A multi-resonance photosensitive lipid nanoparticle with photodynamic and photothermal properties, its preparation method and application.

Abstract

This invention discloses a photosensitive lipid nanoparticle with a multiple resonance structure, its preparation method, and its applications, belonging to the field of biomedical materials technology. The photosensitizer structure in this invention is characterized by a multiple resonance fused-ring diboron-dinitrogen molecular framework, with the introduction of sulfur atoms exhibiting heavy atom effects. This accelerates the intersystem crossing process between singlet and triplet states and reduces energy level differences, promoting the generation of reactive oxygen species. The lipid nanoparticles NIR-BN@NPs prepared by ultrasound have absorption wavelengths in the range of 550–700 nm. Under red light irradiation, they can efficiently generate superoxide anion radicals and exhibit excellent photothermal effects. This molecular design strategy provides a new approach for constructing next-generation biotherapeutic photosensitizer molecules.

Description

Technical Field

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

[0002] Phototherapy, as a non-invasive precision medicine technology, offers immense potential for real-time diagnosis and simultaneous in-situ treatment. Therefore, it has received widespread attention in clinical research on malignant tumor elimination. Currently, significant progress has been made in the development of phototherapy diagnostic systems, primarily including photothermal therapy (PTT) and photodynamic therapy (PDT). PTT converts absorbed light energy into heat energy, causing localized high temperatures that ultimately kill tumor cells. It boasts advantages such as high specificity, precise controllability, and minimal damage to normal tissues. Furthermore, PTT can increase vascular saturation oxygen concentration by increasing blood flow rate, while also increasing the uptake of PDT drugs by tumor cells. PDT, as another method for treating tumors, mainly utilizes photosensitizers to generate high concentrations of cytotoxic reactive oxygen species (ROS). These ROS cause irreversible oxidative damage to biological macromolecules (such as DNA, proteins, and lipids) and disrupt cellular metabolism, potentially leading to tumor death. Typically, type II PDT therapy is highly dependent on ambient oxygen concentration; however, tumor tissue exhibits extreme hypoxia. To overcome this limitation, type I photothermal therapy (PDT), which is tolerant to hypoxia, offers a simple method to improve tumor treatment efficacy. A photosensitizer, upon laser irradiation, generates highly cytotoxic free radicals. Therefore, even in hypoxic tumor cell environments, type I PDT can still provide good therapeutic effects. Thus, this synergistic treatment combining type I PDT with photothermal therapy is considered a feasible strategy for achieving better anti-tumor therapeutic outcomes.

[0003] To date, there have been reports on organic photosensitizers used in the synergistic treatment of type I PDT and PTT. These photosensitizers are all based on donor-receptor structures and work by enhancing intramolecular charge transfer (ICT) and reducing the energy difference (ΔE) between singlet and triplet (S1 and T1) states. ST This accelerates 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 values. ST .

[0004] In recent years, the emergence of thermally activated delayed fluorescence (TADF) materials has driven the development of optoelectronic technology. TADF materials utilize purely organic building blocks and, through special molecular design, effectively separate the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), reducing the energy level difference between the lowest excited singlet and triplet states. This enhances the ISC rate and promotes efficient ROS generation. Furthermore, TADF materials offer flexible structural design. Currently, multi-resonance (MR) TADF materials, due to their unique fused-ring molecular structure and structural novelty, have become star molecules in the field of optoelectronic functional materials. Moreover, due to their intramolecular MR effect, their HOMO and LUMO energy levels can be effectively separated to different atoms, thereby achieving short-range intramolecular charge transfer effects and obtaining small ΔE. ST Therefore, it can be prepared into targeted photosensitive lipid nanoparticles to achieve highly efficient phototherapy applications. However, to date, there are no reports on photosensitizers with MR structures.

[0005] Therefore, developing a new high-performance MR photosensitizer is of great significance. Summary of the Invention

[0006] The purpose of this invention is to design and prepare an MR molecule and photosensitive lipid nanoparticles that simultaneously possess highly efficient photothermal and photodynamic effects. Under red laser irradiation, these nanoparticles can rapidly convert triplet oxygen into superoxide anion free radicals, while simultaneously generating heat that raises the local temperature by approximately 20-25°C. This is more effective than commercially available photosensitizers used in photodynamic and photothermal therapy, and can be applied to highly efficient photodynamic and photothermal synergistic therapy for tumors.

[0007] The photosensitizer NIR-BN, which possesses both photodynamic and photothermal therapeutic properties, is characterized by a multi-resonance fused-ring diboron-dinitrogen molecular framework, with the introduction of sulfur atoms exhibiting heavy atom effects to further accelerate the ISC process. Its structure is as follows:

[0008]

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

[0010] (1) Synthesis route

[0011]

[0012] (2) Synthesis steps

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

[0014] Step 2: Using compound 2 and 3,6-di-tert-butylcarbazole as raw materials, compound 3 can be prepared by heating in Lewis base and N,N-dimethylformamide to carry out nucleophilic substitution reaction.

[0015] Step 3: Intermediate 3 undergoes a lithium halide exchange reaction with tert-butyllithium, followed by a boronization reaction with boron tribromide, and finally N,N-diisopropylethylamine is added to obtain the target molecule NIR-BN.

[0016] The nucleophilic substitution reaction temperature in steps one and two is 100-120℃; the Lewis base is preferably cesium carbonate.

[0017] In step one, it is inevitable for those skilled in the art that post-processing of the product is involved. Specifically, the product obtained after the reaction is cooled to room temperature and extracted three times with dichloromethane and water. The combined organic phases are 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 the eluent to obtain a white solid product.

[0018] In step two, it is inevitable for those skilled in the art that post-processing of the product is included. Specifically, the product obtained after the reaction is cooled to room temperature and extracted three times with dichloromethane and water. The combined organic phases are 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 the eluent to obtain a pale yellow solid product.

[0019] In some embodiments, in step three, compound 3 and tert-butylbenzene are added to a pressure-resistant bottle under argon protection and stirred for half an hour. A tert-butyllithium solution is slowly added under an ice bath, and after stirring for half an hour, the mixture is allowed to react at room temperature for 3 hours. Then, boron tribromide is added at -50°C to -30°C, and the reaction mixture is stirred at room temperature for 2-3 hours; under an ice bath, N,N-diisopropylethylamine is added, and the reaction mixture is slowly restored to room temperature, then heated to 150-160°C and reacted for 10-12 hours.

[0020] In step three, it is inevitable for those skilled in the art that post-processing of the product is involved. Specifically, 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 phases are dried over anhydrous sodium sulfate and concentrated under reduced pressure. Then, silica gel column chromatography is performed to separate the product into an orange-dark green solid.

[0021] This invention provides lipid nanoparticles NIR-BN@NPs, wherein the photodynamic and photothermal therapy MR molecule NIR-BN is processed with distearate phosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG). 2000 Lipid nanoparticles NIR-BN@NPs were prepared by sonicating amino-polyethylene glycol folic acid (NH2-PEG-FA) in tetrahydrofuran (THF) solution.

[0022] The specific steps are as follows: NIR-BN, DSPE-PEG, and NH2-PEG-FA are dissolved in THF to obtain a mixed solution; this mixed solution is injected into deionized water and sonicated for 10-15 minutes to obtain a lipid microemulsion; the lipid microemulsion is transferred into a dialysis bag (8KD-14KD) and dialyzed with deionized water for 30-35 hours, with the deionized water being replaced every 2-3 hours, so that the photosensitizer is encapsulated by the polymer material and self-assembled into nanoparticles; at the same time, after removing THF, it is lyophilized and stored for later use to obtain lipid nanoparticles NIR-BN@NPs.

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

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

[0025] In some preferred embodiments, irradiation with a red laser (e.g., at 550–680 nm) can rapidly convert triplet oxygen into superoxide anion radicals, while simultaneously generating heat that raises the local temperature by approximately 20–25°C. The nanoparticles remain stable for more than a week.

[0026] Another technical solution of the present invention is to provide a catalytic degradation agent for dye organic compounds, comprising the aforementioned lipid nanoparticles NIR-BN@NPs. Specifically, the photodynamic and photothermal therapeutic lipid nanoparticles NIR-BN@NPs are used as a photodynamic therapeutic agent in the degradation of 2,7-dichlorofluorescein diacetate (DCFH-DA) and dihydrorhodamine 123 (DHR123). The photodynamic effect of this compound is investigated using total reactive oxygen species (ROS) yield and superoxide anion radicals, and the degradation kinetics curves of the ROS indicators DCFH-DA and DHR 123 are tested.

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

[0028] Another technical solution of the present invention is the application of the aforementioned photodynamic and photothermal lipid nanoparticles NIR-BN@NPs as a photothermal photosensitizer in the preparation of a drug 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 significant cytotoxicity. However, irradiation with a 660nm red laser resulted in significant cytotoxicity to tumor cells. 25μM NIR-BN@NPs could efficiently kill tumor cells under light irradiation, demonstrating superior phototherapy effects.

[0030] The tumor cell toxicity described in this invention is achieved through the synergistic effect of photodynamic and photothermal processes.

[0031] The photosensitizer provided by this invention is relatively simple to synthesize and has a high yield. The prepared lipid nanoparticles have small particle size and high stability; the yield of superoxide radicals is significantly higher than that of commercial photosensitizers, with excellent photothermal properties and good stability, achieving a dual phototherapy effect. Attached Figure Description

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

[0033] Figure 2 Example 2 was performed at 660 nm and 0.4 W / cm. 2 The fluorescence intensity of the total reactive oxygen species indicator DCFH-DA induced by NIR-BN@NPs at 525 nm as a function of time increases under laser irradiation.

[0034] Figure 3Example 3 was performed at 660 nm and 0.4 W / cm. 2 The fluorescence intensity of the superoxide anion radical indicator DHR 123 induced by NIR-BN@NPs at 529 nm as a function of time increases under laser irradiation.

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

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

[0037] Figure 6 The figures show the results of tumor cell dark toxicity and phototoxicity experiments of NIR-BN@NPs in Examples 6 and 7. Detailed Implementation

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

[0039] The absorption spectroscopy test was performed using a UV-Vis spectrophotometer.

[0040] The particle size and potential were measured using a nanoparticle size potentiometer.

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

[0042] The tumor cells used in the tumor cell lethality experiment were MCF-7, etc.

[0043] The following experiments and examples are used to further illustrate, but are not limited to, the present invention.

[0044] Example 1

[0045] (1) Synthesis route

[0046]

[0047] (2) Synthesis steps

[0048] Preparation of Compound 2: A 150 mL two-necked flask was filled with phenothiazine (1.99 g, 10 mmol), cesium carbonate (6.52 g, 20 mmol), and 40 mL of N,N-dimethylformamide under argon protection. The mixture was reacted at 50 °C for 1 hour. Then, 1,4-dibromotetrafluorobenzene (1.54 g, 5 mmol) was rapidly added, and the mixture was heated to 100 °C and reacted for 12 hours. After cooling to room temperature, the mixture was extracted three times with dichloromethane and water. The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane / petroleum ether (v / v = 1 / 4) as the eluent to give 3.16 g of a white solid, 95% yield. 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: In a 150 mL two-necked flask, under argon protection, 3,6-di-tert-butylcarbazole (2.79 g, 10 mmol), cesium carbonate (6.52 g, 20 mmol), and 40 mL of N,N-dimethylformamide were added, and the mixture was reacted at 50 °C for 1 hour. Compound 2 (3.33 g, 5 mmol) was then rapidly added, and the mixture was heated to 100 °C and reacted for 12 hours. After cooling to room temperature, the mixture was extracted three times with dichloromethane and water. The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane / petroleum ether (v / v = 1 / 2) as the eluent to give 5.81 g of a pale 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: Compound 3 (7.11 g, 6 mmol) and 60 mL of tert-butylbenzene were added to a 100 mL pressure-resistant bottle under argon protection, and the mixture was stirred for half an hour. Under ice bath conditions, a tert-butyllithium solution (9.23 mL, 1.30 M, 12 mmol) was slowly added, and the mixture was stirred for half an hour before being allowed to react at room temperature for 3 hours. Then, boron tribromide (1.14 mL, 12 mmol) was added at -40 °C, and the reaction mixture was stirred at room temperature for 3 hours. Under ice bath conditions, N,N-diisopropylethylamine (0.45 mL, 12 mmol) was added, and the reaction mixture was slowly brought back to room temperature, then heated to 150 °C and reacted for 12 hours. After cooling to room temperature, the reaction mixture was filtered through diatomaceous earth and extracted three times with dichloromethane and water. The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure. Separation was then performed by silica gel column chromatography to give 1.19 g of an orange-black solid (19% yield). 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, was prepared by dissolving the compound NIR-BN, DSPE-PEG, and NH2-PEG-FA obtained in Example 1 in THF to obtain a mixed solution. The mixed solution was injected into deionized water and sonicated for 10-15 min to obtain a lipid microemulsion. The lipid microemulsion was transferred into a dialysis bag (8KD-14KD) and dialyzed with deionized water for 30-35 h, with the deionized water being replaced every 2-3 h. This allowed the photosensitizer to be encapsulated by the polymer material and self-assembled into nanoparticles. After removing THF, the nanoparticles were lyophilized and stored for later use, thus obtaining the lipid nanoparticles NIR-BN@NPs.

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

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

[0055] A 20.0 μM aqueous solution of NIR-BN@NPs was prepared, and its absorption spectrum was measured using a UV spectrophotometer. The results showed that the absorption wavelength of the photosensitizer did not change significantly after it was prepared into nanomaterials. It can be excited by a 660 nm laser to generate photodynamic therapy and photothermal therapy.

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

[0057] Using DCFH-DA as the total reactive oxygen species indicator, the test solution was prepared with a concentration of 20.0 μM for the photosensitizer NIR-BN@NPs and a concentration of 5.0 μM for DCFH-DA. The test was conducted at 660 nm and 0.4 W / cm². 2 The photodynamic therapy (PDT) effect of NIR-BN@NPs was evaluated by the degree of degradation of DCFH-DA to DCF under laser irradiation. The results are shown in the figure. Under laser irradiation, the total reactive oxygen species indicator DCFH-DA induced by NIR-BN@NPs was converted to DCF, and the fluorescence signal at 525 nm under an excitation wavelength of 488 nm increased over time. This indicates that NIR-BN@NPs can generate reactive oxygen species and has good photodynamic therapy potential.

[0058] Example 3

[0059] Experiment on O2˙ˉ production by 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 prepared to be 20.0 μM, and the concentration of DCFH-DA was 5.0 μM. At 660 nm, 0.4 W / cm²... 2The photodynamic therapy (PDT) effect of NIR-BN@NPs was evaluated by the degree to which DHR 123 was oxidized to highly fluorescent DHR 123 under laser irradiation. The results are shown in the figure. Under laser irradiation, the superoxide anion reactive oxygen species indicator DHR 123 induced by NIR-BN@NPs was converted to highly fluorescent DHR 123, and the fluorescence signal at 529 nm increased over time at an excitation wavelength of 507 nm. This indicates that NIR-BN@NPs can generate superoxide anion reactive oxygen species and has good photodynamic therapy potential.

[0061] Example 4

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

[0063] A certain amount of NIR-BN@NPs was taken and diluted with water to a photosensitizer concentration of 120 μM. The photosensitizer was then tested at 660 nm and 0.6 W / cm². 2 Under laser irradiation, a temperature probe was inserted to monitor the temperature change of the system in real time over 10 minutes, and a temperature-time curve was plotted. The experimental results show that under light irradiation, the temperature of NIR-BN@NPs rises rapidly, from room temperature to 16℃ in 5 minutes and to 23℃ in 10 minutes, exhibiting excellent photothermal conversion effect.

[0064] Example 5

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

[0066] Example 4 was subjected to repeated light-cooling-light cycles, and the temperature change of the system was monitored. The experimental results showed that the temperature rise of NIR-BN@NPs remained stable after light-heating, cooling and then light-heating. The temperature rise remained stable for five experimental cycles, indicating that the system has a stable photothermal effect and can repeatedly generate a highly efficient photothermal conversion effect.

[0067] Example 6

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

[0069] Using human breast cancer cell line MCF-7 as an example, the dark cytotoxicity of NIR-BN@NPs lipid nanoparticles was investigated. MCF-7 cells were cultured in 10 wells per well. 5Cells were seeded at a density of 100 μL in 96-well plates. After 24 hours of culture, 100 μL of fresh culture medium containing lipid nanoparticles was added to each well (the photosensitizer concentration in each well after adding the culture medium was 1.0 μM, 5.0 μM, 10.0 μM, 15.0 μM, 25.0 μM, and 30.0 μM, respectively). After 48 hours of culture, 20 μL of MTT solution (prepared from sterile PBS buffer at a concentration of 5 mg / mL) was added to each well. After 4 hours of incubation, the culture medium was removed from each well, and 150 μL of DMSO was added to each well. The absorbance at 490 nm was recorded using a microplate reader to evaluate the cytotoxicity of NIR-BN@NPs. The results showed that when the photosensitizer concentration in the lipid nanoparticles reached 30 μM, the survival rate of MCF-7 cells and HepG-2 cells still reached over 70%. Figure 6 This indicates that NIR-BN@NPs lipid nanoparticles have low cytotoxicity.

[0070] Example 7

[0071] Phototoxicity assay of NIR-BN@NPs paper nanoparticles in tumor cells:

[0072] Using human breast cancer cell line MCF-7 as an example, the tumor phototherapy activity of NIR-BN@NPs lipid nanoparticles was investigated. MCF-7 cells were cultured in 10-1 cells per well. 5 Cells were seeded at a density of 100 μL in 96-well plates; after 24 h of culture, 100 μL of fresh culture medium containing lipid nanoparticles was added to each well (the photosensitizer concentrations in each well after adding the culture medium were 1.0 μM, 5.0 μM, 10.0 μM, 15.0 μM, 25.0 μM, and 30.0 μM, respectively); after 24 h of culture, the culture plate was placed at 660 nm (0.6 W / cm²). 2 Irradiation under a laser for 5 min was performed, with a light-protected culture plate as a control. After 24 h of culture, 20 μL of MTT solution (prepared from sterile PBS buffer at a concentration of 5 mg / mL) was added to each well; after 4 h of incubation, the culture medium was removed from each well, and 150 μL of DMSO was added to each well. The absorbance at 490 nm was recorded using a microplate reader to evaluate the phototoxicity of NIR-BN@NPs. The results showed that under light irradiation, the survival rate of MCF-7 cells decreased significantly with increasing NIR-BN concentration in the lipid nanoparticles. When the NIR-BN concentration in the lipid nanoparticles reached 25 μM, the survival rate of MCF-7 cells was only about 6%, indicating that NIR-BN@NPs of lipid nanoparticles have high phototoxicity and good tumor phototherapy activity.

Claims

1. A photosensitizer NIR-BN that simultaneously possesses photodynamic and photothermal therapeutic properties, characterized in that, With a multi-resonance fused-ring diboron-dinitrogen as the molecular framework and the introduction of sulfur atoms with heavy atom effects, its structure is as follows: 。 2. The preparation method of the photosensitizer NIR-BN with both photodynamic and photothermal therapeutic properties according to claim 1, characterized in that, Includes the following steps: Step 1: Using 1,4-dibromotetrafluorobenzene and phenothiazine as raw materials, in a Lewis base and solvent... N , N Compound 2 can be prepared by heating dimethylformamide to carry out a nucleophilic substitution reaction; Step 2: Using compounds 2 and 3,6-di-tert-butylcarbazole as raw materials, in a Lewis base and N , N Compound 3 can be prepared by heating dimethylformamide to carry out a nucleophilic substitution reaction; Step 3: Intermediate 3 undergoes a lithium halide exchange reaction via tert-butyllithium, followed by a boronization reaction with boron tribromide, and finally... N , N -Diisopropylethylamine, yielding the target molecule NIR-BN; The synthetic route is as follows: 。 3. The preparation method of the photosensitizer NIR-BN with both photodynamic and photothermal therapeutic properties according to claim 2, characterized in that, The nucleophilic substitution reaction temperature in steps one and two is 100-120℃.

4. A lipid nanoparticle NIR-BN@NPs, characterized in that, The photodynamic and photothermal bifunctional molecule NIR-BN as described in claim 1, distearate phosphatidylethanolamine-polyethylene glycol, and aminopolyethylene glycol folic acid were dissolved in tetrahydrofuran to obtain a mixed solution; the mixed solution was injected into deionized water and sonicated to obtain a lipid microemulsion; the lipid microemulsion was transferred into a dialysis bag and dialyzed with deionized water to obtain lipid nanoparticles NIR-BN@NPs.

5. The lipid nanoparticles NIR-BN@NPs according to claim 4, characterized in that: The mass ratio of the photodynamic and photothermal bifunctional compound NIR-BN, distearate phosphatidylethanolamine-polyethylene glycol, and aminopolyethylene glycol folic acid is 1:6-10:3-5.

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

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

8. The dye catalytic degradation agent according to claim 7, characterized in that, The dye organic compound is 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 as described in claim 4 or 5.

10. The application of the photothermal 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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