Photosensitizer targeting mitochondria and having photodynamic therapy effect and synthesis method thereof

Abstract

The invention discloses a mitochondria-targeting photosensitizer with a photodynamic therapy effect and a synthesis method thereof. The mitochondria-targeting photosensitizer with the photodynamic therapy effect is formed by connecting a hexane unit and a triphenylphosphine element with a luminous group. According to the preparation method, 1, 6-dibromohexane is selected to react with PPAB groups with hydroxyl groups at two ends so as to prolong halogen atom sites and avoid steric hindrance, then triphenylphosphine is used as a raw material and is subjected to Wittig reaction with PPAB groups with long alkyl chains at two ends, the raw materials are easy to obtain, the method is simple, and the obtained product is solid powder, easy to store and good in stability; the photosensitizer obtained by the preparation method can target mitochondria; the photosensitizer obtained by the preparation method can generate singlet oxygen; the photosensitizer obtained by the preparation method can generate a photodynamic therapy effect on tumor cells.

Description

Technical Field

[0001] The present invention belongs to the technical field of photosensitizers, and relates to a photosensitizer that targets mitochondria and has a photodynamic therapy effect, as well as a synthesis method and application thereof. Background Art

[0002] Malignant tumors have become a major threat to global public health, and existing treatment options urgently need innovation. While traditional surgical resection, radiotherapy, and chemotherapy are widely used, they often suffer from inherent drawbacks such as poor selectivity, high systemic toxicity, and the development of drug resistance. To address these clinical challenges, the medical community is actively exploring innovative treatment strategies, including targeted therapies, immunomodulatory therapies, and novel therapeutic modalities based on physical and chemical principles, which have garnered significant attention in recent years. Among these emerging therapies, photodynamic therapy (PDT) offers unique advantages. This technology leverages the ability of photosensitizers to generate reactive oxygen species (ROS) upon irradiation with light of specific wavelengths, enabling precise targeting of tumor tissue. This invention focuses on the development of an innovative photosensitizer with the following notable features: excellent mitochondrial targeting, efficient singlet oxygen generation, and exceptional aggregate stability. This photosensitizer selectively accumulates in tumor cell mitochondria and, under illumination, exerts its anti-tumor effects by inducing mitochondrial dysfunction. However, existing photosensitizer systems still face two key bottlenecks: aggregation-induced quenching due to the planar molecular structure, which significantly reduces therapeutic efficacy; and the widespread problem of insufficient singlet oxygen quantum yield. These technical defects seriously limit the clinical application prospects of photodynamic therapy.

[0003] Therefore, the development of new photosensitizer molecules with both high stability and high efficiency has important scientific significance and application value for promoting photodynamic therapy from the laboratory to the clinic. At present, the means adopted to improve the singlet oxygen yield of photosensitizer molecules mainly include the following: First, by introducing heavy atoms, such as iodine atoms and bromine atoms, into the structure of photosensitizer molecules, the ability of intersystem crossing is improved, thereby increasing the singlet oxygen yield; second, structural modification of photosensitizers, introduction of water-soluble groups, and improvement of the stability of photosensitizer molecules in aqueous or polar solutions, thereby increasing the singlet oxygen yield; third, designing photosensitizer molecules with rigid structures. Due to the small rotational / vibrational energy within the molecules, non-radiative transitions are reduced, the energy of the triplet excited state is increased, and thus the singlet oxygen yield is increased. Although the above strategies have improved the singlet oxygen yield of photosensitizer molecules to a certain extent, the singlet oxygen yield in the aggregated state is still relatively low, which is not enough to complete photodynamic therapy for tumors, greatly hindering the development of photodynamic therapy in the field of cancer treatment.

[0004] Therefore, the synthesis of a new, stable photosensitizer molecule that targets mitochondria and has photodynamic therapeutic effects on tumors is of great significance for the development of the field of tumor treatment. Summary of the Invention

[0005] Technical problem to be solved: The present invention provides a photosensitizer that targets mitochondria and has a photodynamic therapy effect, as well as a synthesis method and application thereof.

[0006] Technical solution: A photosensitizer targeting mitochondria and having a photodynamic therapy effect, having the structure shown in the following compound 1:

[0007] The synthesis method of the above-mentioned photosensitizer comprises the following steps: step 1, adding DPP-Br and 2-amino-3-((2-hexyldecyl)oxy)pyridine in a molar ratio of 1:(0.8-1.2) to dry toluene; refluxing under N2 protection at 100-120° C., adding TiCl4 after sufficient dissolution, wherein the amount thereof is 1.0-1.2 times the molar amount of DPP-Br, continuing to reflux and stir for 5-15 minutes, and then adding triethylamine, wherein the amount thereof is 2.5-3.0 times the molar amount of DPP-Br; continuing to reflux and stir for 2-4 hours, and after thin layer chromatography monitoring the formation of the intermediate product imine, adding boron trifluoride etherate, wherein the amount thereof is 3.0-3.5 times the molar amount of DPP-Br, and then continuing to reflux for 18-24 hours; extracting with CH2Cl2 during post-treatment, drying the organic layer over anhydrous sodium sulfate, filtering, rotary evaporation, and then performing column chromatography separation to obtain compound 2; step 2, adding compound 2, accounting for 1.5% to 2.5% of the molar amount of DPP-Br, into a reaction vessel. 10-15% of the molar amount of compound 2, Pd(dppf)Cl2·CH2Cl2, 15-20% of the molar amount of compound 2, and 500-700% of the molar amount of compound 2, p-hydroxyphenylboronic acid, are dissolved in dry DMF; the mixture is reacted at 75-85°C for 3-5 hours, methanol is added for post-treatment, filtration is performed, and compound 3 is separated by column chromatography; step 3, dry DMF, compound 3, 500-700% of the molar amount of compound 3, and 300-500% of the molar amount of compound 3, are added to a reaction vessel; the mixture is reacted at 45-55°C for 12-16 hours, and vacuum distillation and column chromatography are performed for post-treatment to obtain compound 4; step 4, compound 4 and triphenylphosphine are added to toluene in a molar ratio of 1:(3.5-4.5), and the mixture is reacted at 95-105°C for 8-12 hours; excess ether is added for post-treatment, and the mixture is filtered to obtain compound 1.

[0008] Preferably, the DPP-Br in step 1 contains bromine atoms at both ends.

[0009] Preferably, the molar ratio of compound 2 to p-hydroxyphenylboronic acid in step 2 is 1:6.

[0010] Preferably, the molar ratio of compound 3 to 1,6-dibromohexane in step 3 is 1:4.

[0011] Preferably, the molar ratio of compound 4 to triphenylphosphine in step 4 is 1:4.

[0012] Preferably, the compound 1 in step 4 has triphenylphosphine at both ends.

[0013] The use of the above-mentioned photosensitizer targeting mitochondria and having photodynamic therapy effect in the preparation of anti-tumor drugs.

[0014] An anti-tumor drug, the active ingredient of which includes the above-mentioned photosensitizer.

[0015] The reaction formula is as follows:

[0016]

[0017] Beneficial Effects: 1. A photosensitizer targeting mitochondria and having a photodynamic therapy effect based on the present invention is formed by linking a hexane unit and a triphenylphosphine moiety with a luminescent group. This preparation method uses 1,6-dibromohexane to react with a PPAB group with hydroxyl groups at both ends to extend the halogen atom site to avoid steric hindrance. Triphenylphosphine is then used as a raw material to undergo a Wittig reaction with the PPAB group with long alkyl chains at both ends. The raw materials are readily available, the method is simple, and the resulting product is a solid powder that is easy to store and has good stability. 2. The photosensitizer obtained by this preparation method can target mitochondria. 3. The photosensitizer obtained by this preparation method can generate singlet oxygen. 4. The photosensitizer obtained by this preparation method can produce a photodynamic therapy effect on tumor cells. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 This is the HRMS spectrum of the photosensitizer prepared in Example 1 that targets mitochondria and has photodynamic therapy effect.

[0019] Figure 2 This is the ultraviolet-fluorescence spectrum of the photosensitizer prepared in Example 1 that targets mitochondria and has a photodynamic therapy effect in tetrahydrofuran.

[0020] Figure 3 This is a comparison chart of the singlet oxygen generation rates of the mitochondria-targeting photosensitizer with photodynamic therapy effect prepared in Example 1 and the commercial dye ZnPc in tetrahydrofuran aqueous solution.

[0021] Figure 4 Schematic diagram of the detection of singlet oxygen in cells by the photosensitizer prepared in Example 1 that targets mitochondria and has photodynamic therapy effect.

[0022] Figure 5The photosensitizer prepared in Example 1 that targets mitochondria and has a photodynamic therapy effect was subjected to an MTT cytotoxicity test before and after 660 nm laser irradiation.

[0023] Figure 6 A cell live-death experiment was performed on the photosensitizer prepared in Example 1 that targets mitochondria and has a photodynamic therapy effect before and after 660 nm laser irradiation.

[0024] Figure 7 This is a diagram showing the luminescence phenomenon of the cell area using fluorescence imaging technology, in which the photosensitizer targeted to mitochondria and having a photodynamic therapy effect prepared in Example 1 is specifically localized to the mitochondria of the cell.

[0025] Figure 8 This is the co-localization fitting of the photosensitizer targeted to mitochondria and having photodynamic therapy effect prepared in Example 1 and mitochondria. DETAILED DESCRIPTION

[0026] The following examples are given to illustrate the present invention in more detail. It is necessary to point out that the following examples cannot be interpreted as limiting the scope of protection of the invention. Some non-essential improvements and adjustments made to the present invention based on the above invention content by technical personnel skilled in the art should still fall within the scope of protection of the present invention.

[0027] Unless otherwise specified, the experimental methods used in this invention are conventional methods. The materials and reagents used in the experiments, unless otherwise specified, can be obtained from commercial sources. All the following reagents used in the examples were commercially available of analytical or chemical purity.

[0028] Example 1

[0029] Based on asymmetric aggregation-induced emission molecules, they were prepared using the following method:

[0030] (1) Preparation of compound DPP-Br

[0031] Sodium (1.8 g, 79 mmol) and a small amount of ferric chloride were added to tert-amyl alcohol (30 mL) and refluxed at 90 ° C for 10 h. After the sodium was dissolved, p-bromobenzonitrile (7.33 g, 41 mmol) was added, followed by a mixed solution of diisopropyl succinate (5.0 mL, 24 mmol) in tert-amyl alcohol (12 mL) and the reaction was continued for 20 h. The mixture was cooled to 60 ° C, and acetic acid (4.6 mL) and methanol (30 mL) were added to the reaction mixture. The reaction solution was filtered and rinsed with a large amount of methanol. The filter residue was retained and dried to obtain compound DPP-Br (4.0 g, yield 43%). 1H NMR (495MHz, DMSO-d6, 298K): δ [ppm] = 11.38 (s, 2H), 8.43 (d, J = 8.4Hz, 4H), 7.80 (d, J = 8.4Hz, 4H).

[0032] The structural formula of the obtained compound DPP-Br is:

[0033]

[0034] (2) Preparation of compound 7-(iodomethyl)pentadecane

[0035] 2-Hexyl-1-decanol (4 mL, 14 mmol), triphenylphosphine (4.4 g, 16 mmol) and imidazole (1.15 g, 17 mmol) were mixed and dissolved in dichloromethane (40 mL), stirred continuously and cooled to 0°C. Subsequently, iodine (4.1 g, 16 mmol) was added to the mixed solution, stirred at 0°C for 15 minutes, then warmed to room temperature and stirred for 24 hours. After the reaction was completed, the reaction mixture was poured into an aqueous sodium thiosulfate solution, and the organic layer was extracted by extraction. The solvent was evaporated and purified by silica gel column with n-hexane as the eluent to obtain compound 7-(iodomethyl)pentadecane (3.7 g, yield 75%). 1 H NMR (500MHz, CDCl3, 295K): δ [ppm] = 3.27 (d, J = 4.5Hz, 2H), 1.45-1.00 (m, 25H), 0.93-0.83 (m, 6H).

[0036] The structural formula of the obtained compound 7-(iodomethyl)pentadecane is:

[0037]

[0038] (3) Preparation of compound 2-amino-3-((2-hexyldecyl)oxy)pyridine

[0039] 2-Amino-3-hydroxypyridine (0.475 g, 4.5 mmol) and NaH (0.145 g, 6.5 mmol) were dissolved in 30 mL of ultra-dry DMF and stirred at room temperature under N2 protection for 1 h. 7-(Iodomethyl)pentadecane (1.85 g, 5.25 mmol) was mixed in 4 mL of ultra-dry DMF and added to the mixture. The mixture was reacted in the dark for 24 h, then dissolved in toluene and the DMF was azeotropically removed under oil pump vacuum. The organic phase was extracted with water and ethyl acetate, dried over anhydrous sodium sulfate and celite, filtered, and loaded onto a column. Impurities were first removed using DCM:n-hexane = 1:1, and then the pyridine was extruded using DCM:methanol = 200:1. The mixture was then dried to obtain 2-amino-3-((2-hexyldecyl)oxy)pyridine (0.92 g, 63% yield). 1H NMR (500MHz, CDCl3, 295K): δ [ppm] = 7.62 (d, J = 5.3Hz, 1H), 6.88 (d, J = 8.3Hz, 1H), 6.59 (dd, J 1 = 7.9Hz, J 2=4.9Hz,1H),4.65(br,2H),3.84(d,J=5.3Hz,2H),1.83-1.75(m,1H),1.48-1.17(m,24H),0.92-0.82(m,6H).

[0040] The structural formula of the obtained compound 2-amino-3-((2-hexyldecyl)oxy)pyridine is:

[0041]

[0042] (4) Preparation of Compound 2

[0043] DPP-Br (264 mg, 3 mmol) and 2-amino-3-((2-hexyldecyl)oxy)pyridine (0.9 g, 2.7 mmol) were added to dry toluene (18 mL) and refluxed at 110°C under N2 protection. After complete dissolution, TiCl4 (0.63 mL, 3.24 mmol) was added to the mixed solution. Reflux and stirring were continued for 10 minutes, followed by the addition of triethylamine (1.2 mL, 8.4 mmol). Reflux and stirring were continued for approximately 2-3 hours. After the formation of the intermediate imine was detected by thin-layer chromatography on silica gel, boron trifluoride etherate (1.1 mL, 9 mmol) was added, and reflux was continued for 18-20 hours to obtain a dark blue mixed solution. The reaction mixture was cooled to room temperature, poured into water, and extracted with CH2Cl2. The organic layer was dried over anhydrous sodium sulfate, filtered, and the CH2Cl2 was removed by rotary evaporation. The crude product was separated by column chromatography to obtain compound 2 (433 mg, 73% yield). 1 H NMR (500MHz, CDCl3, 295K): δ [ppm] = 8.34 (d, J = 9.5Hz, 4H), 7.87 (d, J = 6.0Hz, 2H) ,7.65(d,J=8.5Hz,4H),7.25(d,J=9.5Hz,2H),7.05(dd,J=6.0Hz,J=8.0Hz,2H).

[0044] The structural formula of the obtained compound 2 is:

[0045]

[0046] (5) Preparation of Compound 3

[0047] Compound 2 (30 mg, 0.024 mmol), Pd(dppf)Cl2·CH2Cl2 (5.74 mg, 0.312 mmol), KOAc (40 mg, 0.408 mmol), and p-hydroxyboronic acid (17.5 mg, 0.144 mmol) were added to dry DMF (1.92 mg). The reaction was incubated at 80°C under nitrogen for 4 h. After cooling to room temperature, methanol (30 ml) was added to the reaction mixture, which was then filtered. The resulting green residue was separated by column chromatography to afford compound 3 (yield 71%). 1 H NMR (400MHz, Chloroform-d): δ = 8.56 (d, 4H), 7.87 (d, 2H), 7.74 (m, 4H), 7.62~7.5 3(m,4H),7.20(d,2H),6.99(dd,J=7.9,2H),6.94~6.88(m,4H),3.92~3.87(m,4H).

[0048] The structural formula of the obtained compound 3 is:

[0049]

[0050] (6) Preparation of Compound 4

[0051] Compound 3 (7.2 mg, 0.006 mmol), K2CO3 (36 mg), and 1,6-dibromohexane (5.8 mg, 0.024 mmol) were dissolved in dry DMF (0.9 mg). The mixture was reacted at 50°C overnight under nitrogen. After cooling to room temperature, methanol (30 ml) was added to the reaction mixture and filtered. The green residue was separated by column chromatography to afford compound 4 (yield 63%). 1 H NMR (400MHz, Chloroform-d): δ = 8.60 (m, 4H), 8.05 (s, 2H), 7.87 (d, 2H), 7.77 (m, 4H), 7.67 (m, 4H), 7.20 (d, 2H), 6.94 (m, 6H).

[0052] The structural formula of the obtained compound 4 is:

[0053]

[0054] (7) Preparation of Compound 1

[0055] Compound 4 (18.3 mg, 0.012 mmol), triphenylphosphine (12.6 mg, 0.048 mmol), and toluene (1.2 mL) were reacted in anhydrous and oxygen-free conditions at 100°C overnight. After cooling to room temperature, a large amount of diethyl ether was added to the reaction mixture, resulting in the formation of a green solid which was filtered to afford Compound 1 (yield 47.5%). 1 H NMR (400MHz, Chloroform-d): δ = 8.43 (s, 2H), 7.79 (s, 4H), 7.75 (s, 6H), 7.71 (s, 2H), 7.66 (s, 2H), 7.63 (s, 2H) ,7.57(s,24H),7.49(s,39H),6.99(s,8H),6.80(s,2H),6.60(s,2H),6.50(s,2H),6.46(s,2H),4.00(s,12H).

[0056] The structural formula of the obtained compound 1 is:

[0057]

[0058] HRMS spectrum, NMR spectrum of a photosensitizer targeting mitochondria and having photodynamic therapy effect prepared in Example 1 1 The H-NMR spectra are as follows Figure 1 and Figure 2 , indicating that a photosensitizer targeting mitochondria and having photodynamic therapy effect was successfully synthesized according to the present invention.

[0059] Example 2

[0060] 1,3-Diphenylisobenzofuran (DPBF) was selected as the singlet oxygen ( 1 O2) capture agent, DPBF is 1 O2 is consumed by oxidation, resulting in a decrease in its strong absorption at 410 nm. The ability of the photosensitizer and the commercial dye zinc phthalocyanine (ZnPc) to generate singlet oxygen was evaluated by monitoring the change in DPBF absorption intensity at 410 nm. The experiment used a 20 mW LED light source with an excitation wavelength of 660 nm.

[0061] Comparison of singlet oxygen generation rates of compound 1 and ZnPc used as a standard substance in a mixed solution with a water content of 90% Figure 4 The results showed that compound 1 produced 1 O2 causes DPBF to show obvious bleaching consumption at 410nm. In contrast, ZnPc shows obvious DPBF bleaching consumption only after 50s. Calculated by the formula:

[0062] Φ Δ=Φ (ZnPc) ×t (化合物1) / t (ZnPc)

[0063] Where, Φ (ZnPc) represents the singlet oxygen quantum yield of zinc phthalocyanine used as a standard substance, t (化合物1) represents the decay slope of the singlet oxygen fitting curve of compound 1, t (ZnPc) Represents the decay slope of the singlet oxygen fitting curve of zinc phthalocyanine. The relative singlet oxygen quantum yield Φ of compound 1 Δ It is 47.5% (the standard substance is ZnPc).

[0064] Example 3

[0065] 1. Cytotoxicity Assay

[0066] (1) Cell culture

[0067] Cell cryopreservation: Select cells in good growth condition, remove the culture medium and serum, wash twice with PBS, add trypsin for 3 minutes, terminate digestion, and rapidly centrifuge. Discard the supernatant and add the prepared cell freezing solution. After air-blowing to mix thoroughly, aliquot the suspension into sterile cryovials (1.0 mL each). Seal the tubes, label them with the freezing date and cell name, and place them in a cryovial. Store in a -80°C freezer overnight. For extended storage, remove the cells from the freezer and store in liquid nitrogen.

[0068] Cell Thawing: Remove the cryovial from the -80°C freezer and quickly place it in a preheated 37°C water bath. Rapidly stir the water in the water bath to thaw the cells. Place sterile pipette tips, centrifuge tubes, and culture flasks in a pre-sterilized laminar flow hood. Wipe the outer wall of the cryovial with an alcohol swab and quickly transfer the cryovial to a sterile centrifuge tube. Centrifuge at 1000 rpm for 5 minutes and discard the upper layer of cryovial. Add fresh culture medium, air-dry and mix thoroughly. Inoculate the culture flask. Incubate overnight in a CO2-saturated humidity incubator. Change the culture medium and continue culturing.

[0069] (2) In vitro cytotoxicity assay

[0070] 4T1 cells were grown in a 96-well plate, 100 μL of cell solution was added, and then cultured in an incubator for 24 h to allow the cells to fully adhere to the wall. The density per well was about 1×10 4 The upper solution was removed, and compound 1 was added and mixed with the culture medium solution (volume ratio of 1:9) to prepare different concentrations of 0, 6.25, 12.5, 25, 50, and 100 μg / mL. A PBS blank group was also set up, and 3 parallel wells were set up for each concentration. They were incubated with 4T1 for 24 hours. After reaching the time point, half of the wells in each group were subjected to a power of 0.5 W / cm 2Irradiate with 660nm laser for 5min (irradiate for 5s every 5s), then remove the upper solution, add MTT / culture medium solution, and incubate in the incubator for 4h. Discard the upper solution and wash twice with PBS. Wash gently to prevent the cells from being blown off and affecting the subsequent measurement. Add 100μL of DMSO, dissolve for 5-10min, transfer to a clean culture plate, measure on a microplate reader, and read the OD value. Record the read OD value, then calculate the average OD value of each concentration, divide it by the average value of the blank, and multiply by 100% to obtain the cell survival rate.

[0071] (3) Live and dead cell assay

[0072] The bacterial death caused by compound 1 was evaluated by the Calcein AM / propidium iodide PI co-staining method. First, the bacteria were incubated with PBS and compound 1 at a final concentration of 50 μg / mL for 24 hours. Two dishes of each of PBS and compound 1 were incubated with bacteria. Afterwards, one culture dish of each material was irradiated under a 660nm laser for 5 minutes (5 seconds every 5 seconds). Calcein AM (2 μM) and PI (4 μM) were added to all dishes and incubated for 30 minutes. Finally, the green / red fluorescence of the bacteria from Calcein AM / PI was observed by inverted fluorescence microscopy.

[0073] 2. Mitochondrial Colocalization

[0074] To confirm the specific location of the test material within the cell, we labeled the mitochondria within the cell with a fluorescent probe and added compound 1, which acts as a near-infrared fluorescent dye to emit a fluorescent signal under laser excitation in the 700-900nm range. The fluorescent signals of the fluorescent probes overlapped to form a co-localized fluorescent signal, which was used to identify the location and distribution of the material within the cell. By observing this co-localized fluorescent signal, it can be clearly found that the material is oriented in the mitochondria. This further demonstrates that the material can be fluorescently imaged in cancer cells and oriented in the mitochondria, paving the way for subsequent in vivo experiments.

Claims

1. A photosensitizer targeting mitochondria and having a photodynamic therapy effect, characterized in that: It has the structure shown in the following compound 1:

2. The method for synthesizing the photosensitizer according to claim 1, characterized in that: The method comprises the following steps: step 1, adding DPP-Br and 2-amino-3-((2-hexyldecyl)oxy)pyridine in a molar ratio of 1:(0.8-1.2) to dry toluene; refluxing under N2 protection at 100-120° C., adding TiCl4 after it is fully dissolved, wherein the amount thereof is 1.0-1.2 times the molar amount of DPP-Br; continuing to reflux and stir for 5-15 minutes, and then adding triethylamine, wherein the amount thereof is 2.5-3.0 times the molar amount of DPP-Br; continuing to reflux and stir for 2-4 hours, and performing thin layer chromatography; After the formation of the intermediate imine is detected by flow cytometry, boron trifluoride etherate is added in an amount of 3.0 to 3.5 times the molar amount of DPP-Br, and the mixture is refluxed for 18 to 24 hours; during post-treatment, the mixture is extracted with CH2Cl2, and the organic layer is dried over anhydrous sodium sulfate, filtered, and rotary evaporated, followed by column chromatography to obtain compound 2; step 2, compound 2, Pd(dppf)Cl2·CH2Cl2 (10 to 15% by mole of compound 2), and KOAc (15 to 20% by mole of compound 2) are added to the reaction vessel. and 500-700% of the molar amount of compound 2, dissolved in dry DMF; reacted at 75-85°C for 3-5 hours, added methanol for post-treatment, filtered, and separated by column chromatography to obtain compound 3; step 3, added dry DMF, compound 3, 500-700% of the molar amount of compound 3, and 300-500% of the molar amount of compound 3, 1,6-dibromo-n-hexane were added to the reaction vessel; reacted at 45-55°C for 12-16 hours, post-treated by reduced pressure distillation and column chromatography to obtain compound 4; step 4, compound 4 and triphenylphosphine were added to toluene in a molar ratio of 1:(3.5-4.5), and stirred at 95-105°C. The reaction was continued for 8 to 12 hours; during post-treatment, excess ether was added for precipitation, and the compound 1 was obtained by filtration.

3. The method for preparing a photosensitizer according to claim 2, wherein: The DPP-Br described in step 1 contains bromine atoms at both ends.

4. The method for preparing a photosensitizer according to claim 2, wherein: The molar ratio of compound 2 to p-hydroxyphenylboronic acid in step 2 is 1:

6.

5. The method for preparing a photosensitizer according to claim 2, wherein: The molar ratio of compound 3 to 1,6-dibromohexane in step 3 is 1:

4.

6. The method for preparing a photosensitizer according to claim 2, wherein: The molar ratio of compound 4 to triphenylphosphine in step 4 is 1:

4.

7. The method for preparing a photosensitizer according to claim 2, wherein: The compound 1 in step 4 has triphenylphosphine at both ends.

8. Use of the photosensitizer targeting mitochondria and having photodynamic therapy effect according to claim 1 in the preparation of anti-tumor drugs.

9. An anti-tumor drug, characterized in that: The active ingredient comprises the photosensitizer according to claim 1.

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