Response type orderly assembled magnetic nano imaging probe as well as preparation method and application thereof

Abstract

The invention provides a response type orderly-assembled magnetic nano imaging probe and a preparation method and application thereof.The preparation method comprises the steps that S1, a first iron source and platinum acetylacetonate are dissolved in a mixed solution of oleylamine, oleic acid and dibenzyl ether, a reaction is conducted for 10-60 min under the inert atmosphere condition of 200-300 DEG C, washing, precipitation and centrifugation are conducted through a first non-polar solvent, and a magnetic core is obtained; s2, dispersing the prepared magnetic core, a second iron source and long-chain alcohol in a mixed solution of oleic acid, oleylamine, cyclohexane and octadecene, reacting for 30-90 minutes under the inert atmosphere condition of 200-300 DEG C, washing with a first non-polar solvent, precipitating and centrifuging to obtain oil-phase double-magnetic core-shell nanoparticles; and S3, mixing the prepared oil-phase double-magnetic core-shell nanoparticles with a response type polymer ligand in an organic solvent, then transferring the mixture into water for ultrasonic treatment, and carrying out a self-assembly reaction. The response type orderly assembled magnetic nano imaging probe has response type MPI signal change to microenvironment responders, and can be used for early diagnosis of acute liver injury.

Description

Technical Field

[0001] The invention belongs to the field of preparation of magnetic nanoprobes, and in particular relates to a responsive orderly assembled magnetic nano imaging probe and a preparation method and application thereof. Background Art

[0002] Abnormal molecular features often precede pathological or anatomical changes, so real-time visualization of specific biological processes at the molecular level is critical for early diagnosis and the development of precise treatment strategies. Currently, "intelligent" stimulus-responsive imaging strategies achieve automatic response to endogenous molecular markers (such as pH, enzyme activity, or redox gradients) through changes in probe structure and aggregation state, demonstrating high sensitivity and accuracy in molecular imaging of various diseases. However, techniques such as optical imaging, photoacoustic imaging, and magnetic resonance imaging (MRI) still face challenges and cannot achieve imaging with optimal contrast.

[0003] Magnetic particle imaging (MPI) has emerged as a promising diagnostic tool in biomedical imaging and is widely used for real-time visualization of blood vessels, lung perfusion, brain injury, and tumors. MPI has the characteristics of high sensitivity, spatially resolved imaging without penetration depth limitation, and zero background interference, making it more suitable for monitoring molecular level changes associated with diseases. However, the lack of activatable MPI probes for disease marker-specific imaging has hindered the further development of MPI.

[0004] The aggregation state of magnetic nanoparticles (MNPs) significantly affects their collective magnetization behavior, which in turn affects MPI. Due to the unique imaging principle that MPI directly relies on the magnetization behavior of MNPs, it is more sensitive to changes in collective magnetization behavior caused by the assembly structure. Therefore, designing controllable dynamically assembled MNPs is expected to develop activatable MPI probes. However, precisely controlling the MNP assembly structure and magnetization behavior to achieve an adjustable MPI signal response that meets the requirements of dynamic marker changes remains a difficult goal. Summary of the invention

[0005] The purpose of the present invention is to address the deficiencies in the prior art and provide a responsive ordered assembled magnetic nano-imaging probe and a preparation method and application thereof. The obtained responsive ordered assembled magnetic nano-imaging probe has a responsive MPI signal change to a microenvironmental responder and can perform early diagnosis of acute liver injury in vivo.

[0006] To achieve the above object, the technical solution of the present invention is: A method for preparing a responsive ordered assembled magnetic nano-imaging probe, characterized in that it comprises the following steps: S1: dissolving the first iron source and platinum acetylacetonate in a mixed solution of oleylamine, oleic acid and dibenzyl ether, reacting for 10 to 60 minutes under an inert atmosphere at 200 to 300° C., washing the precipitate with a first non-polar solvent and centrifuging to obtain a magnetic core; S2: dispersing the magnetic core, the second iron source and the long-chain alcohol obtained in step S1 in a mixed solution of oleic acid, oleylamine, cyclohexane and octadecene, reacting for 30 to 90 minutes under an inert atmosphere at 200 to 300° C., washing the precipitate with the first non-polar solvent and centrifuging to obtain oil-phase dual magnetic core-shell nanoparticles; S3: uniformly mixing the oil-phase dual magnetic core-shell nanoparticles prepared in step S2 with the responsive polymer ligand in an organic solvent, and then transferring them into water for sonication to perform a self-assembly reaction to obtain the responsive orderly assembled magnetic nano-imaging probe.

[0007] The present invention obtains an ordered assembly by selecting suitable assembly primitives (oil phase dual magnetic core-shell nanoparticles) and ligands (responsive polymer ligands). First, the saturation magnetization intensity of the oil phase dual magnetic core-shell nanoparticles is high, the magnetic susceptibility is strong, and the magnetic particle sensor signal is high. On the one hand, it is ensured that during the assembly process, an ordered assembly with uniform assembly spacing is formed due to strong dipole interactions. On the other hand, its own high magnetic particle sensor signal ensures signal recovery after disassembly and provides a signal change with greater contrast. Secondly, in the selection of the assembled responsive ligand, an amphiphilic ligand with a relatively flexible hydrophobic end is used. Compared with an amphiphilic ligand with a relatively rigid hydrophobic end, this flexible ligand ensures that it has a confined space in water and does not affect the position of particle assembly, so that it completes the formation of an ordered assembly structure dominated by magnetic dipole interactions. At the same time, its functional group that is responsive to active oxygen or other markers ensures that it can respond to specific markers and disassemble to complete the signal change.

[0008] Preferably, the mass ratio of the oil-phase dual magnetic core-shell nanoparticles to the responsive polymer ligands is (1-10):1. The feeding ratio is changed mainly to change the particle size of the synthesized responsive ordered assembled magnetic nanoimaging probes and the assembly spacing of the oil-phase dual magnetic core-shell nanoparticles. Further preferably, the mass ratio of the oil-phase dual magnetic core-shell nanoparticles to the responsive polymer ligands is 5:1.

[0009] Preferably, the responsive polymer ligand is any one or more combinations of polyvinyl pyrrolidone, long-chain fatty acids, fatty alcohols, polyoxyethylene-polyoxypropylene copolymers, poly(styrene-maleic anhydride) and sodium dodecylbenzene sulfonate.

[0010] Preferably, the organic solvent in step S3 includes one or more combinations of dimethylformamide (DMF), dimethylsulfoxide (DMSO), acetonitrile, acetone and tetrahydrofuran (THF).

[0011] Preferably, the magnetic nano-imaging probe has microenvironment marker-responsive MPI changes, and the microenvironment markers include pH, reactive oxygen species, glutathione, and biological enzymes.

[0012] Preferably, in step S1, the feed ratio of the first iron source, the platinum acetylacetonate, the oleylamine, the oleic acid and the diphenyl ether is (0.2-100) mmol: (0.2-100) mmol: (1-10) mL: (1-10) mL: (10-200) mL; The feed ratio of the second iron source, the long-chain alcohol, the oleylamine, the oleic acid, the cyclohexane and the octadecene in the step S2 is (0.2-100) mmol: (0.1-100) mmol: (1-10) mL: (1-10) mL: (1-10) mL: (10-200) mL.

[0013] Preferably, the first iron source in step S1 is one or more of ferric acetylacetonate, ferrous acetylacetonate, ferrous oleate, ferrous acetate, pentacarbonyl iron, and ferrous gluconate; The second iron source in step S2 is one or more of ferric acetylacetonate, ferrous acetylacetonate, ferrous oleate, ferrous acetate, pentacarbonyl iron, and ferrous gluconate; The long-chain alcohol is one or more of 1,2-hexadecanediol, 1,2-dodecanediol, stearyl alcohol, and oleyl alcohol; The first non-polar solvent is one or more of anhydrous ethanol, acetone, methanol, isopropanol and acetic acid.

[0014] Based on the same inventive concept, the present invention also provides a responsive orderly assembled magnetic nano-imaging probe, which has good biocompatibility and microenvironment marker responsive MPI signal changes.

[0015] The preparation method of the present invention can obtain a responsive ordered assembly structure, which shortens the distance between magnetic particles, enhances the magnetic dipole interaction, and has a higher energy barrier, which makes the assembly structure difficult to be magnetized to the direction of the external magnetic field when stimulated by an external magnetic field, so the magnetic susceptibility is reduced, and a lower magnetic particle sensor signal is generated. When the assembly is in an environment where the reactive oxygen species abnormally increase, the surface reactive oxygen responsive ligand breaks, resulting in the destruction of the assembly structure, and the assembly primitive is released. Without the influence of the magnetic dipole interaction of other surrounding magnetic particles, it is easier to be magnetized, reflecting the increase in magnetic susceptibility and generating a higher magnetic particle sensor signal. Such a contrast-enhanced magnetic particle sensor signal change can indicate the presence of reactive oxygen species. Since the reactive oxygen species in the liver have been abnormally produced before the occurrence of liver pathological changes and the generation of abnormal blood markers in liver damage diseases, the abnormally increased reactive oxygen species production is detected at this time, and liver damage can be diagnosed earlier.

[0016] Furthermore, the present invention also provides an application of a responsive orderly assembled magnetic nano-imaging probe in the preparation of a contrast agent for diagnosing acute liver injury.

[0017] Due to the adoption of the above technical solution, the present invention has the following advantages and positive effects compared with the prior art: (1) The reaction conditions in the present invention are controllable, and the prepared materials have good biocompatibility and extremely high stability.

[0018] (2) The responsive ordered assembled magnetic nanoimaging probes of the present invention have strong magnetic dipole interactions generated by the ordered assembly structure, resulting in an efficient MPI signal quenching effect; after responding to microenvironmental markers, high-contrast responsive MPI signal changes are generated.

[0019] (3) The responsive ordered assembled magnetic nano-imaging probes of the present invention can be effectively enriched in the damaged part of the liver, respond to the reactive oxygen species in the damaged part to produce high-contrast responsive MPI signal changes, and achieve early diagnosis. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 This is a transmission electron microscopy image of the oil-phase dual magnetic core-shell nanoparticles in Example 1 of the present invention; Figure 2a-2b This is a transmission electron microscopy image of the water-phase responsive orderly assembled magnetic nano-imaging probe in Example 2 of the present invention; Figure 3 This is a dynamic light scattering particle size distribution diagram of the water-phase responsive orderly assembled magnetic nano-imaging probe in Example 2 of the present invention; Figure 4 This is a transmission electron microscopy image of the water-phase responsive orderly assembled magnetic nano-imaging probe in Example 2 of the present invention after responding to active oxygen; Figure 5 This is a dynamic light scattering particle size distribution diagram of the water-phase responsive ordered assembled magnetic nano-imaging probe after responding to active oxygen in Example 2 of the present invention; Figure 6 This is a magnetic particle imaging image of the water-phase responsive orderly assembled magnetic nano-imaging probe before and after responding to active oxygen in Example 2 of the present invention; Figure 7 This is a transmission electron microscopy image of the water-phase responsive orderly assembled magnetic nano-imaging probe in Example 3 of the present invention; Figure 8 This is a transmission electron microscopy image of the water-phase responsive orderly assembled magnetic nano-imaging probe in Example 4 of the present invention; Fig. 9 This is a transmission electron microscopy image of the water-phase responsive orderly assembled magnetic nano-imaging probe in Example 5 of the present invention; Fig.10 This is the magnetic particle imaging image of acute liver injury in Application Example 1 of the present invention; Fig.11 These are magnetic particle imaging images of acute liver injuries of different severity in Application Example 2 of the present invention. DETAILED DESCRIPTION

[0021] The following is a further detailed description of a responsive ordered assembled magnetic nano-imaging probe and its preparation method and application proposed by the present invention in conjunction with the accompanying drawings and specific embodiments. The advantages and features of the present invention will become more apparent from the following description.

[0022] Example 1: Synthesis of oil-phase dual magnetic core-shell nanoparticles 0.5 mmol of ferric acetylacetonate and 0.5 mmol of platinum acetylacetonate were dissolved in a mixed solution of 1.6 mL of oleylamine, 1.6 mL of oleic acid and 20 mL of diphenyl ether, and reacted at 300°C under an inert atmosphere for 30 minutes. After the reaction, the solution was precipitated with ethanol and centrifuged and washed to obtain a magnetic core with a medium particle size.

[0023] The magnetic core prepared above, 2.5 mmol of ferric acetylacetonate and 1.5 mmol of oleyl alcohol were dispersed in a mixed solution of 2.6 mL of oleic acid, 2.6 mL of oleylamine, 5 mL of cyclohexane and 30 mL of octadecene, and reacted at 300° C. under an inert atmosphere for 30 minutes. The first non-polar solvent was used to wash the precipitate and centrifuge to obtain oil-phase dual magnetic core-shell nanoparticles. The prepared oil-phase dual magnetic core-shell nanoparticles were characterized by transmission electron microscopy. Figure 1 As shown, the synthesized oil-phase dual magnetic core-shell nanoparticles have an obvious core-shell structure and the particle size is about 18 nm.

[0024] Example 2: Synthesis of water-responsive ordered assembled magnetic nano-imaging probes The dual magnetic core-shell nanoparticles synthesized in Example 1 were prepared into a 2 mg / mL tetrahydrofuran solution, and the active oxygen responsive polymer was prepared into a 2 mg / mL solution; 500 μL of the tetrahydrofuran solution of the dual magnetic core-shell nanoparticles and 500 μL of the tetrahydrofuran solution of the active oxygen responsive polymer were taken and fully mixed, 1 mL of the mixture was ultrasonicated for 15 minutes, and then the mixture was quickly injected into 9 mL of water. After ultrasonication for 15 minutes, the mixed solution was rotary evaporated at 45°C to remove tetrahydrofuran; the reaction solution from which tetrahydrofuran was removed was then washed with water and centrifuged 4 times with a 100K ultrafiltration tube at a speed of 4000 r / min, and the centrifugation time for each time was 10 min to obtain a responsive and orderly assembled magnetic nano-imaging probe in the aqueous phase.

[0025] The prepared water-phase responsive ordered assembled magnetic nano-imaging probe was characterized by transmission electron microscopy morphology, such as Figure 2a-2b As shown, the synthesized water-responsive ordered assembled magnetic nanoimaging probe was successfully assembled, the particle size of each particle was approximately 150 nm, and the assembly spacing was relatively uniform.

[0026] The hydrodynamic particle size was tested by dynamic light scattering. Figure 3 As shown, the dynamic light scattering particle size of the synthesized water-responsive ordered assembled magnetic nanoimaging probe is 110 nm.

[0027] After incubating the responsive ordered assembled magnetic nano-imaging probe with hydrogen peroxide solution, the morphology of the responsive ordered assembled magnetic nano-imaging probe after responding to active oxygen was characterized by transmission electron microscopy. The results are as follows: Figure 4 As shown, the synthesized water-responsive ordered assembled magnetic nanoimaging probe underwent obvious disassembly in the presence of reactive oxygen, changing from an assembly to a monodisperse assembly unit.

[0028] After incubating the responsive ordered assembled magnetic nano-imaging probe with hydrogen peroxide solution, the hydrodynamic particle size of the responsive ordered assembled magnetic nano-imaging probe after responding to active oxygen was tested by dynamic light scattering. The results are as follows: Figure 5 As shown, the synthesized water-responsive ordered assembled magnetic nanoimaging probe underwent obvious disassembly in the presence of reactive oxygen, and the dynamic light scattering particle size changed from 110 nm to 37 nm.

[0029] After incubating the responsive ordered assembled magnetic nano-imaging probe with hydrogen peroxide solution, the MPI signal changes of the responsive ordered assembled magnetic nano-imaging probe before and after responding to reactive oxygen species were measured using a commercial magnetic particle imaging device. The results are as follows: Figure 6As shown, the magnetic particle sensing signal of the synthesized water-responsive ordered assembled magnetic nanoimaging probe was significantly improved in the presence of reactive oxygen, which increased by 3.98 times.

[0030] The above results all prove that the responsive ordered assembled magnetic nanoimaging probe has good responsive MPI imaging capability under reactive oxygen conditions.

[0031] Example 3 The dual magnetic core-shell nanoparticles synthesized in Example 1 were prepared into a 2 mg / mL tetrahydrofuran solution, and the active oxygen responsive polymer was prepared into a 2 mg / mL solution; 1000 μL of the tetrahydrofuran solution of the dual magnetic core-shell nanoparticles and 500 μL of the tetrahydrofuran solution of the active oxygen responsive polymer were taken and fully mixed, 1 mL of the mixture was ultrasonicated for 15 minutes, and then the mixture was quickly injected into 9 mL of water. After ultrasonication for 15 minutes, the mixed solution was rotary evaporated at 45°C to remove tetrahydrofuran; the reaction solution from which tetrahydrofuran was removed was then washed with water and centrifuged 4 times with a 100K ultrafiltration tube at a speed of 4000 r / min, and each centrifugation time was 10 min to obtain a responsive and orderly assembled magnetic nano-imaging probe in the aqueous phase.

[0032] Example 4 The dual magnetic core-shell nanoparticles synthesized in Example 1 were prepared into a 2 mg / mL tetrahydrofuran solution, and the active oxygen responsive polymer was prepared into a 2 mg / mL solution; 2.5 mL of the tetrahydrofuran solution of the dual magnetic core-shell nanoparticles and 500 μL of the tetrahydrofuran solution of the active oxygen responsive polymer were taken and fully mixed, 1 mL of the mixture was ultrasonicated for 15 minutes, and then the mixture was quickly injected into 9 mL of water. After ultrasonication for 15 minutes, the mixed solution was rotary evaporated at 45° C. to remove tetrahydrofuran; the reaction solution from which tetrahydrofuran was removed was then washed with water and centrifuged 4 times with a 100K ultrafiltration tube at a speed of 4000 r / min, and the centrifugation time for each time was 10 min to obtain a responsive and orderly assembled magnetic nano-imaging probe in the aqueous phase.

[0033] Example 5 The dual magnetic core-shell nanoparticles synthesized in Example 1 were prepared into a 2 mg / mL tetrahydrofuran solution, and the active oxygen responsive polymer was prepared into a 2 mg / mL solution; 5 mL of the tetrahydrofuran solution of the dual magnetic core-shell nanoparticles and 500 μL of the tetrahydrofuran solution of the active oxygen responsive polymer were taken and fully mixed, 1 mL of the mixture was ultrasonicated for 15 minutes, and then the mixture was quickly injected into 9 mL of water. After ultrasonication for 15 minutes, the mixed solution was rotary evaporated at 45° C. to remove tetrahydrofuran; the reaction solution from which tetrahydrofuran was removed was then washed with water and centrifuged 4 times with a 100K ultrafiltration tube at a speed of 4000 r / min, and the centrifugation time for each time was 10 min to obtain a responsive and orderly assembled magnetic nano-imaging probe in the aqueous phase.

[0034] The responsive ordered assembled magnetic nano-imaging probes prepared in Example 3-5 were characterized by transmission electron microscopy, and the results were as follows: Figure 7-9 As shown, the results show that ordered assembly structures are obtained, among which the assembly obtained in Example 4 is uniform in size, about 150 nm, and the assembly units have a certain assembly spacing, and the assembly spacing is relatively uniform.

[0035] Application Example 1: Application of responsive ordered assembled magnetic nanoimaging probes for early diagnosis of acute liver injury BALB / c mice were intraperitoneally injected with saline or acetyl-p-aminophenol (APAP) to model acute liver injury. The responsive ordered assembled magnetic nano-imaging probes prepared in Example 2 were intravenously injected into the acute liver injury model mice as the experimental group, and the non-responsive assembled magnetic nanoparticles were intravenously injected into the acute liver injury model mice as the control group. The imaging signal changes in the liver tissue of the experimental group, the control group and the healthy mice were observed. The specific changes are as follows: Fig.10 As shown. Within 1 hour, the responsive orderly assembled magnetic nano-imaging probe gradually produced an enhanced MPI signal in the damaged liver, and the stronger MPI signal did not change significantly within 1 hour to 2 hours; while the MPI signal of healthy mice did not increase, and the MPI signal in the damaged liver of the control group did not change significantly. This proves that the responsive orderly assembled magnetic nano-imaging probe can be used for early diagnosis of acute liver injury.

[0036] Application Example 2: Application of responsive ordered assembled magnetic nanoimaging probes for early diagnosis of acute liver injury of different severity Acute liver injury models of different severity were constructed by intraperitoneal injection of 100, 250 and 500 doses of acetaminophen into female BALB / c mice (the more acetaminophen was injected into the mice, the more severe the acute liver injury was). The responsive ordered assembled magnetic nano-imaging probe prepared in Example 2 was injected intravenously, and the changes in the imaging signals of the liver tissue were observed 0-2 hours after injection. The specific changes were as follows: Fig.11 As shown in the figure, the results showed that as the severity of liver injury increased, the responsive MPI signal generated increased, indicating that the degree of MPI signal enhancement was positively correlated with the APAP dose used to induce ALI. It was demonstrated that the responsive ordered assembled magnetic nanoimaging probe can diagnose acute liver injury of different severity.

[0037] The embodiments of the present invention are described in detail above in conjunction with the accompanying drawings, but the present invention is not limited to the above embodiments. Even if various changes are made to the present invention, if these changes fall within the scope of the claims of the present invention and their equivalents, they still fall within the protection scope of the present invention.

Claims

1. A method for preparing a responsive ordered assembled magnetic nano-imaging probe, characterized in that: The following steps are involved: S1: dissolving the first iron source and platinum acetylacetonate in a mixed solution of oleylamine, oleic acid and dibenzyl ether, reacting for 10 to 60 minutes under an inert atmosphere at 200 to 300° C., washing the precipitate with a first non-polar solvent and centrifuging to obtain a magnetic core; S2: dispersing the magnetic core, the second iron source and the long-chain alcohol obtained in step S1 in a mixed solution of oleic acid, oleylamine, cyclohexane and octadecene, reacting for 30 to 90 minutes under an inert atmosphere at 200 to 300° C., washing the precipitate with the first non-polar solvent and centrifuging to obtain oil-phase dual magnetic core-shell nanoparticles; S3: uniformly mixing the oil-phase dual magnetic core-shell nanoparticles prepared in step S2 with the responsive polymer ligand in an organic solvent, and then transferring them into water for sonication to perform a self-assembly reaction to obtain the responsive orderly assembled magnetic nano-imaging probe.

2. The method for preparing the responsive ordered assembled magnetic nano-imaging probe according to claim 1, characterized in that: The mass ratio of the oil phase dual magnetic core-shell nanoparticles to the responsive polymer ligand is (1-10):

1.

3. The method for preparing the responsive ordered assembled magnetic nano-imaging probe according to claim 1, characterized in that: The responsive polymer ligand is any one or more combinations of polyvinyl pyrrolidone, long-chain fatty acids, fatty alcohols, polyoxyethylene-polyoxypropylene copolymers, poly(styrene-maleic anhydride) and sodium dodecylbenzene sulfonate.

4. The method for preparing the responsive ordered assembled magnetic nano-imaging probe according to claim 1, characterized in that: The organic solvent in step S3 includes one or more combinations of dimethylformamide, dimethyl sulfoxide, acetonitrile, acetone and tetrahydrofuran.

5. The method for preparing the responsive ordered assembled magnetic nano-imaging probe according to claim 1, characterized in that: The magnetic nano-imaging probe has microenvironment marker-responsive MPI changes, and the microenvironment markers include pH, active oxygen, glutathione, and biological enzymes.

6. The method for preparing the responsive ordered assembled magnetic nano-imaging probe according to claim 1, characterized in that: The feed ratio of the first iron source, the platinum acetylacetonate, the oleylamine, the oleic acid and the diphenyl ether in the step S1 is (0.2-100) mmol: (0.2-100) mmol: (1-10) mL: (1-10) mL: (10-200) mL; The feed ratio of the second iron source, the long-chain alcohol, the oleylamine, the oleic acid, the cyclohexane and the octadecene in the step S2 is (0.2-100) mmol: (0.1-100) mmol: (1-10) mL: (1-10) mL: (1-10) mL: (10-200) mL.

7. The method for preparing the responsive ordered assembled magnetic nano-imaging probe according to claim 1 or 6, characterized in that: The first iron source in step S1 is one or more of ferric acetylacetonate, ferrous acetylacetonate, ferrous oleate, ferrous acetate, pentacarbonyl iron, and ferrous gluconate; The second iron source in step S2 is one or more of ferric acetylacetonate, ferrous acetylacetonate, ferrous oleate, ferrous acetate, pentacarbonyl iron, and ferrous gluconate; The long-chain alcohol is one or more of 1,2-hexadecanediol, 1,2-dodecanediol, stearyl alcohol, and oleyl alcohol; The first non-polar solvent is one or more of anhydrous ethanol, acetone, methanol, isopropanol and acetic acid.

8. A responsive ordered assembled magnetic nano-imaging probe prepared by the preparation method according to any one of claims 1 to 7.

9. Use of the responsive ordered assembled magnetic nano-imaging probe as claimed in claim 8 in the preparation of a contrast agent for diagnosing acute liver injury.

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