A near-infrared photothermal / photodynamic / chemotherapy combined nanoplatform for glioblastoma treatment and its preparation method

Abstract

This invention relates to the biomedical field and discloses a targeted nanodelivery system based on curcumin (Cur) and the near-infrared aggregation-induced emission (AIE) molecule BDTA, and its application in the treatment of glioblastoma (GBM). The nanoplatform comprises macrophage membrane-modified nanoparticles (MPMs@Cur-BDTA NPs). Curcumin and BDTA are coprecipitated, and macrophage membrane modification enhances tumor targeting. This nanoplatform combines photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy, achieving multiple therapeutic effects. Curcumin in this platform downregulates the expression of the heat shock protein HSP-70, enhancing PTT sensitivity. Furthermore, through the Förster resonance energy transfer (FRET) mechanism, it effectively increases photothermal conversion efficiency (87.6%) and singlet oxygen generation (1.7 times higher than the control group). In in vitro experiments on glioblastoma, this nanoplatform demonstrated synergistic therapeutic effects combining photothermal therapy, photodynamic therapy, and chemotherapy. The present invention provides an intelligent treatment platform that integrates photothermal therapy, photodynamic therapy and chemotherapy, providing an efficient and safe innovative treatment strategy for the precise treatment of glioblastoma.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine, and in particular to a near-infrared photothermal / photodynamic / chemotherapy combined nano-platform for treating glioblastoma and a preparation method thereof. Background Art

[0002] Glioblastoma (GBM) is the most common malignant primary brain tumor in the central nervous system, accounting for approximately 57% of all gliomas and 48% of primary malignant central nervous system tumors. GBM is highly invasive, prone to recurrence after treatment, and has an extremely poor clinical prognosis, making it one of the most lethal cancers.

[0003] Traditional treatments include surgical resection, radiotherapy, and chemotherapy, but these have limited efficacy and significant side effects. In recent years, photothermal therapy (PTT) and photodynamic therapy (PDT) combined with chemotherapy have emerged as new approaches for glioblastoma treatment. The synergistic effects of photothermal / photodynamic therapy can significantly enhance anti-tumor efficacy and mitigate multidrug resistance (MDR) while reducing the dose of chemotherapy drugs. However, current multifunctional therapy technologies still suffer from poor reproducibility and complex pharmacokinetics, limiting their diagnostic and therapeutic effectiveness. Summary of the Invention

[0004] To address the challenges of existing technologies, the present invention discloses a near-infrared photothermal / photodynamic / chemotherapy combined nanoplatform for glioblastoma treatment and its preparation method. The present invention provides a combined photothermal / photodynamic / chemotherapy nanoplatform based on curcumin and the near-infrared aggregation-induced emission molecule BDTA, achieving multiple therapeutic effects in tumor treatment.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions.

[0006] The present invention discloses a near-infrared aggregation-induced emission molecular compound, characterized in that the near-infrared aggregation-induced emission molecular compound is named BDTA and has the structural formula:

[0007] .

[0008] The present invention also discloses a method for preparing the above-mentioned near-infrared aggregation-induced emission molecule, which is characterized by comprising the following steps:

[0009] ;

[0010] Preparation of compound 1: Under nitrogen protection, 2-bromo-4-hexylthiophene (1.00 g, 4.05 mmol), 9,10-dihydro-9,9-dimethylacridine (0.85 g, 4.05 mmol), Pd2(dba)3 (0.38 g, 0.41 mmol), P(tBu)3 (0.23 g, 0.41 mmol) and Na t OBu (1.56 g, 16.20 mmol); the apparatus was vacuum-evacuated and filled with dry nitrogen three times to remove air. 40 mL of anhydrous toluene was then added to the flask, and the reaction was stirred at 120°C overnight. After completion of the reaction, the system was cooled to room temperature and quenched with an appropriate amount of deionized water. The system was then extracted three times with 50 mL of dichloromethane (DCM). The organic phases were combined and dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporation under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (dichloromethane / petroleum ether (v / v = 1 / 10)) to obtain the target compound 1.

[0011] Preparation of Compound 2: Under nitrogen, n-butyllithium (n-BuLi, 2.5 mL, 6 mmol, 2.4 M inhexane) was added dropwise to a flask containing Compound 1 (0.90 g, 2.40 mmol) and 30 mL of anhydrous tetrahydrofuran (THF). The mixture was kept at -78°C and stirred for 1 hour. Bu3SnCl (1.86 g, 6 mmol) was added in one portion. The system was warmed to room temperature and stirred for 12 hours. After completion of the reaction, ice-cold deionized water was added to quench the reaction. The mixture was extracted with 50 mL of n-hexane, and the organic phases were combined and dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporation to obtain the crude product Compound 2.

[0012] Preparation of compound BDTA: Under nitrogen protection, compound 2 (1.33 g, 2.00 mmol), 4,8-dibromo-benzo[1,2-c:4,5-c']bis[1,2,5]thiadiazole (0.28 g, 0.80 mmol), Pd2(dba)3 (0.38 g, 0.41 mmol), P(tBu)3 (0.23 g, 0.41 mmol) and Na t OBu (1.56 g, 16.20 mmol); under a dry nitrogen atmosphere, 20 mL of anhydrous toluene was added as the solvent; the system was heated to reflux and stirred for 24 hours; after completion of the reaction, the reaction was cooled to room temperature and the solvent was removed by rotary evaporation; the crude product was purified by silica gel column chromatography (dichloromethane / petroleum ether (v / v = 1 / 4) to obtain the target product BDTA.

[0013] The present invention also discloses an application of the above-mentioned near-infrared aggregation-induced emission molecular compound BDTA in the preparation of a near-infrared photothermal / photodynamic / chemotherapy combined nano-platform.

[0014] Furthermore, the nanoplatform has significant photothermal conversion ability and singlet oxygen generation ability under 635nm laser irradiation.

[0015] The present invention also discloses a near-infrared photothermal / photodynamic / chemotherapy combined nanoplatform for the treatment of glioblastoma, characterized in that the nanoplatform comprises: the aggregation-induced emission molecular compound BDTA described above or the aggregation-induced emission molecular compound BDTA prepared by the preparation method, as well as curcumin and macrophage membrane.

[0016] Furthermore, the BDTA molecule has balanced radiative transition ability, non-radiative transition ability and efficient intersystem crossing ability.

[0017] Furthermore, the Cur and BDTA achieve energy transfer through Förster resonance energy transfer (FRET) and inhibit the overexpression of heat shock proteins, thereby enhancing the effects of photothermal therapy and photodynamic therapy.

[0018] Furthermore, any of the above-mentioned near-infrared photothermal / photodynamic / chemotherapy combined nanoplatforms for treating glioblastoma is used in the preparation of drugs for treating glioblastoma.

[0019] The present invention also discloses a method for preparing the near-infrared photothermal / photodynamic / chemotherapy combined nano-platform for treating glioblastoma according to claim 5, characterized in that the method comprises the following specific steps:

[0020] Step 1: Prepare the near-infrared luminescent molecule BDTA: It is composed of benzobithiadiazole (BBT) as an electron acceptor, 9,10-dihydro-9,9-dimethylacridine (DDA) and thiophene (TH) as electron donors, and an alkyl group as a shielding group;

[0021] Step 2: Using DSPE-mPEG2000 as a template, BDTA and curcumin (Cur) were co-encapsulated to form core nanoparticles by nano-coprecipitation method;

[0022] Step 3: The extracted cell membrane is modified on the surface of the core nanoparticles by co-extrusion to form macrophage membrane-modified Cur-BDTA nanoparticles, namely MPMs@Cur-BDTA NPs.

[0023] Curcumin (Cur) is a plant polyphenol compound extracted from turmeric, exhibiting antiproliferative, antioxidant, and anti-inflammatory activities. The potential of curcumin in the treatment of glioblastoma has been demonstrated in multiple preclinical studies. Its mechanisms of action include inducing cell cycle arrest, triggering apoptosis, promoting autophagy, and disrupting key molecular signaling pathways. Furthermore, as a heat shock protein inhibitor, curcumin can enhance tumor sensitivity to photothermal therapy and significantly improve its efficacy.

[0024] Phototherapy, a method for treating diseases and promoting recovery through photochemical or photophysical reactions, boasts precise and minimally invasive treatments. However, traditional phototherapy drugs often suffer from poor photostability and high biotoxicity. Aggregation-induced emission molecules (AIEgens) offer an ideal candidate for phototherapy due to their excellent luminescence efficiency, photothermal conversion capabilities, and biocompatibility. By optimizing the energy dissipation pathways of AIEgens through molecular design, multifunctional integration of photothermal therapy and photodynamic therapy can be achieved.

[0025] Compared with the prior art, the present invention has the following beneficial effects.

[0026] The BDTA molecule disclosed in the present invention is composed of benzobithiadiazole (BBT) as an electron acceptor, 9,10-dihydro-9,9-dimethylacridine (DDA) and thiophene (TH) as electron donors, and an alkyl group as a shielding group. It has balanced radiative transition ability, non-radiative transition ability and efficient intersystem crossing ability.

[0027] The nanoplatform provided by the present invention has significant photothermal conversion capabilities under 635nm laser irradiation, with a photothermal conversion efficiency of up to 87.6%. The nanoplatform provided by the present invention generates 1.7 times more singlet oxygen than control nanoparticles without curcumin.

[0028] This invention provides a nanoplatform that combines the AIE molecule BDTA with curcumin and enhances its tumor targeting through macrophage membrane modification. Curcumin not only downregulates the expression of the heat shock protein HSP-70, increasing PTT sensitivity, but also enhances singlet oxygen generation and photothermal conversion efficiency through the Förster resonance energy transfer mechanism, thereby improving the synergistic effect of photothermal and photodynamic therapy. This invention combines photodiagnosis and therapy with natural small molecules, providing new insights into the precision treatment of glioblastoma. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 UV-visible absorption and fluorescence spectra of compound BDTA.

[0030] Figure 2 Aggregation-induced emission spectrum of compound BDTA.

[0031] Figure 3 Transient decay curve of compound BDTA.

[0032] Figure 4 FRET effect between Cur and BDTA.

[0033] Figure 5 Uptake of nanoparticles in C6 cells.

[0034] Figure 6 The photothermal conversion capability of the nanoplatform. A is the temperature-time curve at different concentrations; B is the temperature-time curve at different powers; C is the photostability curve; and D is the time-Lnθ curve of the cooling curve.

[0035] Figure 7 Singlet oxygen generation capability of the nanoplatform.

[0036] Figure 8 HSP-70 expression.

[0037] Figure 9 In vitro synergistic therapeutic effect of the nanoplatform. A is the cell viability at different concentrations; B is the cell apoptosis rate detected by flow cytometry. DETAILED DESCRIPTION

[0038] The present invention is further described in detail below with reference to specific embodiments. However, this should not be construed as limiting the scope of the present invention to the following embodiments, as all technologies implemented based on the present invention fall within the scope of the present invention.

[0039] Unless otherwise specified, all reagents and materials used in the present invention are commercially available.

[0040] Example 1. Preparation of BDTA.

[0041] 1. The structural formula of BDTA is:

[0042] .

[0043] 2. The synthesis reaction formula of the BDTA molecule of the present invention is as follows:

[0044] .

[0045] 3. Preparation process of BDTA molecules described in the present invention.

[0046] 1. Preparation of compound 1, the steps are as follows:

[0047] Under nitrogen protection, 2-bromo-4-hexylthiophene (1.00 g, 4.05 mmol), 9,10-dihydro-9,9-dimethylacridine (0.85 g, 4.05 mmol), Pd2(dba)3 (0.38 g, 0.41 mmol), P( t Bu)3 (0.23 g, 0.41 mmol) and Na t OBu (1.56 g, 16.20 mmol). The apparatus was evacuated under vacuum and filled with dry nitrogen three times to remove air. 40 mL of anhydrous toluene was then added to the flask, and the reaction was stirred at 120°C overnight. After completion of the reaction, the mixture was cooled to room temperature, quenched with an appropriate amount of deionized water, and then extracted three times with dichloromethane (DCM). The organic phases were combined and dried over anhydrous sodium sulfate. After removing the solvent by rotary evaporation under reduced pressure, the crude product was purified by silica gel column chromatography (dichloromethane / petroleum ether (v / v = 1 / 10)) to obtain the target compound in a 60% yield.

[0048] 1 H NMR (400 MHz, CDCl3) δ 7.48 (d, J = 1.7 Hz, 1H), 7.46 (d, J = 1.6 Hz,1H), 7.10 (ddd, J = 8.3, 7.2, 1.6 Hz, 2H), 7.04–6.98 (m, 3H), 6.90 (d, J = 1.7 Hz,1H), 6.72 (d, J = 1.3 Hz, 1H), 6.70 (d, J = 1.3 Hz, 1H), 2.69 (t, J = 7.6 Hz, 2H), 1.70 (s, 6H), 1.46–1.28 (m, 8H), 0.96–0.92 (m, 3H).

[0049] 2. Compound 2 was prepared as follows:

[0050] Under nitrogen, n-butyllithium (n-BuLi, 2.5 mL, 6 mmol, 2.4 M in hexane) was added dropwise to a flask containing compound 1 (0.90 g, 2.40 mmol) and 30 mL of anhydrous tetrahydrofuran (THF). The mixture was maintained at -78°C with stirring for 1 hour. Subsequently, BuSnCl (1.86 g, 6 mmol) was added in one portion. The system was allowed to warm to room temperature and stirred for 12 hours. After completion of the reaction, ice-cold deionized water was added to quench the reaction. The mixture was extracted with n-hexane, and the organic phases were combined and dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporation, and the crude product was used directly in the next reaction.

[0051] 3. Preparation of compound BDTA, the steps are as follows:

[0052] Under nitrogen protection, compound 2 (1.33 g, 2.00 mmol), 4,8-dibromo-benzo[1,2-c:4,5-c']bis[1,2,5]thiadiazole (0.28 g, 0.80 mmol), Pd2(dba)3 (0.38 g, 0.41 mmol), P( t Bu)3 (0.23 g, 0.41 mmol) and Na t OBu (1.56 g, 16.20 mmol). Under a dry nitrogen atmosphere, 20 mL of anhydrous toluene was added as the solvent. The system was heated to reflux and stirred for 24 hours. After completion of the reaction, the mixture was cooled to room temperature and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography (dichloromethane / petroleum ether (v / v = 1 / 4)) to obtain the target product, BDTA, in a 33% yield.

[0053] 1 H NMR (400 MHz, CDCl3) δ 7.47–7.46 (m, 1H), 7.45–7.44 (m, 2H), 7.43(s, 2H), 7.42 (d, J = 1.4 Hz, 1H), 7.24–7.23 (m, 1H), 7.22–7.21 (m, 2H), 7.20(t, J = 1.1 Hz, 1H), 7.07 (d, J = 1.5 Hz, 2H), 7.06 (d, J = 1.4 Hz, 4H), 7.04 (d, J =1.5 Hz, 2H), 1.42 (d, J= 4.9 Hz, 4H), 1.37 (s, 2H), 1.33 (d, J = 2.9 Hz, 2H),1.29 (d, J = 3.3 Hz, 6H), 1.26 (s, 18H), 0.89 (d, J = 6.4 Hz, 2H). 13 C NMR (101MHz, CDCl3) δ 134.14, 130.81, 130.18, 127.64, 77.38, 77.07, 76.75. m / z: calcdforC 56 H 56 N6S4[M+Na], 963.3347; found, 963.3353.

[0054] Example 2. Preparation method of the nanoplatform MPMs@Cur-BDTA NPs described in the present invention.

[0055] 1. The extraction and purification steps of macrophage membranes are as follows: obtain RAW264.7 cell suspension and dilute it to 5×10 7 Cells were cultured at a concentration of 100 μg / mL and incubated on ice overnight under hypotonic conditions. The suspension was then extruded 30 times through a liposome extruder without a polycarbonate membrane to produce a homogenate. A 1M sucrose solution was added to the homogenate to a final concentration of 0.25M. The homogenate was centrifuged at 2000 g for 20 minutes at 4°C, and the supernatant was collected. The supernatant was centrifuged multiple times to remove impurities such as residual nuclear organelles. The supernatant was then centrifuged at 3000 g at 4°C to obtain the precipitate, the macrophage membranes. Finally, the precipitate was washed with ice-cold TM buffer and centrifuged to obtain purified macrophage membranes (MPMs).

[0056] 2. Preparation of the nanoplatform. The specific steps are as follows:

[0057] 1 μmol BDTA and 1 μmol curcumin (Cur) were dissolved in 100 μL tetrahydrofuran (THF), and 20 mg DSPE-mPEG2000 was dissolved in 300 μL THF. The two solutions were mixed, sonicated, and then added dropwise to 5 mL deionized water to form nanoparticles (Cur-BDTA NPs). The THF was then completely removed by nitrogen purging, and the mixture was dialyzed for 24 hours to remove unencapsulated free molecules. Finally, macrophage membranes and Cur-BDTA NPs were co-extruded multiple times through a 220 nm polycarbonate membrane to successfully prepare MPMs@Cur-BDTA NPs.

[0058] Example 3 Performance experiment of the nano-platform MPMs@Cur-BDTA NPs described in the present invention.

[0059] 1. Reagents

[0060] C6 cells and their culture medium, phenylmethanesulfonyl fluoride (PMSF), Cell Counting Kit-8 (CCK-8), Annexin V-FITC / PI apoptosis detection kit, Hoechst 33342 staining solution, DiI cell membrane red fluorescence staining kit, and phosphate-buffered saline (PBS, pH 7.4) were all provided by Wuhan Servicebio. C6 cells were used as a tumor cell model to study the efficacy of the nanoplatform in glioma therapy. The CCK-8 kit was used to assess cell viability, quantifying cell survival under different treatment conditions by correlating color changes with viable cell counts. The Annexin V-FITC / PI kit accurately distinguishes cells in the early and late stages of apoptosis, providing a basis for in-depth understanding of nanoplatform-induced apoptosis. A rat heat shock protein 70 (HSP-70) ELISA kit was purchased from Shanghai Jonlnbio and used to examine the inhibitory effect of curcumin on HSP-70 expression.

[0061] 2. Methods

[0062] 1. UV-visible absorption spectroscopy and fluorescence spectroscopy tests.

[0063] a. Weigh 0.0080 g of BDTA to prepare 10 mL of 1 × 10 -3 mol / L THF solution.

[0064] b. Take 0.5mL of the prepared 1×10 -3 mol / L BDTA solution, prepare 1×10 -5 mol / L tetrahydrofuran solution and tetrahydrofuran solutions with different water contents were prepared for the determination of optical properties.

[0065] 2. Cellular uptake.

[0066] a. C6 glioma cells were plated at 1×10 5 The cells were seeded in a 12-well plate at a density of 100 cells / well and cultured overnight under appropriate culture conditions (37°C, 5% CO2) to allow the cells to adhere to the wall and grow well.

[0067] b. Then, the cells were incubated with PBS, 0.2 μg / mL BDTA, Cur-BDTA NPs, or MPMs@Cur-BDTA NPs for 5 min, respectively.

[0068] c. After incubation, gently wash the cells twice with PBS to remove unbound material. Collect the cells, resuspend them in an appropriate amount of PBS, and analyze them using flow cytometry. Flow cytometry precisely quantifies nanoparticle uptake by cells by detecting specific fluorescent signals emitted by nanoparticles bound to the cell surface or internally, thereby assessing differences in the uptake efficiency of different nanomaterials in C6 cells.

[0069] 3. Photothermal performance evaluation method.

[0070] a. To evaluate the photothermal performance of MPMs@Cur-BDTA NPs, aqueous solutions of nanoparticles with different concentrations (10, 25, 50, 100, and 200 μg / mL) were prepared, and 0.5 mL of each solution was placed in a cuvette.

[0071] b. Using 635nm laser (1.00W / cm 2 ) Nanoparticle solutions of different concentrations were irradiated for 5 minutes. The infrared thermal imager was used to record the changes in the surface temperature of the solution over time in real time, and the temperature-time curves at different concentrations were drawn.

[0072] c. A 0.5 mL aqueous solution of MPMs@Cur-BDTA NPs with a fixed concentration of 200 μg / mL was stirred at different power densities (0.25, 0.5, 0.75, 1 W / cm 2 ) for 5 minutes. Use an infrared thermal imager to continuously record temperature changes during irradiation. Based on the temperature change data, plot temperature-time curves at different powers.

[0073] d. A 0.5 mL aqueous solution of MPMs@Cur-BDTA NPs with a fixed concentration of 200 μg / mL was irradiated with a 635 nm laser (1.0 W / cm 2 ) for five on / off cycles. An infrared thermal imager continuously recorded temperature changes during irradiation. A temperature-time curve was plotted based on the temperature change data. The photothermal conversion efficiency was calculated based on the cooling curve.

[0074] 4. Singlet oxygen monitoring.

[0075] a. Prepare solutions of MPMs@BDTA NPs, MPMs@Cur-BDTA NPs, and methylene blue (MB). Use a spectrophotometer to adjust the concentration of the solution so that its absorbance at 635 nm is approximately 0.2.

[0076] b. Add 60 μL of 1.0 mg / mL 1,3-diphenylisobenzofuran (DPBF) to each solution.

[0077] c. Place the sample at a power of 1.00W / cm 2 The samples were irradiated with a 635nm laser for 150 seconds. During the irradiation process, the absorbance at 410nm was measured every 30 seconds using a spectrophotometer to monitor the oxidation of DPBF. The absorbance data at different time points were collected and analyzed to plot an absorbance-time curve.

[0078] 5. Determination of Heat Shock Protein Expression.

[0079] a. Gently wash adherent cells with ice-cold PBS, then trypsinize and collect the cells by centrifugation at 1000 g for 5 minutes.

[0080] b. Wash the collected cells 3 times with pre-cooled PBS, and 6 200 μL PBS was added to each cell to resuspend it and the cells were disrupted by cell disruptor.

[0081] c. Centrifuge the extract at 1500g for 10 minutes at 2°C. Take the supernatant and treat it with a rat heat shock protein 70 (HSP-70) enzyme-linked immunosorbent assay kit. Measure the absorbance at a wavelength of 450 nm.

[0082] 6. In vitro synergistic therapeutic effect.

[0083] a. Cells were plated at 1×10 5 Cells were seeded in 12-well plates at a density of 100 cells / well and cultured overnight to promote cell attachment.

[0084] b. On the next day, the culture medium was replaced with fresh culture medium containing different concentrations of Cur NPs, MPMs@BDTA NPs, or MPMs@Cur-BDTA NPs.

[0085] c. After 6 hours of incubation, the cells were exposed to 635 nm laser (1.0 W / cm 2 ) for 5 minutes.

[0086] d. Cell viability was assessed using CCK-8 assay (n = 6).

[0087] e. Flow cytometry was used to quantify cell apoptosis at a nanoparticle concentration of 60 µmol / mL. Flow cytometry can distinguish apoptotic cells, necrotic cells, and live cells by staining cells (Annexin V-FITC / PI staining).

[0088] 3. Conclusion

[0089] BDTA has a significant aggregation-induced emission effect, and its radiative transition rate, non-radiative transition rate, and intersystem crossing rate are 1.8×107 s -1 , 7.0×10 7 s -1 , 9.1×10 7 s -1 . There is a potential Förster resonance energy effect between curcumin and BDTA, which helps to sensitize photothermal therapy and photodynamic therapy. Cell uptake experiments showed that macrophage membrane functionalization enhanced the interaction between nanoparticles and C6 cells and improved uptake efficiency. In terms of photothermal performance, concentration and laser power have a significant effect on its photothermal conversion, and the photothermal stability is good, with a photothermal conversion efficiency of 87.6%. Singlet oxygen monitoring shows that the singlet oxygen quantum yield of MPMs@Cur-BDTA NPs is higher than that of MPMs@BDTA NPs. In terms of inhibiting heat shock proteins, Cur can effectively inhibit the expression of HSP-70 in C6 cells and enhance the sensitivity of tumors to photothermal therapy. In vitro synergistic treatment experiments show that the synergistic treatment effects of photothermal, photodynamic and chemotherapy in MPMs@BDTANPs are significant, and the introduction of Cur can effectively improve the treatment effect and reduce the required concentration.

[0090] The foregoing description is merely a preferred embodiment of the present invention and is not intended to limit the scope of the present invention. Those skilled in the art will readily appreciate that the present invention is susceptible to various modifications and variations. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present invention shall be included within the scope of protection of the present invention.

Claims

1. A near-infrared aggregation-induced emission molecular compound, characterized in that: The near-infrared aggregation-induced emission molecular compound is named BDTA, and its structural formula is: 。 2. A method for preparing the near-infrared aggregation-induced emission molecule according to claim 1, characterized in that: The steps include: Preparation of compound 1: Under nitrogen protection, in a 100 mL two-necked flask, 1.00 g (4.05 mmol) of 2-bromo-4-hexylthiophene, 0.85 g (4.05 mmol) of 9,10-dihydro-9,9-dimethylacridine, 0.38 g (0.41 mmol) of Pd2(dba)3, 0.23 g (0.41 mmol) of P(tBu)3 and 1.56 g (16.20 mmol) of Na t OBu; the apparatus was vacuum-evacuated and filled with dry nitrogen three times to remove air; 40 mL of anhydrous toluene was then added to the flask, and the reaction was stirred at 120°C overnight; after completion of the reaction, the system was cooled to room temperature, an appropriate amount of deionized water was added to the system for quenching, and then extracted three times with 50 mL of dichloromethane (DCM); the organic phases were combined and dried over anhydrous sodium sulfate; the solvent was removed by rotary evaporation under reduced pressure, and the resulting crude product was purified by silica gel column chromatography to obtain the target compound 1; Preparation of Compound 2: Under nitrogen, 2.5 mL (6 mmol) of n-BuLi (2.4 M in hexane) was added dropwise to a flask containing 0.90 g (2.40 mmol) of Compound 1 and 30 mL of anhydrous tetrahydrofuran (THF). The temperature was maintained at -78°C and stirred for 1 hour. 1.86 g (6 mmol) of Bu3SnCl was added in one portion. The system was warmed to room temperature and stirred for 12 hours. After completion of the reaction, ice-cold deionized water was added to quench the reaction. The mixture was extracted with 50 mL of n-hexane, and the organic phases were combined and dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporation to obtain the crude product, Compound 2. Preparation of compound BDTA: Under nitrogen protection, 1.33 g (2.00 mmol) of compound 2, 0.28 g (0.80 mmol) of 4,8-dibromo-benzo[1,2-c:4,5-c']bis[1,2,5]thiadiazole, 0.38 g (0.41 mmol) of Pd2(dba)3 (), 0.23 g (0.41 mmol) of P( t Bu)3 and 1.56g (16.20mmol) of Na t OBu; under a dry nitrogen atmosphere, 20 mL of anhydrous toluene was added as a solvent; the system was heated to reflux and stirred for 24 hours; after completion of the reaction, the reaction was cooled to room temperature and the solvent was removed by rotary evaporation; the crude product was purified by silica gel column chromatography to obtain the target product BDTA.

3. Use of the near-infrared aggregation-induced emission molecular compound BDTA according to claim 1 in the preparation of a near-infrared photothermal / photodynamic / chemotherapy combined nanoplatform.

4. The use according to claim 3, characterized in that The nano-platform has significant photothermal conversion ability and singlet oxygen generation ability under 635nm laser irradiation.

5. A near-infrared photothermal / photodynamic / chemotherapy combined nanoplatform for the treatment of glioblastoma, characterized in that: The nano-platform comprises: the aggregation-induced luminescence molecular compound according to claim 1 or the aggregation-induced luminescence molecular compound prepared by the preparation method according to claim 2, curcumin, and macrophage membrane.

6. The nanoplatform according to claim 5, characterized in that The BDTA molecule has balanced radiative transition ability, non-radiative transition ability and intersystem crossing ability.

7. The nanoplatform according to claim 5, characterized in that The Cur and BDTA achieve energy transfer through Förster resonance energy transfer (FRET) and inhibit the overexpression of heat shock proteins, thereby enhancing the effects of photothermal therapy and photodynamic therapy.

8. Use of the near-infrared photothermal / photodynamic / chemotherapy combined nanoplatform for treating glioblastoma according to any one of claims 5 to 7 in the preparation of a drug for treating glioblastoma.

9. A method for preparing the near-infrared photothermal / photodynamic / chemotherapy combined nano-platform for treating glioblastoma according to claim 5, characterized in that: The method specifically comprises the following steps: Step 1: Prepare the near-infrared luminescent molecule BDTA: It is composed of benzobithiadiazole (BBT) as an electron acceptor, 9,10-dihydro-9,9-dimethylacridine (DDA) and thiophene (TH) as electron donors, and an alkyl group as a shielding group; Step 2: Using DSPE-mPEG2000 as a template, BDTA and curcumin (Cur) were co-encapsulated to form core nanoparticles by nano-coprecipitation method; Step 3: The extracted cell membrane is modified on the surface of the core nanoparticles by co-extrusion to form macrophage membrane-modified Cur-BDTA nanoparticles, namely MPMs@Cur-BDTA NPs.

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