A type of water-soluble near-infrared integrated diagnostic and therapeutic probe molecule and its preparation method and application

Abstract

The present invention discloses a class of water-soluble near-infrared integrated diagnostic and therapeutic probe molecules, as well as a preparation method and application thereof. The chemical structural formula thereof is: wherein A is S or Se, and n is 4, 5, ..., 19, 20. It has a D‑π‑A‑π‑D structure, and the triphenylamine group in the molecule acts as an electron donor and rotor unit, distorting the molecular skeleton. The ethylene glycol segment can be used to adjust the hydrophilicity of the probe. The selection of a strong electron acceptor can effectively reduce the band gap of the molecule and extend the absorption / emission wavelength to the near-infrared region. The water-soluble integrated diagnostic and therapeutic probe molecule of the present invention has a simple synthesis route, low cost, and good biocompatibility, and can be used for near-infrared second-zone fluorescence imaging and optical diagnosis and treatment of tumors such as brain gliomas under near-infrared light excitation.

Description

Technical Field

[0001] The present invention relates to the technical field of fluorescent probe molecules, and in particular to a class of water-soluble near-infrared integrated diagnosis and treatment probe molecules and a preparation method and application thereof. Background Art

[0002] Glioblastoma multiforme (GBM) is the most common primary tumor of the central nervous system, accounting for approximately 40% of the total incidence of intracranial malignant tumors. According to the World Health Organization's classification, GBM is a grade IV histological malignancy, and the median survival of glioblastoma patients is only about 12 months. Although various treatments, including surgery, radiotherapy, chemotherapy, and other emerging methods such as photodynamic therapy (PDT), have been used to treat GBM, their effectiveness is far below expectations due to the short blood circulation, limited blood-brain barrier penetration, and insufficient tumor uptake, which results in an inability to obtain effective drug concentrations. Intravenous therapeutic drugs crossing the blood-brain barrier and other biological barriers to enter the tumor remain a challenge in the treatment of GBM.

[0003] Over the past few decades, a large number of materials with long excitation and emission wavelengths have been developed, such as carbon nanotubes, silver sulfide and lead sulfide quantum dots, rare earth-doped upconversion nanoparticles, and organic molecules. Organic small molecule materials have become an excellent choice for constructing phototherapy materials due to their ease of modification, precise structure / purity, and good biocompatibility. Among them, near-infrared organic fluorescent molecules have low background and toxicity risks, high spatial resolution, and deep tissue penetration, especially in the near-infrared second region (NIR-II, 1000-1700nm) window, which shows even better tissue penetration and has great application prospects in the diagnosis and treatment of GBM.

[0004] However, the vast majority of currently reported NIR-II diagnostic and therapeutic probes are insoluble in water and require nanofabrication, such as encapsulation with amphiphilic polymers, to form water-dispersible nanoparticles for use in biological research. However, the nanofabrication process is cumbersome and subject to significant batch-to-batch variability. Designing NIR-II probes that are directly water-soluble could overcome these challenges and hold significant promise for the integrated diagnosis and treatment of GBM. Summary of the Invention

[0005] The technical problem to be solved by the present invention is that the existing water-soluble NIR-II integrated diagnostic and therapeutic probes are mostly polymers with uncertain composition and purity, making subsequent pharmacokinetic studies difficult; in addition, there is a lack of a universal synthesis method. The present invention aims to develop a new method for preparing water-soluble NIR-II diagnostic and therapeutic probes and expand new applications.

[0006] The technical solution adopted by the present invention to solve this technical problem is: by introducing ethylene glycol segments, a new water-soluble NIR-II organic probe small molecule is modularly constructed, and the specific structure is: Wherein, A is S or Se, and n is 4, 5,…, 19, 20.

[0007] The present invention also provides a method for preparing a water-soluble NIR-II organic probe small molecule, the method comprising the following steps:

[0008] Compound VI, N-sulfenylaniline, and trimethylsilyl chloride are added to an ultra-dry pyridine solvent, and heated and stirred under the protection of an inert gas to obtain PEG-TD; Compound VI and selenium dioxide are added to ultra-dry tetrahydrofuran and ultra-dry ethanol solvents, and stirred and heated under the protection of an inert gas to obtain PEG-SD.

[0009] Optionally, in the method for preparing the water-soluble NIR-II organic probe small molecules PEG-TD and PEG-SD, the stirring and reflux temperature is 70-90° C., and the stirring and reflux time is 12-24 h.

[0010] Optionally, the preparation method of the water-soluble NIR-II organic probe small molecule PEG-TD, wherein the molar ratio of the compound VI, N-sulfenylaniline, and trimethylchlorosilane is 1:2:10; the preparation method of the water-soluble NIR-II organic probe small molecule PEG-TD, wherein the molar ratio of the compound VI and selenium dioxide is 1:10.

[0011] Optionally, the method for preparing the water-soluble NIR-II organic probe small molecules PEG-TD and PEG-SD, wherein the steps of purifying the crude products to obtain the novel near-infrared second region excitation aggregation-induced emission material include:

[0012] The crude product is purified by silica gel column chromatography using a mixed solution of dichloromethane and methanol as an eluent to obtain the novel near-infrared second-region excitation aggregation-induced emission material.

[0013] Optionally, in the method for preparing the water-soluble NIR-II organic probe small molecules PEG-TD and PEG-SD, the volume ratio of dichloromethane to methanol in the eluent is 100:1-10:1.

[0014] Beneficial effects: The water-soluble NIR-II organic probe small molecule provided by the present invention has a D-π-A-π-D (D is an electron donor, A is an electron acceptor) structure. The introduction of ethylene glycol oligomer segments imparts controllable hydrophilicity to the material. The resulting water-soluble material can self-assemble into nanoparticles in the aqueous phase. NIR-II fluorescence imaging shows that the material can be enriched in mouse brain gliomas. In addition, the novel water-soluble NIR-II organic probe small molecule provided by the present invention also has good photothermal generation capacity and photodynamic therapy effect, which can achieve efficient optical treatment of GBM. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 This is a synthetic route for the novel water-soluble NIR-II organic probe small molecule provided in Example 1 of the present invention;

[0016] Figure 2 This is a hydrogen nuclear magnetic resonance spectrum of the water-soluble NIR-II organic probe small molecule PEG-TD prepared in Example 1 of the present invention in tetrahydrofuran;

[0017] Figure 3 This is a hydrogen nuclear magnetic resonance spectrum of the water-soluble NIR-II organic probe small molecule PEG-SD prepared in Example 1 of the present invention in tetrahydrofuran;

[0018] Figure 4 This is the carbon NMR spectrum of the water-soluble NIR-II organic probe small molecule PEG-TD prepared in Example 1 of the present invention in tetrahydrofuran

[0019] Figure 5 This is the carbon NMR spectrum of the water-soluble NIR-II organic probe small molecule PEG-SD prepared in Example 1 of the present invention in tetrahydrofuran;

[0020] Figure 6 This is a MALDI-TOF-MS mass spectrum of the water-soluble NIR-II organic probe small molecule PEG-TD prepared in Example 1 of the present invention;

[0021] Figure 7 This is a MALDI-TOF-MS mass spectrum of the water-soluble NIR-II organic probe small molecule PEG-SD prepared in Example 1 of the present invention;

[0022] Figure 8 These are the ultraviolet absorption and fluorescence emission spectra of the PEG-TD and PEG-SD materials prepared in Example 1 of the present invention, indicating that the prepared compounds have a long-wavelength emission effect in the near-infrared region II.

[0023] Figure 91 is a graph showing the fluorescence signal changes at different concentrations of the PEG-TD material prepared in Example 1 of the present invention. It can be seen that the synthesized material has the property of aggregation-induced luminescence.

[0024] Figure 10 The cell survival rate of the PEG-TD material prepared in Example 1 of the present invention and GL261 cells under different treatment modes is shown in FIG. Figure 10 It can be seen that PEG-TD has excellent cell compatibility and has strong phototoxicity under light irradiation.

[0025] Figure 11 This is a fluorescent imaging image of the brain of mice with orthotopic glioma after the PEG-TD material prepared in Example 1 of the present invention was injected. Figure 11 It can be seen that PEG-TD has strong penetrating ability and can be used for imaging diagnosis of brain glioma.

[0026] Figure 12 This is a diagram showing the effect of PEG-TD prepared in Example 1 of the present invention being used for photothermal / photodynamic synergistic anti-mouse brain glioma. DETAILED DESCRIPTION

[0027] The novel water-soluble NIR-II organic probe small molecule preparation method and application provided by the present invention are further described in detail below to make the purpose, technical solutions and advantages of the present invention clearer and clearer. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention. The experimental methods for which specific conditions are not specified in the following examples are selected according to conventional methods and conditions, or according to the product specifications. In addition, it should be understood that after reading the contents taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the claims attached to this application.

[0028] Most currently reported NIR-II diagnostic and therapeutic probes are insoluble in water and require nanofabrication, such as encapsulation with amphiphilic polymers, to form water-dispersible nanoparticles for use in biological research. However, the nanofabrication process is cumbersome and subject to significant batch-to-batch variability. Designing NIR-II probes that are directly water-soluble could overcome these challenges and hold significant promise for the integrated diagnosis and treatment of GBM.

[0029] The present invention provides a water-soluble NIR-II organic probe small molecule, the specific structure of which is: Where A is S or Se, and n is 4, 5, …, 19, or 20. It has a D-π-A-π-D structure, with the triphenylamine group acting as an electron donor and rotor unit, distorting the molecular backbone. The ethylene glycol segment can be used to adjust the hydrophilicity of the probe. The use of a strong electron acceptor can effectively reduce the band gap of the molecule and extend the absorption / emission wavelength into the near-infrared region.

[0030] The present invention also provides a method for preparing a novel water-soluble NIR-II organic probe small molecule, comprising the steps of:

[0031] Adding compound VI, N-sulfenylaniline, and trimethylsilyl chloride to an ultra-dry pyridine solvent, or adding compound VI and selenium dioxide to an ultra-dry tetrahydrofuran and ultra-dry ethanol solvent, heating to 70-90° C. under inert gas protection, and stirring overnight to obtain a crude product;

[0032] Purifying the crude product to obtain the water-soluble near-infrared integrated diagnostic and therapeutic probe molecule;

[0033] The structural formula of the compound VI is:

[0034]

[0035] In the present invention, compound VI can react with N-sulfenylaniline or selenium dioxide to generate the target product (water-soluble near-infrared diagnostic and therapeutic integrated probe molecule). The molar ratio of compound VI, N-sulfenylaniline, and trimethylchlorosilane can be 1:2:5, 1:2:10, 1:2:15, 1:3:5, 1:3:10, 1:3:15, etc., and controlling the ratio can be more conducive to the reaction.

[0036] The molar ratio of the compound VI to selenium dioxide can be 1:10, 1:15, 1:20, etc.

[0037] The crude product obtained in the preparation process is eluted with a mixture of dichloromethane and methanol as the eluent, and the volume ratio of dichloromethane to methanol is 100:1-10:1. By adjusting the composition of the eluting machine, the crude product can be better eluted.

[0038] The technical solution provided by the present invention is further explained below through specific preparation examples.

[0039] Example 1

[0040] The preparation method of compounds PEG-TD and PEG-SD specifically comprises the following steps:

[0041] Step 1: Synthesis of Compound I

[0042] 4-Bromo-N,N-di(4-methoxyphenyl)aniline (10 g, 25.8 mmol) was added to a DCM (50 mL) solution, and boron tribromide (18.829 g, 76 mmol) was slowly added at 0°C. The resulting mixture was stirred overnight and then cooled with water. The mixture was extracted three times with DCM and dried over anhydrous sodium sulfate. The crude product was purified by silica gel column chromatography (DCM:MeOH = 20:1) to a green solid (8.5 g, 93%). 1 H NMR (600MHz, DMSO-d6) δ9.39(s,2H),7.28-7.25(m,2H),6.97-6.93(m,4H),6.77-6.74(m,4H),6.60-6.58(m,2H). 13 C NMR (151MHz, DMSO-d6) δ154.92,148.86,138.50,131.93,127.92,119.81,116.79,110.18.

[0043] Step 2: Synthesis of Compound II

[0044] A solution of polyethylene glycol monomethyl ether (10 g, 23.3 mmol) was added to dry DCM (50 mL), followed by triethylamine (11.61 mL, 27.96 mmol) at 0°C. After stirring for 2 h, 4-formyl chloride (4.45 g, 23.3 mmol) was added, and the reaction was continued for 18 h. After completion of the reaction, water was added, and the mixture was washed three times with dichloromethane. The organic phase was combined, dried over Na2SO4, and the solvent was evaporated under reduced pressure. The product was separated by silica gel column chromatography (DCM:MeOH = 20:1) to afford Compound II (12 g, 88%) as a colorless, transparent, oily liquid. 1 H NMR (400MHz, Chloroform-d) δ7.79 (d, J = 8.2 Hz, 2H), 7.36 (d, J = 8.1 Hz, 2H), 4.17-4.13 (m, 2H), 3.69-3.53 (m, 34H), 3.37 (s, 3H), 2.45 (s, 3H). 13 C NMR (101MHz, Chloroform-d) δ144.52,132.65,129.56,127.65,71.60,70.39,70.27,70.23,70.17,69.00,68.33,58.70.

[0045] Step 3: Synthesis of Compound III

[0046] In a 50 mL two-necked round-bottom flask, I (0.1775 g, 1 mmol) and MeCN (20 mL) were combined, followed by the addition of II (0.4951 g, 3 mmol) and KCO (0.2070 g, 1.5 mmol). The mixture was heated to 85°C and stirred overnight. After completion of the reaction, the solvent was removed by rotary evaporation. Purification by chromatography (PE:DCM = 10:1) afforded the compound as a colorless, transparent oil (0.245 g, 94%). 1 H NMR(500MHz,Chloroform-d)δ7.18-7.14(m,2H),6.94-6.90(m,4H),6.77-6.74(m,4H),6.71(d,J=8.9Hz,2H),4.03(dd,J=5.7,4. 0Hz,4H),3.77(dd,J=5.6,4.1Hz,4H),3.66-3.64(m,4H),3.59-3.57(m,56H),3.48(dd,J=3.9,2.0Hz,4H),3.31(d,J=1.8Hz,6H). 13 C NMR(126MHz,Chloroform-d)δ155.22,147.87,140.69,131.76,126.43,122. 14,115.52,112.44,71.94,70.82,70.64,70.58,70.52,69.76,67.69,59.04.

[0047] Step 4: Synthesis of Compound IV

[0048] n-BuLi (0.44 mL, 1.1 mmol) was added to a solution of III (0.5256 g, 1 mmol) in ultra-dry THF (12 mL). After stirring for 1 hour, tributyltin chloride (1.1 mmol) was added. After stirring overnight at room temperature, the reaction was quenched by addition of KF solution. The mixture was extracted three times with EA, and the combined organic phases were dried over NaSO. After removal of the solvent, the product was used directly without further purification.

[0049] Step 5: Synthesis of Compound V

[0050] A 15 mL sealed tube was charged with the crude product Pd(PPh3)4 (0.0145 g, 0.0125 mmol), 4,7-dibromo-5,6-dinitrobenzo[c][1,2,5]thiadiazole (0.144 mg, 0.375 mmol), and ultra-dry tetrahydrofuran (5 mL). The tube was sealed with a Teflon cap. The reaction mixture was heated to 80°C with stirring overnight. After cooling, the crude product was extracted with DCM. The combined organic phases were dried over Na2SO4. After solvent removal, the crude product was purified by column chromatography (DCM:MeOH = 10:1) to afford the product as a purple solid (0.4890 g, 49%). 1 H NMR(600MHz,Chloroform-d)δ7.37(dt,J=8.9,2.8Hz,4H),7.16(dt,J=8.9,2.9Hz,8H),6.96(dt,J=8.9,2.8Hz,4H),6.91(dq,J=9.1,3.2Hz,8H),4.14(p ,J=3.0Hz,8H),3.87(dt,J=6.0,3.2Hz,8H),3.75(dt,J=5.7,3.2Hz,8H),3.6 6(dd,J=6.9,3.5Hz,112H),3.55(dd,J=6.4,3.2Hz,8H),3.39-3.37(m,12H). 13 C NMR(151MHz,Chloroform-d)δ156.04,153.28,150.46,142.09,139.58,130.14,127.81,1 27.71,120.56,117.91,115.66,71.90,70.81,70.61,70.53,70.47,69.72,67.67,59.03.

[0051] Step 6: Synthesis of Compound VI

[0052] V (0.14 g, 0.12 mmol) and acetic acid (5 mL) were mixed in a 50 mL two-necked round-bottom flask, and iron powder (0.0211 g, 0.3 mmol) was added. The mixture was heated to 80°C and stirred for 4 h. After cooling to room temperature, water was added and the mixture was washed three times with dichloromethane. The organic layer was combined, dried over Na2SO4, and the solvent was evaporated under reduced pressure. The crude product was used without further purification.

[0053] Step 7: Synthesis of compound PEG-TD

[0054] Compound VI (0.24 g, 0.1 mmol), N-sulfenylanilide (0.0278 g, 0.2 mmol), trimethylsilyl chloride (0.108 g, 10 mmol), and ultra-dry pyridine (5 mL) were added to a 15 mL sealed tube and sealed with a Teflon cap. The reaction mixture was heated to 80°C with stirring overnight. After cooling, the crude product was extracted with DCM. The combined organic phases were dried over Na2SO4. After solvent removal, the crude product was purified by column chromatography (DCM:MeOH = 10:1) to afford the product (0.1190 g, 49%) as a purple solid with a bluish-green color. 1 H NMR(600MHz,Chloroform-d)δ8.16(d,J=8.8Hz,4H),7.20(d,J=6.6Hz,4H),7.14(d,J=6.7Hz,2H),6.92(d,J=6.7Hz, 4H), 4.16 (t, J = 4.9Hz, 8H), 3.90 (s, 9H), 3.80-3.75 (m, 5H), 3.68 (d, J = 4.3Hz, 51H), 3.60-3.55 (m, 6H), 3.40 (s, 12H). 13 C NMR(151MHz,Chloroform-d)δ155.63,152.74,149.11,140.34,132.61,127.41,126.82,120.00,118.82,115.5 6,71.94,70.84,70.65,70.60,70.58,70.52,69.78,67.71.MALDI-TOF-MS.ExpectedM.W.2387.17831,Measured MW2387.17569.

[0055] Synthesis of compound PEG-SD

[0056] In a 15 mL sealed tube, compound VI (0.24 g, 0.1 mmol), selenium dioxide (0.110 g, 1 mmol), extra-dry ethanol (2 mL), and extra-dry tetrahydrofuran (2 mL) were added and sealed with a Teflon cap. The reaction mixture was heated to 80°C with stirring overnight. After cooling, the crude product was extracted with DCM. The combined organic phases were dried over Na2SO4. After solvent removal, the crude product was purified by column chromatography (DCM:MeOH = 10:1) to afford the green product (0.0910 g, 41%). 1H NMR(400MHz,THF-d8)δ8.19-8.16(m,4H),7.21-7.18(m,8H),7.07-7.04(m,4H),6.96(d,J=9.0Hz,8H),4.16- 4.12(m,8H),3.86-3.83(m,8H),3.69-3.67(m,8H),3.59-3.56(m,112H),3.46(d,J=4.5Hz,8H),3.31(s,12H). 13 C NMR(126MHz,THF-d8)δ159.31,156.43,153.06,149.16,141.01,133.79,128.97,127.46,119. 97,118.94,115.83,72.45,71.24,71.12,71.06,70.90,70.15,58.45.MALDI-TOF-MS.Expected MW2434.1194,Measured MW2434.11812.

[0057] Example 2

[0058] The preparation method of compounds PEG-TD and PEG-SD specifically comprises the following steps:

[0059] Compound VI, N-sulfenylaniline, and trimethylsilyl chloride are added to an ultra-dry pyridine solvent and stirred and heated under an inert gas atmosphere to obtain PEG-TD. Compound VI and selenium dioxide are added to ultra-dry tetrahydrofuran and ultra-dry ethanol solvents and stirred and heated under an inert gas atmosphere to obtain PEG-SD. The structural formula of Compound VI is:

[0060] like Figure 1 As shown: Figure 1 This is a synthetic route for the novel water-soluble NIR-II organic probe small molecule provided in Example 1 of the present invention;

[0061] like Figure 2 As shown: Figure 2 This is a hydrogen nuclear magnetic resonance spectrum of the water-soluble NIR-II organic probe small molecule PEG-TD prepared in Example 1 of the present invention in tetrahydrofuran;

[0062] like Figure 3 As shown: Figure 3 This is a hydrogen nuclear magnetic resonance spectrum of the water-soluble NIR-II organic probe small molecule PEG-SD prepared in Example 1 of the present invention in tetrahydrofuran;

[0063] like Figure 4 As shown: Figure 4 This is the carbon NMR spectrum of the water-soluble NIR-II organic probe small molecule PEG-TD prepared in Example 1 of the present invention in tetrahydrofuran

[0064] like Figure 5 As shown: Figure 5 This is the carbon NMR spectrum of the water-soluble NIR-II organic probe small molecule PEG-SD prepared in Example 1 of the present invention in tetrahydrofuran;

[0065] like Figure 6 As shown: Figure 6 This is a MALDI-TOF-MS mass spectrum of the water-soluble NIR-II organic probe small molecule PEG-TD prepared in Example 1 of the present invention;

[0066] like Figure 7 As shown: Figure 7 This is a MALDI-TOF-MS mass spectrum of the water-soluble NIR-II organic probe small molecule PEG-SD prepared in Example 1 of the present invention;

[0067] like Figure 8 As shown: Figure 8 These are the ultraviolet absorption and fluorescence emission spectra of the PEG-TD and PEG-SD materials prepared in Example 1 of the present invention, indicating that the prepared compounds have a long-wavelength emission effect in the near-infrared region II.

[0068] like Figure 9 As shown: Figure 9 1 is a graph showing the fluorescence signal changes at different concentrations of the PEG-TD material prepared in Example 1 of the present invention. It can be seen that the synthesized material has the property of aggregation-induced luminescence.

[0069] like Figure 10 As shown: Figure 10 The cell survival rate of the PEG-TD material prepared in Example 1 of the present invention and GL261 cells under different treatment modes is shown in FIG. Figure 10 It can be seen that PEG-TD has excellent cell compatibility and has strong phototoxicity under light irradiation.

[0070] like Figure 11 As shown: Figure 11 This is a fluorescent imaging image of the brain of mice with orthotopic glioma after the PEG-TD material prepared in Example 1 of the present invention was injected. Figure 11 It can be seen that PEG-TD has strong penetrating ability and can be used for imaging diagnosis of brain glioma.

[0071] like Figure 12 As shown: Figure 12 This is a diagram showing the effect of PEG-TD prepared in Example 1 of the present invention being used for photothermal / photodynamic synergistic anti-mouse brain glioma.

[0072] In summary, the present invention provides a novel water-soluble NIR-II organic probe small molecule, the chemical structure of which is as follows: Wherein, A is S or Se, and n is 4, 5, ..., 19, 20. It has a D-π-A-π-D structure, and the triphenylamine group in the molecule acts as an electron donor and rotor unit, distorting the molecular skeleton. The ethylene glycol segment can be used to adjust the hydrophilicity of the probe. The selection of a strong electron acceptor can effectively reduce the band gap of the molecule and extend the absorption / emission wavelength to the near-infrared region. The water-soluble integrated diagnosis and treatment probe molecule of the present invention has a simple synthesis route, low cost, and good biocompatibility, and can be used for near-infrared second-zone fluorescence imaging and optical diagnosis and treatment of tumors such as brain gliomas under near-infrared light excitation.

[0073] It should be understood that the application of the present invention is not limited to the above examples. For those skilled in the art, improvements or changes can be made based on the above description. All these improvements and changes should fall within the scope of protection of the claims attached to the present invention.

Claims

1. A type of water-soluble near-infrared integrated diagnostic and therapeutic probe molecule, characterized in that: Its chemical structural formula is: Among them, A is S and n is 8.

2. A method for preparing a water-soluble near-infrared integrated diagnostic and therapeutic probe molecule according to claim 1, characterized in that: include: Add compound VI, N-sulfenylaniline, and trimethylsilyl chloride to ultra-dry pyridine solvent, heat to 70-90°C under inert gas protection, and stir for 12-24 hours to obtain a crude product; Purifying the crude product to obtain the water-soluble near-infrared integrated diagnostic and therapeutic probe molecule; The structural formula of the compound VI is:

3. The method for preparing a water-soluble near-infrared integrated diagnosis and treatment probe molecule according to claim 2, characterized in that: The molar ratio of the compound VI, N-sulfenylaniline and trimethylchlorosilane is 1:2-3:5-15.

4. The method for preparing a water-soluble near-infrared integrated diagnosis and treatment probe molecule according to claim 2, characterized in that: The step of purifying the crude product to obtain the water-soluble near-infrared integrated diagnostic and therapeutic probe molecule comprises: The crude product is purified by silica gel column chromatography using a mixture of dichloromethane and methanol as an eluent to obtain the water-soluble near-infrared integrated diagnostic and therapeutic probe molecule.

5. The method for preparing the water-soluble near-infrared integrated diagnosis and treatment probe molecule according to claim 4, characterized in that: The volume ratio of dichloromethane to methanol in the eluent is 100:1-10:

1.

6. Use of the water-soluble near-infrared integrated diagnosis and treatment probe molecule as claimed in claim 1 in the preparation of an integrated tumor diagnosis and treatment reagent.

7. Use of the water-soluble near-infrared integrated diagnosis and treatment probe molecule according to claim 6 in the preparation of an integrated tumor diagnosis and treatment reagent, characterized in that: The tumor is glioblastoma multiforme.

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