阅读说明：本技术 一种磁性等离子体纳米材料及其制备方法与应用 (Magnetic plasma nano material and preparation method and application thereof ) 是由 吴爱国 高昊 卫珍妮 祖柏儿 于 2020-05-20 设计创作，主要内容包括：本申请公开了一种磁性等离子体纳米材料及其制备方法与应用,所述磁性等离子体纳米材料包括中心颗粒和包覆在所述中心颗粒外的金属氧化物,所述中心颗粒为金属纳米颗粒,所述金属纳米颗粒中的金属及所述金属氧化物中的金属中至少有一种为磁性金属。该材料具有磁性和光学活性,具有同时进行磁性和光学检测的潜力。此外,磁性等离子体纳米体系具有良好的T1弛豫性能,还具有较强的近红外吸收峰和良好的光热加热能力。(The application discloses a magnetic plasma nano material and a preparation method and application thereof, wherein the magnetic plasma nano material comprises a central particle and a metal oxide coated outside the central particle, the central particle is a metal nano particle, and at least one of metal in the metal nano particle and metal in the metal oxide is magnetic metal. The material has magnetic and optical activity and has the potential of carrying out magnetic and optical detection simultaneously. In addition, the magnetic plasma nano system has good T1 relaxation performance, and also has a strong near infrared absorption peak and good photo-thermal heating capacity.)

1. The magnetic plasma nano material is characterized by comprising a central particle and a metal oxide coated outside the central particle, wherein the central particle is a metal nano particle, and at least one of metal in the metal nano particle and metal in the metal oxide is magnetic metal.

2. The magnetic plasma nanomaterial of claim 1, wherein the metal nanoparticles are selected from at least one of Gd, Dy, Mn, Fe, Co, Ni, Pt, Ag, Cu, Pd, Au;

preferably, the metal oxide is selected from Fe₃O₄、Fe₂O₃、Gd₂O₃、Mn₃O₄、CoO、Co₂O₃And NiO;

preferably, the magnetic plasma nano material further comprises a polymer layer coated outside the metal oxide;

preferably, the polymer layer is selected from at least one of poloxamer, polyether, polyoxyethylene polyoxypropylene block copolymer;

preferably, the central particle is an Au nanoparticle, and the metal oxide is Mn₃O₄。

3. The magnetic plasma nanomaterial according to claim 1, wherein the diameter of the central particle is 1 to 100nm, and the diameter of the magnetic plasma nanomaterial is 20 to 150 nm;

preferably, the diameter of the central particle is 1-50 nm, and the diameter of the magnetic plasma nano material is 20-100 nm;

more preferably, the diameter of the central particle is 1-20 nm, and the diameter of the magnetic plasma nano material is 20-50 nm.

4. The magnetic plasma nanomaterial as claimed in claim 1, wherein the longitudinal relaxation rate r1 is greater than or equal to 4s^-1mM^-1；

Preferably, the magnetic plasma nano material is in a flower shape, a dumbbell shape or a star shape.

5. A method for preparing magnetic plasma nanometer material as claimed in any one of claims 1 to 4, characterized by comprising at least the following steps:

(1) preparing metal nano particles;

(2) preparing a metal oxide precursor, wherein the metal oxide precursor is metal oleate;

(3) and (3) reacting and roasting the mixed solution containing the metal nano particles, the metal oxide precursor and the surfactant to obtain the magnetic plasma nano material.

6. The method for preparing a magnetic plasma nanomaterial as defined in claim 5, wherein the magnetic transition metal nanoparticles are prepared by a one-step synthesis method in step (1).

7. The method for preparing a magnetic plasma nanomaterial as defined in claim 5, wherein the method for preparing a metal oxide precursor in the step (2) specifically comprises:

reacting an aqueous solution containing a metal source and oleate to obtain a metal oxide precursor, wherein the metal source is preferably selected from soluble salts of metals;

preferably, the soluble salt of the metal is selected from at least one of the group consisting of chloride of Fe, nitrate of Fe, sulfate of Fe, chloride of Gd, nitrate of Gd, chloride of Mn, nitrate of Mn, sulfate of Mn, chloride of Co, nitrate of Co, sulfate of Co, chloride of Ni, nitrate of Ni and sulfate of Ni;

preferably, the oleate is selected from at least one of sodium oleate, potassium oleate and magnesium oleate, and the mass ratio of the metal source to the oleate is 1: 10-4: 5;

preferably, the reaction is carried out in the step (2) under the condition of stirring, and the reaction temperature is 10-40 ℃;

the reaction time is 0.1-2 hours.

8. The method for preparing magnetic plasma nano-materials as claimed in claim 5, wherein the surfactant in the step (3) is at least one selected from oleic acid and oleylamine;

preferably, the solvent in the mixed solution in the step (3) is 1-octadecene;

preferably, the mass ratio of the metal nanoparticles, the metal oxide precursor and the surfactant in the step (3) is 0.08-0.8: 0.03 to 0.3: 1;

preferably, the reaction temperature of the reaction in the step (3) is 60-180 ℃, and the reaction time is 0.1-3 h;

preferably, the roasting temperature is 300-350 ℃, and the roasting time is 1-3 h.

9. The method for preparing magnetic plasma nano-materials as claimed in claim 5, wherein the step (3) further comprises the following steps after the reaction is finished:

(4) dispersing the material obtained in the step (3) into a polymer dispersion liquid to obtain a magnetic plasma nano material with a polymer layer coated outside a metal oxide;

preferably, the mass ratio of the polymer to the material obtained in step (3) is 1: 0.5 to 4.

10. The magnetic plasma nano-material according to any one of claims 1 to 4 and the magnetic plasma nano-material prepared by the preparation method according to any one of claims 5 to 9 are applied to radiography, tumor diagnosis and tumor ablation.

Technical Field

The application relates to a magnetic plasma nano material and a preparation method and application thereof, belonging to the field of medical materials.

Background

The multifunctional hybrid nano material has excellent performance in the heterojunction part, and thus has wide research prospect in the development of modern science and technology. On the nanometer scale, the electrical, magnetic and optical properties of the hybrid material show remarkable characteristics compared to the single material. Through the structure change of the nanometer scale and the interaction between the hybrid materials, some hidden physical and chemical information can be revealed, so that the hybrid material has wide application prospects in the aspects of heterogeneous catalysis, synchronous biomarkers, protein detection and separation, multi-modal imaging, cancer treatment and the like. However, well-controlled glue or heterojunction between two different nanomaterials remains a challenging issue. In biomedical research, the work of designing colloidal nanocomposite materials with good biocompatibility is yet to be further explored.

In cancer diagnosis, Magnetic Resonance Imaging (MRI), which is a non-invasive imaging means, has advantages that other techniques cannot compare due to its high resolution. Extracellular contrast agents help to further enhance the imaging of the tumor lesion. The contrast agent used clinically at present mainly takes gadolinium chelate as a positive contrast agent. However, gadolinium (Gd3+) in its ionic form may in some cases cause serious complications. In the aspect of treatment, compared with the traditional treatment method, the photothermal therapy (PTT) combined chemotherapy has a remarkable improvement effect, and is a promising tumor ablation technology. In conventional treatments, radiation and chemotherapy may be toxic to normal cells and tissues, resulting in serious side effects. In recent years, gold nanoparticles have great clinical application potential in the aspects of thermotherapy, drug delivery and the like due to good biocompatibility and optical properties. However, if no diagnostic information is referenced, the information provided by the medication alone is less accurate. Therefore, it is a trend of precise medical treatment to combine a contrast agent and a therapeutic agent into the same system. However, combining two separate components into a heterostructure with controllable shape and size without changing the properties of the individual materials is a huge challenge.

Disclosure of Invention

According to a first aspect of the present application, there is provided a magnetic plasma nanomaterial, the material having a magnetic propertySex and optical activity, have the potential to carry on magnetism and optical detection at the same time. In addition, magnetic plasmon nanosystems have good T₁The relaxation property, the near infrared absorption peak and the good photo-thermal heating capacity.

The magnetic plasma nano material comprises a central particle and a metal oxide coated outside the central particle, wherein the central particle is a metal nano particle, and at least one of metal in the metal nano particle and metal in the metal oxide is magnetic metal.

Optionally, the metal nanoparticles are selected from at least one of Gd, Dy, Co, Mn, Fe, Ni, Pt, Ag, Cu, Pd, Au;

the metal oxide is selected from Fe₃O₄、Fe₂O₃、Gd₂O₃、Mn₃O₄、CoO、Co₂O₃And NiO.

Optionally, the magnetic plasma nanomaterial further comprises a polymer layer coated outside the metal oxide;

the polymer layer is selected from poloxamers (poloxamer)F-127), polyether and/or polyoxyethylene-polyoxypropylene block copolymer.

Preferably, the central particle is an Au nanoparticle, and the metal oxide is Mn₃O₄。

Optionally, the manganese ion is derived from at least one of a manganese salt and a derivative thereof. The manganese ions are derived from at least one of manganese chloride and derivatives thereof. The manganese ion is derived from MnCl₃·4H₂O。

Optionally, the diameter of the central particle is 1-100 nm, preferably 1-50 nm, and more preferably 1-20 nm, and the diameter of the magnetic plasma nano material is 20-150 nm, preferably 20-100 nm, and more preferably 20-50 nm.

Alternatively, the longitudinal relaxation rate r1 ≧ 4s^-1mM^-1。

Optionally, the magnetic plasma nanomaterial is in a flower shape, a dumbbell shape, a star shape, or the like.

In a second aspect of the present application, there is provided a method for preparing a magnetic plasma nanomaterial described in any one of the above, comprising at least the following steps:

(1) preparing metal nano particles;

(2) preparing a metal oxide precursor, wherein the metal oxide precursor is metal oleate;

(3) and reacting the mixed solution containing the metal nano-particles, the metal oxide precursor and the surfactant to obtain the magnetic plasma nano-material.

The step utilizes a thermal decomposition method to grow heteroepitaxial metal oxide on the metal nano particles, and the magnetic plasma nano material is obtained. Preferably, the magnetic plasmonic nanomaterial is monodisperse and is uniform in shape and size.

Alternatively, the magnetic transition metal nanoparticles are prepared by a one-step synthesis method in step (1). The specific reaction conditions of the one-step synthesis method can be specifically selected according to the metal properties of the selected central particles and the actual needs. The metal nanoparticles are monodisperse.

In a specific embodiment, the method for preparing metal nanoparticles specifically includes:

and reacting the mixed solution containing the metal source, the organic solvent and the reducing agent to obtain the metal nano-particles.

Optionally, the metal source is selected from at least one of metal salts and metal oxides; preferably, the metal source is selected from HAuCl₄·3H₂O、Fe₃O₄、Gd₂O₃、Mn₃O₄、GdO、CoO、Co₂O₃And NiO;

optionally, the organic solvent is selected from at least one of oleylamine, n-hexane, cyclohexane and carbon trichloride;

preferably, the organic solvent is a mixed solvent formed by mixing oleylamine and n-hexane according to a volume ratio of 1: 1-1.5.

The reducing agent is selected from at least one of citric acid, ascorbic acid and tetrabutylammonium bromide;

optionally, the content of the metal source in the mixed solution is 0.02% to 0.8%; the mass ratio of the reducing agent to the metal source is 0.05-0.5: 1.

optionally, the reaction is carried out under stirring and anaerobic conditions, the reaction temperature is 10-30 ℃, and the reaction time is 0.2-2 h.

Optionally, the preparation method of the metal oleate described in the step (2) specifically includes:

and (3) reacting the aqueous solution containing the metal source and the oleate to obtain the metal oxide precursor.

Alternatively, the metal source is selected from soluble salts of metals;

the soluble salt of the metal is selected from at least one of Fe chloride, Fe nitrate, Fe sulfate, Gd chloride, Gd nitrate, Mn chloride, Mn nitrate, Mn sulfate, Co chloride, Co nitrate, Co sulfate, Ni chloride, Ni nitrate and Ni sulfate;

optionally, the oleate is selected from at least one of sodium oleate, potassium oleate, magnesium oleate.

Optionally, the mass ratio of the metal source to the oleate is 1: 10-4: 5.

Optionally, the reaction temperature in the step (2) is 10-40 ℃;

the reaction time is 0.1-2 h.

Optionally, the surfactant in the step (3) is selected from at least one of oleic acid and oleylamine;

and (4) the solvent in the mixed solution in the step (3) is at least one of 1-octadecene.

Optionally, the mass ratio of the metal nanoparticles, the metal oxide precursor and the surfactant in the step (3) is 0.08-0.8: 0.03 to 0.3: 1.

optionally, the reaction temperature of the reaction in the step (3) is 60-180 ℃, and the reaction time is 0.1-3 h. The roasting temperature is 300-350 ℃, and the roasting time is 1-3 h.

Optionally, the reacting the mixed solution containing the metal nanoparticles, the metal oxide precursor, and the surfactant in step (3) specifically includes:

firstly, carrying out thermal decomposition reaction on a mixed solution of a metal oxide precursor and a surfactant, and then adding the metal nanoparticles for continuous reaction; the reaction temperature of the thermal decomposition reaction is 60-180 ℃, the reaction time is 0.1-2 h, the temperature of the continuous reaction is 60-180 ℃, and the reaction time is 0.5-2 h.

Optionally, after the reaction in step (3) is finished, the method further comprises:

(4) and (4) dispersing the material obtained in the step (3) into a polymer dispersion liquid to obtain the magnetic plasma nano material with the polymer layer coated outside the metal oxide.

Optionally, the mass ratio of the polymer to the material obtained in step (3) is 1: 0.5 to 4.

In a specific embodiment, the preparation method comprises the following steps:

(S1) adding the metal salt solution into Oleylamine (OAM) and n-hexane solution, isolating oxygen, and stirring for a period of time. Pouring a reducing solution into the precursor solution, and precipitating the monodisperse metal nanoparticles to obtain monodisperse metal nanoparticles;

(S2) mixing and reacting hydrated metal chloride and sodium oleate to obtain metal oleate;

(S3) adding the monodisperse metal nanoparticles prepared in (S1) to the dispersion of metal oleate described in step (S1), and reacting to obtain the magnetic plasma nanomaterial.

(S4) use of a drug approved by the United states Food and Drug Administration (FDA)F-127 converts the magnetic plasma nanosystem from an oil phase to a water phase.

In a third aspect of the present application, there is provided an application of the magnetic plasma nanomaterial described in any one of the above and the magnetic plasma nanomaterial prepared by the preparation method described in any one of the above in imaging, tumor diagnosis, and tumor ablation.

In particular, the materials provided herein are useful as contrast agents, which herein include various medical contrast agents, such as Magnetic Resonance Imaging (MRI) contrast agents, Computed Tomography (CT) contrast agents, or Positron Emission Tomography (PET) contrast agents.

Preferably, the contrast agent is a magnetic resonance imaging contrast agent, in particular a magnetic resonance imaging T1 contrast agent.

The beneficial effects that this application can produce include:

the magnetic plasma nano material has magnetic and optical activities and has the potential of carrying out magnetic and optical detection simultaneously. In addition, the magnetic plasma nano system has good T1 relaxation performance, and also has a strong near infrared absorption peak and good photo-thermal heating capacity.

Drawings

FIG. 1 is Au @ Mn as prepared in example 1₃O₄A transmission electron microscope characterization picture of the pattern nano material, wherein a picture is a transmission electron microscope picture with a scale of 50nm, and b picture is a high-resolution transmission electron microscope characterization picture;

FIG. 2 is Au @ Mn as prepared in example 1₃O₄The element distribution color visual image of the flower-shaped nanometer material, wherein the picture a is a black-and-white picture of Au and Mn distribution, the picture b is a color picture of Au and Mn distribution, the picture c is a color picture of Au distribution, and the picture d is a color picture of Mn distribution;

FIG. 3 is Au @ Mn as prepared in example 1₃O₄EDS image of element distribution of the pattern type nano material;

FIG. 4 is Au @ Mn as prepared in example 1₃O₄T of @ PF-127 flower type nano material₁A relaxation quantification map;

FIG. 5 is Au @ Mn as prepared in example 1₃O₄T of @ PF-127 flower type nano material₁A map of relaxation effects;

FIG. 6 is Au @ Mn as prepared in example 1₃O₄@ PF-127 flower type nano materialMRI images injected into 4T1 mice, where panel a is 4T1 mice MRI image before nanomaterial injection and panel b is Au @ Mn injection₃O₄4T1 mouse MRI image after 20 minutes of @ PF-127 pattern nanomaterial, panel c is Au @ Mn injection₃O₄4T1 mouse MRI image after 120 minutes of @ PF-127 flower type nanomaterial;

FIG. 7 shows the power density of 1.2W/cm for different concentrations of the nanomaterials prepared in example 1²The temperature rise curve under 808nm laser irradiation, wherein a is Au @ Mn₃O₄Temperature rise curve diagram of @ PF-127 flower type nano material, b diagram is Au @ Mn₃O₄Temperature rise curve graphs of the @ PF-127 flower type nano material under different wave band lasers;

FIG. 8 is a graph of [email protected] Au @ Mn prepared in example 1 at various concentrations₃O₄The power density of the pattern nano material is 1.2W/cm²Heating curve image under 808nm laser irradiation;

FIG. 9 shows a laser (1.2W/cm) at 808nm²) Next, [email protected] Au @ Mn prepared in example 1 was injected intratumorally₃O₄Thermal infrared image of 4T1 tumor-bearing nude mouse after pattern-forming nano material;

FIG. 10 is Au @ Mn obtained in example 1₃O₄The representative photos of different stages of tumor treatment when the flower type PF-127 nano material is used for treating mouse tumors.

Detailed Description

The present application will be described in detail with reference to examples, but the present application is not limited to these examples.

The raw materials in the examples of the present application were all purchased commercially, unless otherwise specified.

Example 1

(1) Synthesis of gold nanoparticles

The monodisperse gold nanoparticles are synthesized by adopting a one-step method:

adding HAuCl₄·3H₂O (0.1g) was added to a mixed solvent composed of OAM (10mL) and n-hexane (10mL) to give an orange solution. The orange solution was stirred in a 15 ℃ thermostatic water bath for 30min under nitrogen.

Tetrabutylammonium bromide TBAB (0.167mmol) (0.008g) was dissolved in a mixed solvent of n-hexane (1mL) and OAm (1mL) to obtain a reduced solution. The reducing solution was then immediately poured into the above orange solution. Reduction reaction (HAuCl)₄·3H₂O) was initiated instantaneously within 5s and the solution turned dark purple. The reaction mixture was left at 15 ℃ for 1h, and then an appropriate amount of ethanol was added to the reaction mixture to precipitate gold nanoparticles. The gold nanoparticles were collected, the final product solution was centrifuged, and washed with ethanol.

(2) Synthesis of manganese oleate

Manganese chloride tetrahydrate (3g) and sodium oleate (10g) were dissolved in water, and after sufficient ultrasonic dispersion for 10min, n-hexane (40mL) and ethanol (24mL) were added to the mixed solution, followed by magnetic stirring for 4h, followed by washing with distilled water 3 times.

(3)[email protected]₃O₄Synthesis of nanoflowers

The heteroepitaxial growth of manganese oxide on gold nanoparticles was carried out using a thermal decomposition method. Specifically, decomposing the manganese oleate (0.5mmol), the oleylamine (8mmol) and the oleic acid (8mmol) prepared in the step (2) in 1-octadecene (30mL) at 120 ℃ for 20min, injecting the prepared gold nanoparticles (1g) into the solution, and keeping the temperature for 1h under the condition of introducing nitrogen to prepare the flower type Au @ Mn₃O₄And (3) nano materials. After 1h, the temperature was gradually raised to 320 ℃ at a rate of 5 ℃/min and maintained at that temperature for 90 minutes. The reaction mixture was cooled to room temperature by removing the heat source. Then, the product was centrifuged, washed repeatedly with ethanol and acetone to remove excess components, and dispersed in cyclohexane for further use.

Finally, in order to improve the biocompatibility of the synthesized magnetic plasmonic nanomaterial, a tri-block copolymer approved by the U.S. Food and Drug Administration (FDA) is employedF-127 converts the magnetic plasma nanomaterial from an organic phase to an aqueous phase. The method comprises the following specific steps: will be provided withF-127 Add 100mL of CHCl₃And (4) performing ultrasonic magnetic stirring for 20min to obtain a clear solution. Subsequently, 1mL of Au @ Mn at a concentration of 1g/mL₃O₄Gradually adding the nano material dispersion liquid into the solution, magnetically stirring for 4h, adding 7mL of water into the solution, carrying out ultrasonic treatment, gradually evaporating trichloromethane at 40 ℃ by using a rotary evaporator, washing the nano particles by using ethanol through the rotary evaporator, and accumulating the nano particles Au @ Mn₃O₄@ PF-127 for further study.

Example 2

The preparation method is the same as in example, with the only difference that HAuCl is used in step (1) of example 1₄·3H₂Substitution of O into Fe respectively₃O₄、GdO、NiO、Dy O、MnO、PtO₂、CoO、Ag₂O, CuO and PdO to obtain Fe @ Mn₃O₄、[email protected]₃O₄、[email protected]₃O₄、[email protected]₃O₄、[email protected]₃O₄、[email protected]₃O₄、[email protected]₃O₄、[email protected]₃O₄、[email protected]₃O₄、[email protected]₃O₄。

Example 3

The preparation method is the same as the example, and the only difference is that the manganese chloride tetrahydrate in the step (2) of the example 1 is respectively replaced by ferric chloride, gadolinium chloride, manganese chloride, nickel chloride and cobalt chloride to correspondingly prepare Au @ Fe₃O₄、[email protected]、[email protected]、[email protected]、[email protected]。

Performance testing and characterization

The morphology and the performance of the embedded magnetic plasma nano-materials obtained in the embodiments 1 to 3 are characterized.

Au @ Mn prepared as in example 1 below₃O₄The results of various morphology and performance characterizations are illustrated as examples. The corresponding products obtained in the other examples have similar properties.

FIG. 1 is a pattern Au @ Mn prepared in example 1₃O₄Nano materialTransmission electron micrograph of the material.

In the invention, the transmission electron microscope model Talos F200x is purchased from Saimer fly instruments, Inc. of China, and the experimental condition is 200 kV.

As can be seen in fig. 1, the transmission image clearly shows that a uniform flower-like morphology is formed throughout the sample. Panel b clearly shows small particles in the center as Au nanoparticles of about 10nm size and petals at the core edge as Mn of 18nm size₃O₄Nanometer petal.

FIG. 2 is a pattern Au @ Mn prepared in example 1₃O₄The element distribution color visual image of the nanometer material, wherein the picture a is a black-and-white picture of Au and Mn distribution, the picture b is a color picture of Au and Mn distribution, the picture c is a color picture of Au distribution, and the picture d is a color picture of Mn distribution.

In the invention, the transmission electron microscope model Talos F200x is purchased from Saimer fly instruments, Inc. of China, and the experimental condition is 200 kV.

FIG. 2 demonstrates Mn₃O₄Petals are grown on Au core nanoparticles.

FIG. 3 is a pattern Au @ Mn prepared in example 1₃O₄EDS image of element distribution of nanomaterials.

In the invention, the transmission electron microscope model Talos F200x is purchased from Saimer fly instruments, Inc. of China, and the experimental condition is 200 kV.

EDS analysis of fig. 3 shows phase purity of the synthesized flower-type nanomaterial, indicating that the prepared flower-type nanomaterial finally consists of Au, Mn, and O. Therefore, the structural analysis results confirmed that Au @ Mn with regular arrangement was successfully formed through the self-assembly growth process₃O₄And (4) a flower type nano material.

FIG. 4 is a pattern Au @ Mn prepared in example 1₃O₄T of @ PF-127 nano material₁Relaxation quantification map.

In the present invention, an MRI scanner model 0.55T MeoMR60, available from pneuma, shanghai, ltd, had an experimental repeat Spin Echo (SE) sequence TR of 300ms and an echo time TE of 18ms, respectively.

As can be seen from FIG. 4, Au @ Mn₃O₄R of @ PF-127 flower type nano material₁The value was 5.74s^-1mM^-1Is a very promising T₁The MR contrast agent is weighted.

FIG. 5 is Au @ Mn as prepared in example 1₃O₄T of @ PF-127 flower type nano material₁And (4) a relaxation effect graph.

In the present invention, an MRI scanner model 0.55T MeoMR60, available from pneuma, shanghai, ltd, had an experimental repeat Spin Echo (SE) sequence TR of 300ms and an echo time TE of 18ms, respectively.

The MRI experiment result of fig. 5 shows that the imaging effect is enhanced with the increase of the manganese concentration.

FIG. 6 is Au @ Mn as prepared in example 1₃O₄The MRI image of the pattern @ PF-127 injected 4T1 mouse with nanomaterial, wherein the figure a is the MRI image of the 4T1 mouse before injecting the nanomaterial, and the figure b is the Au @ Mn injected₃O₄4T1 mouse MRI image after 20 minutes of @ PF-127 pattern nanomaterial, panel c is Au @ Mn injection₃O₄@ PF-127 flower type 4T1 mouse MRI images of nanomaterial 120 minutes later.

In the present invention, an MRI scanner model 0.55T MeoMR60, available from pneuma, shanghai, ltd, had an experimental repeat Spin Echo (SE) sequence TR of 300ms and an echo time TE of 18ms, respectively.

FIG. 6 in vivo MRI images of mice showing Au @ Mn₃O₄The @ PF-127 flower type nano material can obviously enhance T₁Relaxation effect, T being promising₁A weighted MRI contrast agent.

Testing the photo-thermal performance of the magnetic plasma nano material:

the test method comprises the following steps: in the aspect of photothermal effect of the material, the invention uses the mouse 4T1 cells to Au @ Mn₃O₄The @ PF-127 flower type nano material is subjected to an in vitro photo-thermal test. The method comprises the following steps: 4T1 cells were cultured in RPMI medium containing 10% fetal bovine serum for 24h in 96-well plates and then plated with Au @ Mn at various Au concentrations (0, 50, 100, 150, 200. mu.g/mL)₃O₄@ PF-127 flower type nano material for treating cells for 24h at 37 ℃ and 5% CO₂When this is the caseThe Mn concentrations were 0, 140, 210, 280, 350. mu.g/mL, respectively. After culturing for 4h, replacing fresh culture medium with wavelength of 808nm and intensity of 1.2W/cm²Laser irradiation of (2) for 10 min. After 24h incubation, 10. mu.L of MTT solution was added to each well and incubated for 4 h. Finally, after removing the medium, dimethyl sulfoxide (100 μ L) was added to each well to remove the precipitate. Then, the ultraviolet absorption (λ ═ 550nm) of each well was measured using an iMark model 168-1130 microplate reader of Bio-Rad, usa, and the photothermal efficiency was calculated.

FIG. 7 shows the power density of 1.2W/cm for different concentrations of the nanomaterials prepared in example 1²A temperature rise profile under 808nm laser irradiation, wherein:

a is Au @ Mn₃O₄Temperature rise curve diagram of @ PF-127 flower type nano material, b diagram is Au @ Mn₃O₄Temperature rise curve diagram of @ PF-127 type nano material under different wave band laser.

FIG. 7a shows the following Au @ Mn₃O₄The concentration of the @ PF-127 type nanomaterial was increased from 25. mu.g/mL to 200. mu.g/mL, and after 10 minutes of laser irradiation, the temperature was increased from-27 ℃ to-77 ℃. However, the temperature observed for the control water sample did not increase. Since the temperature was highest at a concentration of 200. mu.g/mL of Au, FIG. 7b shows the results of evaluating thermal performance using different laser powers at this concentration. Indicating that at the same power density 1.2W/cm²Next, it was observed that in the same time interval, following Au @ Mn₃O₄The concentration of the @ PF-127 pattern nano material is increased, and the temperature is increased.

FIG. 8 shows Au @ Mn prepared in example 1 at various concentrations₃O₄The power density of the @ PF-127 flower type nano material is 1.2W/cm²The temperature rise curve under 808nm laser irradiation.

Fig. 8 shows temperature rise images taken by a thermal imager at different time intervals (up to 10 minutes).

Testing the photo-thermal treatment effect of the magnetic plasma nano material:

the test method comprises the following steps:

mice were divided into three groups, the first group of whichAu @ Mn using an injection dose of 150. mu.L₃O₄@ PF-127(Mn: 242. mu.g/mL, Au: 92. mu.g/mL) post laser local irradiation treatment, the second group injected 150. mu.L dose of Au @ Mn₃O₄@ PF-127(Mn: 242. mu.g/mL, Au: 92. mu.g/mL) and the third group treated with laser local irradiation alone.

FIG. 9 shows a laser (1.2W/cm) at 808nm²) Next, [email protected] Au @ Mn prepared in example 1 was injected intratumorally₃O₄Thermal infrared image of 4T1 tumor-bearing nude mice after patterning the nanomaterial.

FIG. 9 shows that the temperature rise results were up to 8 minutes at 2 minute intervals.

[email protected]₃O₄The temperature increase of the @ PF-127 type nanometer material and the laser group is changed to 35 ℃ which is enough to ablate cancer cells (the temperature needed for ablating the cancer cells at the tumor part should exceed 42 ℃).

[email protected]₃O₄The @ PF-127 flower type nanometer material group has no obvious temperature rise, and only the laser group has the temperature rise of 12 ℃ below zero, which is not enough to melt tumors.

FIG. 10 is Au @ Mn obtained in example 1₃O₄The representative photos of different stages of tumor treatment when the flower type PF-127 nano material is used for treating mouse tumors.

FIG. 10 shows Au @ Mn injection₃O₄The @ PF127 flower type nano material and the laser irradiation both obviously improve the tumor inhibition rate and the ablation rate. The figure shows the Au @ Mn prepared₃O₄@ PF-127 has potent photothermal therapeutic properties in vivo.

Although the present application has been described with reference to a few embodiments, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the application as defined by the appended claims.