Polythienyl nano composite material for multi-mode combined treatment of tumors and preparation method of polythienyl nano composite material

Abstract

The invention discloses a polythienyl nano composite material for multi-mode combined treatment of tumors and a preparation method of the polythienyl nano composite material, and relates to the technical field of biological medicines. According to the invention, a photosensitizer polydopamine (PDA) is introduced as a'shell 'to coat the MnO2 / PEDOT composite nanoparticles, so that the biocompatibility and in-vivo circulation capability of the nanoparticles can be improved, the water solubility of the synthesized nanoscale MnO2 / PEDOT (PDA) composite material is better, the bioavailability is improved, and meanwhile, the photo-thermal curative effect of PEDOT is also improved, so that MEMRI-guided SDT / CDT / PTT combined treatment of tumors is realized; the whole synthesis process of the polythienyl nano composite material is carried out by heating at 40 DEG C under normal pressure, conditions such as high temperature and high pressure are not needed, the polythienyl nano composite material is relatively mild and safe, only stirring is needed, and the operation is relatively simple and controllable; the poly (3, 4-ethylenedioxythienyl) nano material with good water solubility, which is synthesized by an emulsion polymerization method, has sonodynamic therapy performance and shows a good application prospect.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and in particular to a polythiophene-based nanocomposite material for multimodal combined tumor treatment and a preparation method thereof. Background Art

[0002] ROS are one of the unique characteristics of the tumor microenvironment (TME). As important signaling molecules, they play an important role in every stage of tumor occurrence, growth, invasion and metastasis. In recent years, killing tumor cells based on increasing the concentration of intracellular reactive oxygen species (ROS) has received extensive attention and research, leading to the emergence of some ROS-mediated emerging treatments including chemodynamic therapy (CDT), photodynamic therapy (PDT) and sonodynamic therapy (SDT). However, single therapy has the disadvantage of insufficient efficacy, so multi-therapy combination therapy has become a research hotspot.

[0003] Copolymers of thiophene and its derivatives have excellent intramolecular charge transfer capabilities, such as reversible electrochemical redox, photocatalytic activity and conductivity, and are therefore widely used in electronics, optics, biomedicine and energy. Polythiophene can be prepared into nanoparticles by chemical synthesis methods, and has good biocompatibility and modifiability. It can load bioactive molecules such as drugs, genes, antibodies, etc. to achieve targeted therapy and controlled release effects. In the biomedical field, polythiophene nanoparticles have been developed as a new type of nanocarrier for drug delivery, bioimaging, disease diagnosis and treatment, etc., and polythiophene nanoparticles also have photothermal effects. Therefore, polythiophene nanoparticles can be used in tumor treatment methods such as photothermal therapy.

[0004] The polythiophene nanoparticles synthesized by existing technologies have the disadvantages of complex preparation process, poor water solubility and large size, which to a certain extent limit their application in tumor treatment. At the same time, many technologies use high-temperature and high-pressure methods such as solvothermal method, and the reaction conditions are relatively strict and dangerous, and the requirements for reaction equipment are high. At the same time, organic sonosensitizers such as porphyrin and phthalocyanine generally have the problem of low water solubility and bioavailability.

[0005] Poly (3,4-ethylenedioxythiophene) (PEDOT) is a monomer with high conductivity, good biocompatibility, simple molecular structure, and small energy gap. After being stimulated by ultrasound, PEDOT becomes an excited semiconductor polymer. This polymer can produce ROS in the tumor microenvironment, thus having SDT performance. PEDOT and anionic surfactants can form a structure similar to "core-shell", which greatly improves the water solubility of PEDOT and improves the problems of poor water solubility and low bioavailability of organic sonosensitizers.

[0006] Under acidic conditions, the loaded MnO2 reacts with excess substances in the TME, for example, 1) reacts with H2O2 to produce O2, which can alleviate the hypoxic state in the TME; 2) reacts with glutathione (GSH) to generate Mn 2+ Then a Fenton-like reaction occurs, catalyzing H2O2 to generate ·OH, making the composite nanoparticles have chemical kinetic properties. 2+ It can also be used as a manganese ion enhanced magnetic resonance imaging (MEMRI) probe. In addition, PEDOT has attracted much attention in the fields of photothermal therapy, anti-inflammatory and antibacterial due to its photothermal properties. Therefore, the photosensitizer polydopamine (PDA) is introduced as a "shell" to coat the MnO2 / PEDOT composite nanoparticles. While enhancing the biocompatibility of the nanoparticles and improving the circulation capacity in the body, it also improves the photothermal efficacy of PEDOT, thereby achieving MEMRI-guided SDT / CDT / PTT combined treatment of tumors. In view of this, a polythiophene-based nanocomposite material for multimodal combined treatment of tumors and its preparation method are explored. Summary of the invention

[0007] The present invention provides a polythiophene-based nanocomposite material for multimodal combined tumor treatment and a preparation method thereof, in order to solve the technical problems existing in the background technology.

[0008] To solve the above problems, the technical solution of the present invention is:

[0009] The first invention of the present invention provides a method for preparing a polythiophene-based nanocomposite material for multimodal combined tumor treatment, comprising the following steps:

[0010] Step 1: Weigh 10 mg of MnO2 / PEDOTNPs and disperse them in 10 mL of Tris-HCl buffer solution to obtain a dispersion;

[0011] Step 2: Weigh 20 mg of dopamine hydrochloride and dissolve it in a small amount of Tris-HCl buffer solution, then add it to the dispersion in step 1, stir at room temperature in the dark for 24 hours to obtain the product;

[0012] Step 3: Centrifuge the product in step 2 with pure water at 13000r / min for 10min, repeat the steps, and wash several times to obtain MnO2 / PEDOT@PDANPs.

[0013] As a preferred embodiment of the method for preparing the polythiophene-based nanocomposite material of the present invention, the molar concentration of the Tris-HCl buffer solution in step 1 is 10 mM.

[0014] As a preferred embodiment of the method for preparing the polythiophene-based nanocomposite material of the present invention, the MnO2 / PEDOT@PDANPs in the step 3 need to be stored in a refrigerator at 4°C away from light.

[0015] As a preferred embodiment of the method for preparing the polythiophene-based nanocomposite material of the present invention, the method for preparing the MnO2 / PEDOT nanoparticles in step 1 comprises the following steps:

[0016] Step 1: Prepare 1 mg / mL PEDOT NPs aqueous solution;

[0017] Step 2: Dissolve 5 mg of KMnO4 in a small amount of pure water to obtain a dissolved KMnO4 solution;

[0018] Step 3: Add the KMnO4 solution in step 2 to 15 mL of the PEDOT NPs solution in step 1 and stir for 10 min to obtain the product;

[0019] Step 4: Centrifuge the product in step 3 with pure water at 13000 r / min for 10 min, repeat the steps, collect the precipitate after washing multiple times, and obtain MnO2 / PEDOT nanoparticles.

[0020] Further preferably, the preparation steps of 1 mg / mL PEDOT NPs aqueous solution in step 1 are:

[0021] 15 mg of PEDOT NPs were weighed and dissolved in 15 mL of pure water, and ultrasonic dispersion was performed to obtain a 1 mg / mL PEDOT NPs aqueous solution.

[0022] Further preferably, the method for preparing PEDOT nanoparticles in step 1 comprises the following steps:

[0023] Step 1: Weigh 0.0810 g of sodium dodecylbenzene sulfonate (SDBS) and pour it into a sample bottle filled with H2O. After ultrasonication for 10 min, put it into an oil bath at 40°C and stir until the solution becomes clear to obtain an SDBS aqueous solution.

[0024] Step 2: Add 85.4 μL of 3,4-ethylenedioxythiophene (EDOT) monomer to the SDBS aqueous solution in step 1, and continue stirring in an oil bath at 40° C. for 1 h to obtain a precursor solution;

[0025] Step 3: 0.4564 g of ammonium persulfate (APS) was dissolved in a small amount of H2O and added to the precursor solution in step 2 to obtain a mixture;

[0026] Step 4: After the mixture of step 3 is naturally cooled to room temperature, it is centrifuged with pure water / ethanol at 13000 r / min for 10 min, and the steps are repeated to obtain PEDOT nanoparticles after washing for multiple times.

[0027] Further preferably, the stirring time in step 1 is 30-60 min.

[0028] Further preferably, when preparing the PEDOT nanoparticles, the total volume of H2O is 25 mL, the temperature of the oil bath is maintained at 40°C during the whole process, and the constant temperature stirring time is 18 h.

[0029] The second invention of the present invention provides MnO2 / PEDOT@PDA nanoparticles prepared by the preparation method described in the first aspect.

[0030] The above technical solution of the present invention has the following beneficial technical effects:

[0031] 1. The nano-scale MnO2 / PEDOT@PDA composite material synthesized by the present invention has better water solubility through PDA coating, improved bioavailability, and can broaden its application range;

[0032] 2. The whole synthesis process of the polythiophene-based nanocomposite material of the present invention is carried out by heating at 40°C under normal pressure, without the need for high temperature and high pressure, and is relatively mild and safe. It only requires stirring, and the operation is relatively simple and controllable.

[0033] 3. The water-soluble poly-3,4-ethylenedioxythiophene-based nanomaterial synthesized by the emulsion polymerization method of the present invention has the performance of sonodynamic therapy and shows good application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments are briefly introduced below. It should be understood that the following drawings only show certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other related drawings can be obtained based on these drawings without creative work.

[0035] Figure 1 It is the synthetic route of MnO2 / PEDOT@PDANPs;

[0036] Figure 2 is the thermogravimetric analysis graph of polythiophene-based nanocomposites;

[0037] Figure 3 It is the infrared spectrum of polythiophene-based nanocomposite material. DETAILED DESCRIPTION

[0038] In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention is further described in detail below in conjunction with specific embodiments. It should be understood that these descriptions are exemplary only and are not intended to limit the scope of the present invention. In addition, in the following description, the description of known structures and technologies is omitted to avoid unnecessary confusion of the concept of the present invention.

[0039] The invention provides a polythiophene-based nanocomposite material for multimodal combined treatment of tumors. The composite material is MnO2 / PEDOT@PDA nanoparticles.

[0040] The preparation method of MnO2 / PEDOT@PDA nanoparticles comprises the following steps:

[0041] Step 1: weigh MnO2 / PEDOTNPs and disperse them in Tris-HCl buffer solution to obtain a dispersion;

[0042] Step 2: Weigh dopamine hydrochloride and dissolve it in a small amount of Tris-HCl buffer solution, then add it to the dispersion in step 1, stir at room temperature in the dark for 24 hours to obtain the product;

[0043] Step 3: Centrifuge the product in step 2 with pure water at 13000r / min for 10 minutes, repeat the steps, and wash multiple times to obtain MnO2 / PEDOT@PDANPs. The prepared MnO2 / PEDOT@PDANPs need to be stored in a refrigerator at 4°C away from light.

[0044] In a further embodiment of the present invention, a method for preparing MnO2 / PEDOT nanoparticles is also included, comprising the following steps:

[0045] Step 1: prepare PEDOT NPs aqueous solution;

[0046] Step 2: Dissolve KMnO4 in a small amount of pure water to obtain a dissolved KMnO4 solution;

[0047] Step 3: Add the KMnO4 solution in step 2 to the PEDOT NPs solution in step 1 and stir for 10 min to obtain the product;

[0048] Step 4: Centrifuge the product in step 3 with pure water at 13000 r / min for 10 min, repeat the steps, collect the precipitate after washing multiple times, and obtain MnO2 / PEDOT nanoparticles.

[0049] In a further embodiment of the present invention, a step of preparing a PEDOT NPs aqueous solution is further included, and the weighing step is: weighing PEDOT NPs and dissolving them in pure water, and performing ultrasonic dispersion to obtain a PEDOT NPs aqueous solution.

[0050] In a further embodiment of the present invention, a method for preparing PEDOT nanoparticles is also included, comprising the following steps:

[0051] Step 1: Weigh sodium dodecylbenzene sulfonate (SDBS) and pour it into a sample bottle filled with H2O. After ultrasonication for 10 minutes, put it into an oil bath at 40°C and stir until the solution becomes clear. The stirring time is 30-60 minutes to obtain an SDBS aqueous solution.

[0052] Step 2: Add 3,4-ethylenedioxythiophene (EDOT) monomer to the SDBS aqueous solution in step 1, and continue stirring in an oil bath at 40° C. for 1 h to obtain a precursor solution;

[0053] Step 3: dissolving ammonium persulfate (APS) in a small amount of H2O and adding the resulting solution to the precursor solution in step 2 to obtain a mixture;

[0054] Step 4: After the mixture of step 3 is naturally cooled to room temperature, it is centrifuged with pure water / ethanol at 13000 r / min for 10 min, and the steps are repeated to obtain PEDOT nanoparticles after washing for multiple times.

[0055] Combine the following Figure 1 The technical solution provided by the present invention is further described with specific embodiments; wherein, Figure 1 This is the synthetic route of MnO2 / PEDOT@PDANPs.

[0056] Example 1

[0057] This embodiment provides a PEDOT nanoparticle, and the preparation method thereof comprises the following steps:

[0058] Step 1: Weigh 0.0810 g of sodium dodecylbenzene sulfonate (SDBS) and pour it into a sample bottle filled with H2O. After ultrasonication for 10 minutes, put it into a 40°C oil bath and stir until the solution becomes clear. The stirring time is 30-60 minutes to obtain an SDBS aqueous solution.

[0059] Step 2: Add 85.4 μL of 3,4-ethylenedioxythiophene (EDOT) monomer to the SDBS aqueous solution in step 1, and continue stirring in an oil bath at 40° C. for 1 h to obtain a precursor solution;

[0060] Step 3: 0.4564 g of ammonium persulfate (APS) was dissolved in a small amount of H2O and added to the precursor solution in step 2 to obtain a mixture;

[0061] Step 4: After the mixture of step 3 is naturally cooled to room temperature, it is centrifuged with pure water at 13000 r / min for 10 min, and the steps are repeated to obtain PEDOT nanoparticles after washing for multiple times.

[0062] When preparing PEDOT nanoparticles, the total volume of H2O was 25 mL, the temperature of the oil bath was maintained at 40°C during the whole process, and the constant temperature stirring time was 18 h.

[0063] Example 2

[0064] This embodiment provides a MnO2 / PEDOT nanoparticle, and the preparation method thereof comprises the following steps:

[0065] Step 1: Weigh 15 mg of PEDOT NPs and dissolve them in 15 mL of pure water, perform ultrasonic dispersion, and prepare a 1 mg / mL PEDOT NPs aqueous solution;

[0066] Step 2: Dissolve 5 mg of KMnO4 in a small amount of pure water to obtain a dissolved KMnO4 solution;

[0067] Step 3: Add the KMnO4 solution in step 2 to 15 mL of the PEDOT NPs solution in step 1 and stir for 10 min to obtain the product;

[0068] Step 4: Centrifuge the product in step 3 with pure water at 13000 r / min for 10 min, repeat the steps, collect the precipitate after washing multiple times, and obtain MnO2 / PEDOT nanoparticles.

[0069] Example 3

[0070] This embodiment provides a MnO2 / PEDOT@PDA nanoparticle, and the preparation method thereof comprises the following steps:

[0071] Step 1: Weigh 10 mg of MnO2 / PEDOTNPs and disperse them in 10 mL of Tris-HCl buffer solution, the molar concentration of the Tris-HCl buffer solution is 10 mM, to obtain a dispersion;

[0072] Step 2: Weigh 20 mg of dopamine hydrochloride and dissolve it in a small amount of Tris-HCl buffer solution, then add it to the dispersion in step 1, stir at room temperature in the dark for 24 hours to obtain the product;

[0073] Step 3: Centrifuge the product in step 2 with pure water at 13000r / min for 10 minutes, repeat the steps, and wash multiple times to obtain MnO2 / PEDOT@PDANPs. The prepared MnO2 / PEDOT@PDANPs need to be stored in a refrigerator at 4°C away from light.

[0074] In the above preparation process, the entire synthesis process of the polythiophene-based nanocomposite material is carried out by heating at 40°C under normal pressure, without the need for high temperature and high pressure conditions, and is relatively gentle and safe. It only requires stirring, and the operation is relatively simple and controllable.

[0075] Performance Testing

[0076] 1. Thermogravimetric analysis test

[0077] In order to verify the loading rate and coverage rate of MnO2 and PDA in polythiophene-based nanocomposites, thermogravimetric analysis tests were performed on the PEDOT nanoparticles, MnO2 / PEDOT nanoparticles and MnO2 / PEDOT@PDA nanoparticles prepared in Examples 1-3. The test increased the material temperature from 50°C to 800°C at a heating rate of 10°C / min in a nitrogen atmosphere, and the mass ratio was evaluated by calculating the weight of the remaining material.

[0078] Test results such as Figure 2 As shown, the residual mass of MnO2 / PEDOTNPs is 9.33% more than that of single PEDOT NPs. It can be inferred that MnO2 accounts for about 9.33% in MnO2 / PEDOT NPs and the loading rate is about 25.18%.

[0079] Similarly, the remaining mass after loading PDA is 46.81%, which is 9.76% more than that of MnO2 / PEDOT NPs. Therefore, it can be determined that the mass proportion of PDA in MnO2 / PEDOT@PDANPs is about 9.76%, and the coverage rate is 20.86%.

[0080] 2. Infrared spectrum analysis test

[0081] In order to verify the existence, interaction and influence of different components (including PEDOT, MnO2, PDA and surfactant) in polythiophene-based nanocomposites on the structure and chemical properties, the PEDOT nanoparticles, MnO2 / PEDOT nanoparticles and MnO2 / PEDOT@PDA nanoparticles prepared in Examples 1-3 were subjected to infrared spectroscopy analysis. The test was carried out at an indoor temperature of 23°C and a humidity of 33%, and the samples were in powder form.

[0082] Test results such as Figure 3 As shown, the peaks of the three curves at 2820-2925 cm-1 correspond to the symmetric and asymmetric stretching vibration peaks of saturated CH;

[0083] 1350, 1385, 1595, 1631cm -1 The left and right peaks correspond to the stretching vibration peaks of C=C of the thiophene ring and the aromatic ring (sodium dodecylbenzenesulfonate was introduced as a surfactant in the experiment, so the relevant characteristic peaks of the aromatic ring appeared);

[0084] 1120cm -1 The left and right peaks correspond to the stretching vibration peaks of COC; 617, 760 and 940 cm -1 The left and right ones correspond to the bending vibration peaks of CSC;

[0085] After loading MnO2, the curves of MnO2 / PEDOT NPs and MnO2 / PEDOT@PDANPs showed peaks at 460 and 540 cm -1 The characteristic peaks on the left and right correspond to the stretching vibration peaks of the Mn-O bond;

[0086] In addition, the 3420 cm -1 The peaks nearby correspond to the symmetric stretching peaks of OH and NH.

[0087] Compared with the curve of PEDOT NPs, some peaks in the curves of MnO2 / PEDOTNPs and MnO2 / PEDOT@PDANPs showed a red shift. This may be because the introduction of MnO2 and PDA affects the conformation, stacking mode and electron cloud density of the conjugated skeleton in the PEDOT structure. The curve becomes flatter, which may also be caused by the addition of inorganic components diluting the infrared absorption of organic components and the shielding effect of PDA.

[0088] In summary, PEDOT, as a sonosensitizer, can generate reactive oxygen species (ROS) under ultrasound stimulation, thereby achieving sonodynamic therapy. Infrared spectroscopy analysis confirmed the presence of PEDOT (1350-1631 cm -1 C=C stretching vibration peak).

[0089] Thermogravimetric analysis shows the presence of MnO2 in the composite material (about 9.33%). PEDOT can form an excited semiconductor polymer under ultrasonic stimulation, and the presence of MnO2 forms a pn-type heterojunction of metal oxides and organic polymers, which can enhance the effect of SDT. In the acidic conditions of the tumor microenvironment (TME), MnO2 can react with H2O2 to produce O2, alleviating the hypoxia of the tumor; at the same time, MnO2 produced by the reaction with GSH can also 2+ It can catalyze H2O2 to generate ·OH through a Fenton-like reaction, showing a chemokinetic therapeutic effect. These ROS can cause oxidative damage to tumor cells and further promote tumor cell death.

[0090] PEDOT has good photothermal conversion performance and can generate heat by absorbing external light sources, thereby increasing the temperature locally. In MnO2 / PEDOT@PDA composite nanoparticles, the PDA coating enhances the photothermal effect of PEDOT, making it more efficient in converting light energy into heat energy. This local high temperature can directly destroy the tumor cell membrane and induce cell apoptosis or necrosis. Infrared spectroscopy analysis confirmed the presence of PDA (3420cm -1 OH and NH symmetric stretching peaks nearby), PDA as a photosensitizer can enhance the photothermal efficacy of PEDOT and achieve photothermal therapy.

[0091] Mn produced by decomposition of MnO2 2+ It can be used as a probe for manganese ion enhanced magnetic resonance imaging (MEMRI). 2+ Ions in MnO2 / PEDOT@PDA composite nanoparticles act as MRI contrast agents, which can enhance the contrast of magnetic resonance imaging, thereby achieving real-time monitoring of tumor localization and treatment effects, and helping to achieve image-guided therapy.

[0092] PDA coating (thermogravimetric analysis shows about 9.76%) can improve the biocompatibility and in vivo circulation ability of nanoparticles; PEDOT and anionic surfactant (SDBS) form a "core-shell" structure, which improves the water solubility of PEDOT and overcomes the problems of poor water solubility and low bioavailability of organic sonosensitizers; by combining SDT, CDT and PTT, and assisting with MRI guidance, polythiophene-based nanocomposites can achieve multimodal synergistic therapeutic effects and enhance the therapeutic effect on tumors.

[0093] The present invention introduces photosensitizer polydopamine (PDA) as a "shell" to coat MnO2 / PEDOT composite nanoparticles, which enhances the biocompatibility of nanoparticles and improves the in vivo circulation capacity while also improving the photothermal efficacy of PEDOT, thereby achieving MEMRI-guided SDT / CDT / PTT combined treatment of tumors. The above examples illustrate that the polythiophene-based nanocomposite material for multimodal combined treatment of tumors and its preparation method provided in the present invention have better market application prospects.

[0094] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing a polythiophene-based nanocomposite material for multimodal combined tumor treatment, characterized in that: The composite material is MnO2 / PEDOT@PDA nanoparticles; The preparation method of the MnO2 / PEDOT@PDA nanoparticles comprises the following steps: Step 1: Weigh 10 mg of MnO2 / PEDOTNPs and disperse them in 10 mL of Tris-HCl buffer solution to obtain a dispersion; Step 2: Weigh 20 mg of dopamine hydrochloride and dissolve it in a small amount of Tris-HCl buffer solution, then add it to the dispersion in step 1, stir at room temperature in the dark for 24 hours to obtain the product; Step 3: Centrifuge the product in step 2 with pure water at 13000 r / min for 10 min, repeat the steps, and wash multiple times to obtain MnO2 / PEDOT@PDANPs.

2. The method for preparing a polythiophene-based nanocomposite material for multimodal combined tumor treatment according to claim 1, characterized in that: The molar concentration of the Tris-HCl buffer solution in step 1 is 10 mM.

3. The method for preparing a polythiophene-based nanocomposite material for multimodal combined tumor treatment according to claim 1, characterized in that: The MnO2 / PEDOT@PDANPs in step 3 need to be stored in a refrigerator at 4°C away from light.

4. The method for preparing a polythiophene-based nanocomposite material for multimodal combined tumor treatment according to claim 1, characterized in that: The method for preparing the MnO2 / PEDOT nanoparticles in step 1 comprises the following steps: Step 1: Prepare 1 mg / mL PEDOT NPs aqueous solution; Step 2: Dissolve 5 mg of KMnO4 in a small amount of pure water to obtain a dissolved KMnO4 solution; Step 3: Add the KMnO4 solution in step 2 to 15 mL of the PEDOT NPs solution in step 1 and stir for 10 min to obtain the product; Step 4: Centrifuge the product in step 3 with pure water at 13000 r / min for 10 min, repeat the steps, collect the precipitate after washing multiple times, and obtain MnO2 / PEDOT nanoparticles.

5. The method for preparing a polythiophene-based nanocomposite material for multimodal combined tumor treatment according to claim 4, characterized in that: The steps for preparing the 1 mg / mL PEDOT NPs aqueous solution in step 1 are as follows: 15 mg of PEDOT NPs were weighed and dissolved in 15 mL of pure water, and ultrasonic dispersion was performed to obtain a 1 mg / mL PEDOT NPs aqueous solution.

6. The method for preparing a polythiophene-based nanocomposite material for multimodal combined tumor treatment according to claim 4, characterized in that: The method for preparing the PEDOT nanoparticles in step 1 comprises the following steps: Step 1: Weigh 0.0810 g of sodium dodecylbenzene sulfonate (SDBS) and pour it into a sample bottle filled with H2O. After ultrasonication for 10 min, put it into an oil bath at 40°C and stir until the solution becomes clear to obtain an SDBS aqueous solution. Step 2: Add 85.4 μL of 3,4-ethylenedioxythiophene (EDOT) monomer to the SDBS aqueous solution in step 1, and continue stirring in an oil bath at 40° C. for 1 h to obtain a precursor solution; Step 3: 0.4564 g of ammonium persulfate (APS) was dissolved in a small amount of H2O and added to the precursor solution in step 2 to obtain a mixture; Step 4: After the mixture of step 3 is naturally cooled to room temperature, it is centrifuged with pure water / ethanol at 13000 r / min for 10 min, and the steps are repeated to obtain PEDOT nanoparticles after washing for multiple times.

7. The method for preparing a polythiophene-based nanocomposite material for multimodal combined tumor treatment according to claim 6, characterized in that: The stirring time in the step 1 is 30-60 min.

8. The method for preparing a polythiophene-based nanocomposite material for multimodal combined tumor treatment according to claim 6, characterized in that: When the PEDOT nanoparticles were prepared, the total volume of H2O was 25 mL, the temperature of the oil bath was maintained at 40°C during the whole process, and the constant temperature stirring time was 18 h.

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