A novel mitochondria-targeting photosensitizer and its application in combined photodynamic and photothermal therapy

Abstract

The application discloses a novel mitochondrion-targeting photosensitizer and application thereof in photodynamic and photothermal combined treatment, and belongs to the field of biomedical materials. The photosensitizer has a D-pi-A type molecular structure and a strong intramolecular charge transfer (ICT) effect. Under near-infrared laser irradiation, the photosensitizer can simultaneously and efficiently generate reactive oxygen species (ROS) and undergo photothermal conversion, and the photothermal conversion efficiency is high. With the near-infrared fluorescence emission characteristics, the material can realize photodynamic and photothermal synergistic treatment under fluorescence imaging guidance, and is suitable for diagnosis and treatment integration of tumors and removal of subcutaneous superficial tumors. As a positively charged salt molecule, the photosensitizer has lipophilic cation characteristics, can precisely target mitochondria of tumor cells through electrostatic interaction, and thus effectively kills cancer cells.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials, specifically relating to a novel mitochondrial-targeting photosensitizer and its application in combined photodynamic and photothermal therapy. Background Technology

[0002] Cancer is one of the major diseases threatening human health. In the field of tumor treatment, photodynamic therapy (PDT) and photothermal therapy (PTT) have received widespread attention as two non-invasive or minimally invasive treatment methods. PDT involves a photosensitizer transferring energy to surrounding oxygen molecules under laser irradiation of a specific wavelength, generating cytotoxic reactive oxygen species (ROS), thereby inducing tumor cell apoptosis. PTT utilizes the photothermal conversion capability of a photosensitizer to convert light energy into heat energy, causing tumor tissue necrosis through localized high temperatures. Due to the strong tissue penetration capability of near-infrared lasers, the development of small organic molecule photosensitizers with near-infrared response characteristics has become a research focus in this field. In practical applications, the energy absorbed by the photosensitizer is mainly consumed through three pathways: fluorescence emission, ROS generation, and heat production. Currently, single treatment modalities often fail to achieve ideal results. Furthermore, since mitochondria are the cell's energy factories and are highly sensitive to ROS and heat, enhancing the photosensitizer's targeting ability to mitochondria can significantly improve the killing efficiency against cancer cells. Therefore, developing photosensitizers that combine reactive oxygen species generation capacity with photothermal conversion efficiency and precise targeting to achieve integrated diagnosis and treatment and photodynamic-photothermal synergistic therapy is a fundamental requirement in the field of tumor photophysical therapy. Summary of the Invention

[0003] This invention provides a mitochondrial-targeting photosensitizer and its application in combined photodynamic and photothermal therapy. The invention designs and prepares small organic molecule photosensitizers (TPA-TQ and TPA-TA) based on the D-π-A molecular configuration for synergistic near-infrared light-excited tumor photodynamic (PDT) and photothermal (PTT) therapy. This photosensitizer system uses triphenylamine as an electron donor and introduces quinoline salt and acridine salt as strong electron acceptors, respectively, exhibiting a strong intramolecular charge transfer effect. Under light irradiation, it can effectively induce type I and type II photochemical reactions, generating highly cytotoxic free radicals and singlet oxygen, and can efficiently generate heat through non-radiative transition pathways, achieving synergistic killing of tumor cells. Simultaneously, this type of photosensitizer possesses excellent water solubility and biocompatibility. Utilizing the positive charge characteristics within the molecule, it can specifically recognize and target the negatively charged cancer cell membrane through electrostatic interactions, thereby precisely targeting the mitochondria. This material exhibits significant phototoxicity and therapeutic activity against human liver cancer cells (HepG2), showing promising application prospects in tumor treatment.

[0004] The mitochondrial-targeting photosensitizer of this invention is selected from compounds with the following structures:

[0005] .

[0006] The preparation method of the mitochondrial-targeted photosensitizer of the present invention is divided into two synthetic routes according to its different structures.

[0007] The preparation method of the mitochondrial-targeted quinoline salt photosensitizer of the present invention includes the following steps:

[0008] Step 1: Synthesis of 5-[4-(diphenylamino)phenyl]thiophene-2-carboxaldehyde

[0009] Triphenylaminoboronic acid was dissolved in tetrahydrofuran, and 5-bromothiophene-2-carboxaldehyde, cesium carbonate, and tetratriphenylphosphine palladium were added to obtain a mixture. The mixture was stirred at 75-85°C for 24 hours under a nitrogen atmosphere, extracted, dried, concentrated, and purified by column chromatography to obtain 5-[4-(diphenylamino)phenyl]thiophene-2-carboxaldehyde.

[0010] The mass fraction of 5-bromothiophene-2-carboxaldehyde and the volume fraction of tetrahydrofuran are in the ratio of 100:(15-20), where the mass fraction is in mg and the volume fraction is in mL.

[0011] Step 2: Synthesis of 1-Butyl-4-methylquinoline iodide

[0012] Dissolve 4-methylquinoline in anhydrous acetone, add n-butane iodide, and stir the reaction at 60-70°C. After the reaction is complete, cool to room temperature to precipitate 1-butyl-4-methylquinoline iodide, which does not require purification.

[0013] The molar ratio of 4-methylquinoline to iodobutane is 2:3-5.

[0014] Step 3: Synthesis of TPA-TQ

[0015] 5-[4-(diphenylamino)phenyl]thiophene-2-carboxaldehyde and 1-butyl-4-methylquinoline iodide were added to anhydrous ethanol and reacted at 60-80 °C with the catalyst piperidine. After the reaction was completed, the mixture was cooled to room temperature and purified to obtain TPA-TQ.

[0016] The synthesis route is shown below:

[0017]

[0018] The preparation method of the mitochondrial-targeted acridine salt photosensitizer of the present invention includes the following steps:

[0019] Step 1: Synthesis of 9,10-dimethylacridine iodide

[0020] Take 9-methylacridine and iodomethane, add a mixed solvent of anhydrous acetonitrile and anhydrous tetrahydrofuran, and stir the reaction at 60-75℃ in the dark. After the reaction is completed, cool to room temperature, filter and collect the product to obtain 9,10-dimethylacridine iodide.

[0021] Step 2: Synthesis of TPA-TA

[0022] 5-[4-(diphenylamino)phenyl]thiophene-2-carboxaldehyde and 9,10-dimethylacridine iodide were dissolved in anhydrous ethanol, and piperidine was added dropwise to the system as a catalyst. The mixture was stirred and refluxed in an oil bath for 24 h, and the resulting blue solid TPA-TA was obtained after purification.

[0023] The volume ratio of anhydrous tetrahydrofuran to anhydrous acetonitrile is (2-3):1, and the unit of volume fraction is mL.

[0024] The synthesis route is shown below:

[0025]

[0026] The mitochondrial-targeted photosensitizer of the present invention is dispersed in water in the form of nanoparticles with particle sizes of 87.3 nm and 85.6 nm, respectively.

[0027] The present invention relates to the application of mitochondrial-targeted photosensitizers in the preparation of photodynamic therapy drugs for tumor diseases.

[0028] The present invention relates to the application of mitochondrial-targeted photosensitizers in the preparation of photothermal therapy drugs for tumor diseases.

[0029] The present invention relates to the application of mitochondrial-targeted photosensitizers in the preparation of drugs for the combined photodynamic and photothermal therapy of tumor diseases.

[0030] The photosensitizer of this invention possesses a D-π-A molecular structure and a strong intramolecular charge transfer (ICT) effect. Under near-infrared laser irradiation, it can simultaneously and efficiently generate reactive oxygen species (ROS) and undergo photothermal conversion, with high photothermal conversion efficiency. Leveraging its near-infrared fluorescence emission characteristics, this material can achieve photodynamic and photothermal synergistic therapy guided by fluorescence imaging, suitable for integrated diagnosis and treatment of tumors and the removal of superficial subcutaneous tumors. As a positively charged salt molecule, this type of photosensitizer possesses lipophilic cation characteristics, enabling precise targeting of tumor cell mitochondria through electrostatic interactions, thereby achieving effective killing of cancer cells. Furthermore, the photosensitizer of this invention allows for flexible adjustment of photodynamic performance and photothermal conversion efficiency by regulating the electron-donating ability of the donor and the degree of intramolecular free rotation, exhibiting excellent comprehensive therapeutic potential.

[0031] Compared with the prior art, the beneficial effects of the present invention are reflected in:

[0032] 1. This invention prepares a novel type of photosensitizer, TPA-TQ and TPA-TA, which use quinoline salt and acridine salt as acceptors and triphenylamine as electron donor groups for combined PDT and PTT therapy. The photosensitizer generates type I and type II ROS under aggregation conditions and has good photothermal conversion efficiency under 660 nm laser irradiation, realizing combined photothermal and photodynamic therapy.

[0033] 2. This invention prepares a class of mitochondrial-targeting small molecule photosensitizers. As positively charged salt molecules, these photosensitizers have lipophilic cationic characteristics and can precisely target tumor cell mitochondria using electrostatic interactions, thereby killing cancer cells. Furthermore, due to their small salt molecule nature, they have good water solubility and biocompatibility, which greatly enhances their application potential.

[0034] 3. This invention prepares a class of mitochondrial-targeting basic small molecule photosensitizers TPA-TQ and TPA-TA. The preparation process is simple, easy to use, and the raw materials can be used for industrial production. Attached Figure Description

[0035] Figure 1 This is the 1H NMR spectrum of compound TPA-TQ.

[0036] Figure 2 This is the carbon NMR spectrum of compound TPA-TQ.

[0037] Figure 3 This is the mass spectrum of compound TPA-TQ.

[0038] Figure 4 This is the 1H NMR spectrum of compound TPA-TA.

[0039] Figure 5 This is the carbon NMR spectrum of compound TPA-TA.

[0040] Figure 6 This is the mass spectrum of compound TPA-TA.

[0041] Figure 7 The particle size distribution diagrams are for compounds TPA-TQ (a) and TPA-TA (b).

[0042] Figure 8 The absorption diagrams of compounds TPA-TQ (a) and TPA-TA (b) under light irradiation are shown.

[0043] Figure 9 The DHE emission diagrams of compounds TPA-TQ (a) and TPA-TA (b) under light irradiation are shown.

[0044] Figure 10HPF emission diagrams of compounds TPA-TQ (a) and TPA-TA (b) under light irradiation.

[0045] Figure 11 The temperature changes of compounds TPA-TQ and TPA-TA under 660 nm light radiation at different times are shown in (a), and the photothermal conversion efficiency of TPA-TQ (b) and TPA-TA (c) is shown in (c).

[0046] Figure 12 Mitochondrial targeting diagrams for compounds TPA-TQ and TPA-TA.

[0047] Figure 13 Cell viability graphs of compounds TPA-TQ (a) and TPA-TA (b) under light or darkness at different concentration gradients.

[0048] Figure 14 The images show the survival or death of cells under light irradiation for compounds TPA-TQ and TPA-TA. Detailed Implementation

[0049] The technical solution of the present invention will be further analyzed and explained through specific embodiments below.

[0050] Example 1: Synthesis of TPA-TQ

[0051]

[0052] 1. Synthesis of 5-[4-(diphenylamino)phenyl]thiophene-2-carboxaldehyde: Under nitrogen protection, triphenylaminoboronic acid (2.55 g, 8.80 mmol), 5-bromothiophene-2-carboxaldehyde (1.52 g, 8.00 mmol), cesium carbonate (14.35 g, 44.00 mmol), and tetraphenylphosphine palladium (0.46 g, 0.40 mmol) were added sequentially to a dry 250 mL round-bottom flask, followed by tetrahydrofuran (THF, 72 mL) and deionized water (8 mL). Magnetic stirring was initiated, and the system was ensured to be oxygen-free through three cycles of vacuuming and nitrogen purging. The reaction system was then transferred to an oil bath preheated to 75 °C and refluxed with stirring for 20 h. 1.75 g of a golden-yellow powder was obtained. The yield was calculated to be 61.5%. 1H NMR (400 MHz, Chloroform-d) δ 9.78 (d, J =1.3 Hz, 1H), 7.63 (d, J = 3.9 Hz, 1H), 7.47-7.41 (m, 2H), 7.23 (d, J = 5.5Hz, 2H), 7.19 (dd, J = 7.4, 1.4 Hz, 2H), 7.09 – 6.96 (m, 7H).

[0053] 2. Synthesis of 1-Butyl-4-methylquinoline iodide: Under nitrogen protection, 4-methylquinoline (13.18 mL, 0.10 mol) and n-butane iodide (12.52 mL, 0.11 mol) were dissolved in anhydrous acetone (150 mL), and the mixture was stirred and refluxed in an oil bath at 65 °C for 24 h. The reaction progress was monitored by thin-layer chromatography (developing solvent: dichloromethane / methanol, 20:3, v / v). Toluene (25 mL) was added to the resulting yellow oily substance, and yellow crystals precipitated after standing at room temperature for 3 min. The precipitate was collected by vacuum filtration through a Buchner funnel and dried under vacuum at 40 °C for 12 h to finally obtain 8.12 g of pale yellow crystalline product, with a yield of 40.40%. 1 H NMR (400MHz, DMSO-d6) δ 9.38 (t, J = 6.5 Hz, 1H), 8.52 (dd, J = 20.8, 8.7 Hz, 2H), 8.22 (p, J = 7.1, 6.7 Hz, 1H), 8.01 (dd, J = 11.2, 6.5 Hz, 2H), 4.97 (q, J =7.3 Hz, 2H), 2.97 (d, J = 6.3 Hz, 3H), 1.89 (h, J = 7.6, 7.1 Hz, 2H), 1.35(p, J = 7.4 Hz, 2H), 0.88 (q, J = 7.0 Hz, 3H).

[0054] 3. Synthesis of TPA-TQ: 5-[4-(diphenylamino)phenyl]thiophene-2-carboxaldehyde (0.20 g, 0.56 mmol) and 1-butyl-4-methylquinoline iodide (0.18 g, 0.56 mmol) were weighed sequentially into a dry 50 mL round-bottom flask, followed by the addition of anhydrous ethanol (15 mL). After magnetic stirring until the starting materials were completely dissolved, piperidine (2 drops, approximately 0.1 mL) was added dropwise as a catalyst. The reaction flask was then transferred to an oil bath preheated to 80 °C and refluxed for 24 h. The crude product was purified by silica gel column chromatography to obtain 0.15 g of a purple solid. The calculated yield was 40%. 1H NMR (400 MHz, DMSO-d6) δ 9.32(dd, J = 17.5, 6.7 Hz, 1H), 8.90 (d, J = 8.4 Hz, 1H), 8.48 (d, J = 8.7 Hz,1H), 8.40 (d, J = 6.4 Hz, 1H), 8.31 (dd, J = 28.5, 15.7 Hz, 1H), 8.19 (t, J =7.9 Hz, 1H), 8.02 – 7.95 (m, 1H), 7.91 (s, 1H), 7.72 (d, J = 3.8 Hz, 1H), 7.60 (d, J = 4.0 Hz, 1H), 7.51 (d, J = 8.0 Hz, 2H), 7.11 (h, J = 7.3 Hz, 8H), 7.01 (d, J = 7.0 Hz, 3H), 6.97 – 6.90 (m, 2H), 4.91 (q, J = 7.5, 6.5 Hz, 2H), 1.88 (p, J = 7.6 Hz, 2H), 1.37 (h, J = 7.3 Hz, 2H), 0.89 (t, J = 7.2 Hz, 3H).

[0055] Example 2: Synthesis of TPA-TA

[0056]

[0057] 1. Synthesis of 9,10-dimethylacridine iodide: Under nitrogen protection, 10 mL of iodomethane and 1.5 g of 9-methylacridine were dissolved in a mixed solvent of anhydrous acetonitrile and anhydrous tetrahydrofuran (2:1, total 9 mL). The reaction was carried out at 60 °C in the dark for 12 hours. After the reaction was completed, the product was collected by filtration to obtain a red solid, which did not require further purification, with a yield of 85.8%. 1 H NMR (400 MHz, DMSO-d6) δ 8.87 (d, J = 8.7 Hz,1H), 8.72 (d, J = 9.2 Hz, 1H), 8.46-8.30 (m, 1H), 7.98 (dd, J = 8.8, 6.7 Hz,1H), 4.77 (s, 2H), 3.47 (s, 2H).

[0058] 2. Synthesis of TPA-TA: 5-[4-(diphenylamino)phenyl]thiophene-2-carboxaldehyde (0.20 g, 0.56 mmol) and 9,10-dimethylacridine iodide (0.18 g, 0.56 mmol) were weighed sequentially into a dry 50 mL round-bottom flask, followed by the addition of anhydrous ethanol (15 mL). After magnetic stirring until the starting materials were completely dissolved, piperidine (2 drops, approximately 0.1 mL) was added dropwise as a catalyst. The reaction flask was then transferred to an oil bath preheated to 80 °C and refluxed with stirring for 24 h. The crude product was purified by silica gel column chromatography (eluting with a gradient of petroleum ether / ethyl acetate, gradually adjusted from 8:1 to 3:1, v / v) to give 0.15 g of a blue solid. The calculated yield was 69.8%. 1 H NMR (400 MHz, DMSO-d6) δ 8.79 (dd, J = 8.8,1.5 Hz, 2H), 8.66 (d, J = 9.3 Hz, 2H), 8.38 – 8.33 (m, 2H), 8.22 (d, J = 15.8Hz, 1H), 7.93 (dd, J = 8.7, 6.7 Hz, 2H), 7.68 – 7.61 (m, 3H), 7.53 (d, J =3.9 Hz, 1H), 7.35-7.30 (m, 5H), 7.11 – 7.04 (m, 8H), 4.72 (s, 3H).

[0059] Example 3: Test Characterization

[0060] 1. The particle size and polydispersity index of nanoparticles in water were determined using a dynamic light scattering particle size analyzer (DLS). 0.2 mg of the compound was diluted with 2.5 mL of distilled water, sonicated for 5 min, and then placed in the particle size analyzer for testing. The equilibration time was 5 min, and the measurements were performed three times. Detailed test results can be found in [link to relevant documentation]. Figure 7 . Figure 7 This indicates that the nanomicelle particles have a particle size of around 85 nm and good dispersibility.

[0061] 2. The singlet oxygen indicator ABDA is used to detect the generation of singlet oxygen. ABDA has three characteristic absorption peaks: 359 nm, 379 nm, and 399 nm. When singlet oxygen is present... 1When O2 is generated, the absorption peak intensity decreases. Experimental steps: 1) In a dark environment, dissolve ABDA in DMSO to prepare 10 mL of stock solution (7.5 × 10⁻³ M); 2) Take 20 μL of TPA-TQ and TPA-TA stock solutions in a brown bottle, add 2 mL of PBS buffer, and then add 20 μL of the prepared ABDA solution to the above solution to prepare the test solution; 3) Irradiate the test solution with light every 1 min and observe the changes in the absorption peak intensity of ABDA at 359 nm, 379 nm, and 399 nm. Figure 8 This indicates that both TPA-TQ and TPA-TA generate singlet oxygen to varying degrees.

[0062] 3. Use the superoxide anion indicator DHR123 to detect the generation of superoxide anions. The test steps are as follows: 1) In a dark environment, dissolve DHR123 in DMSO to prepare 10 mL of stock solution (1×10⁻⁶). -3 M); 2) Take 20 μL of TPA-TQ and TPA-TA stock solution into a brown bottle, add 2 mL of PBS buffer, and then add 20 μL of the prepared DHR123 solution to the above solution to prepare the test solution; 3) Irradiate the test solution with light every 10 s and observe the change in fluorescence intensity of DHR123 at about 527 nm. Figure 9 This indicates that both TPA-TQ and TPA-TA generate superoxide anions to varying degrees.

[0063] 4. Use HPF, an indicator of hydroxyl radicals, to detect the generation of hydroxyl radicals. The test steps are as follows: 1) In a dark environment, dissolve HPF in DMSO to prepare 10 mL of stock solution (1×10⁻⁶). -3 M); 2) Take 20 μL of TPA-TQ and TPA-TA stock solution into a brown bottle, add 2 mL of PBS buffer, and then add 3 μL of prepared HPF solution to the above solution to prepare the test solution; 3) Irradiate the test solution with light every 10 s and observe the change in fluorescence intensity of HPF at about 515 nm. Figure 10 This indicates that both TPA-TQ and TPA-TA generate hydroxyl radicals to varying degrees.

[0064] 5. Add TPA-TQ and TPA-TA aqueous solutions (1×10⁻⁶) -4 M, 2.0 mL) was placed in a power density of 1 W / cm³. 2The target compound was irradiated with a 660nm laser, and the temperature change of the aqueous solution was observed using an infrared radiometer, recording the relationship between temperature and irradiation time. During laser irradiation, the aqueous solution temperature was recorded every 30 seconds, and a photograph was taken every 2 minutes; the aqueous solution temperature was also recorded every 30 seconds. Figure 11 As shown, the infrared images of TPA-TQ and TPA-TA change with time, and the temperature increases. The photothermal efficiencies of TPA-TQ and TPA-TA are 42.3% and 43.1%, respectively.

[0065] 6. Human hepatocellular carcinoma cells (HepG2 cells) were cultured in confocal culture dishes for 48 h at 37 ℃ and 5% CO2, then co-incubated with the sample (10 μM) in the dark for 15 min, followed by staining with MTG (1 μM) for 15 min. After incubation, the cells were washed three times with PBS buffer, and then 1 mL of PBS buffer was added. Finally, HepG2 cells were observed under a confocal laser scanning microscope (CLSM) using the following excitation / emission wavelengths (MTG: λ). ex / λ em =488 / 510-530 nm). For example... Figure 12 As shown, both TPA-TQ and TPA-TA have good targeting ability in mitochondria.

[0066] 7. Biocompatibility Test. 1) HepG2 cells were cultured in 96-well plates at 37℃ and 5% CO2 until a cell monolayer covered the bottom of the well; 2) Samples with concentrations ranging from 0-15 μM were added, with a concentration gradient of 3 μM, and three parallel experimental groups were set up for each concentration, and incubated for 24 h; 3) The cells were divided into a dark group (protected from light) and a light group (LED lamp, 400-700 nm, 50 mW / cm²) for irradiation; 4) 10 μL of MTT reagent was added to each well, and the cells were cultured for another 4 h; 5) 150 μL of dissolving solution was added to each well, and the mixture was shaken at low speed until the crystals were fully dissolved; 6) The absorbance (A) of the mixture in each well was measured at 490 nm using a multi-mode microplate reader; 7) The experimental procedure for the control group (without sample) was the same as above. Cell viability was determined as follows:

[0067] Cell viability (%) = (mean value of treatment group A / mean value of control group A) × 100%.

[0068] like Figure 13 As shown, both TPA-TQ and TPA-TA have good biocompatibility.

[0069] 8. HepG2 cells were cultured in confocal culture dishes at 37℃ and 5% CO2 for 48 h, then co-incubated with the sample (10 μM) in the dark for 15 min. After washing the cells three times with PBS buffer, 1 mL of PBS buffer, 400 μL of diluent, and a mixture of Calcein-AM (5 μM) / PI (5 μM) were added to further stain the cells for 15 min. Confocal fluorescence imaging of HepG2 cells was performed before and after light exposure using an objective lens (Calcein-AM: λ). ex / λ em =488 / 500-550 nm; PI: λ ex / λ em =543 / 590-650 nm). For example... Figure 14 As shown, TPA-TQ and TPA-TA have good cancer cell killing ability under light irradiation.

Claims

1. A mitochondrial-targeting photosensitizer, characterized in that... Selected from compounds with the following structures: 。 2. The method for preparing the mitochondrial-targeting quinoline salt photosensitizer of claim 1, characterized in that... Includes the following steps: Step 1: Synthesis of 5-[4-(diphenylamino)phenyl]thiophene-2-carboxaldehyde Triphenylaminoboronic acid was dissolved in tetrahydrofuran, and 5-bromothiophene-2-carboxaldehyde, cesium carbonate, and tetratriphenylphosphine palladium were added to obtain a mixture. The mixture was stirred at 75-85°C under a nitrogen atmosphere, extracted, dried, and concentrated. After purification by column chromatography, 5-[4-(diphenylamino)phenyl]thiophene-2-carboxaldehyde was obtained. Step 2: Synthesis of 1-Butyl-4-methylquinoline iodide 4-Methylquinoline was dissolved in anhydrous acetone, and n-butane iodide was added. The mixture was stirred at 60-70°C and the reaction was completed. After cooling to room temperature, 1-butyl-4-methylquinoline iodide was precipitated. Step 3: Synthesis of TPA-TQ 5-[4-(diphenylamino)phenyl]thiophene-2-carboxaldehyde and 1-butyl-4-methylquinoline iodide were added to anhydrous ethanol and reacted at 60-80 °C with the catalyst piperidine. After the reaction was completed, the mixture was cooled to room temperature and purified to obtain TPA-TQ.

3. The method for preparing the mitochondrial-targeted acridine salt photosensitizer of claim 1, characterized in that... Includes the following steps: Step 1: Synthesis of 9,10-dimethylacridine iodide Take 9-methylacridine and iodomethane, add a mixed solvent of anhydrous acetonitrile and anhydrous tetrahydrofuran, stir the reaction at 60-75℃ in the dark, cool to room temperature after the reaction is completed, filter and collect the product to obtain 9,10-dimethylacridine iodide; Step 2: Synthesis of TPA-TA 5-[4-(diphenylamino)phenyl]thiophene-2-carboxaldehyde and 9,10-dimethylacridine iodide were dissolved in anhydrous ethanol, and piperidine was added dropwise to the system as a catalyst. The mixture was stirred and refluxed in an oil bath for 24 h, and the resulting blue solid TPA-TA was obtained after purification.

4. The use of the mitochondrial-targeting photosensitizer of claim 1 in the preparation of a photodynamic therapy for tumor diseases.

5. The use of the mitochondrial-targeting photosensitizer of claim 1 in the preparation of a photothermal therapy drug for tumor diseases.

6. The use of the mitochondrial-targeting photosensitizer of claim 1 in the preparation of a drug for the combined photodynamic and photothermal therapy of tumor diseases.

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