An organic photosensitizer for integrated tumor diagnosis and treatment and its preparation and application

Abstract

The present invention relates to an organic photosensitizer for integrated tumor diagnosis and treatment and its preparation and application, and the structural formula of the photosensitizer is:. The present invention has developed two single-component photosensitizers with electron-donating and electron-withdrawing structures, which can use 808nm as a therapeutic light source, have a deeper penetration depth and allow a larger amount of skin exposure, which helps to improve the therapeutic effect. It also has multimodal diagnosis and treatment functions, with fluorescence imaging for diagnosis, photodynamics and photothermal for treatment, and has great potential for integrated tumor diagnosis and treatment, and the therapeutic effect on subcutaneous superficial tumors is expected.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical materials, and specifically relates to an organic photosensitizer for integrated tumor diagnosis and treatment, and a preparation and application thereof. Background Art

[0002] In order to achieve multimodal diagnosis and treatment of tumors, current research programs mostly adopt an "all-in-one" strategy, that is, encapsulating reagents with different functions into a nanoparticle and using different components to achieve different functions. This strategy faces the problems of poor reproducibility and complex pharmacokinetics. Therefore, it is imperative to develop a single-component multifunctional photosensitizer.

[0003] In addition, the absorption wavelength of most organic photosensitizers is less than 700nm, so only lasers with a wavelength of 660nm can be used as therapeutic light sources. However, the penetration depth of lasers with a wavelength of 660nm is limited, and the maximum exposure allowed by the skin is low, which means that only lower power can be used during treatment to ensure that normal tissues are not damaged, but the treatment effect will also be greatly reduced. Compared with 660nm, 808nm lasers can penetrate deeper into the skin and allow greater skin exposure, which helps to improve the treatment effect. In addition, photosensitizers with near-infrared fluorescence (NIR) emission can also be used for non-invasive visualization of tumors and can monitor the degree of aggregation of nanoparticles in the tumor site in real time so that light therapy can be performed at the best time. Therefore, the development of single-component photosensitizers with 808nm absorption and NIR fluorescence emission for multimodal photodiagnosis and treatment of tumors is a very promising development direction. Summary of the invention

[0004] The purpose of the present invention is to provide an organic photosensitizer for integrated tumor diagnosis and treatment and a preparation method and application thereof, so as to solve the problems existing in the current technology.

[0005] An organic photosensitizer for integrated tumor diagnosis and treatment, with the structural formula:

[0006]

[0007] The present invention designs and prepares two photosensitizers CZTBT and LVTBT using carbazole-based benzene and phenylcarbazole as electron donors, respectively. The two photosensitizers can be used as organic photosensitizers for integrated tumor diagnosis and treatment and can be used for photodynamic-photothermal therapy guided by near-infrared fluorescence imaging.

[0008] The two photosensitizers CZTBT and LVTBT are isomers of each other, but they have huge differences in molecular structure, reactive oxygen generation, or photothermal conversion. First, LVTBT has a strong intramolecular charge transfer property, which makes it have the smallest HOMO-LUMO energy system (ΔE L-H );ΔEL-H The smaller the ΔE, the longer the emission wavelength of the photosensitizer, so LVTBT has the longest fluorescence emission wavelength; secondly, LVTBT has a smaller singlet-triplet energy system (ΔE S-T ), which is conducive to its generation of reactive oxygen species for photodynamic therapy through intersystem crossing (ISC); finally, LVTBT's relatively flat molecular configuration and stronger intramolecular free rotation enable it to exhibit the best photothermal conversion performance. Therefore, compared with CZTBT, the photosensitizer LVTBT with phenylcarbazole as a donor exhibits the best properties. LVTBT exhibits a longer emission wavelength, excellent photodynamic properties and efficient photothermal conversion capabilities; LVTBT has strong intramolecular charge transfer and a flatter main structure, exhibiting optimal fluorescence emission, reactive oxygen generation and photothermal conversion capabilities, which is conducive to the realization of multimodal photodiagnosis and treatment.

[0009] The preparation method of the above-mentioned photosensitizer comprises the following steps:

[0010] (1) 4,8-dibromo-6-(2-ethylhexyl)-[1,2,5]thiadiazole[3,4-F]benzotriazole, 2-thiopheneboronic acid, 1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium Pd(dppf)Cl 2 and K 2 CO 3 The aqueous solution is dissolved in dioxane, and the mixture is refluxed at 80-100° C. After the reaction is completed, the mixture is washed and the solvent is removed, and then purified by column chromatography to obtain molecular formula 2;

[0011] (2) adding the molecular formula 2 obtained in step (1) to anhydrous tetrahydrofuran, and adding n-butyl lithium at -75°C to -80°C under a nitrogen environment; stirring the mixture, adding trimethyltin chloride, and slowly heating the mixture to room temperature;

[0012] (3) quenching the reaction mixture with an aqueous potassium fluoride solution, washing, drying, concentrating under reduced pressure, and chromatographically purifying to obtain a compound of formula 3;

[0013] (4) Formula 3, 2-bromo-9-phenyl-9H-carbazole, tris(dibenzylideneacetone)dipalladium Pd 2 (dba) 3 and tri(o-methylphenyl)phosphine P(o-tol) 3 Mix in anhydrous toluene and stir overnight at 100-120°C under nitrogen atmosphere;

[0014] (5) After cooling to room temperature, the reaction mixture was extracted with chloroform, washed, dried, concentrated under reduced pressure, and purified by column chromatography;

[0015] The structural formula of the molecular formula 2 is:

[0016]

[0017] The structural formula of the molecular formula 3 is:

[0018]

[0019] Furthermore, the added molar ratio of molecular formula 3 and 2-bromo-9-phenyl-9H-carbazole is 1:2.5-5.

[0020] Furthermore, the method further comprises step (6): encapsulating the photosensitizer obtained in step (5) with an amphiphilic organic polymer (preferably DSPE-mPEG2000).

[0021] Furthermore, step (6) specifically comprises: adding the amphiphilic organic polymer solution and the photosensitizer obtained in step (5) into deionized water at a weight ratio of 3-8:1, ultrasonicating at 50% output power, stirring for 1-2 hours, and purifying by ultrafiltration centrifuge tube.

[0022] Furthermore, the amphiphilic organic polymer includes PEG series polymers and polyoxypropylene-polyoxyethylene copolymers.

[0023] The use of the above photosensitizer in the preparation of therapeutic preparations for tumors.

[0024] The above photosensitizer is used in the preparation of photodynamic and photothermal combined therapy preparations.

[0025] A tumor diagnosis and treatment integrated preparation, comprising the above-mentioned photosensitizer.

[0026] Compared with the prior art, the present invention has developed two single-component photosensitizers with electron-donating and electron-withdrawing structures, which can use 808nm as a therapeutic light source, have a larger skin exposure, and help improve the therapeutic effect. The photosensitizer of the present invention has multimodal diagnostic and therapeutic functions, with fluorescence imaging used for diagnosis, and photodynamic and photothermal treatments used for treatment, and has great potential for integrated tumor diagnosis and treatment. Under the irradiation of 808nm laser, the photosensitizer LVTBT of the present invention can not only produce type I reactive oxygen species, but also has extremely high photothermal conversion efficiency; combined with its own inherent near-infrared fluorescence emission, it is conducive to fluorescence imaging-guided photodynamic-photothermal synergistic therapy, and the therapeutic effect on subcutaneous superficial tumors is expected. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 are the structural formulas of two photosensitizers of the present invention;

[0028] Figure 2 Schematic diagram of the preparation of two photosensitizers of the present invention;

[0029] Figure 3(a) is the ultraviolet absorption spectrum of the photosensitizer of the present invention; (b) is the normalized fluorescence spectrum of the photosensitizer of the present invention;

[0030] Figure 4 (a) is the optimized molecular structure of the photosensitizer of the present invention; (b) is the electronic orbital arrangement of the photosensitizer of the present invention; and (c) is the singlet-triplet energy gap of the photosensitizer of the present invention.

[0031] Figure 5 The morphology and particle size of the nanoparticles of the photosensitizer of the present invention;

[0032] Figure 6 (a) is the ultraviolet absorption spectrum of the photosensitizer nanoparticles of the present invention; (b) is the fluorescence spectrum of the photosensitizer nanoparticles of the present invention;

[0033] Figure 7 (a) is the total reactive oxygen generation capacity of CZTBT nanoparticles; (b) is the total reactive oxygen generation capacity of LVTBT nanoparticles; (c) is the identification of hydroxyl radicals generated by LVTBT NPs using electron spin resonance spectroscopy; (d) is the identification of superoxide radicals generated by LVTBT NPs using electron spin resonance spectroscopy;

[0034] Figure 8 (a) is the temperature change of CZTBT and LVTBT nanoparticle solutions with laser irradiation time; (b) is the concentration dependence of the temperature change of the LVTBT nanoparticle solution; (c) is the power dependence of the temperature change of the LVTBT nanoparticle solution; (d) is the photothermal stability of the LVTBT nanoparticle solution; (e) is the photothermal conversion efficiency of the LVTBT nanoparticle solution; (f) is the change of the photoacoustic signal intensity of the LVTBT nanoparticles with concentration;

[0035] Fig. 9 are the transient absorption spectra of CZTBT and LVTBT at different delay times;

[0036] Fig.10 are the three-dimensional femtosecond transient emission and absorption spectra of CZTBT and LVTBT;

[0037] Fig.11 is the molecular structure of CZTBT and LVTBT in the S1 state, and the changes in the corresponding dihedral angles;

[0038] Fig.12 It is near-infrared fluorescence imaging to monitor the changes of fluorescence signals at the tumor position of tumor-bearing mice over time;

[0039] Fig.13This is the metabolism of LVTB nanoparticles in the blood and major organs; 1-heart; 2-liver; 3-spleen; 4-lung; 5-kidney; 6-stomach; 7-intestine; 8-tumor. DETAILED DESCRIPTION

[0040] In order to make the objectives, technical solutions and advantages of the present invention more clear, the present invention will be further described in detail below with reference to the accompanying drawings.

[0041] Example 1

[0042] A method for preparing an organic photosensitizer CZTBT for integrated tumor diagnosis and treatment, such as Figure 2 As shown, including:

[0043] (1) Under argon atmosphere, molecule 1 (4,8-dibromo-6-(2-ethylhexyl)-[1,2,5]thiadiazole[3,4-F]benzotriazole, 6 mmol), 2-thiopheneboronic acid (14 mmol), Pd(dppf)Cl 2 (0.30mmol) and K 2 CO 3 The aqueous solution (2M) was dissolved in dioxane, and the mixture was refluxed at 90°C overnight. After the reaction was completed, the mixture was washed and the solvent was removed, and then purified by column chromatography to obtain molecule 2 (thienyl thiadiazole benzotriazole);

[0044] (2) Add molecule 2 (thienyl thiadiazole benzotriazole, 2.60 mM) to anhydrous tetrahydrofuran (30 mL), and add n-butyl lithium (1.3 mL) at -78°C under a nitrogen atmosphere. Stir the mixture at the same temperature for one hour, then add trimethyltin chloride (3.4 mL). Allow the reaction to slowly warm to room temperature and stir overnight. Quench the reaction mixture with aqueous potassium fluoride, wash with water and brine, and dry over sodium sulfate. Concentrate under reduced pressure to obtain a crude product. Purify by column chromatography to obtain molecule 3 (thienyl thiadiazole benzotriazole derivative);

[0045] (3) Molecules 3 (thienylthiadiazole benzotriazole derivative, 0.22 mmol), 9-(4-bromophenyl)carbazole (0.67 mmol), Pd 2 (dba) 3 (0.022mmol) and P(o-tol) 3 (0.18mmol) was mixed in anhydrous toluene (10mL) and stirred at 110°C overnight under nitrogen. After cooling to room temperature, the reaction mixture was extracted with chloroform, washed with potassium fluoride aqueous solution, water and brine, and dried over sodium sulfate. Concentrated under reduced pressure to obtain a crude product. Purified by column chromatography to obtain CZTBT.

[0046] Since the water solubility of organic photosensitizers is poor, the hydrophobic organic photosensitizer CZTBT is encapsulated by the amphiphilic polymer DSPE-mPEG2000 in this embodiment, and CZTBT nanoparticles (NPs) with good water solubility are prepared by nanoprecipitation. The specific method is as follows: 1 mL of tetrahydrofuran solution containing 1 mg CZTBT and 5 mg DSPE-mPEG2000 is poured into 9 mL of deionized water. The solution is ultrasonically treated at 50% output power for 1 minute, then stirred for 2 hours and purified with an ultrafiltration centrifuge tube to obtain CZTBT NPs.

[0047] Example 2

[0048] A method for preparing an organic photosensitizer LVTBT for integrated tumor diagnosis and treatment, such as Figure 2 As shown, including:

[0049] (1) Under argon atmosphere, molecule 1 (4,8-dibromo-6-(2-ethylhexyl)-[1,2,5]thiadiazole[3,4-F]benzotriazole, 6 mmol), 2-thiopheneboronic acid (14 mmol), Pd(dppf)Cl 2 (0.30mmol) and K 2 CO 3 The aqueous solution (2M) was dissolved in dioxane, and the mixture was refluxed at 90°C overnight. After the reaction was completed, the mixture was washed and the solvent was removed, and then purified by column chromatography to obtain molecule 2 (thienyl thiadiazole benzotriazole);

[0050] (2) Add molecule 2 (thienyl thiadiazole benzotriazole, 2.60 mM) to anhydrous tetrahydrofuran (30 mL), and add n-butyl lithium (1.3 mL) at -78°C under a nitrogen atmosphere. Stir the mixture at the same temperature for one hour, then add trimethyltin chloride (3.4 mL). Allow the reaction to slowly warm to room temperature and stir overnight. Quench the reaction mixture with aqueous potassium fluoride, wash with water and brine, and dry over sodium sulfate. Concentrate under reduced pressure to obtain a crude product. Purify by column chromatography to obtain molecule 3 (thienyl thiadiazole benzotriazole derivative);

[0051] (3) Molecules 3 (thienylthiadiazole benzotriazole derivative, 0.22 mmol), 2-bromo-9-phenyl-9H-carbazole (0.67 mmol), Pd 2 (dba) 3 (0.022mmol) and P(o-tol) 3(0.18 mmol) was mixed in anhydrous toluene (10 mL) and stirred at 110 ° C overnight under nitrogen. After cooling to room temperature, the reaction mixture was extracted with chloroform, washed with potassium fluoride aqueous solution, water and brine, and dried over sodium sulfate. Concentrated under reduced pressure to obtain a crude product. Purified by column chromatography to obtain LVTBT.

[0052] Since the water solubility of organic photosensitizers is poor, the hydrophobic organic photosensitizer LVTBT is encapsulated by the amphiphilic polymer DSPE-mPEG2000 in this embodiment, and LVTBT nanoparticles (NPs) with good water solubility are prepared by nanoprecipitation. The specific method is as follows: 1 mL of tetrahydrofuran solution containing 1 mg LVTBT and 5 mg DSPE-mPEG2000 is poured into 9 mL of deionized water. The solution is ultrasonically treated at 50% output power for 1 minute, then stirred for 2 hours and purified with an ultrafiltration centrifuge tube to obtain LVTBT NPs.

[0053] Performance Testing:

[0054] 1. Optical properties

[0055] First, the photophysical properties of organic photosensitizers CZTBT and LVTBT were investigated using UV-visible absorption spectroscopy and fluorescence emission spectroscopy. Figure 3 As shown in (a), CZTBT and LVTBT in CH 2 Cl 2 The maximum absorption peaks in the solution are 711 and 746 nm, and their molar extinction coefficients are 41120 M -1 cm -1 and 53690M -1 cm -1 In addition, from Figure 3 As can be seen in (b), the maximum emission wavelengths of CZTBT and LVTBT solutions are at 790 and 817 nm, respectively, both located in the NIR-I region, showing great potential for fluorescence imaging.

[0056] 2. Theoretical calculation

[0057] In order to further understand the photophysical and photochemical properties of CZTBT and LVTBT, DFT and TD-DFT theoretical calculations were performed using the Gauss16 program. First, the optimal structure of the photosensitizer in the ground state and the corresponding electronic orbital distribution were calculated at the B3LYP / 6-31G** level. Figure 4From the optimized geometric structure of (a), it can be seen that the dihedral angle between the electron-withdrawing unit and the π bridge in the two photosensitizers is close to 180°, while the dihedral angle between the electron-donating unit and the π bridge is between 25° and 28°, but the angle between the carbazole and the phenyl group is very different. The angle between the carbazole and the benzene ring in CZTBT is 56.79°, which is much larger than the 2.36° in LVTBT. It can be seen that the molecular structure of LVTBT has the best flatness, so its molar extinction coefficient is larger. In addition, the electrons in the HOMO orbitals of the two photosensitizers are mainly distributed on the electron-donating unit and the π bridge, while the electrons in the LUMO orbitals are mainly concentrated on the electron-withdrawing group in the middle, which further proves the intrinsic intramolecular charge transfer properties of the photosensitizer itself. Figure 4 As shown in (b), with the enhancement of the electron-donating and electron-withdrawing ability, the separation between the HOMO and LUMO orbitals of LVTBT becomes more obvious, and its ΔE L-H is 1.65eV, which is smaller than 1.71eV of CZTBT. LVTBT has a smaller ΔE L-H , so LVTBT exhibits a longer fluorescence emission wavelength. Perturbation theory shows that the reduction of electron exchange energy and the highly separated charge distribution will lead to a small ΔE S-T , which is conducive to accelerating the ISC process. On this basis, the present invention also calculated the ΔE of the two photosensitizers S-T .like Figure 4 As shown in (c), the ΔE of CZTBT and LVTBT S-T are 1.02 and 0.99 eV respectively, with a smaller ΔE S-T The LVTBT is expected to have excellent PDT performance.

[0058] 3. Preparation of nanoparticles and their optical properties

[0059] The CZTBT NPs and LVTBT NPs prepared in the present invention both exhibit good water dispersibility. Figure 5 As shown, transmission electron microscopy confirmed that the prepared CZTBT NPs and LVTBT NPs had a uniform spherical morphology and the particle size was 100 nm.

[0060] The present invention further explores the optical properties of CZTBT NPs and LVTBT NPs. Figure 6 As shown in (a), the absorption wavelengths of the two nanoparticles are mainly concentrated in 600-900nm, which is similar to the absorption band of the solution and is located in the near-infrared region (NIR-I). Among them, the extinction molar coefficient of LVTBT NPs is larger, which is conducive to fully absorbing light energy. Figure 6The fluorescence spectra in (b) demonstrate that the fluorescence emission wavelengths of both nanoparticles are located in the NIR-I region, reaching peaks at 789 and 816 nm, respectively, showing great potential for in vivo NIR fluorescence imaging.

[0061] 4. In vitro photodynamic performance

[0062] In order to further detect the photodynamic activity of NPs, the present invention uses DCFH to evaluate the total ROS generation performance of NPs. Figure 7 As shown in the figure, after DCFH was mixed with CZTBT NPs and LVTBT NPs respectively, the fluorescence intensity gradually increased within 5 minutes of irradiation. The fluorescence intensity of DCFH in the presence of LVTBT NPs was more than twice that of CZTBT NPs, which means that LVTBT NPs have excellent ROS generation ability. Furthermore, the present invention uses electron spin resonance (ESR) to identify the reactive oxygen species generated by LVTBTNPs. Figure 7 As shown, after 5 minutes of laser irradiation, LVTBT NPs had obvious hydroxyl radical and superoxide radical signals, indicating that LVTBT NPs can generate type I reactive oxygen species for photodynamic therapy.

[0063] 5. In vitro photothermal performance

[0064] The photothermal conversion performance of the photosensitizer LVTBT NPs of the present invention was further tested. Figure 8 As shown in (a), the temperature of the aqueous solution of the two nanoparticles gradually increased during the 1-minute irradiation time. Among them, LVTBT NPs has the best photothermal conversion performance, and the temperature can rise to more than 65°C within 1 minute. Subsequently, the concentration dependence and power dependence of the nanoparticles for photothermal conversion were tested. Figure 8 As shown in (b) and (c), at 0.6 W cm -2 At the power of 100ug mL -1 At a concentration of , the temperature of the LVTBT NPs solution gradually increases with the increase of laser power. After three cycles of laser on and off, it can be seen that the maximum temperature of the solution has no obvious decrease, indicating that LVTBT NPs have excellent cycle stability, as shown in Figure 8 (d). After testing and calculation, the photothermal conversion efficiency of BTBT NPs is 36.3%, as shown in Figure 8 (d). Figure 8 (e) The good photothermal conversion performance of LVTBT NPs further motivates us to monitor whether they also have the ability of photoacoustic imaging. Figure 8 As shown in (f), with the gradual increase in concentration, the photoacoustic signal intensity of LVTBT NPs becomes higher and higher, indicating that it also has excellent potential for photoacoustic imaging.

[0065] 6. Exploration of the mechanism of photothermal conversion capability

[0066] In order to further explain why the photothermal conversion capabilities of the two photosensitizers, which are isomers of each other, are so different, the present invention conducted an in-depth mechanism exploration. First, the transient absorption spectra of the two photosensitizers were tested. Fig. 9 and Fig.10 As shown in the figure, compared with CZTBT, the ESA band and CT band of LVTBT can be observed to have a significant red shift, accompanied by a faster decay curve. The above results show that compared with carbazole benzene (CZTBT), phenylcarbazole (LVTBT) promotes charge transfer and molecular rotation, improves the non-radiative transition efficiency of excited state energy, and is conducive to the efficient conversion of light and heat. Subsequently, the molecular structures of CZTBT and LVTBT in the singlet excited state were calculated, as shown in Fig.11 The present invention calculates the two dihedral angles from the ground state (S 0 ) to the excited state (S 1 It can be found that in LVTBT, the two dihedral angles change by 1.32° and 1.29°, respectively, which are larger than 0.99° and 1.26° of CZTBT, indicating that LVTBT will undergo stronger intramolecular rotation when returning to the ground state, which is beneficial to photothermal conversion.

[0067] 7. In vivo imaging performance

[0068] LVTBT NPs were injected into subcutaneous tumors of tumor-bearing mice via tail vein to study their in vivo fluorescence imaging capability. Fig.12 As shown, the fluorescence signals of the tumor sites of tumor-bearing mice were recorded at different time points (1, 2, 4, 8, 12, 18 and 24 h) after injection of LVTBT NPs. As the incubation time of the nanoparticles in the mice gradually increased, the fluorescence intensity at the tumor site gradually increased. After 12 hours, the most nanoparticles were accumulated at the tumor site. Subsequently, the metabolism of LVTBT NPs in mice was investigated. Fig.13 As shown in the figure, the fluorescence intensity of LVTBT NPs in the blood gradually decreased, and almost no fluorescence was seen after 10 days. In addition, LVTBT NPs mainly accumulated in the lungs, stomach, intestines and tumors. After 10 days, only a small amount of fluorescence was visible in the stomach and intestines. The above shows that LVTBT NPs can be metabolized well and have good biosafety.

Claims

1. An organic photosensitizer for integrated tumor diagnosis and treatment, characterized in that: The structural formula is as follows: 。 2. The method for preparing a photosensitizer according to claim 1, characterized in that: The following steps are involved: (1) dissolving 4,8-dibromo-6-(2-ethylhexyl)-[1,2,5]thiadiazole[3,4-F]benzotriazole, 2-thiopheneboronic acid, [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride and K2CO3 aqueous solution in dioxane, and reflux the mixture at 80-100° C.; after the reaction is completed, washing, removing the solvent, and purifying by column chromatography to obtain molecule 2; (2) adding the molecule 2 obtained in step (1) to anhydrous tetrahydrofuran, and adding n-butyl lithium at -75°C to -80°C under a nitrogen environment; stirring the mixture, adding trimethyltin chloride, and slowly heating the mixture to room temperature; (3) quenching the reaction mixture with an aqueous potassium fluoride solution, washing, drying, concentrating under reduced pressure, and chromatographically purifying to obtain molecule 3; (4) molecule 3, 2-bromo-9-phenyl-9H-carbazole, tris(dibenzylideneacetone)dipalladium and tris(o-methylphenyl)phosphine were mixed in anhydrous toluene and stirred at 100-120°C overnight under nitrogen atmosphere; (5) After cooling to room temperature, the reaction mixture was extracted with chloroform, washed, dried, concentrated under reduced pressure, and purified by column chromatography; The structural formula of the molecular formula 2 is: The structural formula of the molecular formula 3 is:

3. The preparation method according to claim 2, characterized in that: In step (1), the molar ratio of 4,8-dibromo-6-(2-ethylhexyl)-[1,2,5]thiadiazole[3,4-F]benzotriazole and 2-thiopheneboronic acid is 1:2-4.

4. The method for preparing a photosensitizer according to claim 2, characterized in that: The added molar ratio of molecule 3 and 2-bromo-9-phenyl-9H-carbazole is 1:2.5-5.

5. The method for preparing nanoparticles of photosensitizer according to claim 1, characterized in that: The method comprises encapsulating the photosensitizer according to claim 1 with an amphiphilic organic polymer.

6. The preparation method according to claim 5, characterized in that: include: The amphiphilic organic polymer solution and the photosensitizer according to claim 1 are added into deionized water in a weight ratio of 3-8:1, ultrasonicated at 50% output power, then stirred for 1-2 hours, and purified by ultrafiltration centrifuge tube.

7. The preparation method according to claim 6, characterized in that: The amphiphilic organic polymer includes PEG series polymers and polyoxypropylene polyoxyethylene copolymers.

8. Use of the photosensitizer according to claim 1 in preparing a therapeutic preparation for tumors.

9. Use of the photosensitizer according to claim 1 in the preparation of a photodynamic and photothermal combined therapy preparation.

10. An integrated tumor diagnosis and treatment preparation, characterized in that: The photosensitizer according to claim 1.

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