CN114159588B

CN114159588B - Ternary alloy PtW-Mn-based nano probe, preparation method and application thereof

Info

Publication number: CN114159588B
Application number: CN202111496548.6A
Authority: CN
Inventors: 宋国胜; 刘慧怡; 关国强; 张�成
Original assignee: Hunan University
Current assignee: Hunan University
Priority date: 2021-12-09
Filing date: 2021-12-09
Publication date: 2022-10-11
Anticipated expiration: 2041-12-09
Also published as: CN114159588A

Abstract

The invention discloses a nano probe based on ternary alloy PtW-Mn, which takes a ternary alloy nano material PtW-Mn as a core and a pH response polymer as a surface modification layer, and has a structural formula of PtW-Mn @ pH response polymer nano probe. The PtW-Mn @ pH response polymer nano probe disclosed by the invention is dissociated under the stimulation of a tumor acidic environment, a large number of metal ions are released, and the serious damage to normal tissues in a conveying process is reduced. The method has the advantages that the method shows good Fenton reaction catalytic effect, utilizes lower pH in the tumor microenvironment to activate the release of manganese ions, catalyzes endogenous highly-expressed hydrogen peroxide of cancer cells to generate highly-toxic hydroxyl free radicals, exhausts over-expressed GSH, and causes the damage of intracellular DNA, so that the cancer cells are subjected to apoptosis and necrosis, the oxygen consumption of the tumor cells is reduced, the metastasis of the cancer cells is inhibited, and the high-efficiency inhibition on the tumor growth is realized. Meanwhile, the Magnetic Resonance Imaging (MRI) can be used for high-specificity imaging and guided treatment of tumors in vivo by T1-T2 dual-mode MRI along with the release of manganese ions.

Description

Ternary alloy PtW-Mn-based nano probe, preparation method and application thereof

Technical Field

The invention belongs to the field of nano material preparation, and particularly relates to a ternary alloy PtW-Mn-based nano probe, a preparation method and application thereof.

Background

Cancer, one of the major life health problems worldwide, is still one of the diseases with the highest mortality rate in the 21 st century, and the precise diagnosis and treatment thereof are crucial to the health of human beings. The traditional treatment methods comprise surgical treatment, chemotherapy, radiotherapy and the like, and the main problems exist: 1) The surgical treatment is difficult to completely remove the tumor tissue, and the tumor can be relapsed; 2) The dose of the chemotherapy drug which can be accurately delivered to the tumor part is limited, and the chemotherapy drug has high toxic and side effects on normal tissues; 3) Radiotherapy has a high ionizing radiation.

Currently, highly toxic Reactive Oxygen Species (ROS) -based approaches have been widely used in cancer therapy, such as photodynamic therapy (PDT), chemokinetic therapy (CDT), and the like. In recent years, chemokinetic therapy (CDT) has received much attention due to its high selectivity and low toxic side effects. The chemical kinetic therapy adopts Fenton or Fenton-like reaction in the tumor microacid environment by simulating nano enzyme to convert hydrogen peroxide in the tumor into hydroxyl free radical (OH) with high oxidizability, thereby providing great opportunity for tumor therapy. Although the rapid development of nanotechnology offers a promising approach to the promotion of cancer therapy through the fenton reaction, many challenges remain to be overcome. For example: (1) The nonselective catalytic activity of most of the nano-catalysts has obvious side effect on surrounding normal tissues; (2) The low efficiency of chemokinetic treatment greatly limits the clinical application of this treatment. Therefore, many research teams are dedicated to develop a nano material capable of efficiently and specifically performing CDT catalytic reaction in tumor. However, how to achieve specific activation of nanomaterials in the tumor microenvironment and improve the efficiency of chemokinetic treatment remains a challenging task.

It is well known that the tumor microenvironment has its own properties, such as being slightly acidic and highly expressing H ₂ O ₂ And Glutathione (GSH), hypoxia, certain high-expression enzymes and the like, so that the design of the nano material which is only activated in a tumor microenvironment can make a highly specific reaction on tumor tissues, and is vital to realizing accurate treatment and reducing the toxic and side effects of treatment means on normal tissues.

Biomedical imaging is essential for the early detection and diagnosis of cancer. At present, optical imaging and magnetic imaging attract wide attention due to excellent performances such as low ionizing radiation and real-time quantification, but each method still has limitations. Among other things, optical imaging tends to be limited by the depth of tissue penetration. In addition, magnetic Resonance Imaging (MRI), which is a medical imaging method commonly used in clinical practice at present, has good spatial resolution and tissue penetration, and can generate MRI contrast by measuring water proton relaxation to obtain anatomical, physiological process and molecular information in vivo. However, T1 contrast agents are not highly sensitive in molecular imaging, and T2 contrast agents are difficult to distinguish from tissues (e.g., bone, lung) that are themselves magnetic resonance signals when imaged. In recent years, many scientists have achieved an increase in resolution by increasing the magnetic field strength and scan time to increase the signal-to-noise ratio. With the development of high-field MRI, people are expected to see microscopic organisms that cannot be seen by low-field MRI. Therefore, it is crucial to develop nanomaterials that can provide superior imaging sensitivity in tumor diagnosis and treatment.

Disclosure of Invention

Aiming at the defects of the prior art, the invention aims to provide a ternary alloy PtW-Mn-based nanoprobe, a preparation method and application thereof.

The invention provides the following technical scheme:

a ternary alloy PtW-Mn-based nano probe takes a ternary alloy nano material PtW-Mn as a core, takes a pH response polymer as a surface modification layer, and has a structural formula of PtW-Mn @ pH response polymer nano probe.

Preferably, the ternary alloy nano material PtW-Mn is in a uniform cubic structure, and the particle size of the ternary alloy nano material is 2-50 nm.

More preferably, the particle size of the ternary alloy nano material PtW-Mn is 5-15 nm.

Preferably, the average particle diameter of the PtW-Mn @ pH responsive polymer nanoprobe is 20 to 500nm.

More preferably, the PtW-Mn @ pH responsive polymer nanoprobe has an average particle diameter of 50 to 150nm.

The invention provides a preparation method of a ternary alloy PtW-Mn-based nano probe, which comprises the following steps:

(1) Synthesizing a ternary alloy PtW-Mn nano material: mixing platinum diacetone (Pt (acac) ₂ ) Manganese chloride (MnCl) ₂ ) Adding oleic acid and oleylamine into a reactor, vacuumizing, stirring the mixed solution in an inert atmosphere, heating, and quickly adding tungsten hexacarbonyl (W (CO) ₆ ) After the reflux reaction is carried out for a set time, filtering and washing to obtain the ternary alloy nano material PtW-Mn, and dispersing the ternary alloy nano material PtW-Mn in tetrahydrofuran for storage;

(2) Synthesis of pH-responsive polymer: adding PEG-RAFT, 2- (diisopropylamino) ethyl methacrylate (DPA), AIBN and dioxane into a reactor, vacuumizing, heating and stirring the mixed solution under an inert atmosphere, reacting for a preset time, dialyzing the mixture with pure water, and freeze-drying the solution to obtain the pH response polymer;

(3) Synthesis of PtW-Mn @ pH responsive polymer nanoprobe: and (3) placing the ternary alloy nano material PtW-Mn obtained in the step (1) and the pH response polymer obtained in the step (2) in THF, carrying out first ultrasonic treatment, quickly injecting the mixed solution into water, carrying out second ultrasonic treatment, carrying out rotary evaporation on the mixed solution, and removing tetrahydrofuran to obtain the PtW-Mn @ pH response polymer nano probe.

Further, in the step (1), pt (acac) ₂ 、MnCl ₂ And W (CO) ₆ The molar ratio of the oleic acid to the oleylamine is 1 (0.5-2) to 0.5-2, and the molar volume ratio of the oleic acid to the oleylamine is 1 (3-5).

Further, in the step (1), the vacuumizing temperature is 70-90 ℃, and the vacuumizing time is 20-40 min; the temperature is increased to 100-130 ℃ for the first time, the reflux reaction temperature is 250-350 ℃, and the reflux reaction time is 0.5-2 h; the washing adopts a mixed solution of cyclohexane and ethanol with the volume ratio of 1 (2-6), and the washing times are 2-4.

Further, in the step (2), a reversible addition-fragmentation chain transfer (RAFT) polymerization method is adopted to synthesize the responsive polymer, and the molar ratio of PEG-RAFT, DPA and AIBN is 1 (90-150) to 0.1-0.5; deoxidizing through multiple times of liquid nitrogen freezing-unfreezing circulation; and heating and stirring the mixed solution under the inert atmosphere, wherein the reaction temperature is 60-80 ℃, and the reaction time is 2-3 days.

Further, in the step (3), the mass ratio of the ternary alloy nano material PtW-Mn to the pH response polymer is 1 (5-15), and the mass volume ratio of the ternary alloy nano material PtW-Mn to THF is 0.06-0.15 mg/mL; the volume ratio of THF to water is 1 (8-10); the first ultrasonic treatment time is 8-12 min, the second ultrasonic treatment time is 8-12 min, and the rotary evaporation temperature is 40-50 ℃.

Furthermore, in the step (3), the mass ratio of the ternary alloy nano material PtW-Mn to the pH response polymer is 1 (9-11), and the mass-volume ratio of the ternary alloy nano material PtW-Mn to THF is 0.06-0.15 mg/mL; the volume ratio of THF to water is 1 (8-10); the first ultrasonic treatment time is 9-11 min, the second ultrasonic treatment time is 9-11 min, and the rotary evaporation temperature is 40-50 ℃.

The invention provides application of the ternary alloy PtW-Mn-based nano probe, which is used as a catalytic reaction material for precise tumor treatment; the nano probe based on the ternary alloy PtW-Mn can realize specific 'opening' in a tumor microenvironment to release a large number of metal ions (manganese ions) so as to accurately and efficiently treat tumors.

The invention also provides application of the ternary alloy PtW-Mn-based nano probe, which is used as a contrast agent for tumor imaging; the nanometer material is accurately opened in a tumor microenvironment for imaging through the change of the T1-T2 dual-mode magnetic resonance image, and the T1-T2 dual-mode magnetic resonance imaging with enhanced acidity can be realized.

The invention provides a PtW-Mn @ pH response polymer nano probe capable of efficiently generating ROS and delivering with high specificity, which is formed by entering manganese and tungsten ions into a platinum-based carrier, and a novel metal delivery system capable of specifically releasing a large amount of manganese and platinum ions in a tumor microenvironment along with the reduction of a pH value is discovered for the first time. Meanwhile, the nanoprobe is an antiferromagnetic nano particle, so that artifacts of an 'always on' contrast agent and a 'non-selective' contrast agent can be effectively avoided, and released manganese ions can effectively avoid weakening the T2 attenuation effect and influencing the relaxation of water protons T1, so that the T1-T2 weighted MR imaging effect is enhanced.

The principle of the invention is as follows: the PtW-Mn @ pH response polymer nano probe can realize the release of tumor specific metal ions and the generation of ROS, and is used for high-field T1-T2-guided chemical kinetic treatment. The PtW-Mn @ pH response polymer nano probe is prepared by modifying PtW-Mn and a pH response polymer. In the slightly acidic environment of tumor, the structure of the acid-responsive polymer changes from hydrophilic to hydrophobic under acidic conditions (in the acidic environment, the acid-responsive polymer binds to intracellular H ⁺ Protonation), the PtW-Mn @ pH response polymer nano probe can be rapidly decomposed to release the ternary alloy nanocube PtW-Mn. Subsequently, the nanocubes gradually release platinum and manganese ions in the acidic environment of the tumor microenvironment. Due to the pH response dissociation behavior, the specific accumulation in the tumor of the PtW-Mn nanocube is obviously improved. Further, the released manganese ions may react with H ₂ O ₂ A fenton-like reaction occurs to generate highly toxic ROS, resulting in oxidative stress-induced apoptosis. Due to the effects, the PtW-Mn @ pH response polymer nano probe can greatly improve the efficacy of chemokinetic treatment so as to inhibit the growth of tumors. In addition, the PtW-Mn @ pH response polymer nano probe has good magnetism and can be used for high-field magnetic resonance to guide and track cancer treatment. Therefore, the PtW-Mn @ pH response polymer nano probe can remarkably improve the accuracy and specificity of cancer imaging and treatmentDifferent in nature, and has great application prospect.

Compared with the prior art, the invention has the beneficial effects that:

(1) The invention provides a ternary alloy PtW-Mn-based nano probe and a preparation method and application thereof.

(2) The PtW-Mn @ pH response polymer nano probe provided by the invention has a good Fenton-like reaction catalysis effect under the stimulation of a tumor acidic environment, utilizes a lower pH in a tumor microenvironment to activate the release of PtW-Mn, further releases manganese ions, exhausts over-expressed GSH, realizes the 'opening' of catalytic activity, catalyzes endogenous highly-expressed hydrogen peroxide of cancer cells to generate highly toxic hydroxyl radicals, causes the damage of DNA in the cells, induces the apoptosis and necrosis of the cancer cells, and realizes the efficient inhibition of the tumor growth. The specific opened chemical kinetic treatment method effectively reduces the influence of the nano material on normal tissues. (the action process is shown in figure 1).

(3) The invention prepares the nanoprobe by a simple nano coprecipitation method, and has short preparation flow, simple operation and low cost.

(4) The invention also provides application of the PtW-Mn @ pH response polymer nanoparticle in the aspect of tumor detection. The imaging and the accurate detection of the nano material to the tumor are realized through magnetic resonance imaging by utilizing the better magnetic property of the nano particles. Therefore, the nanoprobe has clinical guidance significance for the diagnosis and treatment of cancer.

Drawings

FIG. 1 is a schematic diagram of the action process of PtW-Mn @ pH responsive polymer nanoprobe of the present invention;

FIG. 2 is a diagram of the process for preparing a PtW-Mn @ pH responsive polymer nanoprobe according to the present invention;

FIG. 3 is a TEM image of a PtW-Mn ternary alloy nanocube prepared in example 1;

FIG. 4 is a graph showing the magnetic properties of PtW-Mn @ pH responsive polymer nanoprobe in example 2;

FIG. 5 is a graph showing the effect of catalytic performance of the PtW-Mn @ pH responsive polymer nanoprobe in example 2;

FIG. 6 is a GSH consumption analysis graph of PtW-Mn @ pH responsive polymer nanoprobe in example 2;

FIG. 7 is a graph showing the cytotoxicity analysis of PtW-Mn @ pH responsive polymer nanoprobe for cancer cells in example 2;

FIG. 8 is a graph of the data analysis of the inhibition of tumor growth by PtW-Mn @ pH responsive polymer nanoprobe in example 2.

Detailed Description

The following examples further illustrate embodiments of the present invention, but the embodiments of the present invention are not limited to the following examples.

The preparation process of the PtW-Mn @ pH response polymer nanoprobe is shown in figure 2 and comprises the following steps:

(1) Synthesizing a ternary alloy PtW-Mn nano material: diacetone platinum (Pt (acac) ₂ ) Manganese chloride (MnCl) ₂ ) Adding oleic acid and oleylamine into a three-necked flask, vacuumizing, stirring the mixed solution under inert atmosphere, heating, and rapidly adding tungsten hexacarbonyl (W (CO) ₆ ) After the reflux reaction is carried out for a set time, filtering and washing are carried out to obtain a ternary alloy PtW-Mn nano material, and the ternary alloy PtW-Mn nano material is dispersed in tetrahydrofuran for storage;

(2) Synthesis of pH-responsive polymers and control polymers: synthesizing a response type polymer by adopting a reversible addition-fragmentation chain transfer (RAFT) polymerization method, adding PEG-RAFT, 2- (diisopropylamino) ethyl methacrylate (DPA), AIBN and dioxane into a reactor, deoxidizing through liquid nitrogen freezing-unfreezing circulation, heating and stirring a mixed solution under an inert atmosphere, dialyzing the mixture with pure water after reaction, and finally freeze-drying the solution to obtain a pH response type polymer;

when synthesizing a pH-unresponsive control polymer, RAFT, methyl methacrylate, AIBN, and dioxane were added to the flask, and other steps were similar to the preparation of the pH-responsive polymer;

(3) Synthesis of PtW-Mn @ pH responsive Polymer nanoprobes and PtW-Mn @ control Polymer nanoparticles: placing the ternary alloy PtW-Mn nano material prepared in the step 1) and the pH response polymer in THF, performing ultrasonic treatment, quickly injecting the mixture into water, performing secondary ultrasonic treatment, performing rotary evaporation on the mixed solution, and removing tetrahydrofuran to obtain a solution containing a PtW-Mn @ pH response polymer nano probe;

in the synthesis of PtW-Mn @ control polymer nanoparticles, nanocubes of PtW-Mn and control polymer were placed in THF, with other steps similar to the synthesis of PtW-Mn @ pH responsive polymer nanoprobes.

The following is further illustrated by the specific examples and figures.

Example 1

The preparation process of the PtW-Mn @ pH response polymer nano probe comprises the following steps:

(1) Synthesizing a ternary alloy PtW-Mn nano material: mixing Pt (acac) ₂ (0.1mmol)，MnCl ₂ (0.05mmol)、W(CO) ₆ (0.1 mmol), 4mL of oleic acid, and 16mL of oleylamine were added to a three-necked flask equipped with a stirring magneton, and vacuum was applied at 80 ℃ for 30 minutes. The mixture was heated to 110 ℃ under a stream of nitrogen, and W (CO) was added rapidly ₆ And heated twice to 250 ℃ for reflux for 1h, then cooled to room temperature, and the reaction mixture is cooled to room temperature by the reaction of cyclohexane in a volume ratio of 1: washing the product with ethanol solution for 3 times, and storing in tetrahydrofuran;

(2) Synthesis of pH-responsive polymer: synthesizing a responsive polymer by adopting a reversible addition-fragmentation chain transfer (RAFT) polymerization method, adding PEG-RAFT, DPA, AIBN and dioxane into a reactor, wherein the molar ratio of PEG-RAFT, DPA and AIBN is 1; deoxidizing through three rounds of liquid nitrogen freezing-unfreezing cycles, heating and stirring the mixed solution under an inert atmosphere, wherein the reaction temperature is 70 ℃, the reaction time is 2 days, then dialyzing the mixture with pure water, and freeze-drying the solution to obtain the pH response polymer;

preparing the synthesized ternary alloy PtW-Mn nano material into a tetrahydrofuran solution of 3mg/mL, preparing a surfactant pH response polymer into a solution of 10mg/mL, and storing in a refrigerator at 4 ℃;

(3) Synthesis of PtW-Mn @ pH response polymer nanoprobe: firstly, taking 50 mu L of a tetrahydrofuran solution of PtW-Mn and 150 mu L of a tetrahydrofuran solution of a pH response polymer, then adding 800 mu L of tetrahydrofuran, carrying out ultrasonic treatment on the 1mL of mixture for 10 minutes, then quickly injecting the mixture into 9mL of water, carrying out ultrasonic treatment on the mixture for 10 minutes, and then carrying out rotary evaporation on the mixed solution at 45 ℃ to remove the tetrahydrofuran; then the reaction solution without tetrahydrofuran is washed and centrifuged for 3 times by a 100K ultrafiltration tube, the rotating speed is 4700r/min, and the centrifuging time is 4min each time.

The ternary alloy PtW-Mn nanomaterial prepared in this example was subjected to TEM testing, and the results are shown in FIG. 3, and it can be seen from FIG. 3 that the PtW-Mn nanocubes prepared in this example have an average size of 10nm.

Example 2

1. Magnetic property test based on ternary alloy PtW-Mn nano material:

the ternary alloy PtW-Mn nanomaterial obtained in example 1 and the aqueous solution of PtW-Mn @ pH responsive polymer nanoprobe were prepared into different concentration gradient aqueous solutions, and the T1 and T2 weighted relaxation times were measured by Bruker Minispec analyzer (60 MHz), and the results are shown in FIG. 4. From FIG. 4, it can be seen that the PtW-Mn @ pH responsive polymer nanoprobe has T1-T2 imaging effect, because PtW-Mn nanoparticles can release a large amount of manganese ions to moderately relax T2 of the surrounding water protons, and the lifetime (. Tau.m) of water molecules in the second sphere is increased by close hydrophilic surface modification to accelerate relaxation of T1 of water protons.

2. The Fenton reaction effect determination based on the pH response of the PtW-Mn @ pH response polymer nano probe is as follows:

using the PtW-Mn @ pH-responsive polymer nanoprobe prepared in example 1 (final concentration of 60. Mu.g/mL), it was reacted with equal amounts of phosphate buffers of different pH (7.4, 6.4,5.4, 4.4) for 2H, and then equal amounts of 3, 5-Tetramethylbenzidine (TMB) (final concentration of 0.5 mM), H, were added respectively ₂ O ₂ (final concentration 0.2 mM), incubating at room temperature for 30min, and measuring ultraviolet-visible absorption spectrum (400-8)00nm)。

FIG. 5 is a graph showing the effect of the catalytic activity of the nano-drug, which is demonstrated in H ₂ O ₂ In the presence of PtW-Mn, it can catalyze hydrogen peroxide to generate enough hydroxyl radicals to oxidize TMB. The reason is that under the slightly acidic condition of the tumor, the PtW-Mn @ pH response polymer nano probe is decomposed to release manganese ions which can react with endogenous H of cancer cells ₂ O ₂ The reaction generates highly toxic ROS-hydroxyl free radical (the hydroxyl free radical can oxidize TMB), causes DNA damage of cancer cells, and efficiently kills the cancer cells.

3. GSH consumption effect determination of pH response based on PtW-Mn @ pH response polymer nanoprobe:

using the PtW-Mn @ pH-responsive polymer nanoprobe prepared in example 1 (final concentration of 60. Mu.g/mL), it was reacted with equal amounts of phosphate buffers of different pH (7.4, 6.4,5.4, 4.4) for 24H, and then an equal amount of 5,5' -dithiodinitrobenzoic acid (DTNB) (final concentration of 0.6 mM), H, was added thereto ₂ O ₂ (final concentration 0.2 mM), and measuring the ultraviolet-visible absorption spectrum (300-600 nm) after incubating for 15min at room temperature.

FIG. 6 is a graph of GSH depletion effect of nano-drugs demonstrated in acidic solution and H ₂ O ₂ In the presence of this condition, the peak value of DTNB decreases rapidly with decreasing pH from 7.4 to 4.4, because under tumor microacid conditions, the more manganese ions released, the more GSH content is effectively consumed and PtW-Mn can act as an oxidase mimic to catalyze the generation of oxygen from hydrogen peroxide.

4. Based on PtW-Mn @ pH response polymer nanoprobe cytotoxicity analysis:

a) And (3) toxicity analysis: cancer cells (4T 1) were cultured in 96-well plates, and after the cells were attached to the wall, materials (two groups of PtW-Mn @ control polymer, ptW-Mn @ pH responsive polymer nanoprobes) at different concentrations were added and incubated for 24h, followed by toxicity testing using a standard MTT method. FIG. 7 shows the toxicity analysis results of the nano-drugs with different concentrations on cancer cells, and it can be seen from FIG. 7 that the PtW-Mn @ pH responsive polymer nano-probe pair has a good killing effect on cancer cells 4T 1.

From the above analysis, it can be known that the nanomaterial prepared in example 1 can be taken up by cancer cells, which results in the generation of ROS in the cancer cells, the over-expressed GSH is consumed, the killing effect of the nanomaterial on tumors is promoted, and the chemokinetic treatment of the tumor microenvironment response is realized.

5. The growth inhibition effect of the polymer nano probe on tumor cells based on PtW-Mn @ pH response:

animal experiments were divided into four groups (blank, ptW-Mn @ control polymer nanoparticles and PtW-Mn @ pH responsive polymer nanoprobes) using intratumoral injection (containing PtW-Mn 2 mg/mL) and tumor sizes were recorded every 1 day from day 1.

FIG. 8 is a tumor growth curve, and it can be seen from FIG. 8 that the PtW-Mn @ pH responsive polymer nanoprobe can significantly inhibit the growth of tumors.

The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.

Claims

1. A nanometer probe based on ternary alloy PtW-Mn is characterized in that the nanometer probe takes ternary alloy nanometer material PtW-Mn as a core and takes a pH response polymer as a surface modification layer, and the structural formula of the nanometer probe is PtW-Mn @ pH response polymer nanometer probe.

2. The nano probe based on the ternary alloy PtW-Mn as claimed in claim 1, wherein the ternary alloy nano material PtW-Mn is in a uniform cubic structure, and the particle size of the ternary alloy nano material PtW-Mn is 2 to 50nm.

3. The nano probe based on the ternary alloy PtW-Mn as claimed in claim 2, wherein the particle size of the ternary alloy nano material PtW-Mn is 5 to 15nm.

4. The ternary alloy PtW-Mn based nanoprobe according to claim 1, wherein the PtW-Mn @ pH responsive polymer nanoprobe has an average particle size of 20 to 500nm.

5. The ternary alloy PtW-Mn based nanoprobe of claim 4, wherein the average particle size of the PtW-Mn @ pH responsive polymer nanoprobe is 50 to 150nm.

6. The method for preparing the ternary alloy PtW-Mn based nanoprobe according to any one of claims 1 to 5, which is characterized by comprising the following steps:

(1) Synthesizing a ternary alloy PtW-Mn nano material: mixing platinum diacetylacetonate Pt (acac) ₂ MnCl, manganese chloride ₂ Adding oleic acid and oleylamine into a reactor, vacuumizing, stirring the mixed solution in an inert atmosphere, heating, and quickly adding tungsten hexacarbonyl W (CO) ₆ After the reflux reaction is carried out for a set time, filtering and washing are carried out to obtain the ternary alloy nano material PtW-Mn, and the ternary alloy nano material PtW-Mn is dispersed in tetrahydrofuran THF for storage;

7. The method for preparing the ternary alloy PtW-Mn based nanoprobe according to claim 6, wherein in the step (1), pt (acac) ₂ 、MnCl ₂ And W (CO) ₆ The molar ratio of (1) to (0.5) to (2), and the molar volume ratio of oleic acid to oleylamine is 1 to (3) to (5); drawerThe vacuum temperature is 70 to 90 ℃, and the vacuumizing time is 20 to 40min; heating to 100-130 ℃ for the first time, wherein the reflux reaction temperature is 250-350 ℃, and the reflux reaction time is 0.5-2h; the washing adopts a mixed solution of cyclohexane and ethanol with the volume ratio of 1 (2 to 6), and the washing times are 2 to 4.

8. The method for preparing the ternary alloy PtW-Mn based nanoprobe according to claim 6, wherein in the step (2), a pH response polymer is synthesized by a reversible addition-fragmentation chain transfer polymerization method, and the molar ratio of PEG-RAFT, DPA and AIBN is 1 (90-150): 0.1-0.5; deoxidizing through multiple times of liquid nitrogen freezing-unfreezing circulation; and (3) under an inert atmosphere, heating and stirring the mixed solution, wherein the reaction temperature is 60 to 80 ℃, and the reaction time is 2 to 3 days.

9. The preparation method of the ternary alloy PtW-Mn based nanoprobe according to claim 6, wherein in the step (3), the mass ratio of the ternary alloy nanomaterial PtW-Mn to the pH response polymer is 1 (5 to 15), and the mass-volume ratio of the ternary alloy nanomaterial PtW-Mn to THF is 0.06 to 0.15mg/mL; the volume ratio of THF to water is 1 (8 to 10); the first ultrasonic time is 8 to 12min, the second ultrasonic time is 8 to 12min, and the rotary steaming temperature is 40 to 50 ℃.

10. The application of the ternary alloy PtW-Mn based nanoprobe according to any one of claims 1 to 5, wherein the ternary alloy PtW-Mn based nanoprobe is applied to the preparation of a catalytic reaction material for the precise treatment of tumors; or in the preparation of a contrast agent for tumor imaging.