Multiple resonance type photosensitive lipid nanoparticle with photodynamic and photo-thermal properties, preparation method and application

Abstract

The invention discloses photosensitive lipid nanoparticles containing multiple resonance structures, a preparation method and application, and belongs to the technical field of biomedical materials. The photosensitizer is structurally characterized in that multiple resonance fused ring diboron and dinitrogen are taken as a molecular skeleton, and sulfur atoms with a heavy atom effect are introduced, so that the intersystem crossing process between a single triplet state and a triplet state can be accelerated, the energy level difference can be reduced, and the generation of active oxygen can be promoted. The absorption wavelength of the lipid nanoparticles NIR-BN-coated NPs prepared by ultrasound is in a range of 550 to 700 nm. Under the irradiation of red light, superoxide anion free radicals can be efficiently generated, and an excellent photothermal effect is achieved. The molecular design strategy provides a new scheme for constructing a new generation of photosensitizer molecules for biological diagnosis and treatment.

Description

Technical Field

[0001] The invention relates to a method for preparing a new generation of lipid nanoparticles with a multi-resonance structure, and can simultaneously achieve efficient photothermal and photodynamic effects, belonging to the field of modern phototherapy. Background Art

[0002] As a non-invasive precision medical technology, phototherapy offers great potential for real-time diagnosis and simultaneous in situ treatment. Therefore, it has received extensive attention in the study of clinical malignant tumor elimination. At present, the development of phototherapy diagnostic systems has made significant progress, mainly including photothermal therapy (PTT) and photodynamic therapy (PDT). Among them, PTT converts the absorbed light energy into heat energy, causing local high temperature and ultimately killing tumor cells. It has the advantages of high specificity, precise controllability and little damage to normal tissues. In addition, PTT can increase the saturated oxygen concentration of blood vessels by increasing the blood flow rate, and at the same time increase the uptake of PDT drugs by tumor cells. PDT, as another method for treating tumor diseases, mainly uses photosensitizers to produce high concentrations of cytotoxic reactive oxygen species (ROS), because they can cause irreversible oxidative damage to biological macromolecules (such as DNA, proteins, lipids, etc.) and cell metabolic disorders, which can lead to the death of malignant tumors. Generally, type II PDT therapy is very dependent on the concentration of surrounding oxygen, but tumor tissue has the characteristics of extreme hypoxia. To overcome this shortcoming, type I PDT, which is tolerant to hypoxia, provides a simple way to improve the therapeutic effect of tumors. After laser irradiation, photosensitizers can produce highly cytotoxic free radicals. Therefore, even in the hypoxic environment of tumor cells, type I PDT can still provide good therapeutic effects. Therefore, this synergistic treatment combining type I PDT with photothermal therapy is considered to be a feasible strategy to achieve better anti-tumor therapeutic effects.

[0003] So far, there have been reports on organic photosensitizers for type I PDT and PTT synergistic therapy. These photosensitizers are based on donor-acceptor structures and enhance intramolecular charge transfer (ICT) and reduce the energy level difference (ΔE) between singlet and triplet states (S1 and T1). ST ), accelerating the intersystem crossing (ISC) process between S1 and T1, thereby enhancing the ability to produce ROS. However, these photosensitizer molecules are all traditional fluorescent materials with large ΔE ST .

[0004] In recent years, the emergence of thermally activated delayed fluorescence (TADF) materials has promoted the development of optoelectronic technology. TADF materials use pure organic building blocks and effectively separate the highest occupied molecular orbital (HOMO) and the highest unoccupied molecular orbital (LUMO) through special molecular design, reducing the energy level difference between the lowest excited singlet state and the triplet state, thereby increasing the ISC rate and promoting the efficient generation of ROS. In addition, the structural design of thermally activated delayed fluorescence materials is flexible. At present, multi-resonance (MR) thermally activated delayed fluorescence materials have become star molecules in the field of optoelectronic functional materials due to their unique condensed ring molecular structure characteristics and structural novelty. In addition, due to their intramolecular MR effect, their HOMO and LUMO energy levels can be effectively separated to different atoms, thereby realizing a short-range intramolecular charge transfer effect and obtaining a small ΔE ST Therefore, it can be prepared as targeted photosensitive lipid nanoparticles to achieve efficient phototherapy applications. However, up to now, there has been no report on photosensitizers with MR structures.

[0005] Therefore, it is of great significance to develop a new type of high-performance MR photosensitizer. Summary of the invention

[0006] The purpose of the present invention is to design and prepare a MR molecule and photosensitive lipid nanoparticles that have efficient photothermal and photodynamic effects. Under red laser irradiation, the nanoparticles can rapidly convert triplet oxygen into superoxide anion free radicals, while generating heat to raise the local temperature by about 20-25°C, which is better than commercial photosensitizers used for photodynamic and photothermal therapy, and can be used for efficient photodynamic and photothermal synergistic therapy of tumors.

[0007] The photosensitizer NIR-BN, which has both photodynamic and photothermal therapeutic properties, has a structural feature of using a multi-resonance fused ring diboron dinitrogen as a molecular skeleton and introducing sulfur atoms with heavy atom effects to further accelerate the ISC process. Its structure is:

[0008]

[0009] The method for preparing the MR photosensitizer NIR-BN comprises the following steps:

[0010] (1) Synthesis route

[0011]

[0012] (2) Synthesis steps

[0013] Step 1: Using 1,4-dibromotetrafluorobenzene and phenothiazine as raw materials, heating in a Lewis base and a solvent N,N-dimethylformamide to carry out a nucleophilic substitution reaction, compound 2 can be prepared;

[0014] Step 2: Compound 2 and 3,6-di-tert-butylcarbazole are used as raw materials, heated in Lewis base and N,N-dimethylformamide, and subjected to nucleophilic substitution reaction to prepare compound 3;

[0015] Step 3: The intermediate 3 is first subjected to lithium halogen exchange reaction with tert-butyl lithium, and then boron tribromide is added for borylation reaction, and finally N,N-diisopropylethylamine is added to obtain the target molecule NIR-BN.

[0016] The nucleophilic substitution reaction temperature in step 1 and step 2 is 100-120° C.; the Lewis base is preferably cesium carbonate.

[0017] In the step 1, it is inevitable for those skilled in the art to include post-treatment after obtaining the product, specifically, the product obtained after the reaction is cooled to room temperature and extracted three times with dichloromethane and water. The combined organic phase is dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product is purified by silica gel column chromatography using dichloromethane / petroleum ether (v / v=1 / 4) as an eluent to obtain a white solid product.

[0018] In the step 2, for those skilled in the art, it is inevitable to include post-treatment after obtaining the product, specifically, after the product obtained after the reaction is cooled to room temperature, it is extracted three times with dichloromethane and water. The combined organic phase is dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product is purified by silica gel column chromatography using dichloromethane / petroleum ether (v / v=1 / 2) as eluent to obtain a light yellow solid product.

[0019] In some embodiments, in step 3, compound 3 and tert-butylbenzene are added to a pressure-resistant bottle under argon protection and stirred for half an hour. Under an ice bath, tert-butyl lithium solution is slowly added, stirred for half an hour, and then transferred to room temperature for reaction for 3 hours. Boron tribromide is then added at -50°C to -30°C, and the reaction mixture is stirred at room temperature for 2-3 hours; N,N-diisopropylethylamine is added under an ice bath, and the reaction mixture is slowly restored to room temperature, and heated to 150-160°C for reaction for 10-12 hours.

[0020] In the step 3, for those skilled in the art, it is inevitable to include post-treatment after obtaining the product, specifically, after the product obtained after the reaction is cooled to room temperature, the reaction mixture is filtered through diatomaceous earth, and extracted three times with dichloromethane and water. The combined organic phase is dried over anhydrous sodium sulfate and concentrated under reduced pressure. Then, silica gel column chromatography is used to separate to obtain an orange-dark green solid product.

[0021] The present invention provides a lipid nanoparticle NIR-BN@NPs, wherein the MR molecule NIR-BN for photodynamic and photothermal therapy is treated with distearoyl phosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG 2000 ) and aminopolyethylene glycol folic acid (NH2-PEG-FA) were ultrasonically treated in tetrahydrofuran (THF) solution to obtain lipid nanoparticles NIR-BN@NPs.

[0022] The specific steps are as follows: dissolving the compounds NIR-BN, DSPE-PEG and NH2-PEG-FA in THF to obtain a mixed solution; injecting the mixed solution into deionized water, ultrasonicating for 10-15 minutes to obtain a lipid microemulsion, transferring the lipid microemulsion into a dialysis bag (8KD-14KD) and dialyzing with deionized water for 30-35 hours, replacing the deionized water every 2-3 hours, so that the photosensitizer is wrapped by the polymer material and self-assembled into nanoparticles, and at the same time removing THF and freeze-drying for storage for later use to obtain lipid nanoparticles NIR-BN@NPs.

[0023] The mass ratio of the photodynamic and photothermal therapy organic molecules (NIR-BN), distearoyl phosphatidylethanolamine-polyethylene glycol 2000, and aminopolyethylene glycol folic acid is 1:6-10:3-5, and is further preferably 1:6.6:3.7.

[0024] The prepared lipid nanoparticles NIR-BN@NPs have a particle size of 140-160 nm, a z-potential of -20-23 mv, and an absorption wavelength of 550-680 nm.

[0025] In some preferred embodiments, triplet oxygen can be rapidly converted into superoxide anion free radicals by irradiation with red laser (e.g., at 550-680 nm), and heat is generated to raise the local temperature by about 20-25° C. The nanoparticles are stable for more than one week.

[0026] Another technical solution of the present invention is to provide a dye organic catalytic degradation agent, including the lipid nanoparticles NIR-BN@NPs. That is, the photodynamic and photothermal therapy lipid nanoparticles NIR-BN@NPs are used as photodynamic therapy agents to degrade 2,7-dichlorofluorescein diacetate (DCFH-DA) and dihydrorhodamine 123 (DHR123). The photodynamic effect of the compound is investigated by the total active oxygen production rate and superoxide anion free radicals, and the degradation kinetic curves of active oxygen indicators DCFH-DA and DHR 123 are tested.

[0027] Another technical solution of the present invention is to provide a photothermal therapy photosensitizer, which includes the lipid nanoparticles NIR-BN@NPs. The photodynamic and photothermal therapy lipid nanoparticles NIR-BN@NPs are used as photothermal therapy photosensitizers. The photothermal effect of the compound is investigated by real-time temperature monitoring.

[0028] Another technical solution of the present invention is to use the lipid nanoparticles NIR-BN@NPs for photodynamic and photothermal therapy as photothermal therapy photosensitizers in the preparation of drugs for treating breast cancer, wherein the breast cancer is human breast cancer MCF-7 cells.

[0029] Adding lipid nanoparticles NIR-BN@NPs to tumor cells and culturing them for 48 hours showed no obvious cytotoxicity, but under 660nm red laser irradiation, tumor cell toxicity was obvious. 25μM NIR-BN@NPs can efficiently kill tumor cells under light, showing excellent phototherapy effect.

[0030] The tumor cell toxicity described in the present invention is achieved through the synergy of photodynamic and photothermal effects.

[0031] The photosensitizer provided by the present invention is relatively simple to synthesize and has a high yield. The prepared lipid nanoparticles have a small particle size and high stability; the yield of superoxide free radicals is significantly higher than that of commercial photosensitizers, and the photothermal performance is excellent and the stability is good, so that the light therapy effect of killing two birds with one stone can be achieved. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 This is the ultraviolet absorption spectrum of NIR-BN@NPs in aqueous solution in Example 1.

[0033] Figure 2 For Example 2 at 660nm, 0.4W / cm 2 Under laser irradiation, the fluorescence intensity of the total reactive oxygen indicator DCFH-DA at 525 nm caused by NIR-BN@NPs increases with time.

[0034] Figure 3For Example 3 at 660nm, 0.4W / cm 2 Under laser irradiation, the fluorescence intensity of the superoxide anion radical indicator DHR 123 at 529 nm caused by NIR-BN@NPs increases with time.

[0035] Figure 4 For Example 4 at 660nm, 0.6W / cm 2 Temperature variation curve of NIR-BN@NPs over time under laser irradiation.

[0036] Figure 5 This is the stability performance diagram of NIR-BN@NPs photothermal conversion in Example 5.

[0037] Figure 6 The results of the dark toxicity and phototoxicity experiments on tumor cells of NIR-BN@NPs in Example 6 and Example 7 are shown. DETAILED DESCRIPTION

[0038] The ultrasonic instrument used for preparing the lipid nanoparticles is a probe-type ultrasonic generator.

[0039] The absorption spectrum test adopts an ultraviolet visible spectrophotometer.

[0040] The particle size and potential test adopts a nanometer particle size potential instrument.

[0041] The laser used in the photodynamic photothermal effect test is a 660nm semiconductor laser lamp.

[0042] The tumor cells used in the tumor cell lethality experiment are MCF-7 and the like.

[0043] The following experiments and examples are intended to further illustrate but not limit the present invention.

[0044] Example 1

[0045] (1) Synthesis route

[0046]

[0047] (2) Synthesis steps

[0048] Preparation of compound 2: Take a 150mL two-necked flask, add phenothiazine (1.99g, 10mmol), cesium carbonate (6.52g, 20mmol) and 40mL of N,N-dimethylformamide under argon protection, react at 50°C for 1 hour; quickly add 1,4-dibromotetrafluorobenzene (1.54g, 5mmol), heat to 100°C, react for 12 hours; after cooling to room temperature, extract with dichloromethane and water three times. The combined organic phase is dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product is purified by silica gel column chromatography using dichloromethane / petroleum ether (v / v=1 / 4) as eluent to obtain 3.16g of white solid with a yield of 95%. 1 H NMR (400MHz, CDCl3) δ [ppm]: 6.87–6.79 (m, 8H), 6.76–6.70 (m, 4H), 5.82 (d, J = 8.0Hz, 4H).

[0049] Preparation of compound 3: Take a 150mL two-necked flask, add 3,6-di-tert-butylcarbazole (2.79g, 10mmol), cesium carbonate (6.52g, 20mmol) and 40mL of N,N-dimethylformamide under argon protection, react at 50°C for 1 hour; quickly add compound 2 (3.33g, 5mmol), heat to 100°C, react for 12 hours; after cooling to room temperature, extract with dichloromethane and water three times. The combined organic phase is dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product is purified by silica gel column chromatography using dichloromethane / petroleum ether (v / v=1 / 2) as eluent to obtain 5.81g of light yellow solid with a yield of 98%. 1 H NMR (400MHz, CDCl3) δ [ppm]: 8.12 (s, 4H), 7.10 (dd, J = 8.5, 1.5Hz, 4H), 6.73 (t, J = 8.5Hz, 4H), 6.60 ( d, J=8.5Hz, 4H), 6.52 (d, J=7.5Hz, 4H), 6.34 (d, J=8.5Hz, 4H), 6.16 (d, J=9.0Hz, 4H), 1.46 (s, 36H).

[0050] Preparation of NIR-BN: Take a 100mL pressure-resistant bottle, add compound 3 (7.11g, 6mmol) and 60mL tert-butylbenzene under argon protection, and stir for half an hour. In an ice bath, slowly add tert-butyl lithium solution (9.23mL, 1.30M, 12mmol), stir for half an hour, and then transfer to room temperature for 3 hours. Then add boron tribromide (1.14mL, 12mmol) at -40°C, and the reaction mixture is stirred at room temperature for 3 hours; in an ice bath, add N,N-diisopropylethylamine (0.45mL, 12mmol), slowly restore the reaction mixture to room temperature, and heat to 150°C for 12 hours. After cooling to room temperature, the reaction mixture is filtered through diatomaceous earth and extracted three times with dichloromethane and water. The combined organic phase is dried over anhydrous sodium sulfate and concentrated under reduced pressure. Then separate by silica gel column chromatography to obtain 1.19g of orange-dark green solid with a yield of 19%. 1 H NMR(400MHz,CD2Cl2)δ[ppm]:8.79(d,J=1.9Hz,2H),8.59(dd,J=7.3,1.2Hz,2H ),8.40(d,J=1.9Hz,2H),7.90(d,J=1.3Hz,2H),7.66–7.60(m,6H),7.39(t,J=7. 6Hz,2H),6.59(dd,J=7.9,1.8Hz,2H),6.39(td,J=7.9,1.1Hz,2H),5.90(ddd,J =8.8,7.4,1.9Hz,2H),5.82(dd,J=8.7,1.4Hz,2H),1.58(s,18H),1.49(s,18H). 13 CNMR(100MHz,CD2Cl2)δ[ppm]:150.01,148.46,145.11,145.00,141.12,14 0.99,137.01,130.02,129.84,128.62,127.63,125.01,124.88,124.20,12 4.11,123.62,123.31,122.21,121.91,121.35,121.20,120.40,118.71,11 6.01,114.96,113.61,113.41,35.41,34.89,32.41,32.01.HRMS:(ESI)m / z calcd for C 70 H 59 B2N4S2[M+H] + :1041.4367; found:1041.4362.

[0051] Example 2

[0052] A lipid nanoparticle NIR-BN@NPs is prepared by dissolving the compound NIR-BN, DSPE-PEG and NH2-PEG-FA prepared in Example 1 in THF to obtain a mixed solution; injecting the mixed solution into deionized water, ultrasonicating for 10-15 minutes to obtain a lipid microemulsion, transferring the lipid microemulsion into a dialysis bag (8KD-14KD) and dialyzing with deionized water for 30-35 hours, replacing the deionized water every 2-3 hours, so that a photosensitizer is wrapped by a polymer material and self-assembled into nanoparticles, and at the same time removing THF and freeze-drying and storing for later use to obtain the lipid nanoparticle NIR-BN@NPs.

[0053] The mass ratio of the photodynamic and photothermal therapy organic molecules (NIR-BN), distearoyl phosphatidylethanolamine-polyethylene glycol 2000, and aminopolyethylene glycol folic acid is 1 / 6.6 / 3.7.

[0054] UV absorption spectrum test of NIR-BN@NPs in aqueous solution:

[0055] A 20.0 μM NIR-BN@NPs aqueous solution was prepared, and its absorption spectrum was measured using an ultraviolet spectrophotometer, indicating that the absorption wavelength of the photosensitizer did not change significantly after it was prepared into a nanomaterial, and it could be excited by a 660 nm laser to produce photodynamic therapy and photothermal therapy.

[0056] Experiment on total ROS production of paper nanoparticles NIR-BN@NPs in aqueous solution:

[0057] DCFH-DA was used as the total active oxygen indicator, and the concentration of photosensitizer NIR-BN@NPs in the test solution was 20.0 μM, and the concentration of DCFH-DA was 5.0 μM. At 660 nm, 0.4 W / cm 2 Laser irradiation, the degree of degradation of DCFH-DA to DCF was used to evaluate the PDT effect of NIR-BN@NPs. The results are shown in the figure. Under laser irradiation, the total reactive oxygen indicator DCFH-DA caused by NIR-BN@NPs was converted into DCF, and the fluorescence signal of 525nm at an excitation wavelength of 488nm increased over time. This shows that NIR-BN@NPs can produce reactive oxygen and have good photodynamic therapy potential.

[0058] Example 3

[0059] Experiment on producing O2˙ˉ from paper nanoparticles NIR-BN@NPs in aqueous solution:

[0060] Using DHR123 as the O2˙ˉ indicator, the concentration of photosensitizer NIR-BN@NPs in the test solution was 20.0μM, and the concentration of DCFH-DA was 5.0μM. At 660nm, 0.4W / cm 2Laser irradiation, the degree to which DHR 123 was oxidized to highly fluorescent DHR 123 was used to evaluate the PDT effect of NIR-BN@NPs. The results are shown in the figure. Under laser irradiation, the superoxide anion reactive oxygen indicator DHR 123 caused by NIR-BN@NPs was converted into highly fluorescent DHR 123. The fluorescence signal of 529nm increased over time at an excitation wavelength of 507nm. This shows that NIR-BN@NPs can produce superoxide anion reactive oxygen and has good photodynamic therapy potential.

[0061] Example 4

[0062] Photothermal effect experiment of paper nanoparticles NIR-BN@NPs:

[0063] Take a certain amount of NIR-BN@NPs, dilute with water to a photosensitizer concentration of 120 μM, and illuminate at 660 nm, 0.6 W / cm 2 Under laser irradiation, a temperature probe was inserted to monitor the temperature change of the system in real time within 10 minutes, and a temperature change curve was drawn over time. The experimental results show that under light irradiation, the temperature of NIR-BN@NPs rises rapidly, from room temperature to 16°C in 5 minutes and to 23°C in 10 minutes, showing an excellent photothermal conversion effect.

[0064] Example 5

[0065] Photothermal cycling experiment of paper nanoparticles NIR-BN@NPs:

[0066] Example 4 was subjected to repeated illumination-cooling-illumination cycle tests to monitor the temperature changes of the system. The experimental results showed that the NIR-BN@NPs heated up after illumination, and the temperature rise was maintained after cooling and then illumination. The temperature rise remained stable during five experimental cycles, indicating that the system has a stable photothermal effect and can produce efficient photothermal conversion effects repeatedly.

[0067] Example 6

[0068] Dark cytotoxicity experiment of paper nanoparticles NIR-BN@NPs:

[0069] Taking human breast cancer cells MCF-7 as an example, the dark cytotoxicity of lipid nanoparticles NIR-BN@NPs was investigated. MCF-7 cells were inoculated with 10 5The cell density (100 μL) was inoculated in a 96-well plate; after culturing for 24 hours, 100 μL of fresh culture medium containing lipid nanoparticles was added to each well (after adding the culture medium, the photosensitizer concentrations in each well were 1.0 μM, 5.0 μM, 10.0 μM, 15.0 μM, 25.0 μM, and 30.0 μM, respectively). After culturing for 48 hours, 20 μL of MTT solution was added to each well (the MTT solution was prepared with sterilized PBS buffer at a concentration of 5 mg / mL); after incubation for 4 hours, the culture medium was removed from each well and 150 μL of DMSO was added to each well. The absorbance value of each well at 490 nm was recorded by an enzyme marker to evaluate the cytotoxicity of NIR-BN@NPs. The experimental results show that when the photosensitizer concentration in the lipid nanoparticles reaches 30 μM, the survival rate of MCF-7 cells and HepG-2 cells still reaches more than 70% ( Figure 6 ), indicating that lipid nanoparticles NIR-BN@NPs have lower cytotoxicity.

[0070] Example 7

[0071] Tumor cell phototoxicity experiment of paper nanoparticles NIR-BN@NPs:

[0072] Taking human breast cancer cells MCF-7 as an example, the tumor phototherapy activity of lipid nanoparticles NIR-BN@NPs was investigated. MCF-7 cells were plated at 10 5 The cells were inoculated at a density of 100 μL in a 96-well plate. After culturing for 24 h, 100 μL of fresh medium containing lipid nanoparticles was added to each well (after adding the medium, the photosensitizer concentrations in each well were 1.0 μM, 5.0 μM, 10.0 μM, 15.0 μM, 25.0 μM, and 30.0 μM, respectively). After culturing for 24 h, the culture plate was placed at 660 nm (0.6 W / cm 2 ) laser for 5 minutes, and the light-proof culture plate was used as a control. After 24 hours of culture, 20 μL of MTT solution was added to each well (the MTT solution was prepared from sterilized PBS buffer with a concentration of 5 mg / mL); after 4 hours of incubation, 150 μL of DMSO was added to each well after the culture medium was removed from each well. The absorbance value of each well at 490 nm was recorded by an ELISA instrument to evaluate the cell phototoxicity of NIR-BN@NPs. The experimental results show that under light conditions, with the increase of NIR-BN concentration in lipid nanoparticles, the survival rate of MCF-7 cells has a significant downward trend. When the concentration of NIR-BN in lipid nanoparticles reaches 25 μM, the survival rate of MCF-7 cells is only about 6%, indicating that NIR-BN@NPs of lipid nanoparticles have higher phototoxicity and better tumor phototherapy activity.

Claims

1. Photosensitizer NIR-BN with both photodynamic and photothermal therapeutic properties, characterized in that: The molecular skeleton is based on multi-resonance fused ring diboron dinitrogen, and sulfur atoms with heavy atom effect are introduced. Its structure is: 。 2. The method for preparing the photosensitizer NIR-BN having both photodynamic and photothermal therapeutic properties according to claim 1, characterized in that: The steps include: Step 1: Use 1,4-dibromotetrafluorobenzene and phenothiazine as raw materials, in the presence of Lewis base and solvent N , N -Heating in dimethylformamide to undergo nucleophilic substitution reaction can prepare compound 2; Step 2: Using compound 2 and 3,6-di-tert-butylcarbazole as raw materials, in the presence of Lewis base and N , N -Heating in dimethylformamide to undergo nucleophilic substitution reaction can prepare compound 3; Step 3: Firstly, the intermediate 3 is subjected to lithium halogen exchange reaction with tert-butyl lithium, then boron tribromide is added for borylation reaction, and finally, N , N -Diisopropylethylamine, to obtain the target molecule NIR-BN; The synthetic route is as follows 。 3. The method for preparing the photosensitizer NIR-BN having both photodynamic and photothermal therapeutic properties according to claim 2, characterized in that: The nucleophilic substitution reaction temperature in step 1 and step 2 is 100-120°C.

4. A lipid nanoparticle NIR-BN@NPs, characterized in that: The photodynamic and photothermal bifunctional molecule NIR-BN, distearoylphosphatidylethanolamine-polyethylene glycol, and aminopolyethylene glycol folic acid described in claim 1 are dissolved in tetrahydrofuran to obtain a mixed solution; the mixed solution is injected into deionized water, and a lipid microemulsion is obtained by ultrasound; the lipid microemulsion is transferred into a dialysis bag and dialyzed with deionized water to obtain lipid nanoparticles NIR-BN@NPs.

5. The lipid nanoparticle NIR-BN@NPs according to claim 3, characterized in that: The mass ratio of the photodynamic and photothermal bifunctional compound NIR-BN, distearoylphosphatidylethanolamine-polyethylene glycol, and aminopolyethylene glycol folic acid is 1:6-10:3-5.

6. The lipid nanoparticle NIR-BN@NPs according to claim 4 or 5, characterized in that: The particle size of the prepared lipid nanoparticles NIR-BN@NPs is 140 ~ 160 nm. z -Electric potential is -20 ~ 23 mv; absorption wavelength is 550 ~ 680nm.

7. A dye organic catalytic degradation agent, characterized in that: Includes the lipid nanoparticles NIR-BN@NPs described in claim 4 or 5.

8. The dye catalytic degradation agent according to claim 7, characterized in that: The organic dye includes 2,7-dichlorofluorescein diacetate or dihydrorhodamine 123.

9. A photosensitizer for photothermal therapy, characterized in that: The photothermal therapy photosensitizer includes the lipid nanoparticles NIR-BN@NPs described in claim 4 or 5.

10. Use of the photothermal therapy photosensitizer according to claim 9 in the preparation of a drug for treating breast cancer, wherein the breast cancer is human breast cancer MCF-7 cells.

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