A Pd-based alloy with magnetic particle imaging properties, MPI contrast agent, preparation method and application thereof

Abstract

The present invention discloses a Pd-based alloy with magnetic particle imaging properties, an MPI contrast agent, a preparation method and an application thereof. The general structural formula of the Pd-based alloy is PdM; wherein M represents any one or more combinations of transition metal elements; and the transition metal elements include one or more of Fe, Mn, Co, Ni, Cu, Zn, Cd, Re, Zr, Ba, Mg, Sr, Al, Cr, Nd, Gd, Sm, La, Dy, Eu, Er, Tb, Ho, Tm, Yb and Y elements. The present invention uses alloy nanoparticles with a Pd structure as a carrier through structural design, can load transition metal elements, uses a responsive polymer as a surfactant, and obtains nanoparticles (MPI contrast agent) with good biocompatibility through ultrasonic treatment. The present invention also provides the application of the contrast agent in in vivo imaging. The system contains PdM as a contrast agent and can construct an MPI imaging system with tumor microenvironment response.

Description

Technical Field

[0001] The invention belongs to the field of magnetic particle imaging materials, and in particular relates to a Pd-based alloy with magnetic particle imaging properties, an MPI contrast agent, a preparation method and applications thereof. Background Art

[0002] Cancer is one of the major life and health problems in the world and remains one of the diseases with the highest mortality rate in the 21st century. Accurate diagnosis of tumors is crucial to human health. Most tumors cannot be found and located from early symptoms or blood. Tumors (such as ovarian, pancreatic and non-small cell lung cancer) are only discovered after they have developed to a certain stage. Early detection of tumors can lead to a better prognosis. Imaging examination is one of the most powerful weapons for early detection and a broad-spectrum cancer screening and detection method.

[0003] At present, the main clinical tumor imaging examinations include computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound imaging. Magnetic particle imaging (MPI) is a new in vivo biological imaging technology that has emerged in recent years. Its imaging is different from traditional anatomical imaging methods such as CT, MRI, and ultrasound. It is similar to the examination of tracers in nuclear medicine. It has the advantages of high sensitivity, no background interference, and is not affected by the depth of the scanned tissue and no ionizing radiation. Therefore, it can show high contrast for the distribution of tracers. So far, MPI has been widely used in different preclinical fields of medicine and has shown good application prospects. Its applications are mainly concentrated in preclinical studies such as cell tracing, vascular imaging, and tumor imaging and treatment. MPI is based on the imaging principle of nonlinear magnetization curves in the Langevin paramagnetic law, that is, magnetic nanoparticles can be magnetized by an external magnetic field and show nonlinear response under conditions close to zero magnetic field. Therefore, the performance of MPI is highly dependent on the physical properties of the contrast agent, such as size, shape, composition and crystallinity. The tracer currently used in MPI is usually iron oxide. In order to develop and use MPI more efficiently, it is still necessary to develop new and efficient MPI contrast agents.

[0004] Compared with normal tissues, the tumor microenvironment has its own characteristics, such as acidic outside of tumor cells, high expression of H2O2 and excessive glutathione, hypoxia and certain highly expressed enzymes, as well as its physiological characteristics, the interaction between tumor cells and stromal cells, and the extracellular matrix, which affect the occurrence and development of tumors, including proliferation, angiogenesis, invasion, migration, drug resistance, etc. Therefore, designing MPI contrast agents that are activated only in the tumor microenvironment and can respond highly specifically to tumor tissues is crucial to achieve precise treatment and reduce the toxic side effects of treatment methods on normal tissues. Summary of the invention

[0005] In view of the shortcomings of the prior art, the object of the present invention is to provide a Pd-based alloy with magnetic particle imaging properties, an MPI contrast agent, a preparation method and applications thereof; the present invention, through structural design, utilizes the stability of Pd as a carrier of transition metal ions (such as Fe, Mn, Co, Ni, Cu, Zn, Cd, Re, Zr, Ba, Mg, Sr, Al, Cr, Nd, Gd, Sm, La, Dy, Eu, Er, Tb, Ho, Tm, Yb, Y, etc.), utilizes a responsive polymer as a surfactant, and obtains an MPI contrast agent through ultrasonic treatment, which can achieve MPI precise imaging.

[0006] In order to achieve the above object, the present invention provides the following technical solutions:

[0007] The present invention provides a Pd-based alloy with magnetic particle imaging properties. The general structural formula of the Pd-based alloy is PdM, wherein M represents any one or more combinations of transition metal elements.

[0008] Preferably, the transition metal element includes one or more of Fe, Mn, Co, Ni, Cu, Zn, Cd, Re, Zr, Ba, Mg, Sr, Al, Cr, Nd, Gd, Sm, La, Dy, Eu, Er, Tb, Ho, Tm, Yb, and Y. The structural formula of the Pd-based alloy includes PdFe, PdFeMn, PdCo, ​​PdNi, PdFeCoNi, PdCuFe, PdNdFe, etc.

[0009] Preferably, the Pd-based alloy is uniform nanoparticles with a particle size of 1 to 1000 nm.

[0010] The invention provides an MPI contrast agent based on a Pd-based alloy. The MPI contrast agent comprises a Pd-based alloy and a responsive polymer. The Pd-based alloy uses Pd as a carrier and is doped with one or more transition metal elements M, and the general structural formula thereof is PdM.

[0011] As a further improvement of the above scheme, the responsive polymer 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.

[0012] As a further improvement of the above scheme, the contrast agent has tumor microenvironment-responsive MPI changes, and the tumor microenvironment responders include pH, hydrogen peroxide, glutathione, and biological enzymes.

[0013] As a further improvement of the above solution, the size of the MPI contrast agent is 1 to 1000 nm.

[0014] The present invention also provides a method for preparing an MPI contrast agent based on a Pd-based alloy, comprising the following steps:

[0015] (1) Preparation of PdM alloy nanomaterials;

[0016] (2) Preparation of PdM@responsive polymer contrast agent: The PdM alloy nanomaterial and responsive polymer obtained in step (1) are placed in THF, subjected to a first ultrasonic treatment, the mixed solution is quickly injected into water, subjected to a second ultrasonic treatment, and then subjected to rotary evaporation to remove tetrahydrofuran to obtain the Pd-based alloy-based MPI contrast agent.

[0017] As a preferred embodiment of the above scheme, the preparation process of the PdM alloy nanomaterial is as follows:

[0018] Acetylacetonate palladium (Pd(acac)2), a transition metal salt, oleic acid and oleylamine are mixed and added to a reactor. After evacuation, the mixed solution is stirred in an inert atmosphere. After heating, tungsten hexacarbonyl (W(CO)6) is quickly added. After reflux reaction for a set time, the mixture is filtered and washed to obtain the PdM alloy nanomaterial, which is then dispersed in tetrahydrofuran for storage.

[0019] Further preferably, the preparation process of the PdM alloy nanomaterial is:

[0020] The molar ratio of Pd(acac)2, transition metal salt and W(CO)6 is 1:(0.01-5):(0.2-3), and the molar volume ratio of oleic acid to oleylamine is 1:(2-12); the vacuuming temperature is 60-100°C, and the vacuuming time is 0.2-6h; the temperature is raised to 110-150°C, the reflux reaction temperature is 220-320°C, and the reflux reaction time is 0.25-4h; washing is performed using a mixed solution of cyclohexane and ethanol in a volume ratio of 1:(1-15), and the number of washing times is 3-6 times.

[0021] As a preferred embodiment of the above scheme, the preparation process of the PdM@responsive polymer contrast agent is as follows:

[0022] The mass ratio of PdM alloy nanomaterials and responsive polymers is 1:(3-30), the mass volume ratio of PdM alloy nanomaterials and THF is 0.05-0.5 mg / mL; the volume ratio of THF and water is 1:(5-15); the first ultrasonic time is 5-25 min, the second ultrasonic time is 5-25 min, and the temperature during rotary evaporation is 37-52°C.

[0023] The present invention also provides the use of an MPI contrast agent based on a Pd-based alloy, which is used as a contrast agent in tumor MPI imaging.

[0024] Compared with the prior art, the present invention has the following beneficial technical effects:

[0025] The present invention uses alloy nanoparticles with a Pd structure as carriers through structural design, can load transition metal elements, uses responsive polymers as surfactants, and obtains nanoparticles (MPI contrast agents) with good biocompatibility through ultrasonic treatment.

[0026] The present invention also provides the use of the contrast agent in in vivo imaging. The system contains PdM as a contrast agent and can construct an MPI imaging system with tumor microenvironment response. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 Schematic diagram of the action process of the PdFe@acid-responsive polymer nanocontrast agent of the present invention.

[0028] Figure 2 Diagram of the preparation process of the PdFe@acid-responsive polymer nanocontrast agent of the present invention.

[0029] Figure 3 TEM image of the PdFe binary alloy nanoparticles prepared in Example 1.

[0030] Figure 4 TEM image of PdCo binary alloy nanoparticles prepared in Example 2.

[0031] Figure 5 TEM image of PdNi binary alloy nanoparticles prepared in Example 3.

[0032] Figure 6 This is the characterization of the MPI performance of the PdFe@acid-responsive polymer nanocontrast agent in Example 13.

[0033] Figure 7 This is a diagram showing the cytotoxicity analysis of the PdFe@acid-responsive polymer nanocontrast agent in Example 13 on normal cells. DETAILED DESCRIPTION

[0034] The specific embodiments of the present invention are further described below by way of examples, but the specific embodiments of the present invention are not limited to the following examples.

[0035] The present invention provides a Pd-based alloy with magnetic particle imaging properties. The general structural formula of the Pd-based alloy is PdM, wherein M represents any one or more combinations of transition metal elements.

[0036] The transition metal elements include one or more of Fe, Mn, Co, Ni, Cu, Zn, Cd, Re, Zr, Ba, Mg, Sr, Al, Cr, Nd, Gd, Sm, La, Dy, Eu, Er, Tb, Ho, Tm, Yb, and Y. The structural formulas of Pd-based alloys include PdFe, PdFeMn, PdCo, ​​PdNi, PdFeCo, PdFeCoNi, PdCuFe, PdNdFe, PdDyFe, and PdGdFe.

[0037] The invention provides an MPI contrast agent based on a Pd-based alloy. The MPI contrast agent comprises a Pd-based alloy and a responsive polymer. The Pd-based alloy uses Pd as a carrier and is doped with one or more transition metal elements M, and the general structural formula thereof is PdM.

[0038] The responsive polymer 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.

[0039] The contrast agent has a tumor microenvironment-responsive MPI change, and the tumor microenvironment responders include pH, hydrogen peroxide, glutathione, and biological enzymes.

[0040] Taking PdFe@ responsive polymer nanocontrast agent as an example, the schematic diagram of its action process is as follows Figure 1 shown.

[0041] The preparation process of the PdFe@responsive polymer nanocontrast agent is as follows Figure 2 As shown, the following steps are included:

[0042] (1) Synthesis of PdFe binary alloy nanomaterials: Palladium acetylacetonate (Pd(acac)2), ferrous sulfate (FeSO4·7H2O)), oleic acid and oleylamine are mixed and added to a three-necked flask. After evacuation, the mixed solution is stirred under an inert atmosphere. After heating, tungsten hexacarbonyl (W(CO)6) is quickly added. After reflux reaction for a set time, the mixture is filtered and washed to obtain PdFe binary alloy nanomaterials, which are dispersed in tetrahydrofuran for storage;

[0043] (2) Synthesis of responsive polymers: Reversible addition-fragmentation chain transfer (RAFT) polymerization was used to synthesize responsive polymers. PEG-RAFT, 2-(diisopropylamino)ethyl methacrylate (DPA), AIBN and dioxane were mixed and added to a reactor. The mixture was deoxygenated by freezing and thawing in liquid nitrogen. The mixed solution was heated and stirred under an inert atmosphere. After the reaction, the mixture was dialyzed with pure water. Finally, the solution was freeze-dried to obtain a pH-responsive polymer.

[0044] (3) Synthesis of PdFe@responsive polymer nanocontrast agent: The PdFe alloy nanomaterial prepared in step (1) and the pH responsive polymer prepared in step (2) are placed in THF, and after sonication, they are quickly injected into water and sonicated for a second time. The mixed solution is then rotary evaporated to remove tetrahydrofuran, thereby obtaining a solution containing the PdFe@pH responsive polymer nanocontrast agent.

[0045] The following is further described through specific embodiments and drawings.

[0046] Example 1

[0047] The preparation process of PdFe@ responsive polymer nanocontrast agent includes the following steps:

[0048] (1) Synthesis of PdFe alloy nanomaterials: Pd(acac)2 (0.1mmol), FeSO4·7H2O (0.03mmol), W(CO)6 (0.1mmol), 3mL oleic acid and 17mL oleylamine were mixed and added to a three-necked flask equipped with a stirring magnet, and vacuumed at 85℃ for 90 minutes. Under an argon flow, the mixture was heated to 120℃, W(CO)6 was quickly added, and the temperature was raised to 235℃ for 1h, then cooled to room temperature, washed 4 times with a cyclohexane:ethanol solution with a volume ratio of 1:6, and redispersed in tetrahydrofuran for storage;

[0049] (2) Responsive polymer modified nanomaterials: The responsive polymer is any one or more combinations of commercially available polyvinyl pyrrolidone, long-chain fatty acids, fatty alcohols, polyoxyethylene-polyoxypropylene copolymers, poly(styrene-maleic anhydride) and sodium dodecylbenzene sulfonate, or modifications made thereon.

[0050] The synthesized PdFe alloy nanomaterials were prepared into a 4 mg / mL tetrahydrofuran solution, and the responsive polymer was prepared into a 20 mg / mL solution, and stored in a refrigerator at 4°C;

[0051] (3) Synthesis of PdFe@pH-responsive polymer nanocontrast agent: First, take 40 μL of PdFe tetrahydrofuran solution and 80 μL of acid-responsive polymer tetrahydrofuran solution, then add 880 μL of tetrahydrofuran, sonicate 1 mL of the mixture for 15 minutes, and then quickly inject the mixture into 10 mL of water. After sonication for 15 minutes, the mixture is rotary evaporated at 44°C to remove tetrahydrofuran; then the reaction solution from which tetrahydrofuran has been removed is washed with water and centrifuged 4 times using a 100K ultrafiltration tube at a speed of 4000 r / min, with each centrifugation time being 6 min.

[0052] The PdFe binary alloy nanomaterial prepared in this example was tested by TEM, and the results are as follows: Figure 3As shown, from Figure 3 It can be seen that the size of the PdFe nanoparticles prepared in this example is 5-15 nm.

[0053] Example 2

[0054] The preparation process of PdCo@ responsive polymer nanocontrast agent includes the following steps:

[0055] Synthesis of PdCo alloy nanomaterials: Pd(acac)2 (0.1mmol), CoCl2 (0.03mmol), W(CO)6 (0.1mmol), 1mL oleic acid and 19mL oleylamine were mixed and added to a three-necked flask equipped with a stirring magnet, and vacuumed at 85°C for 90 minutes. Under an argon flow, the mixture was heated to 120°C, W(CO)6 was quickly added, and the temperature was raised to 230°C for 1h, then cooled to room temperature, and the product was washed 4 times with a cyclohexane:ethanol solution with a volume ratio of 1:6, and then dispersed in tetrahydrofuran for storage; the subsequent modification process was consistent with (2) and (3) of Example 1.

[0056] Example 3

[0057] The preparation process of PdNi@responsive polymer nanocontrast agent includes the following steps:

[0058] Synthesis of PdNi alloy nanomaterials: Pd(acac)2 (0.1mmol), Ni(ac)2 (0.03mmol), W(CO)6 (0.1mmol), 1mL oleic acid and 19mL oleylamine were mixed and added to a three-necked flask equipped with a stirring magnet, and vacuumed at 85°C for 90 minutes. Under an argon flow, the mixture was heated to 120°C, W(CO)6 was quickly added, and the temperature was raised to 235°C for a second time and refluxed for 1h, then cooled to room temperature, and the product was washed 4 times with a cyclohexane:ethanol solution with a volume ratio of 1:6, and then dispersed in tetrahydrofuran for storage; the subsequent modification process was consistent with (2) and (3) of Example 1.

[0059] Example 4

[0060] The preparation process of PdFeMn@ responsive polymer nanocontrast agent includes the following steps:

[0061] Synthesis of PdFeMn alloy nanomaterials: Pd(acac)2 (0.1mmol), FeSO4·7H2O (0.02mmol), MnCl2 (0.01mmol), W(CO)6 (0.1mmol), 3mL oleic acid and 17mL oleylamine were mixed and added to a three-necked flask equipped with a stirring magnet, and vacuumed at 85°C for 90 minutes. Under an argon flow, the mixture was heated to 120°C, W(CO)6 was quickly added, and the temperature was raised to 235°C for 1h, then cooled to room temperature, and the product was washed 4 times with a cyclohexane:ethanol solution with a volume ratio of 1:6, and then dispersed in tetrahydrofuran for storage; the subsequent modification process was consistent with (2) and (3) of Example 1.

[0062] Example 5

[0063] The preparation process of PdCuFe@ responsive polymer nanocontrast agent includes the following steps:

[0064] Synthesis of PdCuFe alloy nanomaterials: Pd(acac)2 (0.1mmol), FeSO4 (0.01mmol), Cu(ac)2 (0.02mmol), W(CO)6 (0.1mmol), 3mL oleic acid and 17mL oleylamine were mixed and added to a three-necked flask equipped with a stirring magnet, and vacuumed at 85°C for 90 minutes. Under an argon flow, the mixture was heated to 120°C, W(CO)6 was quickly added, and the temperature was raised to 235°C for 1h, then cooled to room temperature, and the product was washed 4 times with a cyclohexane:ethanol solution with a volume ratio of 1:6, and then dispersed in tetrahydrofuran for storage; the subsequent modification process was consistent with (2) and (3) of Example 1.

[0065] Example 6

[0066] The preparation process of PdGdFe@ responsive polymer nanocontrast agent includes the following steps:

[0067] Synthesis of PdGdFe alloy nanomaterials: Pd(acac)2 (0.1mmol), FeSO4·7H2O (0.02mmol), GdCl2 (0.01mmol), W(CO)6 (0.1mmol), 3mL oleic acid and 17mL oleylamine were mixed and added to a three-necked flask equipped with a stirring magnet, and vacuumed at 85°C for 90 minutes. Under an argon flow, the mixture was heated to 120°C, W(CO)6 was quickly added, and the temperature was raised to 235°C for 1h, then cooled to room temperature, and the product was washed 4 times with a cyclohexane:ethanol solution with a volume ratio of 1:6, and then dispersed in tetrahydrofuran for storage; the subsequent modification process was consistent with (2) and (3) of Example 1.

[0068] Example 7

[0069] The preparation process of PdNdFe@ responsive polymer nanocontrast agent includes the following steps:

[0070] Synthesis of PdNdFe alloy nanomaterials: Pd(acac)2 (0.1mmol), FeSO4·7H2O (0.02mmol), Nd(NO3)35H2O (0.01mmol), W(CO)6 (0.1mmol), 3mL oleic acid and 17mL oleylamine were mixed and added to a three-necked flask equipped with a stirring magnet, and vacuumed at 85°C for 90 minutes. Under an argon flow, the mixture was heated to 120°C, W(CO)6 was quickly added, and the temperature was raised to 235°C for 1h, then cooled to room temperature, and the product was washed 4 times with a cyclohexane:ethanol solution with a volume ratio of 1:6, and then dispersed in tetrahydrofuran for storage; the subsequent modification process was consistent with (2) and (3) of Example 1.

[0071] Example 8

[0072] The preparation process of PdLaFe@ responsive polymer nanocontrast agent includes the following steps:

[0073] Synthesis of PdLaFe alloy nanomaterials: Pd(acac)2 (0.1mmol), FeSO4·7H2O (0.02mmol), La(NO3)3·6H2O (0.01mmol), W(CO)6 (0.1mmol), 3mL oleic acid and 17mL oleylamine were mixed and added to a three-necked flask equipped with a stirring magnet, and vacuumed at 85°C for 90 minutes. Under an argon flow, the mixture was heated to 120°C, W(CO)6 was quickly added, and the temperature was raised to 235°C for 1h, then cooled to room temperature, and the product was washed 4 times with a cyclohexane:ethanol solution with a volume ratio of 1:6, and then dispersed in tetrahydrofuran for storage; the subsequent modification process was consistent with (2) and (3) of Example 1.

[0074] Example 9

[0075] The preparation process of PdCoFe@ responsive polymer nanocontrast agent includes the following steps:

[0076] Synthesis of PdCoFe alloy nanomaterials: Pd(acac)2 (0.1mmol), FeSO4·7H2O (0.01mmol), CoCl2 (0.02mmol), W(CO)6 (0.1mmol), 3mL oleic acid and 17mL oleylamine were mixed and added to a three-necked flask equipped with a stirring magnet, and vacuumed at 85°C for 90 minutes. Under an argon flow, the mixture was heated to 120°C, W(CO)6 was quickly added, and the temperature was raised to 235°C for 1h, then cooled to room temperature, and the product was washed 4 times with a cyclohexane:ethanol solution with a volume ratio of 1:6, and then dispersed in tetrahydrofuran for storage; the subsequent modification process was consistent with (2) and (3) of Example 1.

[0077] Example 10

[0078] The preparation process of PdCoNi@ responsive polymer nanocontrast agent includes the following steps:

[0079] Synthesis of PdCoNi alloy nanomaterials: Pd(acac)2 (0.1mmol), Ni(ac)2 (0.01mmol), CoCl2 (0.02mmol), W(CO)6 (0.1mmol), 3mL oleic acid and 17mL oleylamine were mixed and added to a three-necked flask equipped with a stirring magnet, and vacuumed at 85°C for 90 minutes. Under an argon flow, the mixture was heated to 120°C, W(CO)6 was quickly added, and the temperature was raised to 235°C for 1h, then cooled to room temperature, and the product was washed 4 times with a cyclohexane:ethanol solution with a volume ratio of 1:6, and then dispersed in tetrahydrofuran for storage; the subsequent modification process was consistent with (2) and (3) of Example 1.

[0080] Embodiment 11

[0081] The preparation process of PdCoFeNi@ responsive polymer nanocontrast agent includes the following steps:

[0082] Synthesis of PdCoFeNi alloy nanomaterials: Pd(acac)2 (0.1mmol), FeSO4·7H2O (0.01mmol), Ni(ac)2 (0.01mmol), CoCl2 (0.01mmol), W(CO)6 (0.1mmol), 3mL oleic acid and 17mL oleylamine were mixed and added to a three-necked flask equipped with a stirring magnet, and vacuumed at 85°C for 90 minutes. Under an argon flow, the mixture was heated to 120°C, W(CO)6 was quickly added, and the temperature was raised to 235°C for 1h, then cooled to room temperature, and the product was washed 4 times with a cyclohexane:ethanol solution with a volume ratio of 1:6, and then dispersed in tetrahydrofuran for storage; the subsequent modification process was consistent with (2) and (3) of Example 1.

[0083] Example 12

[0084] The preparation process of PdDyFe@ responsive polymer nanocontrast agent includes the following steps:

[0085] Synthesis of PdDyFe alloy nanomaterials: Pd(acac)2 (0.1mmol), FeSO4·7H2O (0.02mmol), DyCl3 (0.01mmol), W(CO)6 (0.1mmol), 3mL oleic acid and 17mL oleylamine were mixed and added to a three-necked flask equipped with a stirring magnet, and vacuumed at 85°C for 90 minutes. Under an argon flow, the mixture was heated to 120°C, W(CO)6 was quickly added, and the temperature was raised to 235°C for 1h, then cooled to room temperature, and the product was washed 4 times with a cyclohexane:ethanol solution with a volume ratio of 1:6, and then dispersed in tetrahydrofuran for storage; the subsequent modification process was consistent with (2) and (3) of Example 1.

[0086] Embodiment 13

[0087] 1. Magnetic properties test based on PdFe binary alloy nanomaterials:

[0088] The PdFe binary alloy nanomaterial and the PdFe@pH responsive polymer nanocontrast agent aqueous solution obtained in Example 1 were prepared into aqueous solutions with different concentration gradients, and the intensity of MPI was measured using a magnetic particle imaging system (Momentum, Magnetic Insight, Inc.). The results are shown in FIG. Figure 4 As shown, from Figure 4 It can be seen that the PdFe@pH-responsive polymer nanocontrast agent has an MPI imaging effect, because PdFe nanoparticles can release a large amount of iron ions to weaken the MPI performance.

[0089] 2. Cytotoxicity analysis based on PdFe@surfactant nanocontrast agent:

[0090] a) Toxicity analysis: Normal cells (HEK293) were cultured in 96-well plates. After the cells adhered to the plate, different concentrations of materials (PdFe@surfactant nanocontrast agent) were added and incubated for 24 h. The toxicity test was then performed using the standard MTT method. Figure 5 The toxicity analysis results of nanomedicines at different concentrations on cancer cells are shown in Figure 2. Figure 5 It can be seen that both groups of PdFe@surfactant nanocontrast agents are safe and non-toxic to normal cells.

[0091] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. A method for preparing a Pd-based alloy MPI contrast agent, characterized in that: The following steps are involved: (1) Preparation of PdM alloy nanomaterials; (2) Preparation of PdM@responsive polymer contrast agent: placing the PdM alloy nanomaterial and responsive polymer obtained in step (1) in THF, performing a first ultrasonic treatment, rapidly injecting the mixed solution into water, performing a second ultrasonic treatment, and then performing rotary evaporation on the mixed solution to remove tetrahydrofuran, thereby obtaining the Pd-based alloy-based MPI contrast agent; The MPI contrast agent comprises a Pd-based alloy and a responsive polymer, wherein the Pd-based alloy has magnetic particle imaging properties; the Pd-based alloy uses Pd as a carrier and is doped with one or more transition metal elements M, and its general structural formula is PdM; The transition metal element M includes one or more of Fe, Mn, Co, Ni, Cu, Zn, Cd, Re, Zr, Ba, Mg, Sr, Al, Cr, Nd, Gd, Sm, La, Dy, Eu, Er, Tb, Ho, Tm, Yb, and Y elements; The responsive polymer 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; The contrast agent has a tumor microenvironment-responsive MPI change, and the tumor microenvironment responders include pH, hydrogen peroxide, glutathione, and biological enzymes; The preparation process of the PdM alloy nanomaterial is as follows: Acetylacetonate palladium (Pd(acac)2), transition metal salt, oleic acid and oleylamine are mixed and added into a reactor. After evacuation, the mixed solution is stirred under an inert atmosphere, and hexacarbonyl tungsten (W(CO)6) is quickly added after heating. After reflux reaction for a set time, the mixture is filtered and washed to obtain the PdM alloy nanomaterial, which is dispersed in tetrahydrofuran for storage; The preparation process of the PdM@responsive polymer contrast agent is as follows: The mass ratio of PdM alloy nanomaterials and responsive polymers is 1:(3~30), the mass volume ratio of PdM alloy nanomaterials and THF is 0.05~0.5 mg / mL; the volume ratio of THF to water is 1:(5~15); the first ultrasonic time is 5~25 min, the second ultrasonic time is 5~25 min, and the temperature during rotary evaporation is 37~52°C.

2. The method for preparing the Pd-based alloy MPI contrast agent according to claim 1, characterized in that: The preparation process of the PdM alloy nanomaterial is as follows: The molar ratio of Pd(acac)2, transition metal salt and W(CO)6 is 1:(0.01~5):(0.2~3), the molar volume ratio of oleic acid to oleylamine is (0~12):1; the vacuum temperature is 60~100℃, and the vacuum time is 0.2~6h; the temperature is raised to 110~150℃, the reflux reaction temperature is 220~320℃, and the reflux reaction time is 0.25~4h; washing uses a mixed solution of cyclohexane and ethanol in a volume ratio of 1:(1~15), and the number of washing times is 3~6 times.

3. The method for preparing the Pd-based alloy MPI contrast agent according to claim 1, characterized in that: The Pd-based alloy is uniform nanoparticles with a particle size of 1-1000 nm.

4. The use of the Pd-based alloy MPI contrast agent according to any one of claims 1 to 3, characterized in that: It is used as a contrast agent in tumor MPI imaging.

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