Acid response magnetic particle imaging probe as well as preparation method and application thereof

Abstract

The invention provides an acid response magnetic particle imaging probe and a preparation method and application thereof.The preparation method comprises the steps that S1, a magnetic core, an iron precursor and long-chain alcohol diol are dispersed in a mixed solution of oleic acid, oleylamine, cyclohexane and octadecene, a reaction is conducted for 30-90 minutes under the inert atmosphere condition of 200-300 DEG C, a first non-polar solvent is used for washing, precipitation and centrifugation, and a first non-polar solvent is obtained; the oil-phase double-magnetic core-shell nanoparticles are obtained; s2, preparing water-phase aminated double-magnetic core-shell nanoparticles from the oil-phase double-magnetic core-shell nanoparticles and polymers with amino groups by adopting a film dispersion method or a nano coprecipitation method; s3, the aqueous-phase aminated double-magnetic core-shell nanoparticles and a compound with multiple aldehyde groups are subjected to an aldehyde-amine condensation reaction, a stable imine bond mediated nanometer assembly structure is formed, and the acid response magnetic particle imaging probe is obtained. The probe provided by the invention can respond to the change of the acid microenvironment, has high sensitivity, low background noise and a relatively strong imaging effect, and is suitable for dynamically monitoring diseases related to the acid microenvironment in real time.

Description

Technical Field

[0001] The invention relates to the technical field of biomedical imaging and molecular probes, and in particular to an acid-responsive magnetic particle imaging probe and a preparation method and application thereof. Background Art

[0002] As an important standard of acid-base balance, pH plays an important role in various disease microenvironments (such as tumors, sepsis, myocardial ischemia and atherosclerosis, etc.), for example, by regulating cell metabolism, proliferation and migration, aggravating tissue damage and promoting pathological processes. Therefore, the development of acid-responsive magnetic particle imaging probes can effectively promote the early diagnosis of diseases related to acidic microenvironment, provide more accurate imaging information, and help achieve real-time monitoring of lesion areas.

[0003] Magnetic particle imaging has become a promising medical imaging technology due to its unique advantages (including high sensitivity, zero background signal, and no ionizing radiation). However, most existing magnetic particle probes are "normally open" probes, which have significant background signal interference and cannot accurately reflect the dynamic changes of pathological markers, limiting their application in clinical disease diagnosis. Disease microenvironment-responsive imaging probes can achieve accurate and real-time imaging signal regulation by responding to changes in the expression levels of disease-related pathological markers, but there is currently a lack of high-performance magnetic particle imaging probes based on disease microenvironment-responsive magnetic particle assemblies. Summary of the invention

[0004] In view of the defects in the prior art, the purpose of the present invention is to provide an acid-responsive magnetic particle imaging probe and its preparation method and application. By constructing a dynamic assembly structure of dual magnetic core-shell nanoparticles and acid-sensitive ligands, the magnetic dipole interaction between particles and the response characteristics of the acidic microenvironment are regulated. Specifically, by introducing an acid-sensitive covalent bond-mediated dual magnetic core-shell nanoparticle assembly structure, a probe with dynamic response capability is designed, which can maintain magnetic particle imaging signal suppression under neutral conditions, quickly activate magnetic particle imaging signals in an acidic environment, improve the sensitivity and specificity of magnetic particle imaging, and reduce the interference of background signals on the imaging effect.

[0005] The technical solution of the present invention is:

[0006] The first aspect of the present invention provides a method for preparing an acid-responsive magnetic particle imaging probe, comprising the following steps:

[0007] S1, dissolving ferric acetylacetonate and platinum acetylacetonate in a mixed solution of oleylamine, oleic acid and benzyl ether, reacting under an inert atmosphere at 200-300° C. for 10-60 minutes, washing the precipitate with a first non-polar solvent and centrifuging to obtain a magnetic core of an oil-phase dual magnetic core-shell nanoparticle; the feed ratio of the ferric acetylacetonate, the platinum acetylacetonate, the oleylamine, the oleic acid and the benzyl ether is 0.2-100 mmol: 0.2-100 mmol: 1-10 mL: 1-10 mL: 10-200 mL;

[0008] S2, dispersing the magnetic core, iron precursor and long-chain alcohol diol prepared in 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 a first non-polar solvent and centrifuging to obtain oil-phase dual magnetic core-shell nanoparticles; the feed ratio of the iron precursor, the long-chain alcohol diol, the oleylamine, the oleic acid, the cyclohexane and the octadecene is 0.2 to 100 mmol: 0.1 to 100 mmol: 1 to 10 mL: 1 to 10 mL: 1 to 10 mL: 1 to 10 mL: 10 to 200 mL;

[0009] S3, the oil phase dual magnetic core-shell nanoparticles obtained in step S2 and a polymer having an amino group are subjected to a thin film dispersion method or a nanometer coprecipitation method to obtain aqueous phase amino dual magnetic core-shell nanoparticles; wherein the polymer having an amino group is at least one of amino polyethylene glycol, polyethylene imine, polydopamine, aminosilane, amino polyacrylic acid, and distearoyl phosphatidylethanolamine-polyethylene glycol-amino;

[0010] S4, subjecting the aqueous aminated dual magnetic core-shell nanoparticles obtained in step S3 to an aldehyde-amine condensation reaction with a compound having a multi-aldehyde group to form a stable imine bond-mediated nanoassembly structure, thereby obtaining an acid-responsive magnetic particle imaging probe; wherein the compound having a multi-aldehyde group is at least one of glutaraldehyde, succinaldehyde, adipaldehyde, trimesic acid, 1,3,5-tris(4-benzaldehyde)benzene, 4,4',4"-(1,3,5-triazine-2,4,6-tris)tris-1-(4-benzaldehyde)pyridine chloride, 2,4,6-tris(4-formaldehydephenyl)-1,3,5-triazine, and trialdehyde pyrrolidone.

[0011] Further preferably, the first non-polar solvent is at least one of anhydrous ethanol, acetone, methanol, isopropanol and acetic acid; the iron precursor is at least one of ferric acetylacetonate, ferrous acetylacetonate, ferrous oleate, ferrous acetate, pentacarbonyl iron, and ferrous gluconate; and the long-chain alcohol diol is at least one of 1,2-hexadecanediol, 1,2-dodecanediol, stearyl alcohol, and oleyl alcohol.

[0012] Furthermore, the step of preparing aqueous phase aminated dual magnetic core-shell nanoparticles by the thin film dispersion method includes: adding the oil phase dual magnetic core-shell nanoparticles into an organic solvent, adding hydrophilic molecules, and reacting at room temperature to obtain aqueous phase aminated dual magnetic core-shell nanoparticles.

[0013] Furthermore, the step of preparing aqueous phase aminated dual magnetic core-shell nanoparticles by the nano-coprecipitation method includes: adding the oil phase dual magnetic core-shell nanoparticles to a mixed solvent of an organic solvent and a second non-polar solvent, adding hydrophilic molecules, and ultrasonically reacting at room temperature to obtain aqueous phase aminated dual magnetic core-shell nanoparticles.

[0014] More preferably, the second polar solvent is at least one of 2-(N-morpholine)ethanesulfonic acid buffer, phosphate buffer solution, water, dimethyl sulfoxide, and N,N-dimethylformamide.

[0015] More preferably, the hydrophilic molecule is at least one of aminopolyethylene glycol, polyethyleneimine, polydopamine, aminosilane, aminopolyacrylic acid, and distearoylphosphatidylethanolamine-polyethylene glycol-amino.

[0016] A second aspect of the present invention provides an acid-responsive magnetic particle imaging probe, which is obtained according to the above-mentioned method for preparing the acid-responsive magnetic particle imaging probe.

[0017] The third aspect of the present invention provides the use of the above-mentioned acid-responsive magnetic particle imaging probe in a product for diagnosing and / or treating diseases associated with an acidic microenvironment.

[0018] Compared with the prior art, the present invention has the following beneficial effects:

[0019] 1. The acid-responsive magnetic particle imaging probe provided by the present invention can undergo significant changes in structure under different pH conditions (pH 6.5 and pH 7.4); and the magnetic particle imaging signal varies with the mass of the acid-responsive magnetic particle imaging probe. The greater the mass of the acid-responsive magnetic particle imaging probe, the more obvious the magnetic particle imaging signal.

[0020] 2. The acid-responsive magnetic particle imaging probe provided by the present invention can significantly regulate the magnetic particle imaging signal in the acidic microenvironment of sepsis. Compared with healthy mice, septic mice showed obvious changes in magnetic particle imaging signals, which proves that the acid-responsive magnetic particle imaging probe has the ability to diagnose septic mice and can achieve a highly sensitive response to the lesion area.

[0021] 3. The acid-responsive magnetic particle imaging probe provided by the present invention has a low background signal, which can effectively avoid the problem of unclear imaging caused by tissue background signal interference in traditional imaging methods. The preparation method is simple and easy, and it can play a role in a variety of acidic microenvironments (such as liver, spleen, kidney, heart, and lungs). BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Other features, objects and advantages of the present invention will become more apparent from the detailed description of non-limiting embodiments made with reference to the following drawings:

[0023] Figure 1 This is a transmission electron microscopy image of the oil-phase dual magnetic core-shell nanoparticles provided in Example 1 of the present invention;

[0024] Figure 2 This is a hysteresis regression curve diagram of the oil-phase dual magnetic core-shell nanoparticles provided in Example 1 of the present invention;

[0025] Figure 3 This is a transmission electron microscopy image of aqueous phase aminated dual magnetic core-shell nanoparticles provided in Example 2 of the present invention;

[0026] Figure 4 The hydrodynamic particle size diagram of the aqueous phase aminated dual magnetic core-shell nanoparticles provided in Example 2 of the present invention;

[0027] Figure 5 Transmission electron microscopy images of the acid-responsive magnetic particle imaging probe at different pH values ​​provided in Example 3 of the present invention;

[0028] Figure 6 The hydrodynamic particle size diagram of the acid-responsive magnetic particle imaging probe at different pH values ​​provided in Example 3 of the present invention;

[0029] Figure 7 Magnetic particle imaging images of the acid-responsive magnetic particle imaging probe at different pH values ​​provided in Example 3 of the present invention;

[0030] Figure 8 A transmission electron microscope image of the acid-responsive magnetic particle imaging probe provided in Example 4 of the present invention;

[0031] Fig. 9 A transmission electron microscope image of the acid-responsive magnetic particle imaging probe provided in Example 5 of the present invention;

[0032] Fig.10 Magnetic particle imaging images of healthy mice and septic mice provided in Application Example 1 of the present invention;

[0033] Fig.11Magnetic particle imaging images of different severities of sepsis in different organs of mice provided in Application Example 2 of the present invention (MPI: refers to magnetic particle imaging; a: magnetic particle imaging signal image of whole body organs of mouse sepsis model 2 hours after injection of acid-responsive magnetic particle imaging probe; Figure b: MPI signal intensity presented by injection of different doses of lipopolysaccharide in the liver; Figure c: MPI signal intensity presented by injection of different doses of lipopolysaccharide in the spleen; Figure d: MPI signal intensity presented by injection of different doses of lipopolysaccharide in the kidney; Figure e: MPI signal intensity presented by injection of different doses of lipopolysaccharide in the heart; Figure f: MPI signal intensity presented by injection of different doses of lipopolysaccharide in the lung). DETAILED DESCRIPTION

[0034] The present invention is described in detail below in conjunction with specific embodiments, and the following embodiments will help those skilled in the art to further understand the present invention, but are not intended to limit the present invention in any form. It should be noted that, for those of ordinary skill in the art, several changes and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention.

[0035] Example 1

[0036] This embodiment provides a method for preparing oil-phase dual magnetic core-shell nanoparticles, comprising the following steps:

[0037] In some embodiments, ferric acetylacetonate and platinum acetylacetonate are dissolved in a mixed solution of oleylamine, oleic acid and benzyl ether, reacted under an inert atmosphere at 200-300°C for 10-60 minutes, and the precipitate is washed with a first non-polar solvent and centrifuged to obtain the magnetic core of the oil-phase dual magnetic core-shell nanoparticles; the feed ratio of ferric acetylacetonate, platinum acetylacetonate, oleylamine, oleic acid and benzyl ether is 0.2-100 mmol: 0.2-100 mmol: 1-10 mL: 1-10 mL: 10-200 mL.

[0038] In some embodiments, the magnetic core of the oil-phase dual magnetic core-shell nanoparticles prepared above, the iron precursor and the long-chain alcohol diol are dispersed in a mixed solution of oleic acid, oleylamine, cyclohexane and octadecene, and reacted under an inert atmosphere at 200-300°C for 30-90 minutes. The precipitate is washed with a first non-polar solvent and centrifuged to obtain the oil-phase dual magnetic core-shell nanoparticles; the feed ratio of the iron precursor, the long-chain alcohol diol, oleylamine, oleic acid, cyclohexane and octadecene is 0.2-100 mmol: 0.1-100 mmol: 1-10 mL: 1-10 mL: 1-10 mL: 10-200 mL.

[0039] In some embodiments, the first non-polar solvent is at least one of anhydrous ethanol, acetone, methanol, isopropanol and acetic acid; the iron precursor is at least one of ferric acetylacetonate, ferrous acetylacetonate, ferrous oleate, ferrous acetate, pentacarbonyl iron, and ferrous gluconate; and the long-chain alcohol diol is at least one of 1,2-hexadecanediol, 1,2-dodecanediol, stearyl alcohol, and oleyl alcohol.

[0040] In this embodiment, iron acetylacetonate is selected as the iron precursor, and the long-chain alcohol diol is 1,2-hexadecanediol. The specific preparation method is as follows:

[0041] 0.25mmol of ferric acetylacetonate and 0.25mmol of platinum acetylacetonate were dissolved in a mixed solution of 1mL of oleylamine, 1mL of oleic acid and 10mL of dibenzyl ether, reacted at 300°C under an inert atmosphere for 30 minutes, precipitated and centrifuged with anhydrous ethanol for washing, and the magnetic core of the oil-phase dual magnetic core-shell nanoparticles was obtained.

[0042] All the magnetic cores of the oil-phase dual magnetic core-shell nanoparticles obtained by the above preparation method, 2.5mmol ferric acetylacetonate and 1.5mmol 1,2-hexadecanediol were dispersed in a mixed solution of 2.6mL oleic acid, 2.6mL oleylamine, 5mL cyclohexane and 30mL octadecene, reacted under an inert atmosphere at 300°C for 30 minutes, and the anhydrous ethanol precipitation was centrifuged to obtain oil-phase dual magnetic core-shell nanoparticles.

[0043] The prepared oil phase dual magnetic core-shell nanoparticles were characterized by transmission electron microscopy. Figure 1 As shown, the oil-phase dual magnetic core-shell nanoparticles provided in this embodiment do not have agglomeration phenomenon, and the particles are uniform in size and good in morphology.

[0044] The magnetization strength is tested using a magnetic performance measurement system. The results are as follows: Figure 2 As shown in the figure, the magnetization intensity increases significantly with the increase of the external magnetic field, and the measured saturation magnetization intensity is 51emu·g -1 .

[0045] Example 2

[0046] This embodiment provides a method for preparing aqueous phase aminated dual magnetic core-shell nanoparticles.

[0047] The oil phase dual magnetic core-shell nanoparticles obtained in Example 1 and a polymer having an amino group are mixed by a thin film dispersion method or a nanometer coprecipitation method to obtain aqueous phase aminated dual magnetic core-shell nanoparticles.

[0048] In some embodiments, the polymer having an amino group is at least one of amino polyethylene glycol, polyethylene imine, polydopamine, amino silane, amino polyacrylic acid, and distearoyl phosphatidylethanolamine-polyethylene glycol-amino.

[0049] The steps of preparing aqueous phase aminated dual magnetic core-shell nanoparticles by thin film dispersion method include: adding oil phase dual magnetic core-shell nanoparticles into organic solvent, adding hydrophilic molecules, and reacting at room temperature to obtain aqueous phase aminated dual magnetic core-shell nanoparticles.

[0050] The steps of preparing aqueous phase aminated dual magnetic core-shell nanoparticles by nano-coprecipitation method include: adding oil phase dual magnetic core-shell nanoparticles into a mixed solvent of an organic solvent and a second non-polar solvent, adding hydrophilic molecules, and ultrasonically reacting at room temperature to obtain aqueous phase dual magnetic core-shell nanoparticles.

[0051] In some embodiments, the second polar solvent is at least one of 2-(N-morpholine)ethanesulfonic acid buffer, phosphate buffer solution, water, dimethyl sulfoxide, and N,N-dimethylformamide.

[0052] In some embodiments, the hydrophilic molecule is at least one of aminopolyethylene glycol, polyethyleneimine, polydopamine, aminosilane, aminopolyacrylic acid, and distearoylphosphatidylethanolamine-polyethylene glycol-amino.

[0053] This embodiment adopts a thin film dispersion method to prepare aqueous phase amino dual magnetic core-shell nanoparticles. The polymer with amino group and the hydrophilic molecule are both distearoyl phosphatidylethanolamine-polyethylene glycol-amino. The specific steps are as follows:

[0054] 2 mg of the oil-phase dual magnetic core-shell nanoparticles obtained in Example 1 were weighed and mixed with 10 mg of distearoyl phosphatidylethanolamine-polyethylene glycol-amino in 10 mL of chloroform solution. After 5 minutes of ultrasonic treatment, the solvent was evaporated at 60° C. for 1 hour. Subsequently, 4 mL of distilled water was added and reacted at room temperature to obtain aqueous phase aminated dual magnetic core-shell nanoparticles.

[0055] The prepared aqueous dual magnetic core-shell nanoparticles were characterized by transmission electron microscopy. Figure 3 As shown, the aqueous phase aminated dual magnetic core-shell nanoparticles provided in this embodiment have uniform particle sizes and are evenly dispersed.

[0056] The hydrodynamic particle size was tested by dynamic light scattering. Figure 4 As shown, the particle size of the obtained aqueous phase aminated dual magnetic core-shell nanoparticles is mostly 28 nm.

[0057] Example 3

[0058] This embodiment provides a method for preparing an acid-responsive magnetic particle imaging probe.

[0059] The aqueous aminated dual magnetic core-shell nanoparticles are subjected to an aldehyde-amine condensation reaction with a compound having multiple aldehyde groups to form a stable imine bond-mediated nanoassembly structure, thereby obtaining an acid-responsive magnetic particle imaging probe.

[0060] In some embodiments, the compound having multiple aldehyde groups is at least one of glutaraldehyde, succinaldehyde, adipaldehyde, trimesic acid, 1,3,5-tris(4-benzaldehyde)benzene, 4,4',4"-(1,3,5-triazine-2,4,6-tris)tris-1-(4-benzaldehyde)pyridine chloride, 2,4,6-tris(4-formylphenyl)-1,3,5-triazine, and trialdehyde pyrrolidone.

[0061] The polyaldehyde compound selected in this embodiment is 2,4,6-tris(4-formaldehydephenyl)-1,3,5-triazine, and the preparation steps are as follows:

[0062] 50 mg of 2,4,6-tris(4-formylphenyl)-1,3,5-triazine and 1 mg of the aqueous phase aminated dual magnetic core-shell nanoparticles provided in Example 2 were dissolved in 10 mL of water, the pH value was adjusted to 8-9, and stirred at room temperature for 5 hours. After dialysis and ultrafiltration, an acid-responsive magnetic particle imaging probe was obtained.

[0063] The morphology of the obtained acid-responsive magnetic particle imaging probe was characterized by transmission electron microscopy at pH 7.4 and pH 6.5. Figure 5 As shown, the acid-responsive magnetic particle imaging probe provided in this embodiment can respond to pH changes and produce structural changes.

[0064] The particle size distribution of the acid-responsive magnetic particle imaging probe at pH 7.4 and pH 6.5 was analyzed by dynamic light scattering. Figure 6 As shown, the particle size at pH 7.4 is significantly larger than that at pH 6.5, indicating that the hydrodynamic particle size of the acid-responsive magnetic particle imaging probe provided in this embodiment can respond to pH changes and produce obvious structural changes.

[0065] The signal value of the acid-responsive magnetic particle imaging probe changes with pH changes. Figure 7 As shown, when the mass of the acid-responsive magnetic particle imaging probe is the same, the signal intensity at pH 6.5 is significantly greater than the signal intensity at pH 7.4, indicating that the acid-responsive magnetic particle imaging probe can respond to pH changes and produce obvious MPI (magnetic particle imaging) signal changes.

[0066] The above results all prove that the structure of the acid-responsive magnetic particle imaging probe can undergo significant changes under different pH conditions, and produce significant changes in the magnetic particle imaging signal.

[0067] Example 4

[0068] This embodiment provides a method for preparing an acid-responsive magnetic particle imaging probe.

[0069] The synthesis was carried out according to the preparation process of Example 3, except that the amount of the added polyaldehyde compound was changed to 40 mg, such as Figure 8 As shown, the acid-responsive magnetic particle imaging probe can still be obtained by referring to the preparation process of Example 3. The acid-responsive magnetic particle imaging probe provided in this example has uniform size and is evenly dispersed.

[0070] Example 5

[0071] This embodiment provides a method for preparing an acid-responsive magnetic particle imaging probe.

[0072] The synthesis was carried out according to the preparation process of Example 3, except that the amount of the added polyaldehyde compound was changed to 60 mg, such as Fig. 9 As shown, the acid-responsive magnetic particle imaging probe can still be obtained by referring to the preparation process of Example 3. The acid-responsive magnetic particle imaging probe provided in this example has uniform size and is evenly dispersed.

[0073] Through the verification of Example 4 and Example 5, it can be proved that the preparation method provided by the present invention can obtain acid-responsive magnetic particle probes with uniform size and stable shape.

[0074] Application Example 1

[0075] This application example provides the application of the acid-responsive magnetic particle imaging probe in Example 3 in imaging of septic mice.

[0076] A sepsis model was established using healthy female BALB / c mice (intraperitoneal injection of lipopolysaccharide), and an acid-responsive magnetic particle imaging probe (prepared according to the method in Example 3) was injected through the tail vein. The whole-body MPI (magnetic particle imaging) results of the mice were observed 2 hours after the injection. The specific changes were as follows: Fig.10 As shown, 2 hours after tracer injection, septic mice showed obvious MPI signal changes compared with healthy mice, proving that the acid-responsive magnetic particle imaging probe can respond to changes in acidity in the lesion area of ​​septic mice to produce obvious MPI signal changes and thus diagnose sepsis with high sensitivity.

[0077] Application Example 2

[0078] This application example provides the application of the acid-responsive magnetic particle imaging probe in Example 3 in imaging mice with different degrees of sepsis severity.

[0079] Lipopolysaccharide (LPS) is an endotoxin of Gram-negative bacteria that can simulate sepsis caused by bacterial infection. The dose of LPS is closely related to the clinical manifestations of sepsis. Low doses may cause mild inflammatory responses, while high doses may cause severe sepsis symptoms and even organ failure. In experimental studies, LPS is often used to induce sepsis models. By injecting different doses of LPS, the severity of sepsis can be regulated. Therefore, by adjusting the injection dose of LPS, the severity of sepsis can be controlled, which helps to simulate the progression of sepsis.

[0080] A sepsis model was constructed using healthy female BALB / c mice (intraperitoneal injection of different doses of lipopolysaccharide), and the acid-responsive magnetic particle imaging probe (prepared according to the method of Example 3) was injected through the tail vein. The changes in the magnetic particle imaging signals of the organs of the whole body were observed 2 hours after the injection. The specific changes were as follows: Fig.11 As shown in the figure, 2 hours after the injection of the acid-responsive magnetic particle imaging probe, with the increase of lipopolysaccharide dose, obvious MPI (magnetic particle imaging) signal changes were detected in all major organs, and the higher the lipopolysaccharide dose, the more significant the magnetic particle imaging signal ( Fig.11 a), proved that the acid-responsive magnetic particle imaging probe can accurately detect sepsis of different severity. Fig.11 b-11f) and other organs develop sepsis and produce an acidic microenvironment, the acid-responsive magnetic particle imaging probe provided in this application example can also play a role, and the higher the lipopolysaccharide dose, the more significant the magnetic particle imaging signal.

[0081] The above describes the specific embodiments of the present invention. It should be understood that the present invention is not limited to the above specific embodiments, and those skilled in the art can make various changes or modifications within the scope of the claims, which does not affect the essence of the present invention. In the absence of conflict, the embodiments of the present application and the features in the embodiments can be combined with each other arbitrarily.

Claims

1. A method for preparing an acid-responsive magnetic particle imaging probe, characterized in that: The following steps are involved: S1, dissolving ferric acetylacetonate and platinum acetylacetonate in a mixed solution of oleylamine, oleic acid and benzyl ether, reacting under an inert atmosphere at 200-300° C. for 10-60 minutes, washing the precipitate with a first non-polar solvent and centrifuging to obtain a magnetic core of an oil-phase dual magnetic core-shell nanoparticle; the feed ratio of the ferric acetylacetonate, the platinum acetylacetonate, the oleylamine, the oleic acid and the benzyl ether is 0.2-100 mmol: 0.2-100 mmol: 1-10 mL: 1-10 mL: 10-200 mL; S2, dispersing the magnetic core, iron precursor and long-chain alcohol diol prepared in 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 a first non-polar solvent and centrifuging to obtain oil-phase dual magnetic core-shell nanoparticles; the feed ratio of the iron precursor, the long-chain alcohol diol, the oleylamine, the oleic acid, the cyclohexane and the octadecene is 0.2 to 100 mmol: 0.1 to 100 mmol: 1 to 10 mL: 1 to 10 mL: 1 to 10 mL: 1 to 10 mL: 10 to 200 mL; S3, the oil phase dual magnetic core-shell nanoparticles obtained in step S2 and a polymer having an amino group are subjected to a thin film dispersion method or a nanometer coprecipitation method to obtain aqueous phase amino dual magnetic core-shell nanoparticles; wherein the polymer having an amino group is at least one of amino polyethylene glycol, polyethylene imine, polydopamine, aminosilane, amino polyacrylic acid, and distearoyl phosphatidylethanolamine-polyethylene glycol-amino; S4, subjecting the aqueous aminated dual magnetic core-shell nanoparticles obtained in step S3 to an aldehyde-amine condensation reaction with a compound having a multi-aldehyde group to form a stable imine bond-mediated nanoassembly structure, thereby obtaining an acid-responsive magnetic particle imaging probe; wherein the compound having a multi-aldehyde group is at least one of glutaraldehyde, succinaldehyde, adipaldehyde, trimesic acid, 1,3,5-tris(4-benzaldehyde)benzene, 4,4',4"-(1,3,5-triazine-2,4,6-tris)tris-1-(4-benzaldehyde)pyridine chloride, 2,4,6-tris(4-formaldehydephenyl)-1,3,5-triazine, and trialdehyde pyrrolidone.

2. The method for preparing the acid-responsive magnetic particle imaging probe according to claim 1, characterized in that: The first non-polar solvent is at least one of anhydrous ethanol, acetone, methanol, isopropanol and acetic acid; the iron precursor is at least one of ferric acetylacetonate, ferrous acetylacetonate, ferrous oleate, ferrous acetate, pentacarbonyl iron and ferrous gluconate; the long-chain alcohol diol is at least one of 1,2-hexadecanediol, 1,2-dodecanediol, stearyl alcohol and oleyl alcohol.

3. The method for preparing the acid-responsive magnetic particle imaging probe according to claim 1, characterized in that: The step of preparing aqueous phase aminated dual magnetic core-shell nanoparticles by the thin film dispersion method comprises: adding the oil phase dual magnetic core-shell nanoparticles into an organic solvent, adding hydrophilic molecules, and reacting at room temperature to obtain aqueous phase aminated dual magnetic core-shell nanoparticles.

4. The method for preparing the acid-responsive magnetic particle imaging probe according to claim 1, characterized in that: The steps of preparing aqueous phase aminated dual magnetic core-shell nanoparticles by the nano-coprecipitation method include: adding the oil phase dual magnetic core-shell nanoparticles into a mixed solvent of an organic solvent and a second non-polar solvent, adding hydrophilic molecules, and ultrasonically reacting at room temperature to obtain aqueous phase dual magnetic core-shell nanoparticles.

5. The method for preparing the acid-responsive magnetic particle imaging probe according to claim 4, characterized in that: The second polar solvent is at least one of 2-(N-morpholine)ethanesulfonic acid buffer, phosphate buffer solution, water, dimethyl sulfoxide, and N,N-dimethylformamide.

6. The method for preparing the acid-responsive magnetic particle imaging probe according to any one of claims 4 to 5, characterized in that: The hydrophilic molecule is at least one of aminopolyethylene glycol, polyethyleneimine, polydopamine, aminosilane, aminopolyacrylic acid, and distearoylphosphatidylethanolamine-polyethylene glycol-amino.

7. An acid-responsive magnetic particle imaging probe, characterized in that: The method for preparing the acid-responsive magnetic particle imaging probe according to any one of claims 1 to 6 is obtained.

8. Use of the acid-responsive magnetic particle imaging probe according to claim 7 in a product for diagnosis and / or treatment monitoring of diseases associated with an acidic microenvironment.

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