An acid-responsive magnetic particle imaging probe, and a preparation method and application thereof

Abstract

The application provides an acid-responsive magnetic particle imaging probe and a preparation method and application thereof, and the preparation steps are as follows: S1, dispersing a magnetic core, an iron precursor and a long-chain alcohol diol in a mixed solution of oleic acid, oleylamine, cyclohexane and octadecene, and reacting under the condition of an inert atmosphere at 200-300 DEG C for 30-90 minutes, washing and centrifuging the precipitate to obtain oil-phase double-magnetic-core-shell nanoparticles; S2, using a thin film dispersion method or a nano-coprecipitation method, the oil-phase double-magnetic-core-shell nanoparticles are reacted with a polymer with an amino group to obtain water-phase aminated double-magnetic-core-shell nanoparticles; S3, carrying out an aldehyde-amine condensation reaction between the water-phase aminated double-magnetic-core-shell nanoparticles and a compound with multiple aldehyde groups to form a stable imine bond-mediated nano-assembly structure, and obtaining the acid-responsive magnetic particle imaging probe. The probe provided by the application can respond to acid microenvironment changes, has high sensitivity, low background noise and strong imaging effect, and is suitable for real-time dynamic monitoring of acid microenvironment related diseases.

Description

Technical Field

[0001] This invention relates to the fields of biomedical imaging and molecular probe technology, and in particular to an acid-responsive magnetic particle imaging probe, its preparation method, and its application. Background Technology

[0002] pH, as an important standard for acid-base balance, plays a crucial role in the microenvironments of various diseases (such as tumors, sepsis, myocardial ischemia, and atherosclerosis). For example, it exacerbates tissue damage and promotes pathological processes by regulating cell metabolism, proliferation, and migration. Therefore, developing acid-responsive magnetic particle imaging probes can effectively promote the early diagnosis of diseases related to acidic microenvironments, providing more accurate imaging information and helping to achieve real-time monitoring of lesion areas.

[0003] Magnetic particle imaging has become a promising medical imaging technique due to its unique advantages, including high sensitivity, zero background signal, and no ionizing radiation. However, most existing magnetic particle probes are normally-on probes, which suffer from significant background signal interference and cannot accurately reflect the dynamic changes of pathological biomarkers, limiting their application in clinical disease diagnosis. Disease microenvironment-responsive imaging probes can achieve precise and real-time modulation of imaging signals by responding to changes in the expression levels of disease-related pathological biomarkers, but high-performance magnetic particle imaging probes based on disease microenvironment-responsive magnetic particle assemblies are currently lacking. Summary of the Invention

[0004] To address the shortcomings of existing technologies, the present invention aims to provide an acid-responsive magnetic particle imaging probe, its preparation method, and its applications. 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 in acidic microenvironments are modulated. Specifically, an acid-sensitive covalent bond-mediated dual magnetic core-shell nanoparticle assembly structure is introduced to design a probe with dynamic response capabilities. This probe maintains magnetic particle imaging signal suppression under neutral conditions and rapidly activates the magnetic particle imaging signal in acidic environments, thereby improving the sensitivity and specificity of magnetic particle imaging while reducing background signal interference on the imaging effect.

[0005] The technical solution of this invention is as follows:

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

[0007] S1. Iron acetylacetone and platinum acetylacetone are dissolved in a mixed solution of oleylamine, oleic acid and dibenzyl ether. The mixture is reacted at 200-300°C under an inert atmosphere for 10-60 minutes. The precipitate is washed with a first polar solvent and centrifuged to obtain the magnetic core of oil-phase dual magnetic core-shell nanoparticles. The feeding ratio of iron acetylacetone, platinum acetylacetone, oleylamine, oleic acid and dibenzyl ether is 0.2-100 mmol: 0.2-100 mmol: 1-10 mL: 1-10 mL: 10-200 mL.

[0008] S2. The magnetic core, iron precursor, and long-chain glycol prepared in S1 are dispersed in a mixed solution of oleic acid, oleylamine, cyclohexane, and octadecene. The mixture is reacted at 200-300°C under an inert atmosphere for 30-90 minutes. The precipitate is washed with a first polar solvent and centrifuged to obtain oil-phase dual magnetic core-shell nanoparticles. The feed ratio of the iron precursor, the long-chain glycol, the oleylamine, the oleic acid, the cyclohexane, and the octadecene is 0.2-100 mmol: 0.1-100 mmol: 1-10 mL: 1-10 mL: 1-10 mL: 10-200 mL.

[0009] S3. The oil-phase dual magnetic core-shell nanoparticles obtained in step S2 are combined with an amino-containing polymer using a thin-film dispersion method or a nano-co-precipitation method to obtain aqueous-phase aminated dual magnetic core-shell nanoparticles; wherein the amino-containing polymer is at least one of amino polyethylene glycol, polyethyleneimine, polydopamine, aminosilane, amino polyacrylic acid, and distearate phosphatidylethanolamine-polyethylene glycol-amino.

[0010] S4. The aqueous aminated dual magnetic core-shell nanoparticles obtained in step S3 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; wherein the compound having multiple aldehyde groups is at least one of glutaraldehyde, succinate, adipaldehyde, pyromellitic pyrrolidone, 1,3,5-tris(4-benzaldehyde)benzene, 4,4',4”-(1,3,5-triazine-2,4,6-tri)tri-1-(4-benzaldehyde)pyridine, 2,4,6-tris(4-aldehydephenyl)-1,3,5-triazine, and trialdehyde-resorcinol.

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

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

[0013] Furthermore, the step of preparing aqueous 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 polar solvent, adding hydrophilic molecules, and ultrasonically reacting at room temperature to obtain aqueous aminated dual magnetic core-shell nanoparticles.

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

[0015] More preferably, the hydrophilic molecule is at least one selected from amino polyethylene glycol, polyethyleneimine, polydopamine, aminosilane, amino polyacrylic acid, and distearate phosphatidylethanolamine-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-described method for preparing an acid-responsive magnetic particle imaging probe.

[0017] The third aspect of this invention provides the application of the above-mentioned acid-responsive magnetic particle imaging probe in diagnostic and / or therapeutic monitoring products for diseases related to acidic microenvironments.

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

[0019] 1. The structure of the acid-responsive magnetic particle imaging probe provided by the present invention can change significantly under different pH conditions (pH 6.5 and pH 7.4); and the magnetic particle imaging signal changes 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 this invention can significantly modulate the magnetic particle imaging signal in the acidic microenvironment of sepsis. Compared with healthy mice, sepsis mice show obvious changes in magnetic particle imaging signal, which proves that the acid-responsive magnetic particle imaging probe has the ability to diagnose sepsis mice and can achieve a highly sensitive response to the lesion area.

[0021] 3. The acid-responsive magnetic particle imaging probe provided by this 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. Moreover, the preparation method is simple and easy to implement, and it can play a role in a variety of acidic microenvironments (such as liver, spleen, kidney, heart, and lungs). Attached Figure Description

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

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

[0024] Figure 2 This is a hysteresis regression curve 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 microscope image of the aqueous aminated dual magnetic core-shell nanoparticles provided in Example 2 of the present invention.

[0026] Figure 4 Hydrodynamic particle size distribution of aqueous aminated dual magnetic core-shell nanoparticles provided in Example 2 of this 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 Hydrodynamic particle size distribution of the acid-responsive magnetic particle imaging probe at different pH values ​​provided in Example 3 of this invention;

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

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

[0031] Figure 9 Transmission electron microscope image of the acid-responsive magnetic particle imaging probe provided in Example 5 of the present invention;

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

[0033] Figure 11The following are magnetic particle imaging images (MPI: magnetic particle imaging; a: magnetic particle imaging signal of whole-body organs in mouse sepsis model 2 hours after injection of acid-responsive magnetic particle imaging probe; b: MPI signal intensity of different doses of lipopolysaccharide injected into the liver; c: MPI signal intensity of different doses of lipopolysaccharide injected into the spleen; d: MPI signal intensity of different doses of lipopolysaccharide injected into the kidney; e: MPI signal intensity of different doses of lipopolysaccharide injected into the heart; f: MPI signal intensity of different doses of lipopolysaccharide injected into the lung) provided in Application Example 2 of the present invention. Detailed Implementation

[0034] The present invention will be described in detail below with reference to specific embodiments. These embodiments will help those skilled in the art to further understand the present invention, but do not limit the present invention in any way. It should be noted that those skilled in the art can make several changes and improvements without departing from the concept of the present invention, and these all fall within 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, including the following steps:

[0037] In some embodiments, ferric acetylacetone and platinum acetylacetone are dissolved in a mixed solution of oleylamine, oleic acid and dibenzyl ether, and reacted at 200-300°C under an inert atmosphere for 10-60 minutes. The precipitate is washed with a first polar solvent and centrifuged to obtain the magnetic core of oil-phase dual magnetic core-shell nanoparticles. The feed ratio of ferric acetylacetone, platinum acetylacetone, oleylamine, oleic acid and dibenzyl 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, iron precursor, and long-chain glycol of the oil-phase dual magnetic core-shell nanoparticles prepared above are dispersed in a mixed solution of oleic acid, oleylamine, cyclohexane, and octadecene. The mixture is reacted at 200-300°C under an inert atmosphere for 30-90 minutes. The precipitate is washed with a first polar solvent and centrifuged to obtain oil-phase dual magnetic core-shell nanoparticles. The feed ratio of iron precursor, long-chain glycol, 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 polar solvent is at least one of anhydrous ethanol, acetone, methanol, isopropanol, and acetic acid; the iron precursor is at least one of ferric acetylacetone, ferrous acetylacetone, ferric oleate, ferrous acetate, ferric pentacarbonyl, 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, acetylacetone iron was selected as the iron precursor, and 1,2-hexadecanediol was selected as the long-chain alcohol diol. The specific preparation method is as follows:

[0041] 0.25 mmol ferric acetylacetone and 0.25 mmol platinum acetylacetone were dissolved in a mixed solution of 1 mL oleylamine, 1 mL oleic acid and 10 mL dibenzyl ether. The mixture was reacted at 300 °C under an inert atmosphere for 30 minutes. The mixture was then precipitated with anhydrous ethanol and washed by centrifugation to obtain the magnetic core of oil-phase dual magnetic core-shell nanoparticles.

[0042] All the magnetic cores of the oil-phase dual magnetic core-shell nanoparticles obtained by the above preparation method, 2.5 mmol of iron acetylacetone and 1.5 mmol of 1,2-hexadecanediol 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. The mixture was reacted at 300 °C under an inert atmosphere for 30 minutes, and then precipitated with anhydrous ethanol and centrifuged to obtain the oil-phase dual magnetic core-shell nanoparticles.

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

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

[0045] Example 2

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

[0047] The oil-phase dual magnetic core-shell nanoparticles obtained in Example 1 were combined with amino-containing polymers and dispersed in thin film or coprecipitated in nanoparticles to obtain aqueous-phase aminated dual magnetic core-shell nanoparticles.

[0048] In some embodiments, the amino-containing polymer is at least one of amino polyethylene glycol, polyethyleneimine, polydopamine, aminosilane, amino polyacrylic acid, and distearate phosphatidylethanolamine-polyethylene glycol-amino.

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

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

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

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

[0053] In this embodiment, aqueous aminated dual magnetic core-shell nanoparticles were prepared using a thin-film dispersion method. The amino-containing polymer and the hydrophilic molecule were both distearate phosphatidylethanolamine-polyethylene glycol-amino. The specific steps are as follows:

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

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

[0056] The hydrodynamic particle size was tested using dynamic light scattering, and the results are as follows: Figure 4 As shown, the obtained aqueous aminated bimagnetic core-shell nanoparticles mostly have a particle size of 28 nm.

[0057] Example 3

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

[0059] Aqueous aminated dual magnetic core-shell nanoparticles were subjected to an aldehyde-amine condensation reaction with compounds containing 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 a polyaldehyde group is at least one of glutaraldehyde, succinate, adipaldehyde, pyromellitic pyrrolizaldehyde, 1,3,5-tris(4-benzaldehyde)benzene, 4,4',4”-(1,3,5-triazine-2,4,6-tri)tri-1-(4-benzaldehyde)pyridine, 2,4,6-tris(4-aldehydephenyl)-1,3,5-triazine, and trialdehyde-resorcinol.

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

[0062] 50 mg of 2,4,6-tris(4-aldehydephenyl)-1,3,5-triazine and 1 mg of the aqueous aminated dual magnetic core-shell nanoparticles provided in Example 2 were dissolved in 10 mL of water, the pH was adjusted to 8-9, and the solution was 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 using transmission electron microscopy at pH 7.4 and pH 6.5, and the results are as follows: Figure 5 As shown, the acid-responsive magnetic particle imaging probe provided in this embodiment can respond to pH changes and produce structural transformations.

[0064] The particle size distribution of acid-responsive magnetic particle imaging probes at pH 7.4 and pH 6.5 was analyzed using dynamic light scattering, and the results are as follows: 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 significant structural changes.

[0065] The signal value of the acid-responsive magnetic particle imaging probe changes with pH variations, as shown in the following results. 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 that at pH 7.4, indicating that the acid-responsive magnetic particle imaging probe can respond to pH changes and produce significant MPI (magnetic particle imaging) signal changes.

[0066] All the above results demonstrate that the structure of this acid-responsive magnetic particle imaging probe can change significantly under different pH conditions, and at the same time, it produces significant changes in magnetic particle imaging signals.

[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 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 uniform dispersion.

[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 added polyaldehyde compound was changed to 60 mg, such as Figure 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 uniform dispersion.

[0073] The verification results of Examples 4 and 5 demonstrate 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 demonstrates the use of the acid-responsive magnetic particle imaging probe from Example 3 in imaging septic mice.

[0076] A sepsis model was established in healthy female BALB / c mice (by intraperitoneal injection of lipopolysaccharide). An acid-responsive magnetic particle imaging probe (prepared according to the method described in Example 3) was injected via the tail vein. The whole-body MPI (magnetic particle imaging) results were then observed 2 hours post-injection. Specific changes are as follows: Figure 10 As shown, 2 hours after injection of the tracer, septic mice showed significant changes in MPI signal compared to healthy mice, demonstrating that the acid-responsive magnetic particle imaging probe can respond to changes in acidity in the lesion area of ​​septic mice to generate significant changes in MPI signal, thus providing high sensitivity for diagnosing sepsis.

[0077] Application Example 2

[0078] This application example demonstrates the use of the acid-responsive magnetic particle imaging probe from Example 3 in imaging mice with varying degrees of sepsis.

[0079] Lipopolysaccharide (LPS) is an endotoxin of Gram-negative bacteria that can mimic sepsis caused by bacterial infection. The dosage of LPS is closely related to the clinical manifestations of sepsis; low doses may induce a mild inflammatory response, while high doses may lead to 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 modulated. Therefore, adjusting the LPS injection dosage can control the severity of sepsis and help simulate the progression of sepsis.

[0080] A sepsis model was constructed using healthy female BALB / c mice (by intraperitoneal injection of different doses of lipopolysaccharide). An acid-responsive magnetic particle imaging probe (prepared according to the method in Example 3) was injected via the tail vein. Changes in magnetic particle imaging signals of systemic organs were observed 2 hours after injection. Specific changes are as follows: Figure 11 As shown, 2 hours after injection of the acid-responsive magnetic particle imaging probe, significant changes in MPI (magnetic particle imaging) signals were detected in all major organs with increasing lipopolysaccharide (LPS) dose, and the higher the LPS dose, the more significant the MPI signal. Figure 11 (a) demonstrates that acid-responsive magnetic particle imaging probes can accurately detect sepsis of varying severity. This is demonstrated in major organs throughout the body, such as the liver, spleen, kidneys, lungs, and heart. Figure 11 When organs such as b-11f develop an acidic microenvironment due to sepsis, 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] Specific embodiments of the present invention have been described above. It should be understood that the present invention is not limited to the specific embodiments described above, and those skilled in the art can make various changes or modifications within the scope of the claims, which do not affect the essence of the present invention. Unless otherwise specified, the embodiments and features described in this application can be arbitrarily combined with each other.

Claims

1. A method for preparing an acid-responsive magnetic particle imaging probe, characterized in that, Includes the following steps: S1. Iron acetylacetone and platinum acetylacetone are dissolved in a mixed solution of oleylamine, oleic acid and dibenzyl ether. The mixture is reacted at 200-300°C under an inert atmosphere for 10-60 minutes. The precipitate is washed with a first polar solvent and centrifuged to obtain the magnetic core of oil-phase dual magnetic core-shell nanoparticles. The feeding ratio of iron acetylacetone, platinum acetylacetone, oleylamine, oleic acid and dibenzyl ether is 0.2-100 mmol: 0.2-100 mmol: 1-10 mL: 1-10 mL: 10-200 mL. S2. The magnetic core, iron precursor, and long-chain glycol prepared in S1 are dispersed in a mixed solution of oleic acid, oleylamine, cyclohexane, and octadecene. The mixture is reacted at 200-300°C under an inert atmosphere for 30-90 minutes. The precipitate is washed with a first polar solvent and centrifuged to obtain oil-phase dual magnetic core-shell nanoparticles. The feed ratio of the iron precursor, the long-chain glycol, the oleylamine, the oleic acid, the cyclohexane, and the octadecene is 0.2-100 mmol: 0.1-100 mmol: 1-10 mL: 1-10 mL: 1-10 mL: 10-200 mL. The iron precursor is at least one of ferric acetylacetone, ferrous acetylacetone, ferric oleate, ferrous acetate, ferric pentacarbonyl, and ferrous gluconate. S3. The oil-phase dual magnetic core-shell nanoparticles obtained in step S2 are combined with an amino-containing polymer using a thin-film dispersion method or a nano-co-precipitation method to obtain aqueous-phase aminated dual magnetic core-shell nanoparticles; wherein the amino-containing polymer is at least one of amino polyethylene glycol, polyethyleneimine, polydopamine, aminosilane, amino polyacrylic acid, and distearate phosphatidylethanolamine-polyethylene glycol-amino. S4. The aqueous aminated dual magnetic core-shell nanoparticles obtained in step S3 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; wherein the compound having multiple aldehyde groups is at least one of glutaraldehyde, succinate, adipaldehyde, pyromellitic pyrrolidone, 1,3,5-tris(4-benzaldehyde)benzene, 4,4',4”-(1,3,5-triazine-2,4,6-tri)tri-1-(4-benzaldehyde)pyridine, 2,4,6-tris(4-aldehydephenyl)-1,3,5-triazine, and trialdehyde-resorcinol.

2. The method for preparing an acid-responsive magnetic particle imaging probe according to claim 1, characterized in that, The first polar solvent is at least one of anhydrous ethanol, acetone, methanol, isopropanol and acetic acid; 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 an acid-responsive magnetic particle imaging probe according to claim 1, characterized in that, The steps for preparing aqueous aminated dual magnetic core-shell nanoparticles by the thin film dispersion method include: adding the oil-phase dual magnetic core-shell nanoparticles to an organic solvent, adding hydrophilic molecules, and reacting at room temperature to obtain aqueous aminated dual magnetic core-shell nanoparticles.

4. The method for preparing an acid-responsive magnetic particle imaging probe according to claim 1, characterized in that, The steps for preparing aqueous-phase aminated dual magnetic core-shell nanoparticles by the nano-coprecipitation method include: adding the oil-phase dual magnetic core-shell nanoparticles to a mixed solvent of an organic solvent and a second 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 an acid-responsive magnetic particle imaging probe according to claim 4, characterized in that, The second polar solvent is at least one of 2-(N-morpholino)ethanesulfonic acid buffer, phosphate buffer, water, dimethyl sulfoxide, and N,N-dimethylformamide.

6. The method for preparing an acid-responsive magnetic particle imaging probe according to any one of claims 4-5, characterized in that, The hydrophilic molecule is at least one of amino polyethylene glycol, polyethyleneimine, polydopamine, aminosilane, amino polyacrylic acid, and distearate phosphatidylethanolamine-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 1-6 is as follows.

8. The application of the acid-responsive magnetic particle imaging probe according to claim 7 in the preparation of diagnostic and / or therapeutic monitoring products for diseases related to acidic microenvironments; wherein, The disease in question is sepsis.

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