Phospholipid-polyethylene glycol modified monoiodine aza-BODIPY photosensitizer as well as synthesis method and application thereof

Abstract

The invention relates to the technical field of drug synthesis, and particularly provides a phospholipid-polyethylene glycol modified mono-iodine aza-BODIPY photosensitizer as well as a synthesis method and application thereof, and the phospholipid-polyethylene glycol modified mono-iodine aza-BODIPY photosensitizer has good photosensitization activity and tumor inhibition activity, and can be used for preparing drugs for treating tumors. The compound can be developed into efficient cell membrane targeted photodynamic antitumor drugs, and can be used for photodynamic therapy of non-specific wide tumors, such as pancreatic cancer, cervical cancer, brain glioma, lung cancer, gastric cancer, bladder cancer, ovarian cancer, colon cancer, skin cancer, prostatic cancer and the like.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical synthesis technology, specifically to a phospholipid-polyethylene glycol modified monoiodide aza-BODIPY photosensitizer, its synthesis method, and its application. Background Technology

[0002] Photodynamic therapy (PDT) is a non-invasive technique that has emerged in the last 30 years, utilizing the photodynamic effect for the diagnosis and treatment of diseases. PDT offers advantages such as high precision, non-invasiveness, controllability, low toxicity, repeatability, and low likelihood of drug resistance, and has therefore been used clinically to treat some tumors and skin diseases. Photosensitizers are one of the key elements for exerting the photodynamic killing effect. Aza-BODIPY is a class of BODIPY dyes in which the carbon atom at the meso position is replaced by a nitrogen atom. These BODIPY dyes possess high molar absorptivity, desirable stability, and near-infrared absorption wavelengths. Therefore, aza-BODIPY is a more suitable molecular framework for modification into photosensitizers.

[0003] Studies show that introducing heavy atoms into aza-BODIPY effectively increases the singlet oxygen yield, thereby improving photodynamic therapy efficacy. Furthermore, introducing an iodine atom at position 6 of aza-BODIPY results in a high singlet oxygen yield (Φ... Δ =0.52, DMF) and a stable photosensitizer (photosensitizer 13), the structural formulas of which are shown below:

[0004]

[0005] However, the application of aza-BODIPY photosensitizers in photodynamic therapy remains highly limited due to the lack of relatively effective targeting strategies. Furthermore, untargeted photosensitizers may lead to poor photodynamic efficacy and safety issues. Therefore, improving the effective accumulation of aza-BODIPY photosensitizers at the disease site through targeted modification is particularly important. Summary of the Invention

[0006] To address the technical limitation of aza-BODIPY photosensitizers in photodynamic therapy due to their lack of targeted modification, this invention provides a phospholipid-polyethylene glycol-modified monoiodine aza-BODIPY photosensitizer, its synthesis method, and its applications. The phospholipid-polyethylene glycol-modified monoiodine aza-BODIPY photosensitizer provided by this invention has been used in anti-tumor photodynamic research. The phospholipid-polyethylene glycol-modified monoiodine aza-BODIPY photosensitizer exhibits excellent photosensitizing activity and cell membrane targeting, and may be developed into a novel photodynamic therapy drug.

[0007] The present invention adopts the following technical solution:

[0008] This invention provides a phospholipid-polyethylene glycol modified monoiodide aza-BODIPY photosensitizer, wherein the photosensitizer is a compound having the following structural formula:

[0009]

[0010] Where n is an integer from 1 to 16, and the dashed line indicates whether the CC key exists or not.

[0011] Furthermore, the photosensitizer is a compound with any of the following chemical structures:

[0012]

[0013]

[0014]

[0015] This invention provides a method for synthesizing a phospholipid-polyethylene glycol modified monoiodide aza-BODIPY photosensitizer, comprising the following steps:

[0016] Step 1: Dissolve aza-BODIPY precursor 1 in DMF, add potassium carbonate and tert-butyl bromoacetate, react at 90°C for 1 h, after the reaction is complete, extract and dry to obtain precursor 2;

[0017] The structural formula of the aza-BODIPY precursor 1 is as follows:

[0018]

[0019] Step 2: Dissolve precursor 2 in a mixed solvent of dichloromethane and trifluoroacetic acid, react at room temperature for 3 h, then adjust the pH of the solution to 5, recrystallize in petroleum ether and dichloromethane and collect the solid, then dissolve the solid in a mixed solution of dichloromethane and acetic acid, add N-iodosuccinimide (abbreviated as NIS), react at room temperature for 2 h, after the reaction is completed, evaporate the solvent to obtain precursor 3.

[0020] Step 3: Dissolve precursor 3 in dichloromethane, then add phospholipid-polyethylene glycol derivative, N,N-diisopropylethylamine (DIPEA) and 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (HATU), react at room temperature for 2 h, extract and dry to obtain the final product.

[0021] The structural formula of the phospholipid-polyethylene glycol derivative is as follows:

[0022]

[0023] Where n is an integer from 1 to 16.

[0024] The reaction route is shown below:

[0025]

[0026] Furthermore, in step 1, the molar ratio of aza-BODIPY precursor 1, potassium carbonate, and tert-butyl bromoacetate is 1:2:2.

[0027] Furthermore, in step 2, the volume ratio of dichloromethane to trifluoroacetic acid in the mixed solvent of dichloromethane and trifluoroacetic acid is 1:1, and the volume ratio of dichloromethane to acetic acid in the mixed solution of dichloromethane and acetic acid is 3:1.

[0028] Furthermore, the molar ratio of precursor 2 to N-iodosuccinimide is 1:1.1.

[0029] Furthermore, the molar ratio of precursor 3, phospholipid-polyethylene glycol derivative, DIPEA, and HATU is 1:1.5:2:2.

[0030] Furthermore, the synthesis method includes the following steps:

[0031] Step 1: Dissolve 1 mmol of aza-BODIPY precursor 1 in 100 mL of DMF, slowly add 2 mmol of potassium carbonate and 2 mmol of tert-butyl bromoacetate, react at 90 °C for 1 h, after the reaction is complete, extract with water and dichloromethane, collect the organic phase and dry it, remove the solvent by vortex to obtain precursor 2.

[0032] Step 2: Dissolve precursor 2 in 50 mL of a mixed solvent of dichloromethane and trifluoroacetic acid, with a volume ratio of 1:1. React at room temperature for 3 h. Then adjust the pH of the solution to 5, recrystallize in petroleum ether and dichloromethane and collect the solid. Then dissolve the solid in 50 mL of a mixed solution of dichloromethane and acetic acid (3:1), add 1.1 mmol of N-iodosuccinimide (NIS), and react at room temperature for 2 h. After the reaction is complete, evaporate the solvent to obtain precursor 3.

[0033] Step 3: Dissolve precursor 3 in dichloromethane, then slowly add 1.5 mmol of phospholipid-polyethylene glycol derivative, 2 mmol of DIPEA and 2 mmol of HATU, react at room temperature for 2 h, extract with water and dichloromethane, collect and dry the organic phase, remove the solvent by rotary evaporation and then perform silica gel column chromatography to obtain the final product.

[0034] This invention provides the application of a phospholipid-polyethylene glycol-modified monoiodine aza-BODIPY photosensitizer in the preparation of cell membrane-targeted photodynamic therapy drugs.

[0035] This invention provides the application of a phospholipid-polyethylene glycol-modified monoiodine aza-BODIPY photosensitizer in the preparation of a photodynamic therapy drug for nonspecific, broad-spectrum tumors.

[0036] Furthermore, the nonspecific broad tumors include pancreatic cancer, cervical cancer, glioma, lung cancer, stomach cancer, bladder cancer, ovarian cancer, colon cancer, skin cancer, or prostate cancer.

[0037] Compared with the prior art, the present invention has the following technical effects:

[0038] 1. The phospholipid-polyethylene glycol modified monoiodide aza-BODIPY photosensitizer synthesized in this invention has good photosensitizing activity and tumor inhibitory activity. It can be developed into a highly efficient cell membrane-targeted photodynamic antitumor drug and can be used for photodynamic therapy of a wide range of nonspecific tumors, such as pancreatic cancer, cervical cancer, glioma, lung cancer, gastric cancer, bladder cancer, ovarian cancer, colon cancer, skin cancer, prostate cancer and other tumors.

[0039] 2. Zinc phthalocyanine (ZnPc, Ф) Δ =0.56, DMF) is the reference compound, and the phospholipid-polyethylene glycol modified monoiodide aza-BODIPY photosensitizer 1-12 (Ф) synthesized in this invention Δ =0.51~0.59, DMF) all exhibit the same properties as the photosensitizer 13 (Ф) described in the background art. Δ =0.52, DMF) similar singlet oxygen yield. Photosensitizer 6 has the highest singlet oxygen yield in DMF (Ф Δ =0.59). In the in vitro antitumor activity assay of cervical cancer cells (HeLa), the reference compound ZnPc had an IC50 of 0.59. 50 The IC50 value is 3.76 μM, which is the IC50 value of photosensitizers 1-12 synthesized in this invention. 50 The values ​​were all below 0.17 μM, among which, photosensitizer 12 had an IC50 value for HeLa cells. 50 With a concentration of only 0.09 μM, the photosensitizers mentioned in this invention all exhibit superior antitumor activity compared to photosensitizer 13 described in the background art. Attached Figure Description

[0040] Figure 1 This is a diagram of the organelle localization experiment using photosensitizer 12; Detailed Implementation

[0041] The present invention will be further described below with reference to the accompanying drawings and specific embodiments.

[0042] Example 1

[0043] This embodiment synthesized 12 phospholipid-polyethylene glycol modified monoiodide aza-BODIPY photosensitizers. The synthetic routes of photosensitizers 1 to 12 are shown below:

[0044]

[0045] The specific synthesis methods for photosensitizers 1 to 12 include the following steps:

[0046] Aza-BODIPY precursor 1 (1 mmol) was dissolved in 100 mL of DMF, and potassium carbonate (2 mmol) and tert-butyl bromoacetate (2 mmol) were slowly added. The reaction was carried out at 90 °C for 1 h. After the reaction was completed, the mixture was extracted with water and dichloromethane, the organic phase was collected and dried, and the solvent was removed by rotary evaporation to obtain precursor 2.

[0047] Precursor 2 was dissolved in 50 mL of a mixed solvent of dichloromethane (DCM) and trifluoroacetic acid (TFA) (v:v = 1:1) and reacted at room temperature for 3 h. The pH of the solution was then adjusted to 5, and the mixture was recrystallized in petroleum ether and dichloromethane, and the solid was collected. This solid was then dissolved in 50 mL of a mixed solution of dichloromethane and acetic acid (3:1), and NIS (1.1 mmol) was added. The mixture was reacted at room temperature for 2 h. After the reaction was complete, the solvent was evaporated to obtain precursor 3.

[0048] Precursor 3 was dissolved in dichloromethane, followed by the slow addition of a phospholipid-polyethylene glycol derivative (1.5 mmol), DIPEA (2 mmol), and HATU (2 mmol), and the reaction was carried out at room temperature for 2 h. The mixture was extracted with water and dichloromethane, and the organic phase was collected, dried, and the solvent was removed by rotary evaporation before silica gel column chromatography to obtain the final product.

[0049] The structural formula of photosensitizer 1 is as follows:

[0050]

[0051] The yield of photosensitizer 1 was 51%, and the NMR data for photosensitizer 1 are as follows: 1 H NMR(600MHz, CDCl3)8.09-7.99(m,4H),7.86-7.80(m,2H),7.70(d,J=8.6Hz, 2H),7.54-7.42(m,3H),7.37(dd,J=5.2,1.9Hz,3H),7.12(s,1H),7.04-6.99 (m,2H),6.98-6.93(m,2H),6.75(s,1H),4.45(s,2H),4.15(s,2H),3.88(s,3 H),3.8-3.72(m,4004H),2.35(m,4H),1.66(m,4H),1.25(m,8H),0.88(s,6H).

[0052] The structural formula of photosensitizer 2 is as follows:

[0053]

[0054] The yield of photosensitizer 2 was 47%, and the NMR data for photosensitizer 2 are as follows: 1 H NMR (600MHz, CDCl3) δ8.43 (d, J = 9.1Hz, 1H), 7.81-7.74 (m, 3H), 7.65-7.60 (m, 2H) ),7.59-7.55(m,2H),7.53-7.49(m,3H),7.47-7.41(m,2H),7.29(s,1H),7.13(d ,J=7.3Hz,3H),6.75(s,1H),4.66(s,2H),4.50-4.42(m,3H),4.15(s,2H),3.91( s,3H),3.8-3.72(m,4004H),2.35(m,4H),1.66(m,4H),1.25(m,8H),0.88(s,6H).

[0055] The structural formula of photosensitizer 3 is as follows:

[0056]

[0057] The yield of photosensitizer 3 was 36%, and the NMR data for photosensitizer 3 are as follows: 1 H NMR(600MHz, CDCl3)8.09-7.99(m,4H),7.86-7.80(m,2H),7.70(d,J=8.6Hz, 2H),7.54-7.42(m,3H),7.37(dd,J=5.2,1.9Hz,3H),7.12(s,1H),7.04-6.99( m,2H),6.98-6.93(m,2H),6.75(s,1H),4.45(s,2H),4.15(s,2H),3.88(s,3H ),3.8-3.72(m,4004H),2.35(m,4H),1.66(m,4H),1.25(m,16H),0.88(s,6H).

[0058] The structural formula of photosensitizer 4 is as follows:

[0059]

[0060] The yield of photosensitizer 4 was 62%, and the NMR data for photosensitizer 4 are as follows: 1H NMR (600MHz, CDCl3) δ8.43 (d, J = 9.1Hz, 1H), 7.81-7.74 (m, 3H), 7.65-7.60 (m, 2H) ),7.59-7.55(m,2H),7.53-7.49(m,3H),7.47-7.41(m,2H),7.29(s,1H),7.13(d, J=7.3Hz,3H),6.75(s,1H),4.66(s,2H),4.50-4.42(m,3H),4.15(s,2H),3.91(s ,3H),3.8-3.72(m,4004H),2.35(m,4H),1.66(m,4H),1.25(m,16H),0.88(s,6H).

[0061] The structural formula of photosensitizer 5 is as follows:

[0062]

[0063] The yield of photosensitizer 5 was 74%, and the NMR data for photosensitizer 5 are as follows: 1 H NMR(600MHz, CDCl3)8.09-7.99(m,4H),7.86-7.80(m,2H),7.70(d,J=8.6Hz, 2H),7.54-7.42(m,3H),7.37(dd,J=5.2,1.9Hz,3H),7.12(s,1H),7.04-6.99( m,2H),6.98-6.93(m,2H),6.75(s,1H),4.45(s,2H),4.15(s,2H),3.88(s,3H ),3.8-3.72(m,4004H),2.35(m,4H),1.66(m,4H),1.25(m,24H),0.88(s,6H).

[0064] The structural formula of photosensitizer 6 is as follows:

[0065]

[0066] The yield of photosensitizer 6 was 48%, and the NMR data for photosensitizer 6 are as follows: 1H NMR (600MHz, CDCl3) δ8.43 (d, J = 9.1Hz, 1H), 7.81-7.74 (m, 3H), 7.65-7.60 (m, 2H) ),7.59-7.55(m,2H),7.53-7.49(m,3H),7.47-7.41(m,2H),7.29(s,1H),7.13(d, J=7.3Hz,3H),6.75(s,1H),4.66(s,2H),4.50-4.42(m,3H),4.15(s,2H),3.91(s ,3H),3.8-3.72(m,4004H),2.35(m,4H),1.66(m,4H),1.25(m,24H),0.88(s,6H).

[0067] The structural formula of photosensitizer 7 is as follows:

[0068]

[0069] The yield of photosensitizer 7 was 55%, and the NMR data for photosensitizer 7 are as follows: 1 H NMR(600MHz, CDCl3)8.09-7.99(m,4H),7.86-7.80(m,2H),7.70(d,J=8.6Hz, 2H),7.54-7.42(m,3H),7.37(dd,J=5.2,1.9Hz,3H),7.12(s,1H),7.04-6.99( m,2H),6.98-6.93(m,2H),6.75(s,1H),4.45(s,2H),4.15(s,2H),3.88(s,3H ),3.8-3.72(m,4004H),2.35(m,4H),1.66(m,4H),1.25(m,32H),0.88(s,6H).

[0070] The structural formula of photosensitizer 8 is as follows:

[0071]

[0072] The yield of photosensitizer 8 was 63%, and the NMR data for photosensitizer 8 are as follows: 1H NMR (600MHz, CDCl3) δ8.43 (d, J = 9.1Hz, 1H), 7.81-7.74 (m, 3H), 7.65-7.60 (m ,2H),7.59-7.55(m,2H),7.53-7.49(m,3H),7.47-7.41(m,2H),7.29(s,1H),7 .13(d,J=7.3Hz,3H),6.75(s,1H),4.66(s,2H),4.50-4.42(m,3H),4.15(s,2H ),3.91(s,3H),3.8-3.72(m,4004H),2.35(m,4H),1.66(m,4H),1.25(m,32H).

[0073] The structural formula of photosensitizer 9 is as follows:

[0074]

[0075] The yield of photosensitizer 9 was 71%, and the NMR data for photosensitizer 9 are as follows: 1 H NMR(600MHz, CDCl3)8.09-7.99(m,4H),7.86-7.80(m,2H),7.70(d,J=8.6Hz, 2H),7.54-7.42(m,3H),7.37(dd,J=5.2,1.9Hz,3H),7.12(s,1H),7.04-6.99( m,2H),6.98-6.93(m,2H),6.75(s,1H),4.45(s,2H),4.15(s,2H),3.88(s,3H ),3.8-3.72(m,4004H),2.35(m,4H),1.66(m,4H),1.25(m,40H),0.88(s,6H).

[0076] The structural formula of photosensitizer 10 is as follows:

[0077]

[0078] The yield of photosensitizer 10 was 59%, and the NMR data for photosensitizer 10 are as follows: 1H NMR (600MHz, CDCl3) δ8.43 (d, J = 9.1Hz, 1H), 7.81-7.74 (m, 3H), 7.65-7.60 (m, 2H) ),7.59-7.55(m,2H),7.53-7.49(m,3H),7.47-7.41(m,2H),7.29(s,1H),7.13(d, J=7.3Hz,3H),6.75(s,1H),4.66(s,2H),4.50-4.42(m,3H),4.15(s,2H),3.91(s ,3H),3.8-3.72(m,4004H),2.35(m,4H),1.66(m,4H),1.25(m,40H),0.88(s,6H).

[0079] The structural formula of photosensitizer 11 is as follows:

[0080]

[0081] The yield of photosensitizer 11 was 66%, and the NMR data for photosensitizer 11 are as follows: 1 H NMR(600MHz, CDCl3)8.09-7.99(m,4H),7.86-7.80(m,2H),7.70(d,J=8.6Hz, 2H),7.54-7.42(m,3H),7.37(dd,J=5.2,1.9Hz,3H),7.12(s,1H),7.04-6.99( m,2H),6.98-6.93(m,2H),6.75(s,1H),4.45(s,2H),4.15(s,2H),3.88(s,3H ),3.8-3.72(m,4004H),2.35(m,4H),1.66(m,4H),1.25(m,48H),0.88(s,6H).

[0082] The structural formula of photosensitizer 12 is as follows:

[0083]

[0084] The yield of photosensitizer 12 was 68%, and the NMR data for photosensitizer 1 are as follows: 1H NMR (600MHz, CDCl3) δ8.43 (d, J = 9.1Hz, 1H), 7.81-7.74 (m, 3H), 7.65-7.60 (m, 2H) ),7.59-7.55(m,2H),7.53-7.49(m,3H),7.47-7.41(m,2H),7.29(s,1H),7.13(d, J=7.3Hz,3H),6.75(s,1H),4.66(s,2H),4.50-4.42(m,3H),4.15(s,2H),3.91(s ,3H),3.8-3.72(m,4004H),2.35(m,4H),1.66(m,4H),1.25(m,48H),0.88(s,6H).

[0085] Example 2: Singlet oxygen yield test

[0086] The photosensitizers in this embodiment are photosensitizers 1-12, zinc phthalocyanine (ZnPc), and photosensitizer 13 (the structure of which can be found in the background section of this invention).

[0087] 2 mL of DPBF solution (100 μM) and 2 mL of photosensitizer DMF solution (2 μM) were mixed thoroughly and placed in a quartz cuvette. The mixture was then irradiated for different durations, with an interval of 10 s. The cutoff filter wavelength was 550 nm. The UV-Vis absorption spectra of the photosensitizer solution after different irradiation durations (0 s, 10 s, 20 s, 30 s, 40 s, 50 s, 60 s) were measured. The singlet oxygen yield of the photosensitizer was calculated based on the change in DPBF absorbance at 415 nm. The singlet oxygen yield data of the phospholipid-polyethylene glycol modified monoiodine aza-BODIPY photosensitizer synthesized in this invention are shown in Table 1.

[0088] Table 1

[0089] photosensitizer 1 2 3 4 5 6 7 8 9 10 11 12 ZnPc 13 <![CDATA[Φ Δ ]]> 0.56 0.57 0.57 0.52 0.51 0.59 0.57 0.54 0.55 0.56 0.55 0.58 0.56 0.52

[0090] The results showed that zinc phthalocyanine (ZnPc, Ф) was the most effective... Δ =0.56, DMF) is the reference compound, photosensitizer 1-12 (Ф Δ =0.51~0.59, DMF) all showed similarity to photosensitizer 13 (Ф Δ =0.52, DMF) with a singlet oxygen yield similar to that of the photosensitizer. This indicates that phospholipid-polyethylene glycol modification does not affect the photosensitization efficiency of the photosensitizer. Among them, photosensitizer 6 has the highest singlet oxygen yield, with Φ in DMF being similar to that in DMF. Δ It is 0.59.

[0091] Example 3: In vitro antitumor activity test

[0092] The photosensitizers in this embodiment are photosensitizers 1-12, zinc phthalocyanine (ZnPc), and photosensitizer 13 (the structure of which can be found in the background section of this invention).

[0093] The in vitro antitumor activity of the photosensitizer was determined using the CCK-8 assay. 5000 HeLa cells were seeded into each well of a 96-well plate and cultured overnight at 37°C. After discarding the original culture medium, 100 μL of culture medium containing different concentrations (10 μM, 2.5 μM, 0.625 μM, 156.25 nM, 39.06 nM, and 9.77 nM) of photosensitizer was added to each well, with each experiment repeated three times. The cells were incubated at 37°C for 6 hours and then subjected to light treatment at a light dose of 27 J / cm². 2 The light source was a 90mW halogen lamp. After light treatment, the cells were cultured for another 24 hours. The culture medium was then removed, and DMEM medium containing 10% CCK-8 was added. The cells were incubated at 37°C for another 2 hours. The OD value (450nm) was measured using a microplate reader. The IC50 value was calculated based on the microplate reader reading, and the specific results are shown in Table 2. Table 2 shows the phototoxicity and dark toxicity test results (IC50) of the photosensitizer synthesized in this invention on HeLa cells. 50 Value, unit: μM).

[0094] Table 2

[0095]

[0096] IC reference for compound ZnPc 50 The value is 3.76 μM, which is the IC50 value of photosensitizers 1-12 mentioned in this invention. 50 The values ​​were all below 0.17 μM, among which photosensitizer 12 exhibited the strongest phototoxicity, with an IC50 value of [missing value] for HeLa cells. 50 With a concentration of only 0.09 μM, the photosensitizers synthesized in this invention all exhibit superior phototoxicity compared to ZnPc, and all photosensitizers synthesized in this invention exhibit superior antitumor activity compared to the reference photosensitizer 13.

[0097] Example 4: Organelle Colocalization Test

[0098] HeLa cells were cultured in DMEM medium for 24 hours, then incubated with DMEM medium containing photosensitizer 12 at 37°C for 6 hours. The original medium was discarded, and the cells were washed three times with PBS. Medium containing the cell membrane localization dye CFTM350 WGA (500 nM) was then added, and incubation continued for 15 minutes. Finally, the medium was discarded, and fresh medium was added. The distribution of the cell membrane localization dye and photosensitizer at the cell sites was observed using laser confocal microscopy. Results are as follows: Figure 1As shown, the photosensitizer 12 synthesized in this invention exhibits good cell membrane localization ability. Therefore, the phospholipid-polyethylene glycol modified monoiodine aza-BODIPY photosensitizer involved in this invention can be prepared into a novel membrane-targeted photodynamic therapy drug.

[0099] The embodiments described above are merely preferred embodiments of the present invention and are only used to explain the present invention. They are not intended to limit the scope of the present invention. For those skilled in the art, other implementation methods can be easily made by substitution or modification based on the technical content disclosed in this specification. Therefore, all changes and improvements made to the principles and process conditions of the present invention should be included within the scope of the patent application of the present invention.

Claims

1. A phospholipid-polyethylene glycol modified monoiodide aza-BODIPY photosensitizer, characterized in that, The photosensitizer is a compound having the following structural formula: Where n is an integer from 1 to 16, and the dashed line indicates whether the CC key exists or not.

2. The phospholipid-polyethylene glycol modified monoiodide aza-BODIPY photosensitizer according to claim 1, characterized in that, The photosensitizer is a compound with any of the following chemical structures:

3. The method for synthesizing a phospholipid-polyethylene glycol modified monoiodide aza-BODIPY photosensitizer according to any one of claims 1 to 2, characterized in that, Includes the following steps: Step 1: Dissolve aza-BODIPY precursor 1 in DMF, add potassium carbonate and tert-butyl bromoacetate, react at 90°C for 1 h, after the reaction is complete, extract and dry to obtain precursor 2; The structural formula of the aza-BODIPY precursor 1 is as follows: Step 2: Dissolve precursor 2 in , react at room temperature for 3 h, then adjust the pH of the solution to 5, recrystallize in petroleum ether and dichloromethane and collect the solid, then dissolve the solid in a mixed solution of dichloromethane and acetic acid, add N-iodosuccinimide, react at room temperature for 2 h, after the reaction is complete, evaporate the solvent to obtain precursor 3. Step 3: Dissolve precursor 3 in dichloromethane, then add phospholipid-polyethylene glycol derivative, DIPEA and HATU, react at room temperature for 2 h, extract and dry to obtain the final product.

4. The method for synthesizing a phospholipid-polyethylene glycol modified monoiodide aza-BODIPY photosensitizer according to claim 3, characterized in that, Includes the following steps: Step 1: Dissolve 1 mmol of aza-BODIPY precursor 1 in 100 mL of DMF, add 2 mmol of potassium carbonate and 2 mmol of tert-butyl bromoacetate, react at 90 °C for 1 h, after the reaction is complete, extract with water and dichloromethane, collect the organic phase and dry it, remove the solvent by vortexing to obtain precursor 2. Step 2: Dissolve precursor 2 obtained in Step 1 in 50 mL of a mixed solvent of dichloromethane and trifluoroacetic acid, with a volume ratio of dichloromethane to trifluoroacetic acid of 1:

1. React at room temperature for 3 h. Then adjust the pH of the solution to 5, recrystallize in petroleum ether and dichloromethane and collect the solid. Then dissolve the solid in 50 mL of a mixed solution of dichloromethane and acetic acid, with a volume ratio of dichloromethane to acetic acid of 3:

1. Add 1.1 mmol of N-iodosuccinimide and react at room temperature for 2 h. After the reaction is complete, evaporate the solvent to obtain precursor 3. Step 3: The precursor 3 obtained in step 2 was dissolved in dichloromethane, and then 1.5 mmol of phospholipid-polyethylene glycol derivative, 2 mmol of DIPEA and 2 mmol of HATU were slowly added. The mixture was reacted at room temperature for 2 h, extracted with water and dichloromethane, the organic phase was collected and dried, the solvent was removed by rotary evaporation and then the final product was obtained by silica gel column chromatography.

5. The use of a phospholipid-polyethylene glycol modified monoiodine aza-BODIPY photosensitizer according to any one of claims 1 to 2 in the preparation of membrane-targeted photodynamic therapy drugs.

6. The use of a phospholipid-polyethylene glycol modified monoiodine aza-BODIPY photosensitizer according to any one of claims 1 to 2 in the preparation of a photodynamic therapy drug for nonspecific and broad-spectrum tumors.

7. The application according to claim 6, characterized in that, The nonspecific, broad-spectrum tumors mentioned include pancreatic cancer, cervical cancer, glioma, lung cancer, stomach cancer, bladder cancer, ovarian cancer, colon cancer, skin cancer, or prostate cancer.

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