Phase-change material microsphere with energy storage and photothermal therapy enhancement functions and preparation method and application of phase-change material microsphere with energy storage and photothermal therapy enhancement functions

Abstract

The invention relates to the field of preparation of functional composite microsphere materials, in particular to a phase change material microsphere with energy storage and photothermal therapy enhancement functions as well as a preparation method and application of the phase change material microsphere. According to the phase change material microspheres, quercetin and dihydroartemisinin serve as ligand molecules, ferric ions serve as coordination metal ions, and nanoparticles are formed through coordination self-assembly; the nano particles and the phase-change material are mixed, and the phase-change material is obtained through a curing method. The phase change material microspheres absorb and store heat generated by photothermal conversion in the laser irradiation process, and delay attenuation of system temperature through release of phase change latent heat after laser is removed, so that the time for maintaining a treatment area in an effective photothermal treatment temperature range is effectively prolonged; and a more continuous and stable photo-thermal treatment effect is realized.

Description

Technical Field

[0001] This invention relates to the field of preparation of functional composite microsphere materials, specifically to a phase change material microsphere with energy storage and enhanced photothermal therapy function, its preparation method, and its application. Background Technology

[0002] Photothermal therapy for tumors currently utilizes near-infrared laser irradiation of the tumor site, converting light energy into heat energy under the action of a photothermal agent, thereby achieving local treatment through thermal damage to tumor cells. Due to its advantages of rapid onset and relatively minimal invasiveness, photothermal therapy has received widespread attention in recent years as a highly effective tumor treatment method and is gradually being translated into practical applications. Current photothermal therapy systems generally rely on the photothermal conversion capabilities of photothermal agents, such as gold nanomaterials, carbon-based materials, or organic dyes. For example, an indocyanine green-hyaluronic acid-peptide conjugate utilizes its good stability and bioactivity to achieve photothermal therapy functionality. However, in actual treatment, laser irradiation cannot be sustained for extended periods and is prone to causing local overheating and damage to normal tissues. Conversely, short-duration photothermal therapy makes it difficult to sustain thermal damage, resulting in a narrower effective treatment window and increased risks of tumor residue and recurrence. To address these issues, some existing technologies attempt to enhance the photothermal therapy effect by improving the enrichment or retention capacity of the photothermal agent at the tumor site, for example, by extending the residence time of the photothermal agent in local tissues through nanostructure design. However, these technical solutions still rely on continuous or repeated external light exposure to maintain the treatment temperature, failing to address the issues of normal tissue damage and the short duration of effective thermal therapy temperature maintenance. Therefore, achieving effective storage and sustained release of heat generated by photothermal therapy without the need for continuous light exposure, thereby extending the duration of treatment temperature maintenance, remains a key technical problem that urgently needs to be solved in current photothermal therapy.

[0003] Phase change materials (PCMs) are functional materials that can absorb or release a large amount of latent heat during solid-liquid or liquid-solid phase transitions, thereby maintaining a stable system temperature for a certain period of time. In existing technologies, PCMs have been widely used in the textile and construction industries for temperature regulation and thermal energy management, such as imparting heat-insulating or temperature-regulating properties to textiles. In the biomedical field, PCMs are also used for heat-responsive drug release, hydrogel wound dressings, and enhancing ultrasound imaging. However, the phase transition temperatures of reported PCM systems are mostly concentrated in fixed ranges, making it difficult to precisely cover the mild treatment temperature range below 50°C or the high-temperature ablation temperature range of 55°C to 65°C required for tumor photothermal therapy, thus limiting their applicability in different tumor treatment scenarios. Summary of the Invention

[0004] To address the aforementioned problems, this invention provides phase change material microspheres with energy storage and enhanced photothermal therapy functions, along with their preparation method and applications. By adjusting the ratio of quercetin to dihydroartemisinin and the amount of phase change material, this invention enables the adjustable design of the phase change temperature of the microspheres within a certain range. This allows the resulting composite system to be adapted to mild treatment temperature zones below 50°C or high-temperature ablation temperature zones of 55°C to 65°C. During laser irradiation, the phase change material absorbs and stores the heat generated by the photothermal conversion. After laser removal, the release of latent heat from the phase change delays the temperature decay of the system, effectively extending the time the treatment area remains within the effective photothermal therapy temperature range, achieving a more continuous and stable photothermal therapy effect.

[0005] To achieve the above objectives, the technical solution of the present invention is as follows.

[0006] The first aspect of this invention provides a phase change material microsphere with energy storage and enhanced photothermal therapy function, which uses quercetin and dihydroartemisinin as ligand molecules and ferric ions as coordinating metal ions to form nanoparticles through coordination self-assembly; the nanoparticles are mixed with phase change material and obtained by curing method; the mass ratio of the nanoparticles to the phase change material is 1:1~10. The phase transition temperature of the phase change material microspheres is 43.6℃~68.2℃.

[0007] In this application, both quercetin and dihydroartemisinin contain hydroxyl structures and coordinate with iron ions to form infinitely coordinated polymer nanoparticles. Quercetin acts as the main ligand, coordinating with iron through 3-hydroxy-4-carbonyl sites, and endowing the material with strong light absorption in the near-infrared region through a ligand-metal charge transfer mechanism. Dihydroartemisinin, as an auxiliary ligand, inserts into the coordination layer of iron ions, distorting the originally planar quercetin-iron coordination field. In the excited state, this greatly promotes the internal molecular motion and lattice vibration of the molecule, resulting in more absorbed light energy being converted into heat energy. This significantly improves the photothermal conversion efficiency from 15% to 25%, thus meeting the photothermal therapy requirements in the mild treatment temperature range below 50°C or the high-temperature ablation temperature range of 55°C to 65°C. Furthermore, this provides a material basis for the subsequent preparation of phase change materials as continuous and binding phases to effectively encapsulate and reorganize dispersed nanoparticles into structurally stable microspherical composite microspheres.

[0008] In another preferred embodiment, the phase change material is a mixture of lauric acid and stearic acid in a mass ratio of 1~100:100~1. This ratio is designed to adapt to different temperature requirements in photothermal therapy. When lauric acid, with a melting point of approximately 43°C, is used alone, the phase change temperature is too low. When stearic acid, with a melting point of approximately 69°C, is used alone, the phase change temperature is too high. Some tumors are surrounded by functional nerves or normal tissue, making them unsuitable for higher-temperature photothermal therapy and suitable for low-temperature photothermal therapy below 50°C. In this case, a mixture of high lauric acid and low stearic acid can be selected to precisely adjust the phase change temperature to a mild photothermal therapy range. Some tumors, such as subcutaneous tumors, do not require excessive protection and can utilize the efficient temperature window of 55~60°C for photothermal therapy. In this case, a mixture of high stearic acid and low lauric acid can be selected. This invention provides the ratio of lauric acid (LA) to stearic acid (SA) in different temperature photothermal therapies in various embodiments and measures their phase change temperature points.

[0009] In another preferred embodiment, the mass ratio of quercetin to dihydroartemisinin is 1~10:10~1.

[0010] A second aspect of the present invention provides a method for preparing the aforementioned phase change material microspheres, comprising the following steps: Quercetin and dihydroartemisinin were mixed in an organic reagent at a mass ratio of 1~10:10~1 to obtain a ligand-drug mixture stock solution. Add 5 mg / mL to 20 mg / mL ferric chloride hexahydrate ethanol solution dropwise to the ligand drug mixture stock solution and stir to obtain ligand drug pre-reaction mixture A; The ligand-drug pre-reaction mixture A was mixed with an alkaline buffer solution and a surfactant, the pH was adjusted to 8.0-8.5, stirred, dialyzed, and then dried to obtain nanoparticles. Nanoparticles and phase change materials are mixed in a mass ratio of 1:1 to 10 and heated until melted to obtain phase change material melt D. The phase change material melt D is added dropwise to an aqueous stabilizer solution, and crystallization and solidification occur at 45~70℃. The stabilizer is removed, and the mixture is dried to obtain the phase change material microspheres.

[0011] Specifically, the preparation method of the phase change material microspheres is as follows: Preparation of pre-reaction mixture of quercetin and dihydroartemisinin: Quercetin and dihydroartemisinin were dissolved in a solvent at a mass ratio of 1~10:10~1 and thoroughly mixed under 50kHz ultrasonic water bath conditions to prepare ligand drug mixture stock solution. Take 50-200 μL of ferric chloride hexahydrate ethanol solution with a concentration of 5 mg / mL to 20 mg / mL and slowly add it dropwise to the ligand drug mixture stock solution at a rate of 10-20 drops / minute. During this process, stir magnetically at 500 rpm. After the addition is complete, continue stirring to obtain ligand drug pre-reaction mixture A. Preparation of quercetin and dihydroartemisinin infinitely coordinated polymer nanoparticles: A mixture of alkaline buffer solution and surfactant is added to the ligand drug pre-reaction mixture A to adjust the pH of the solution to 8.0-8.5. During this process, magnetic stirring is maintained at 1000 rpm. After addition, stirring is carried out in the dark to obtain an infinite coordination polymer nanoparticle suspension. After dialysis purification by a dialysis bag with a molecular weight cutoff of 7200, the infinite coordination polymer nanoparticles, i.e., the nanoparticle powder, are obtained by freeze-drying. Preparation of mixed phase change material of lauric acid and stearic acid: Solid powders of lauric acid and stearic acid are respectively taken to form a solid mixture with a mass ratio of 0~100:100~0, which is used to prepare phase change material powder C; Nanoparticle powder and phase change material powder C are mixed in a mass ratio of 1:1~10, and then heated to a molten state to obtain a phase change material melt D with uniformly dispersed nanoparticles.

[0012] Preparation of phase change material microspheres with energy storage and enhanced photothermal therapy function: A stabilizer was added to deionized water to prepare an aqueous solution with a mass percentage of 0.1-2%. The solution was heated and stirred until fully dissolved to obtain aqueous solution E. The temperature of aqueous solution E was then adjusted to 45℃-70℃ and continuously stirred at a speed of 200-800 rpm. Subsequently, a uniformly dispersed phase change material melt D containing nanoparticles was slowly added dropwise to aqueous solution E using a syringe. Upon entering the aqueous phase, the molten droplets spontaneously contracted under surface tension to form spherical droplets. After the spherical droplets formed, the system temperature was gradually reduced to room temperature through natural cooling, causing the droplets to crystallize and solidify, forming structurally stable phase change material microspheres encapsulating nanoparticles. The solidified microspheres were collected by centrifugation, washed three times with deionized water to remove residual stabilizer, and then dried at room temperature or under vacuum to obtain the final product.

[0013] In another preferred embodiment, the organic reagent is any one of anhydrous ethanol, methanol, dimethyl sulfoxide, and N,N-dimethylformamide.

[0014] In another preferred embodiment, the alkaline buffer solution is any one of 10 mmol / L tris(hydroxymethyl)aminomethane-hydrochloric acid buffer solution, 0.001 mol / L sodium hydroxide, or 0.1% triethylamine solution by mass; the pH of the alkaline buffer solution is 8.0~8.5.

[0015] The surfactant is any one of Pronic F127, Pronic F68, and polyoxyethylene lauryl ether, and the surfactant has a mass percentage of 0.2% to 0.4%.

[0016] In another preferred embodiment, the stabilizer aqueous solution has a mass percentage of 0.1% to 2%.

[0017] The third aspect of this invention provides the application of the phase change material microspheres in photothermal therapy.

[0018] In another preferred embodiment, the photothermal therapy is tumor photothermal therapy.

[0019] In another preferred embodiment, the photothermal therapy is low-temperature photothermal therapy below 50°C or high-temperature ablation temperature zone photothermal therapy of 55°C to 65°C.

[0020] Compared with the prior art, the present invention has the following beneficial effects: This invention involves the self-assembly of quercetin and dihydroartemisinin with ferric ions under alkaline conditions to form nanoparticles. Quercetin acts as the main ligand, co-coordinating with ferric ions to form infinitely coordinated polymer nanoparticles. Dihydroartemisinin, as an auxiliary ligand, inserts into the coordination layer of ferric ions, enabling a greater conversion of absorbed light energy into heat energy, significantly increasing the photothermal conversion efficiency from 15% to 25%. Furthermore, this is combined with a tunable proportion of phase change material to construct phase change material microspheres with energy storage and enhanced photothermal therapy functions. By adjusting the proportion of nanoparticles and the ratio of phase change material, photothermal therapy microsphere systems with different phase change temperature points can be obtained.

[0021] The phase change material-nanoparticle microsphere structure constructed in this invention does not rely on complex chemical reactions or highly toxic organic solvents. It can be solidified simply by pH adjustment and warm water droplet curing. The preparation process is simple and controllable, with good scalability, making it suitable for large-scale preparation. The lauric acid / stearic acid phase change material system can cover the low-temperature photothermal therapy window below 50°C or the high-temperature ablation window of 55°C to 65°C, improving the system's adaptability to different tumor treatment scenarios. The final product exists in the form of microspheres, with a stable structure, facilitating storage, transportation, and on-demand application. Attached Figure Description

[0022] Figure 1 The preparation process of phase change material microsphere composites with energy storage and enhanced photothermal therapy function.

[0023] Figure 2 The images show microscopic and transmission electron microscopy photographs, particle size analyzer measurements, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy results of the phase change material microspheres and precursor nanoparticles in the synthesis process in Example 1.

[0024] Figure 3 The results show the photothermal efficiency, calorimeter results, and infrared thermal imaging results of the phase change material microspheres obtained in Example 1.

[0025] Figure 4 Figure A shows the results of tumor treatment and tumor quality in the photothermal therapy group for colorectal tumors; Figure B shows the results of the control group without intervention; Figure C shows the results of the phase change material microspheres obtained in Example 1; Figure C shows the results of tumor quality. Detailed Implementation

[0026] The technical solutions of this invention will be clearly and completely described below with reference to specific embodiments. Obviously, the described embodiments are only some embodiments of this invention, and not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0027] There is still an urgent need in this field for a photothermal agent with a phase change temperature below 50°C for mild photothermal therapy and a high-efficiency temperature window of 55-60°C, a long temperature maintenance time, and a simple preparation process, in order to improve the shortcomings of existing photothermal therapy, such as short temperature maintenance time and unstable treatment effect.

[0028] This invention experimentally reveals that combining phase change materials with infinitely coordinated polymer nanoparticles using quercetin and dihydroartemisinin as ligands can construct a composite system possessing both photothermal conversion and phase change energy storage functions. Infinitely coordinated polymers are a class of carrier-free nanoparticles formed by the self-assembly of metal ions and ligand molecules through coordination interactions, exhibiting structural stability, high drug loading capacity, and excellent delivery performance. Experiments showed that after quercetin and dihydroartemisinin coordinate with metal ions, the system's color deepens, demonstrating good photothermal conversion capabilities. Further composites with phase change materials such as lauric acid (LA) and stearic acid (SA) can partially store the heat generated during illumination and maintain the system temperature after the light source is removed through the release of latent heat of phase change, thereby achieving enhanced photothermal therapeutic effects through energy storage. Further research revealed that lauric acid / stearic acid phase change materials can act as a continuous and binding phase during solid-liquid phase transitions, effectively encapsulating and recombining dispersed infinitely coordinated polymer nanoparticles into structurally stable microspherical composites. Under certain temperature or mechanical energy conditions, the LA / SA mixed phase change material softens or partially melts, causing nanoscale, infinitely coordinated polymer particles to redistribute and uniformly coat the phase change material matrix. As the system cools and re-solidifies, a microsphere structure is ultimately formed, with the phase change material as the outer phase and infinitely coordinated polymer nanoparticles as the functional core. This structure does not rely on complex chemical cross-linking reactions or multi-step emulsification processes, but is constructed through physical encapsulation and phase change rearrangement. The preparation conditions are mild, the process is simple, and it exhibits good reproducibility.

[0029] The resulting phase change material-nanoparticle microsphere structure retains the photothermal conversion properties of infinitely coordinated polymer nanoparticles while utilizing the latent heat absorption and release characteristics during the lauric acid / stearic acid phase transition to achieve effective storage and sustained release of photothermal heat. After laser irradiation stops, the phase change material inside the microsphere gradually releases latent heat, significantly slowing the rate of temperature decrease and maintaining the treatment area within the effective temperature range required for photothermal therapy for a longer period, thus improving the problem of short temperature maintenance time in traditional photothermal therapy. Furthermore, by adjusting the ratio of lauric acid to stearic acid, the phase transition temperature of the microsphere can be controllably adjusted to suit different photothermal therapy temperature requirements. Lauric acid (melting point approximately 43°C) alone results in a relatively low phase transition temperature. Stearic acid (melting point approximately 69°C) alone results in an excessively high phase transition temperature. Some tumors are surrounded by functional nerves or normal tissue, making them unsuitable for high-temperature photothermal therapy. Mild photothermal therapy (below 50°C) is more appropriate in these cases. In such cases, a mixed material with a high lauric acid to low stearic acid ratio can be selected, precisely adjusting the phase change temperature to the mild photothermal therapy range. Other tumors, such as subcutaneous tumors, do not require excessive protection and can utilize the efficient temperature window for photothermal therapy (55-60°C). In these cases, a mixed material with a high stearic acid to low lauric acid ratio can be chosen. The microsphere outer layer formed by the phase change material can also, to some extent, isolate the infinitely coordinated polymer nanoparticles from direct contact with the external environment, improving the material's thermal and storage stability, and preventing nanoparticle aggregation or performance degradation. This provides a new technical solution for achieving efficient, controllable, and long-lasting tumor photothermal therapy.

[0030] The following is a detailed description of a phase change material microsphere with energy storage and enhanced photothermal therapy function, its preparation method, and its application.

[0031] Quercetin (Que), dihydroartemisinin (DHA), stearic acid, and lauric acid were purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., with product numbers Q111274, D140839, S432958, and L432090, respectively.

[0032] Example 1 A method for preparing phase change material microspheres with energy storage and enhanced photothermal therapy function, the process is as follows: Figure 1 As shown, it includes the following steps: S1: Dissolve 2.5 mg of quercetin and 2.5 mg of dihydroartemisinin in 1.0 mL of anhydrous ethanol and mix thoroughly under ultrasound at 50 kHz for 10 minutes to prepare a ligand-drug mixture stock solution; then take 10.0 mg / mL -1100 μL of ferric chloride hexahydrate ethanol solution was slowly added dropwise at a rate of 15 drops / min to the ligand drug mixture stock solution. During this process, the mixture was magnetically stirred at 500 rpm. After the addition was completed, the stirring was continued for 10 minutes to obtain ligand drug pre-reaction mixture A. S2: Rapidly add 10.0 mmol L of a solution containing 0.2% (w / w) Pronico F127 to the ligand-drug pre-reaction mixture A described in S1. -1 Tris(hydroxymethyl)aminomethane-hydrochloric acid buffer solution was used to adjust the pH of the solution to 8.5. During this process, magnetic stirring was maintained at 1000 rpm. After addition, stirring was carried out in the dark for 4 hours to obtain a suspension of infinitely coordinated polymer nanoparticles. This suspension was then purified by dialysis using a dialysis bag with a molecular weight cutoff of 7200, and subsequently freeze-dried at -50.0℃ and a vacuum degree of 100 Pa to obtain powder B of infinitely coordinated polymer nanoparticles, which is the nanoparticle itself.

[0033] S3: Take 100 mg of lauric acid and 1 mg of stearic acid solid powder respectively to form a solid mixture with a mass ratio of 100:1, and make phase change material powder C. Then heat it to the molten state to obtain phase change material melt D with uniformly dispersed infinitely coordinated polymer nanoparticles.

[0034] S4: Polyvinyl alcohol is added to deionized water to prepare an aqueous solution with a mass fraction of 1 wt%. The solution is heated and stirred until fully dissolved to obtain aqueous solution E. The temperature of aqueous solution E is then adjusted to 45°C and stirred continuously at a stirring speed of 600 rpm. The phase change material melt D, in which the infinitely coordinated polymer nanoparticles are uniformly dispersed, is then slowly added dropwise to aqueous solution E through a syringe. After the molten droplets enter the aqueous phase, they spontaneously shrink under the action of surface tension to form spherical droplets. After the spherical droplets are formed, the system temperature is gradually reduced to room temperature by natural cooling, thereby causing the droplets to crystallize and solidify, forming structurally stable phase change material microspheres encapsulating infinitely coordinated polymer nanoparticles. The solidified microspheres are collected by centrifugation, washed three times with deionized water to remove residual surfactants, and then dried at room temperature or under vacuum to obtain phase change material microspheres with energy storage and enhanced photothermal therapy functions.

[0035] Figure 2 A is a microscope image of the phase change material microspheres obtained in this case, showing a size of 24.7 ± 5.4 μm. Figure 2 B is an electron microscope image of nanoparticles during the preparation of phase change material microspheres; the particle size measurement results are similar. Figure 2 C represents the particle size measurement result of the phase change material microspheres using a particle size analyzer. Figure 2 D represents the Fourier transform infrared spectrum of the phase change material microspheres. Figure 2E / F represents high-resolution XPS spectroscopy and monolayer XPS spectroscopy analysis. The above characterization results demonstrate the successful synthesis of phase change material microspheres.

[0036] Figure 3 A represents the calculated photothermal efficiency of the phase change material microspheres. Figure 3 B represents the calorimetric results for lauric acid and phase change material microspheres. The results show that the optimal photothermal therapy temperature for this ratio of phase change material microspheres is 43.6℃. Figure 3 C and D are the infrared thermal imaging results of the phase change material microspheres, respectively. The above results prove that the phase change material microspheres have the ability to convert light energy into heat energy in photothermal therapy, and can prolong the effective temperature of mild photothermal therapy at about 43°C.

[0037] Example 2 A method for preparing phase change material microspheres with energy storage and enhanced photothermal therapy function includes the following steps: S1: Dissolve 0.5 mg quercetin and 5.0 mg dihydroartemisinin in 1.0 mL of anhydrous ethanol and mix thoroughly under ultrasound at 50 kHz for 10 minutes to prepare a ligand-drug mixture stock solution; then take 15.0 mg / mL... -1 100 μL of ferric chloride hexahydrate ethanol solution was slowly added dropwise at a rate of 10 drops / min to the ligand drug mixture stock solution. During this process, the mixture was magnetically stirred at 500 rpm. After the addition was completed, the stirring was continued for 10 minutes to obtain ligand drug pre-reaction mixture A. S2: Rapidly add 10.0 mmol·L⁻¹ of a solution containing 0.4% (w / w) Pronico F127 to the ligand-drug pre-reaction mixture A described in S1. -1 Tris(hydroxymethyl)aminomethane-hydrochloric acid buffer solution was used to adjust the pH of the solution to 8.5. During this process, magnetic stirring was maintained at 1000 rpm. After addition, stirring was carried out in the dark for 4 hours to obtain a suspension of infinitely coordinated polymer nanoparticles. After dialysis purification using a dialysis bag with a molecular weight cutoff of 7200, the suspension was freeze-dried in a vacuum freeze dryer at -50.0℃ and a vacuum degree of 100 Pa to obtain powder B of infinitely coordinated polymer nanoparticles.

[0038] S3: Take 80 mg of lauric acid and 20 mg of stearic acid solid powder respectively to form a solid mixture with a mass ratio of 4:1, and prepare phase change material powder C. Then heat it to a molten state to obtain a phase change material melt D in which infinitely coordinated polymer nanoparticles are uniformly dispersed.

[0039] S4: Polyvinyl alcohol was added to deionized water to prepare an aqueous solution with a mass fraction of 0.1 wt%. The solution was heated and stirred until fully dissolved to obtain aqueous solution E. The temperature of aqueous solution E was then adjusted to 50°C and stirred continuously at a speed of 400 rpm. Subsequently, the phase change material melt D, in which the infinitely coordinated polymer nanoparticles were uniformly dispersed, was slowly added dropwise to aqueous solution E using a syringe. Upon entering the aqueous phase, the molten droplets spontaneously contracted under surface tension to form spherical droplets. After the spherical droplets formed, the system temperature was gradually reduced to room temperature through natural cooling, causing the droplets to crystallize and solidify, forming structurally stable phase change material microspheres encapsulating the infinitely coordinated polymer nanoparticles. The solidified microspheres were collected by centrifugation, washed three times with deionized water to remove residual surfactants, and then dried at room temperature or under vacuum to obtain phase change material microspheres with energy storage and enhanced photothermal therapy functions.

[0040] In this embodiment, the phase change material microspheres obtained by this formulation have a size of 32.1±5.8μm and are suitable for photothermal therapy at a temperature of 46.2℃.

[0041] Example 3 A method for preparing phase change material microspheres with energy storage and enhanced photothermal therapy function includes the following steps: S1: Dissolve 5.0 mg of quercetin and 0.5 mg of dihydroartemisinin in 1.0 mL of anhydrous ethanol and mix thoroughly under ultrasound at 50 kHz for 10 minutes to prepare a ligand-drug mixture stock solution; then take 20.0 mg / mL... -1 50 μL of ferric chloride hexahydrate ethanol solution was slowly added dropwise at a rate of 20 drops / min to the ligand drug mixture stock solution. During this process, the mixture was magnetically stirred at 500 rpm. After the addition was completed, the stirring was continued for 10 minutes to obtain ligand drug pre-reaction mixture A. S2: Rapidly add 0.001 mol·L⁻¹ of a solution containing 0.3% (w / w) Pronic F68 to the ligand-drug pre-reaction mixture A described in S1. -1 Sodium hydroxide solution was added to adjust the pH of the solution to 8.5. During this process, magnetic stirring was maintained at 1000 rpm. After adding the sodium hydroxide solution, the mixture was stirred for 4 hours in the dark to obtain a suspension of infinitely coordinated polymer nanoparticles. After dialysis purification using a dialysis bag with a molecular weight cutoff of 7200, the nanoparticles were freeze-dried in a vacuum freeze dryer at -50 °C and a vacuum degree of 100 Pa to obtain powder B of infinitely coordinated polymer nanoparticles.

[0042] S3: Take 70 mg of lauric acid and 30 mg of stearic acid solid powder respectively to form a solid mixture with a mass ratio of 7:3, and prepare phase change material powder C. Then heat it to a molten state to obtain a phase change material melt D in which infinitely coordinated polymer nanoparticles are uniformly dispersed.

[0043] S4: Polyvinyl alcohol (PVA) was added to deionized water to prepare an aqueous solution with a mass fraction of 1.5 wt%. The solution was heated and stirred until fully dissolved to obtain aqueous solution E. The temperature of aqueous solution E was then adjusted to 55 ℃ and continuously stirred at a stirring speed of 800 rpm. Subsequently, the phase change material melt D, in which the infinitely coordinated polymer nanoparticles were uniformly dispersed, was slowly added dropwise to aqueous solution E using a syringe. After entering the aqueous phase, the molten droplets spontaneously contracted under surface tension to form spherical droplets. After the spherical droplets formed, the system temperature was gradually reduced to room temperature through natural cooling, causing the droplets to crystallize and solidify, forming structurally stable phase change material microspheres encapsulating the infinitely coordinated polymer nanoparticles. The solidified microspheres were collected by centrifugation, washed three times with deionized water to remove residual surfactants, and then dried at room temperature or under vacuum to obtain phase change material microspheres with energy storage and enhanced photothermal therapy functions.

[0044] In this embodiment, the phase change material microspheres obtained by this formulation have a size of 32.4±6.7μm and are suitable for photothermal therapy at a temperature of 50.3℃.

[0045] Example 4 A method for preparing phase change material microspheres with energy storage and enhanced photothermal therapy function includes the following steps: S1: Dissolve 4.0 mg of quercetin and 1.0 mg of dihydroartemisinin in 1.0 mL of anhydrous ethanol and mix thoroughly under ultrasound at 50 kHz for 10 minutes to prepare a ligand-drug mixture stock solution; then take 5.0 mg / mL -1 200 μL of ferric chloride hexahydrate ethanol solution was slowly added dropwise to the ligand drug mixture stock solution at a rate of 10 drops / min, while magnetically stirring at 500 rpm during the process. After the addition was completed, stirring was continued for 10 minutes to obtain ligand drug pre-reaction mixture A.

[0046] S2: Quickly add a 0.1% (w / w) triethylamine solution containing 0.2% (w / w) Pronic F68 to the ligand drug pre-reaction mixture A described in S1, and adjust the pH of the solution to 8.0; during this process, maintain magnetic stirring at 1000 rpm, and stir for 4 hours in the dark after addition to obtain an infinite coordination polymer nanoparticle suspension. After dialysis purification using a dialysis bag with a molecular weight cutoff of 7200, freeze-dry in a vacuum freeze dryer at -50℃ and a vacuum degree of 100Pa to obtain infinite coordination polymer nanoparticle powder B. S3: Take 60 mg of lauric acid and 40 mg of stearic acid solid powder respectively to form a solid mixture with a mass ratio of 3:2, and prepare phase change material powder C; then heat it to a molten state to obtain phase change material melt D with uniformly dispersed infinitely coordinated polymer nanoparticles.

[0047] S4: Polyvinyl alcohol was added to deionized water to prepare a 2wt% aqueous solution. The solution was heated and stirred until fully dissolved to obtain aqueous solution E. The temperature of aqueous solution E was then adjusted to 55°C and continuously stirred at 200 rpm. Subsequently, the phase change material melt D, uniformly dispersed with infinitely coordinated polymer nanoparticles from S3, was slowly added dropwise to aqueous solution E using a syringe. Upon entering the aqueous phase, the molten droplets spontaneously contracted under surface tension to form spherical droplets. After the spherical droplets formed, the system temperature was gradually reduced to room temperature through natural cooling, causing the droplets to crystallize and solidify, forming structurally stable phase change material microspheres encapsulating infinitely coordinated polymer nanoparticles. The solidified microspheres were collected by centrifugation, washed three times with deionized water to remove residual surfactants, and then dried at room temperature or under vacuum to obtain phase change material microspheres with energy storage and enhanced photothermal therapy functions.

[0048] In this embodiment, the phase change material microspheres obtained by this formulation have a size of 32.7±9.1μm and are suitable for photothermal therapy at a temperature of 52.3℃.

[0049] Example 5 A method for preparing phase change material microspheres with energy storage and enhanced photothermal therapy function includes the following steps: This example includes the following steps: S1: Dissolve 3.0 mg of quercetin and 2.0 mg of dihydroartemisinin in 1.0 mL of methanol and mix thoroughly under ultrasound at 50 kHz for 10 minutes to prepare a ligand-drug mixture stock solution; then take 10.0 mg / mL... -1 150 μL of ferric chloride hexahydrate ethanol solution was slowly added dropwise to the ligand drug mixture stock solution at a rate of 15 drops / min. During this process, the mixture was magnetically stirred at 500 rpm. After the addition was completed, the stirring was continued for 10 minutes to obtain ligand drug pre-reaction mixture A.

[0050] S2: Quickly add a 0.1% (w / w) triethylamine solution containing 0.4% (w / w) polyoxyethylene lauryl ether to the ligand drug pre-reaction mixture A described in S1, and adjust the pH of the solution to 8.0; during this process, maintain magnetic stirring at 1000 rpm, and stir for 4 hours in the dark after addition to obtain an infinite coordination polymer nanoparticle suspension. After dialysis purification using a dialysis bag with a molecular weight cutoff of 7200, freeze-dry in a vacuum freeze dryer at -50℃ and a vacuum degree of 100Pa to obtain infinite coordination polymer nanoparticle powder B. S3: Take 50 mg of lauric acid and 50 mg of stearic acid solid powder respectively to form a solid mixture with a mass ratio of 1:1, and prepare phase change material powder C. Then heat it to a molten state to obtain a phase change material melt D in which infinitely coordinated polymer nanoparticles are uniformly dispersed.

[0051] S4: Tween-80 was added to deionized water to prepare an aqueous solution with a mass fraction of 1.8 wt%. The solution was heated and stirred until fully dissolved to obtain aqueous solution E. The temperature of aqueous solution E was then adjusted to 60°C and continuously stirred at a speed of 500 rpm. Subsequently, the phase change material melt D, in which the infinitely coordinated polymer nanoparticles were uniformly dispersed, was slowly added dropwise to aqueous solution E using a syringe. Upon entering the aqueous phase, the molten droplets spontaneously contracted under surface tension to form spherical droplets. After the spherical droplets formed, the system temperature was gradually reduced to room temperature through natural cooling, causing the droplets to crystallize and solidify, forming structurally stable phase change material microspheres encapsulating the infinitely coordinated polymer nanoparticles. The solidified microspheres were collected by centrifugation, washed three times with deionized water to remove residual surfactants, and then dried at room temperature or under vacuum to obtain phase change material microspheres with energy storage and enhanced photothermal therapy functions.

[0052] In this embodiment, the phase change material microspheres obtained by this formulation have a size of 27.9±6.5μm and are suitable for photothermal therapy at a temperature of 54.6℃.

[0053] Example 6 A method for preparing phase change material microspheres with energy storage and enhanced photothermal therapy function includes the following steps: S1: Dissolve 2.0 mg of quercetin and 3.0 mg of dihydroartemisinin in 1.0 mL of dimethyl sulfoxide and mix thoroughly under ultrasound at 50 kHz for 10 minutes to prepare a ligand-drug mixture stock solution; then take 15.0 mg / mL -1 100 μL of ferric chloride hexahydrate ethanol solution was slowly added dropwise to the ligand drug mixture stock solution at a rate of 10 drops / min. During this process, the mixture was magnetically stirred at 500 rpm. After the addition was completed, stirring was continued for 10 minutes to obtain ligand drug pre-reaction mixture A.

[0054] S2: Rapidly add 10.0 mmol·L⁻¹ of a solution containing 0.2% (w / w) Pronico F127 to the ligand-drug pre-reaction mixture A described in S1. -1Tris(hydroxymethyl)aminomethane-hydrochloric acid buffer solution was used to adjust the pH of the solution to 8.5. During this process, magnetic stirring was maintained at 1000 rpm. After addition, stirring was carried out in the dark for 4 hours to obtain an infinite coordination polymer nanoparticle suspension. After dialysis purification using a dialysis bag with a molecular weight cutoff of 7200, the suspension was freeze-dried in a vacuum freeze dryer at -50°C and a vacuum degree of 100 Pa to obtain infinite coordination polymer nanoparticle powder B.

[0055] S3: Take 40 mg of lauric acid and 60 mg of stearic acid solid powder respectively to form a solid mixture with a mass ratio of 2:3, and prepare phase change material powder C; then heat it to a molten state to obtain phase change material melt D with uniformly dispersed infinitely coordinated polymer nanoparticles.

[0056] S4: Tween-80 was added to deionized water to prepare an aqueous solution with a mass fraction of 0.6 wt%. The solution was heated and stirred until fully dissolved to obtain aqueous solution E. The temperature of aqueous solution E was then adjusted to 60 ℃ and continuously stirred at a speed of 800 rpm. Subsequently, the phase change material melt D, in which the infinitely coordinated polymer nanoparticles were uniformly dispersed, was slowly added dropwise to aqueous solution E using a syringe. Upon entering the aqueous phase, the molten droplets spontaneously contracted under surface tension to form spherical droplets. After the spherical droplets formed, the system temperature was gradually reduced to room temperature through natural cooling, causing the droplets to crystallize and solidify, forming structurally stable phase change material microspheres encapsulating the infinitely coordinated polymer nanoparticles. The solidified microspheres were collected by centrifugation, washed three times with deionized water to remove residual surfactants, and then dried at room temperature or under vacuum to obtain phase change material microspheres with energy storage and enhanced photothermal therapy functions.

[0057] In this embodiment, the phase change material microspheres obtained by this formulation have a size of 19.2±4.4μm and are suitable for photothermal therapy at a temperature of 55.2℃.

[0058] Example 7 A method for preparing phase change material microspheres with energy storage and enhanced photothermal therapy function includes the following steps: S1: Dissolve 1.0 mg of quercetin and 4.0 mg of dihydroartemisinin in 1.0 mL of N,N-dimethylformamide and mix thoroughly under ultrasonication at 50 kHz for 10 minutes to prepare a ligand-drug mixture stock solution; then take 20.0 mg / mL -1 100 μL of ferric chloride hexahydrate ethanol solution was slowly added dropwise to the ligand drug mixture stock solution at a rate of 10 drops / min. During this process, the mixture was magnetically stirred at 500 rpm. After the addition was completed, stirring was continued for 10 minutes to obtain ligand drug pre-reaction mixture A.

[0059] S2: Rapidly add a 0.1% (w / w) triethylamine solution containing 0.3% (w / w) pronicotinic F127 to the ligand drug pre-reaction mixture A described in S1, and adjust the pH of the solution to 8.0. Maintain magnetic stirring at 1000 rpm during this process, and stir for 4 hours in the dark after addition to obtain an infinite coordination polymer nanoparticle suspension. After dialysis purification using a dialysis bag with a molecular weight cutoff of 7200, freeze-dry the suspension in a vacuum freeze dryer at -5°C and a vacuum degree of 100 Pa to obtain infinite coordination polymer nanoparticle powder B.

[0060] S3: Take 30 mg of lauric acid and 70 mg of stearic acid solid powder respectively to form a solid mixture with a mass ratio of 3:7, and make phase change material powder C. Then heat it to the molten state to obtain phase change material melt D with uniformly dispersed infinitely coordinated polymer nanoparticles.

[0061] S4: Tween-80 was added to deionized water to prepare an aqueous solution with a mass fraction of 0.4 wt%. The solution was heated and stirred until fully dissolved to obtain aqueous solution E. The temperature of aqueous solution E was then adjusted to 60°C and stirred continuously at a speed of 800 rpm. Subsequently, the phase change material melt D, in which the infinitely coordinated polymer nanoparticles were uniformly dispersed, was slowly added dropwise to aqueous solution E using a syringe. Upon entering the aqueous phase, the molten droplets spontaneously contracted under surface tension to form spherical droplets. After the spherical droplets formed, the system temperature was gradually reduced to room temperature through natural cooling, causing the droplets to crystallize and solidify, forming structurally stable phase change material microspheres encapsulating the infinitely coordinated polymer nanoparticles. The solidified microspheres were collected by centrifugation, washed three times with deionized water to remove residual surfactants, and then dried at room temperature or under vacuum to obtain phase change material microspheres with energy storage and enhanced photothermal therapy functions.

[0062] In this embodiment, the phase change material microspheres obtained by this formulation have a size of 21.5±4.8nm and are suitable for photothermal therapy at a temperature of 57.5℃.

[0063] Example 8 A method for preparing phase change material microspheres with energy storage and enhanced photothermal therapy function includes the following steps: S1: Dissolve 3.0 mg of quercetin and 2.0 mg of dihydroartemisinin in 1.0 mL of N,N-dimethylformamide and mix thoroughly under ultrasonication at 50 kHz for 10 minutes to prepare a ligand-drug mixture stock solution; then take 10.0 mg / mL -1 150 μL of ferric chloride hexahydrate ethanol solution was slowly added dropwise to the ligand drug mixture stock solution at a rate of 10 drops / minute, while magnetically stirring at 500 rpm during the process. After the addition was completed, stirring was continued for 10 minutes to obtain ligand drug pre-reaction mixture A.

[0064] S2: Rapidly add 10.0 mmol·L⁻¹ of a solution containing 0.3% (w / w) Pronico F68 to the ligand-drug pre-reaction mixture A described in S1. -1 Tris(hydroxymethyl)aminomethane-hydrochloric acid buffer solution was used to adjust the pH of the solution to 8.5. During this process, magnetic stirring was maintained at 1000 rpm. After addition, stirring was carried out in the dark for 4 hours to obtain an infinite coordination polymer nanoparticle suspension. After dialysis purification by a dialysis bag with a molecular weight cutoff of 7200, the suspension was freeze-dried in a vacuum freeze dryer at -50°C and a vacuum degree of 100 Pa to obtain infinite coordination polymer nanoparticle powder B. S3: Take 20 mg of lauric acid and 80 mg of stearic acid solid powder respectively to form a solid mixture with a mass ratio of 1:4, and prepare phase change material powder C. Then heat it to a molten state to obtain a phase change material melt D in which infinitely coordinated polymer nanoparticles are uniformly dispersed.

[0065] S4: Tween-20 was added to deionized water to prepare an aqueous solution with a mass fraction of 0.8 wt%. The solution was heated and stirred until fully dissolved to obtain aqueous solution E. The temperature of aqueous solution E was then adjusted to 65°C and continuously stirred at a speed of 500 rpm. Subsequently, the phase change material melt D, in which the infinitely coordinated polymer nanoparticles were uniformly dispersed, was slowly added dropwise to aqueous solution E using a syringe. Upon entering the aqueous phase, the molten droplets spontaneously contracted under surface tension to form spherical droplets. After the spherical droplets formed, the system temperature was gradually reduced to room temperature through natural cooling, causing the droplets to crystallize and solidify, forming structurally stable phase change material microspheres encapsulating the infinitely coordinated polymer nanoparticles. The solidified microspheres were collected by centrifugation, washed three times with deionized water to remove residual surfactants, and then dried at room temperature or under vacuum to obtain phase change material microspheres with energy storage and enhanced photothermal therapy functions.

[0066] In this embodiment, the phase change material microspheres obtained by this formulation have a size of 26.7±5.9μm and are suitable for photothermal therapy at a temperature of 60.8℃.

[0067] Example 9 A method for preparing phase change material microspheres with energy storage and enhanced photothermal therapy function includes the following steps: S1: Dissolve 2.0 mg of quercetin and 3.0 mg of dihydroartemisinin in 1.0 mL of dimethyl sulfoxide and mix thoroughly under ultrasound at 50 kHz for 10 minutes to prepare a ligand-drug mixture stock solution; then take 20.0 mg / mL -1150 μL of ferric chloride hexahydrate ethanol solution was slowly added dropwise to the ligand drug mixture stock solution at a rate of 20 drops / min, while magnetically stirring at 500 rpm during the process. After the addition was completed, stirring was continued for 10 minutes to obtain ligand drug pre-reaction mixture A.

[0068] S2: Rapidly add 10.0 mmol·L⁻¹ of a solution containing 0.4% (w / w) polyoxyethylene lauryl ether to the ligand-drug pre-reaction mixture A described in S1. -1 Tris(hydroxymethyl)aminomethane-hydrochloric acid buffer solution was used to adjust the pH of the solution to 8.5. During this process, magnetic stirring was maintained at 1000 rpm. After addition, stirring was carried out in the dark for 4 hours to obtain a suspension of infinitely coordinated polymer nanoparticles. This suspension was then purified by dialysis using a dialysis bag with a molecular weight cutoff of 7200, and subsequently freeze-dried at -50°C and 100 Pa to obtain powder B of infinitely coordinated polymer nanoparticles.

[0069] S3: Take 10 mg of lauric acid and 90 mg of stearic acid solid powder respectively to form a solid mixture with a mass ratio of 1:9, and prepare phase change material powder C; then heat it to a molten state to obtain phase change material melt D with uniformly dispersed infinitely coordinated polymer nanoparticles.

[0070] S4: Tween-20 was added to deionized water to prepare a 1 wt% aqueous solution. The solution was heated and stirred until fully dissolved to obtain aqueous solution E. The temperature of aqueous solution E was then adjusted to 70°C and stirred continuously at 300 rpm. Subsequently, the phase change material melt D, uniformly dispersed with infinitely coordinated polymer nanoparticles from S3, was slowly added dropwise to aqueous solution E using a syringe. Upon entering the aqueous phase, the molten droplets spontaneously contracted under surface tension to form spherical droplets. After the spherical droplets formed, the system temperature was gradually reduced to room temperature through natural cooling, causing the droplets to crystallize and solidify, forming structurally stable phase change material microspheres encapsulating infinitely coordinated polymer nanoparticles. The solidified microspheres were collected by centrifugation, washed three times with deionized water to remove residual surfactants, and then dried at room temperature or under vacuum to obtain phase change material microspheres with energy storage and enhanced photothermal therapy functions.

[0071] In this embodiment, the phase change material microspheres obtained by this formulation have a size of 31.6±8.7μm and are suitable for photothermal therapy at a temperature of 65.7℃.

[0072] Example 10 A method for preparing phase change material microspheres with energy storage and enhanced photothermal therapy function includes the following steps: S1: Dissolve 2.5 mg of quercetin and 2.5 mg of dihydroartemisinin in 1.0 mL of anhydrous ethanol and mix thoroughly under ultrasound at 50 kHz for 10 minutes to prepare a ligand-drug mixture stock solution; then take 10.0 mg / mL -1 150 μL of ferric chloride hexahydrate ethanol solution was slowly added dropwise to the ligand drug mixture stock solution at a rate of 20 drops / min, while magnetically stirring at 500 rpm during the process. After the addition was completed, stirring was continued for 10 minutes to obtain ligand drug pre-reaction mixture A.

[0073] S2: Rapidly add 0.001 mol·L⁻¹ of a solution containing 0.2% (w / w) polyoxyethylene lauryl ether to the ligand-drug pre-reaction mixture A described in S1. -1 Sodium hydroxide solution was added to adjust the pH of the solution to 8.5. During this process, magnetic stirring was maintained at 1000 rpm. After adding the solution, stirring was carried out in the dark for 4 hours to obtain a suspension of infinitely coordinated polymer nanoparticles. After dialysis purification by a dialysis bag with a molecular weight cutoff of 7200, the suspension was freeze-dried in a vacuum freeze dryer at -50℃ and a vacuum degree of 100Pa to obtain powder B of infinitely coordinated polymer nanoparticles. S3: Take 1 mg of lauric acid and 100 mg of stearic acid solid powder respectively to form a solid mixture with a mass ratio of 0:100, and prepare phase change material powder C; then heat it to a molten state to obtain phase change material melt D with uniformly dispersed infinitely coordinated polymer nanoparticles.

[0074] S4: Tween-20 was added to deionized water to prepare an aqueous solution with a mass fraction of 1.4 wt%. The solution was heated and stirred until fully dissolved to obtain aqueous solution E. The temperature of aqueous solution E was then adjusted to 70°C and continuously stirred at a speed of 700 rpm. Subsequently, the phase change material melt D, in which the infinitely coordinated polymer nanoparticles were uniformly dispersed, was slowly added dropwise to aqueous solution E using a syringe. Upon entering the aqueous phase, the molten droplets spontaneously contracted under surface tension to form spherical droplets. After the spherical droplets formed, the system temperature was gradually reduced to room temperature through natural cooling, causing the droplets to crystallize and solidify, forming structurally stable phase change material microspheres encapsulating the infinitely coordinated polymer nanoparticles. The solidified microspheres were collected by centrifugation, washed three times with deionized water to remove residual surfactants, and then dried at room temperature or under vacuum to obtain phase change material microspheres with energy storage and enhanced photothermal therapy functions.

[0075] In this embodiment, the phase change material microspheres obtained by this formulation have a size of 26.2.1 ± 4.5 μm and are suitable for photothermal therapy at a temperature of 68.2 °C.

[0076] Colorectal tumors are located near the intestines, making high-temperature photothermal therapy unsuitable. Therefore, 43.6℃ as described in Example 1 was selected as the photothermal therapy temperature, and the results were as follows: Figure 4 As shown, Figure 4 A represents the results of the no-intervention control group. Figure 4 B represents the tumor treatment results of the colorectal tumor photothermal therapy group using the phase change material microspheres obtained in Example 1. Figure 4 C represents the tumor quality measurement result, from which the tumor inhibition rate can be obtained as 81.2%.

[0077] In summary, this invention first involves preparing a pre-reaction mixture A of quercetin and dihydroartemisinin drug molecules in a specific ratio. Then, an alkaline buffer solution is added to the reaction mixture to adjust the pH. After a period of self-assembly, a suspension of infinitely coordinated polymer nanoparticles is obtained. Following freeze-drying, powdered infinitely coordinated polymer nanoparticles are obtained. Subsequently, the powdered infinitely coordinated polymer nanoparticles are mixed with a mixture C of lauric acid and stearic acid in different mass ratios. After melting, the mixture is solidified using a warm water droplet method to obtain phase change material microspheres with energy storage and enhanced photothermal therapy functions at different phase transition temperatures.

[0078] Although preferred embodiments of the invention have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including both the preferred embodiments and all changes and modifications falling within the scope of the invention.

Claims

1. A phase change material microsphere with energy storage and enhanced photothermal therapy function, characterized in that, Using quercetin and dihydroartemisinin as ligand molecules and ferric ions as coordinating metal ions, nanoparticles are formed through coordination self-assembly; the nanoparticles are then mixed with phase change materials and obtained through a curing method. The mass ratio of the nanoparticles to the phase change material is 1:1 to 10; the phase change temperature of the phase change material microspheres is 43.6℃ to 68.2℃.

2. The phase change material microspheres with energy storage and enhanced photothermal therapy function according to claim 1, characterized in that, The phase change material is composed of lauric acid and stearic acid in a mass ratio of 1~100:100~1.

3. The phase change material microspheres with energy storage and enhanced photothermal therapy function according to claim 2, characterized in that, The mass ratio of quercetin to dihydroartemisinin is 1~10:10~1.

4. A method for preparing phase change material microspheres according to claim 3, characterized in that, Includes the following steps: Quercetin and dihydroartemisinin were mixed in an organic reagent at a mass ratio of 1~10:10~1 to obtain a ligand-drug mixture stock solution. Add 5 mg / mL to 20 mg / mL ferric chloride hexahydrate ethanol solution dropwise to the ligand drug mixture stock solution and stir to obtain ligand drug pre-reaction mixture A; The ligand-drug pre-reaction mixture A was mixed with an alkaline buffer solution and a surfactant, the pH was adjusted to 8-8.5, stirred, dialyzed, and dried to obtain nanoparticles. Nanoparticles and phase change materials are mixed in a mass ratio of 1:1 to 10 and heated until melted to obtain phase change material melt D. The phase change material melt D is added dropwise to an aqueous stabilizer solution, and crystallization and solidification occur at 45℃~70℃. The stabilizer is removed, and the mixture is dried to obtain the phase change material microspheres.

5. The preparation method according to claim 4, characterized in that, The organic reagent is any one of anhydrous ethanol, methanol, dimethyl sulfoxide, and N,N-dimethylformamide.

6. The preparation method according to claim 4, characterized in that, The alkaline buffer solution is any one of the following: 10 mmol / L tris(hydroxymethyl)aminomethane-hydrochloric acid buffer solution, 0.001 mol / L sodium hydroxide, or 0.1% triethylamine solution; the pH of the alkaline buffer solution is 8.0~8.

5. The surfactant is any one of Pronic F127, Pronic F68, and polyoxyethylene lauryl ether, and the surfactant has a mass percentage of 0.2% to 0.4%.

7. The preparation method according to claim 4, characterized in that, The stabilizer aqueous solution has a mass percentage of 0.1% to 2%; the stabilizer is polyvinyl alcohol or Tween-80.

8. The application of the phase change material microspheres according to any one of claims 1 to 3 in photothermal therapy.

9. The application according to claim 8, characterized in that, The photothermal therapy mentioned is tumor photothermal therapy.

10. The application according to claim 8, characterized in that, The photothermal therapy is either low-temperature photothermal therapy below 50°C or high-temperature ablation temperature zone photothermal therapy between 55°C and 65°C.

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