and stir at 80°C for 6 hours to obtain reaction solution G;

[0079] The volume ratio of solution E, solution F, and ethanol is 1:2:1.

[0080] e4. After cooling the reaction solution G to room temperature, centrifuge with excess acetone (10000 rpm, 10 min) to remove water from the reaction solution G. Disperse the resulting precipitate in water and freeze-dry (-80℃, 24 h) to obtain a solid that is then redispersed in water (solid:water = 5 mg:1 mL). This completes the surface modification of the oil-soluble manganese-doped titanium dioxide nanorods and yields the water-soluble manganese-doped titanium dioxide nanorods.

[0081] The samples were characterized by transmission electron microscopy (using a JEOL JEM-1400 transmission electron microscope). The water-soluble manganese-doped titanium dioxide nanorods obtained in Example 2 had a length of approximately 23 nm and a width of approximately 4 nm. The longitudinal molar relaxation rate r1, measured by a 0.5 T magnetic resonance analyzer, was 68.04 mM. -1 S -1 .

[0082] Example 3

[0083] A method for preparing water-soluble manganese-doped titanium dioxide nanorods includes the following steps:

[0084] a. Add titanium tetrachloride to oleic acid, stir evenly, and then keep warm at 50°C for 6 hours to obtain a black opaque solution A. Cool the solution A naturally to room temperature to obtain the titanium oleate complex precursor.

[0085] The mass ratio of titanium tetrachloride to oleic acid volume is 0.1 g / mL.

[0086] b. Add manganese oleate to oleic acid, sonicate to dissolve it, then add the titanium oleate complex precursor, and sonicate to obtain a black opaque solution B, which is the titanium oleate and manganese oleate complex precursor.

[0087] The ratio of the mass of manganese oleate, the volume of oleic acid, and the volume of the titanium oleate composite precursor is 5 g: 0.5 mL: 0.5 mL.

[0088] c. Add the titanium oleate complex precursor to a mixture of oleylamine, oleic acid and octadecene, stir until homogeneous, then heat to 100°C and hold for 1 hour to remove water, and heat to 240°C under nitrogen protection to obtain reaction solution C.

[0089] The volume ratio of the titanium oleate complex precursor, oleic acid, oleylamine and octadecene is 0.5:1:10:10.

[0090] d. At 240℃, the titanium oleate and manganese oleate composite precursor prepared in step b is injected into the reaction solution C prepared in step c within 5 seconds, and the temperature is maintained for 2 hours to obtain solution D. Then, it is naturally cooled to room temperature to obtain oil-soluble manganese-doped titanium dioxide nanorods.

[0091] Wherein: the volume ratio of the titanium oleate and manganese oleate complex precursor to reaction solution C is 1.5 mL: 20 mL;

[0092] e. Water-soluble surface modification of the oil-soluble manganese-doped titanium dioxide nanorods prepared in step d is performed using sodium citrate. The specific steps are as follows:

[0093] e1. Weigh oil-soluble manganese-doped titanium dioxide nanorods into a beaker, add cyclohexane, disperse evenly, and obtain solution E;

[0094] The mass ratio of oil-soluble manganese-doped titanium dioxide nanorods to the volume ratio of cyclohexane is 2:10.

[0095] e2. Add sodium citrate to the flask, then add water and disperse evenly to obtain solution F;

[0096] Wherein: the mass ratio of sodium citrate to water volume is 50 mg: 20 mL;

[0097] e3. Add solution E and ethanol to solution F, and reflux and stir at 30°C for 12 hours to obtain reaction solution G;

[0098] The volume ratio of solution E, solution F, and ethanol is 1:2:1.

[0099] e4. After cooling the reaction solution G to room temperature, centrifuge with excess acetone (10000 rpm, 10 min) to remove water from the reaction solution G. Disperse the resulting precipitate in water and freeze-dry (-80℃, 24 h) to obtain a solid that is then redispersed in water (solid:water = 5 mg:1 mL). This completes the surface modification of the oil-soluble manganese-doped titanium dioxide nanorods and yields the water-soluble manganese-doped titanium dioxide nanorods.

[0100] The samples were characterized by transmission electron microscopy (using a JEOL JEM-1400 transmission electron microscope). The water-soluble manganese-doped titanium dioxide nanorods obtained in Example 3 had a length of approximately 23 nm and a width of approximately 4 nm. The longitudinal molar relaxation rate r1, measured by a 0.5 T magnetic resonance analyzer, was 50.7 mM. -1 S -1 .

[0101] Example 4

[0102] A method for preparing water-soluble manganese-doped titanium dioxide nanorods includes the following steps:

[0103] a. Add titanium tetrachloride to oleic acid, stir evenly, and then keep warm at 100°C for 1 hour to obtain a black opaque solution A. Cool the solution A naturally to room temperature to obtain the titanium oleate complex precursor.

[0104] The mass ratio of titanium tetrachloride to oleic acid volume is 0.15 g / mL.

[0105] b. Add manganese oleate to oleic acid, sonicate to dissolve it, then add the titanium oleate complex precursor, and sonicate to obtain a black opaque solution B, which is the titanium oleate and manganese oleate complex precursor.

[0106] The ratio of the mass of manganese oleate, the volume of oleic acid, and the volume of the titanium oleate composite precursor is 0.3 g : 0.5 mL : 0.5 mL.

[0107] c. Add the titanium oleate complex precursor to a mixture of oleylamine, oleic acid and octadecene, stir until homogeneous, then heat to 100°C and hold for 2 hours to remove water, and heat to 320°C under nitrogen protection to obtain reaction solution C.

[0108] The volume ratio of the titanium oleate complex precursor, oleic acid, oleylamine and octadecene is 0.5:0.5:10:10.

[0109] d. At 320℃, the titanium oleate and manganese oleate composite precursor prepared in step b is injected into the reaction solution C prepared in step c within 5 seconds, and the temperature is maintained for 0.5h to obtain solution D. Then, it is naturally cooled to room temperature to obtain oil-soluble manganese-doped titanium dioxide nanorods.

[0110] Wherein: the volume ratio of the titanium oleate and manganese oleate complex precursor to reaction solution C is 1:20;

[0111] e. Water-soluble surface modification of the oil-soluble manganese-doped titanium dioxide nanorods prepared in step d is performed using sodium citrate. The specific steps are as follows:

[0112] e1. Weigh oil-soluble manganese-doped titanium dioxide nanorods into a beaker, add cyclohexane, disperse evenly, and obtain solution E;

[0113] The mass ratio of oil-soluble manganese-doped titanium dioxide nanorods to the volume of cyclohexane was 2 mg: 10 mL.

[0114] e2. Add sodium citrate to the flask, then add water and disperse evenly to obtain solution F;

[0115] Wherein: the mass ratio of sodium citrate to water volume is 20 mg: 20 mL;

[0116] e3. Add solution E and ethanol to solution F, and reflux and stir at 80°C for 2 hours to obtain reaction solution G;

[0117] The volume ratio of solution E, solution F, and ethanol is 1:2:1.

[0118] e4. After cooling the reaction solution G to room temperature, centrifuge with excess acetone (10000 rpm, 10 min) to remove water from the reaction solution G. Disperse the resulting precipitate in water and freeze-dry (-80℃, 24 h) to obtain a solid that is then redispersed in water (solid:water = 5 mg:1 mL). This completes the surface modification of the oil-soluble manganese-doped titanium dioxide nanorods and yields the water-soluble manganese-doped titanium dioxide nanorods.

[0119] The samples were characterized by transmission electron microscopy (using a JEOL JEM-1400 transmission electron microscope). The water-soluble manganese-doped titanium dioxide nanorods obtained in Example 4 had a length of approximately 20 nm and a width of approximately 4 nm. The longitudinal molar relaxation rate r1, measured by a 0.5 T magnetic resonance analyzer, was 60.72 mM. -1 S -1 .

[0120] Comparative Example 1

[0121] A method for preparing water-soluble manganese-doped titanium dioxide nanocrystals includes the following steps:

[0122] a. Add titanium sulfate to oleic acid, stir evenly, and then keep warm at 100℃ for 48h to obtain black opaque solution A. Cool solution A naturally to room temperature to obtain the titanium oleate complex precursor.

[0123] Wherein, the mass ratio of titanium oleate to the volume of oleic acid is 0.2 g / mL;

[0124] b. Add manganese oleate to oleic acid, sonicate to dissolve it, then add the titanium oleate complex precursor, and sonicate to obtain a black opaque solution B, which is the titanium oleate and manganese oleate complex precursor.

[0125] The ratio of the mass of manganese oleate, the volume of oleic acid, and the volume of the titanium oleate composite precursor is 0.1 g : 0.5 mL : 0.5 mL.

[0126] c. Add the titanium oleate complex precursor to a mixture of oleylamine, oleic acid and octadecene, stir until homogeneous, then heat to 100°C and hold for 0.5 h to remove water, and heat to 280°C under nitrogen protection to obtain reaction solution C.

[0127] The volume ratio of the titanium oleate complex precursor, oleic acid, oleylamine and octadecene is 0.5:0.5:10:10.

[0128] d. At 280℃, the titanium oleate and manganese oleate composite precursor prepared in step b is injected into the reaction solution C prepared in step c within 5 seconds, and the temperature is maintained for 1 hour to obtain solution D. Then, it is naturally cooled to room temperature to obtain oil-soluble manganese-doped titanium dioxide nanocrystals.

[0129] Wherein: the volume ratio of the titanium oleate and manganese oleate complex precursor to reaction solution C is 1:20;

[0130] e. Water-soluble surface modification of the oil-soluble manganese-doped titanium dioxide nanocrystals prepared in step d using sodium citrate, the specific steps of which are as follows:

[0131] e1. Weigh oil-soluble manganese-doped titanium dioxide nanocrystals into a beaker, add cyclohexane, disperse evenly, and obtain solution E;

[0132] The ratio of the mass of oil-soluble manganese-doped titanium dioxide nanocrystals to the volume of cyclohexane was 10 mg: 10 mL.

[0133] e2. Add sodium citrate to the flask, then add water and disperse evenly to obtain solution F;

[0134] Wherein: the mass ratio of sodium citrate to water volume is 500 mg: 20 mL;

[0135] e3. Add solution E and ethanol to solution F, and reflux and stir at 60°C for 24 h to obtain reaction solution G;

[0136] The volume ratio of solution E, solution F, and ethanol is 1:2:1.

[0137] e4. After cooling the reaction solution G to room temperature, centrifuge with excess acetone (10000 rpm, 10 min) to remove water from the reaction solution G. Disperse the resulting precipitate in water and freeze-dry (-80℃, 24 h) to obtain a solid that is then redispersed in water (solid:water = 5 mg:1 mL). This completes the surface modification of the oil-soluble manganese-doped titanium dioxide nanocrystals and yields the water-soluble manganese-doped titanium dioxide nanocrystals.

[0138] Figure 4 The image shows a transmission electron microscope (TEM) image of the oil-soluble manganese-doped titanium dioxide nanocrystals prepared in Comparative Example 1 dispersed in cyclohexane (characterized using a JEOL JEM-1400 TEM). The image shows that the oil-soluble manganese-doped titanium dioxide nanomaterials prepared in Comparative Example 1 are in the form of nanoflowers rather than rods. The water-soluble manganese-doped titanium dioxide nanocrystals obtained in Comparative Example 1 were tested using a 0.5 T magnetic resonance spectrometer, and their longitudinal molar relaxation rate r1 was 0.27 mM. -1 S -1 .

[0139] Comparative Example 2

[0140] A method for preparing water-soluble manganese-doped titanium dioxide nanocrystals includes the following steps:

[0141] a. Add titanium tetrachloride to oleic acid, stir evenly, and then keep warm at room temperature for 24 hours to obtain a black opaque solution A. Cool the solution A naturally to room temperature to obtain the titanium oleate complex precursor.

[0142] The mass ratio of titanium tetrachloride to oleic acid volume is 0.2 g / mL.

[0143] b. Add manganese oleate to oleic acid, sonicate to dissolve it, then add the titanium oleate complex precursor, and sonicate to obtain a black opaque solution B, which is the titanium oleate and manganese oleate complex precursor.

[0144] The ratio of the mass of manganese oleate, the volume of oleic acid, and the volume of the titanium oleate composite precursor is 0.1 g : 0.5 mL : 0.5 mL.

[0145] c. Add the titanium oleate complex precursor to a mixture of oleylamine, oleic acid and octadecene, stir until homogeneous, then heat to 100°C and hold for 0.5 h to remove water, and heat to 200°C under nitrogen protection to obtain reaction solution C.

[0146] The volume ratio of the titanium oleate complex precursor, oleic acid, oleylamine and octadecene is 0.5:0.5:10:10.

[0147] d. At 200℃, the titanium oleate and manganese oleate composite precursor prepared in step b is injected into the reaction solution C prepared in step c within 5 seconds, and the temperature is maintained for 1 hour to obtain solution D. Then, it is naturally cooled to room temperature to obtain oil-soluble manganese-doped titanium dioxide nanocrystals.

[0148] Wherein: the volume ratio of the titanium oleate and manganese oleate complex precursor to reaction solution C is 1:20;

[0149] e. Water-soluble surface modification of the oil-soluble manganese-doped titanium dioxide nanocrystals prepared in step d using sodium citrate, the specific steps of which are as follows:

[0150] e1. Weigh oil-soluble manganese-doped titanium dioxide nanocrystals into a beaker, add cyclohexane, disperse evenly, and obtain solution E;

[0151] The ratio of the mass of oil-soluble manganese-doped titanium dioxide nanocrystals to the volume of cyclohexane was 10 mg: 10 mL.

[0152] e2. Add sodium citrate to the flask, then add water and disperse evenly to obtain solution F;

[0153] Wherein: the mass ratio of sodium citrate to water volume is 500 mg: 20 mL;

[0154] e3. Add solution E and ethanol to solution F, and reflux and stir at 60°C for 24 h to obtain reaction solution G;

[0155] The volume ratio of solution E, solution F, and ethanol is 1:2:1.

[0156] e4. After cooling the reaction solution G to room temperature, centrifuge with excess acetone (10000 rpm, 10 min) to remove water from the reaction solution G. Disperse the resulting precipitate in water and freeze-dry (-80℃, 24 h) to obtain a solid that is then redispersed in water (solid:water = 5 mg:1 mL). This completes the surface modification of the oil-soluble manganese-doped titanium dioxide nanocrystals and yields the water-soluble manganese-doped titanium dioxide nanocrystals.

[0157] Figure 5The image shows a transmission electron microscope (TEM) image of the oil-soluble manganese-doped titanium dioxide nanocrystals prepared in Comparative Example 2 dispersed in cyclohexane (characterized using a JEOL JEM-1400 TEM). As can be seen from the image, the oil-soluble manganese-doped titanium dioxide nanomaterials prepared in Comparative Example 2 are essentially nanodot-shaped with a diameter of approximately 1–2 nm. The water-soluble manganese-doped titanium dioxide nanocrystals obtained in Comparative Example 2, measured by a 0.5 T magnetic resonance spectrometer, have a longitudinal molar relaxation rate r1 of 5.62 mM. -1 S -1 .

[0158] Comparative Example 3

[0159] A method for preparing water-soluble manganese-doped titanium dioxide nanocrystals includes the following steps:

[0160] a. Add titanium tetrachloride to oleic acid, stir evenly, and then keep warm at room temperature for 24 hours to obtain a black opaque solution A. Cool the solution A naturally to room temperature to obtain the titanium oleate complex precursor.

[0161] The mass ratio of titanium tetrachloride to oleic acid volume is 0.2 g / mL.

[0162] b. Add manganese oleate to oleic acid, sonicate to dissolve it, then add the titanium oleate complex precursor, and sonicate to obtain a black opaque solution B, which is the titanium oleate and manganese oleate complex precursor.

[0163] The ratio of the mass of manganese oleate, the volume of oleic acid, and the volume of the titanium oleate composite precursor is 0.1 g : 0.5 mL : 0.5 mL.

[0164] c. Add the titanium oleate complex precursor to a mixture of oleylamine, oleic acid and octadecene, stir until homogeneous, then heat to 100°C and hold for 0.5 h to remove water, and heat to 240°C under nitrogen protection to obtain reaction solution C.

[0165] The volume ratio of the titanium oleate complex precursor, oleic acid, oleylamine and octadecene is 0.5:0.5:10:10.

[0166] d. At 240℃, the titanium oleate and manganese oleate composite precursor prepared in step b is injected into the reaction solution C prepared in step c within 5 seconds. Without keeping it warm, solution D is obtained. Then, it is naturally cooled to room temperature to obtain oil-soluble manganese-doped titanium dioxide nanocrystals.

[0167] Wherein: the volume ratio of the titanium oleate and manganese oleate complex precursor to reaction solution C is 1:20;

[0168] e. Water-soluble surface modification of the oil-soluble manganese-doped titanium dioxide nanocrystals prepared in step d using sodium citrate, the specific steps of which are as follows:

[0169] e1. Weigh oil-soluble manganese-doped titanium dioxide nanocrystals into a beaker, add cyclohexane, disperse evenly, and obtain solution E;

[0170] The ratio of the mass of oil-soluble manganese-doped titanium dioxide nanocrystals to the volume of cyclohexane was 10 mg: 10 mL.

[0171] e2. Add sodium citrate to the flask, then add water and disperse evenly to obtain solution F;

[0172] Wherein: the mass ratio of sodium citrate to water volume is 500 mg: 20 mL;

[0173] e3. Add solution E and ethanol to solution F, and reflux and stir at 60°C for 24 h to obtain reaction solution G;

[0174] The volume ratio of solution E, solution F, and ethanol is 1:2:1.

[0175] e4. After cooling the reaction solution G to room temperature, centrifuge with excess acetone (10000 rpm, 10 min) to remove water from the reaction solution G. Disperse the resulting precipitate in water and freeze-dry (-80℃, 24 h) to obtain a solid that is then redispersed in water (solid:water = 5 mg:1 mL). This completes the surface modification of the oil-soluble manganese-doped titanium dioxide nanocrystals and yields the water-soluble manganese-doped titanium dioxide nanocrystals.

[0176] Figure 6 The image shows a transmission electron microscope (TEM) image of the oil-soluble manganese-doped titanium dioxide nanocrystals prepared in Comparative Example 3 dispersed in cyclohexane (characterized using a JEOL JEM-1400 TEM). As can be seen from the image, the oil-soluble manganese-doped titanium dioxide nanocrystals prepared in Comparative Example 3 are essentially nanodot-shaped with a diameter of approximately 1–2 nm. The water-soluble manganese-doped titanium dioxide nanocrystals obtained in Comparative Example 3, measured by a 0.5 T magnetic resonance spectrometer, have a longitudinal molar relaxation rate r1 of 4.53 mM. -1 S -1 .

[0177] The shape of the nanoparticles obtained in the comparative example of this invention has been changed, and the relaxation rate has been significantly reduced compared with the example. The maximum relaxation rate in the example is about 14 times that of the clinically commonly used T1 type contrast agent Gd-DTPA, which has good research value.

[0178] 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 manganese-doped titanium dioxide nanorods, characterized in that, Includes the following steps: a. Add titanium tetrachloride to oleic acid, stir until homogeneous, and then keep warm at room temperature to 100℃ for 20 min to 48 h to obtain the titanium oleate complex precursor; the mass ratio of titanium tetrachloride to oleic acid volume is 0.05 to 1 g / mL. b. Add manganese oleate to oleic acid, sonicate to dissolve it, then add the titanium oleate complex precursor prepared in step a, and sonicate to obtain the titanium oleate and manganese oleate complex precursor; the ratio of manganese oleate, oleic acid and titanium oleate complex precursor is 0.1~5g:0.5mL:0.5~2mL. c. Add the titanium oleate composite precursor prepared in step a to a mixture of oleylamine, oleic acid and octadecene, stir until homogeneous, then heat to 100~150℃ and keep at that temperature for 0.5~2h to remove water. Heat to 240~320℃ under nitrogen protection to obtain a reaction solution. The volume ratio of titanium oleate composite precursor, oleic acid, oleylamine and octadecene is 0.5~2:0.5~2:10:10~20. d. At 240~320℃, the titanium oleate and manganese oleate composite precursor prepared in step b is rapidly injected into the reaction solution prepared in step c, and the temperature is maintained for 0.2~2h. Then, it is naturally cooled to room temperature to obtain oil-soluble manganese-doped titanium dioxide nanorods. The volume ratio of the titanium oleate and manganese oleate composite precursor to the reaction solution is 1~5:

20. e. The oil-soluble manganese-doped titanium dioxide nanorods prepared in step d are subjected to water-soluble surface modification with sodium citrate to obtain the water-soluble manganese-doped titanium dioxide nanorods.

2. The method for preparing water-soluble manganese-doped titanium dioxide nanorods according to claim 1, characterized in that, Step e specifically includes the following steps: e1. Weigh oil-soluble manganese-doped titanium dioxide nanorods into a container, add cyclohexane, disperse evenly, and obtain solution E; e2. Add sodium citrate to the flask, then add water and disperse evenly to obtain solution F; e3. Add solution E and ethanol to solution F, and reflux and stir at 20~80℃ for 2~24h to obtain reaction solution G; e4. After cooling the reaction solution G to room temperature, centrifuge with excess acetone, disperse the resulting precipitate in water and freeze-dry it to obtain a solid that is then dispersed in water to obtain the water-soluble manganese-doped titanium dioxide nanorods.

3. The method for preparing water-soluble manganese-doped titanium dioxide nanorods according to claim 2, characterized in that, In step e1, the ratio of oil-soluble manganese-doped titanium dioxide nanorods to cyclohexane is 2~20 mg: 5~20 mL; in step e2, the ratio of sodium citrate to water is 2~500 mg: 5~20 mL; in step e3, the volume ratio of solution E, solution F, and ethanol is 1~2: 1~2: 1~2.

4. A water-soluble manganese-doped titanium dioxide nanorod prepared by the preparation method according to any one of claims 1 to 3.

5. The water-soluble manganese-doped titanium dioxide nanorods according to claim 4, characterized in that, The longitudinal molar relaxation rate r1 of the manganese-doped titanium dioxide nanorods is 50.7~69.46 mM. -1 S -1 .

6. The water-soluble manganese-doped titanium dioxide nanorods according to claim 4, characterized in that, The matrix material of the manganese-doped titanium dioxide nanorods is TiO2.

7. The water-soluble manganese-doped titanium dioxide nanorods according to claim 4, characterized in that, The manganese-doped titanium dioxide nanorods have a length of 20-23 nm and a width of 3-6 nm.

8. The application of water-soluble manganese-doped titanium dioxide nanorods as described in any one of claims 4 to 7 in the field of nuclear magnetic resonance.

9. The application according to claim 8, characterized in that, The water-soluble manganese-doped titanium dioxide nanorods are used as contrast agents for T1-type magnetic resonance imaging.

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