Metal-based photosensitizers, pharmaceutical compositions and their applications

Abstract

This invention discloses a metal-based photosensitizer, a pharmaceutical composition, and its applications. The structure of the metal-based photosensitizer is shown in formula (I). This photosensitizer is molecularly designed based on a receptor-donor-receptor π-conjugated structure, and the chalcogen atoms of the receptor backbone molecule, the length of the receptor side chain, the length of the alkyl chain on the central nitrogen of the receptor, and the length of the donor have been adapted and optimized. Its nano-formulation has a maximum absorption peak in the near-infrared region, making it suitable for long-wavelength photodynamic therapy and photothermal therapy with strong tissue penetration. This metal-based photosensitizer not only has strong reactive oxygen species generation properties but also good biocompatibility and strong antitumor activity, showing excellent prospects for application in the preparation of tumor therapeutic drugs.

Description

Technical Field

[0001] This invention relates to photosensitizers, and more particularly to a metal-based photosensitizer, a pharmaceutical composition, and its application. Background Technology

[0002] Photodynamic therapy (PDT) and photothermal therapy (PTT) are cancer treatments based on photosensitizers (PSs) and laser activation, attracting attention due to their non-invasiveness and high spatiotemporal selectivity. PDT utilizes photosensitizers to generate reactive oxygen species (ROS) under specific wavelengths of light, inducing chemical damage to tumor cells. However, its effectiveness is limited by the hypoxic microenvironment commonly found in solid tumors, and traditional type II photosensitizers are highly dependent on oxygen. Meanwhile, PTT uses photothermal converters to convert light energy into heat energy, directly ablating tumor tissue at high temperatures, typically requiring more energy than PDT.

[0003] Combining photothermal therapy (PDT) with total photothermal therapy (PTT) has significant synergistic therapeutic benefits: the localized high temperature generated by the photothermal effect can not only directly kill cells but also improve local blood perfusion in the tumor, alleviating hypoxia and thus enhancing the efficacy of PDT; simultaneously, the photothermal effect can also promote drug release, achieving precise synergy across multiple treatment modalities. This combined strategy is sometimes also integrated with chemotherapy, immunotherapy, and other methods, aiming to compensate for the shortcomings of single therapies, achieve better therapeutic effects, and reduce adverse reactions.

[0004] The development of photosensitizers is crucial for improving the efficacy of phototherapy. Among them, metal complexes have become highly promising photosensitizer materials due to their unique advantages. They typically possess strong spin-orbit coupling effects, effectively promoting intersystem crossing, prolonging excited-state lifetimes, and thus optimizing the photophysical and photochemical properties of the photosensitizer. However, the clinical translation of metal-based photosensitizers still faces challenges: on the one hand, the excitation wavelengths of most metal-based photosensitizers are still mostly in the visible light region, limiting their penetration into deep tissues; on the other hand, many metal complexes are inherently oxygen-dependent, resulting in poor efficacy in hypoxic environments. Summary of the Invention

[0005] Purpose of the invention: The purpose of this invention is to provide a metal-based photosensitizer with an excitation wavelength in the near-infrared band, which can be applied to both photodynamic therapy and photothermal therapy; the second purpose is to provide a pharmaceutical composition containing the metal-based photosensitizer and its application.

[0006] Technical solution: The metal-based photosensitizer of the present invention has the structure shown in formula (I): Formula (I), Wherein, X is selected from either sulfur or selenium, and R1 is selected from... , R2 is selected from any of the following. , , , , R3 is selected from any of the following. , , , , , , , , any of them, Selected from , , , , any of them, 0 or 1 + or 2 + , Composed of 0, 1, or 2 halide ions, trifluoromethanesulfonate, or ClO4 - or PF6 - composition; The Selected from , , , , R is selected from any one of H, halogen, alkyl, and alkoxy; Selected from , , , , any of them, M 1 Selected from iridium or osmium; the Selected from , , any of them, M 2 Selected from ruthenium, osmium, or iridium; the M 3 Selected from manganese or rhenium; the Selected from , , Any one of them.

[0007] Preferably, the metal-based photosensitizer has a structure as shown in formula (Ⅱ-1): Formula (II-1), Among them, X, R1, R2, R3, R is defined as described above, and A is selected from halide ions, trifluoromethanesulfonate ions, and PF6. - Any one of them.

[0008] Preferably, the metal-based photosensitizer has a structure as shown in formula (II-2): Equation (II-2), Among them, X, R1, R2, R3, M 1 As defined above, A is selected from halide ions, trifluoromethanesulfonate ions, and PF6. - Any one of them.

[0009] Preferably, the metal-based photosensitizer has a structure as shown in formula (Ⅱ-3): Formula (II-3), Among them, X, R1, R2, R3, M 2 As defined above, A is selected from halide ions, trifluoromethanesulfonate ions, and PF6. - Any one of them.

[0010] Preferably, the metal-based photosensitizer has a structure as shown in formula (II-4): Equation (II-4), Among them, X, R1, R2, R3, M 3 Same as the definition above.

[0011] Preferably, the metal-based photosensitizer has a structure as shown in formula (II-5): Equation (II-5), Among them, X, R1, R2, R3, Same as the definition above.

[0012] Preferably, the metal-based photosensitizer has a structure as shown in any one of Formulas 1-22: , , , , , , , , , , , , , , , , , , , , , .

[0013] The pharmaceutical composition of the present invention contains the aforementioned metal-based photosensitizer as an active ingredient.

[0014] Preferably, the pharmaceutical composition further comprises pharmaceutically acceptable excipients, specifically including: excipients, diluents, lubricants, flow aids, wetting agents, emulsifiers, pH buffers, solubilizers, cosolvents, or any one or more solvents. The application of the metal-based photosensitizer or pharmaceutical composition described in this invention in the preparation of tumor therapeutic drugs.

[0015] Preferably, the application is in the preparation of drugs for tumor photodynamic therapy and / or photothermal therapy.

[0016] Preferably, the dosage form of the drug includes tablets, capsules, granules, powders, chewable tablets, effervescent tablets, sustained-release tablets, microcapsules, injections, infusions, suspensions, patches, suppositories, transdermal patches, microemulsions, liposomes, and nanoparticles.

[0017] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages: 1. The metal-based photosensitizer is molecularly designed based on the π-conjugated structure of the receptor-donor-receptor, and the chalcogen atoms of the receptor backbone molecule, the length of the receptor side chain, the length of the alkyl chain on the central nitrogen of the receptor, and the length of the donor have been adapted and optimized. Its nano-formulation has the maximum absorption peak in the near-infrared region, which is suitable for long-wavelength photodynamic therapy and photothermal therapy with strong tissue penetration ability; 2. The metal-based photosensitizer not only has strong reactive oxygen generation performance, but also has good biocompatibility and strong anti-tumor activity, and has excellent prospects for application in the preparation of tumor therapeutic drugs. Attached Figure Description

[0018] Figure 1 The graph shows the results of the maximum absorption wavelength determination of the metal-based photosensitizer and its nano-formulation in Example 1. Figure 2 The graph shows the results of the photothermal performance measurement of the metal-based photosensitizer nanoformulation in Example 1. Figure 3 The graph shows the results of the photodynamic reaction performance measurement of the metal-based photosensitizer nanoformulation in Example 1 after 5 min of excitation. Figure 4 The graph shows the results of the cancer cell killing performance determination of the metal-based photosensitizer nanoformation in Example 1. Detailed Implementation

[0019] The technical solution of the present invention will be further described below.

[0020] The compounds in the examples are all based on the small molecule structure of metal-based photosensitizers as shown in formula (I): Formula (I).

[0021] The synthesis route is as follows: .

[0022] Example 1: In the small molecule structure of the metal-based photosensitizer shown in formula (I), for R1 is R2 is R3 is X is sulfur. 1 + , For Cl - Its structure is shown in equation (1):

[0023] Its synthetic route is as follows: .

[0024] The specific preparation method is as follows: (1) Dissolve 500 mg of Ⅰ-1-1 in THF, add 13 mL of 1 mM LiAlH4 THF solution under ice bath conditions, react at 80 °C for 12 h, quench with ice water, extract with dichloromethane, dry with anhydrous magnesium sulfate and then add 300 mg of Ⅰ-1-2 directly to the next step of the reaction.

[0025] (2) 300 mg of I-1-2 and I-1-3 were dissolved in 20 mL of a mixed solution of chloroform and glacial acetic acid (volume ratio 3:1), and reacted at 110 °C for 24 h. The mixture was then separated by column chromatography (eluents were dichloromethane and methanol) to obtain 230 mg of I-1-4. The 1H NMR data are as follows: 1 H NMR (400 MHz, Chloroform- d ) δ 8.74 (dd, J = 4.1, 2.0 Hz, 2H), 8.06 (dd, J = 7.1, 2.0 Hz, 2H), 7.59 (dd, J = 7.1, 4.1 Hz, 2H), 7.19 (s, 2H), 5.39 - 5.27 (m, 2H), 4.27 (dd, J = 5.5, 2.8 Hz, 4H), 2.71 (t, J = 7.5 Hz, 4H), 1.84 (pt, J= 6.8, 5.5 Hz, 2H), 1.65 - 1.52 (m, 4H), 1.45 - 1.22 (m, 64H), 0.89(tdd, J = 7.3, 3.5, 2.0 Hz, 19H).

[0026] (3) 230 mg of I-1-4 was dissolved in 20 mL of 1,2-dichloroethane and 5 mL of DMF, and 2 mL of phosphorus oxychloride was added. The mixture was reacted at 70 °C for 12 h. The reaction was separated by column chromatography (eluents were dichloromethane and methanol) to obtain 182 mg of I-1-5. The 1H NMR data are as follows: 1 H NMR (400 MHz, Chloroform- d ) δ 9.87 (s, 2H), 8.74 (dd, J = 4.1, 2.0Hz, 2H), 8.06 (dd, J = 7.1, 2.0 Hz, 2H), 7.59 (dd, J = 7.1, 4.1 Hz, 2H), 5.39 -5.27 (m, 2H), 4.27 (dd, J = 5.5, 2.8 Hz, 4H), 2.91 (td, J = 7.7, 1.2 Hz, 4H), 1.84 (pt, J = 6.8, 5.5 Hz, 2H), 1.65 - 1.52 (m, 4H), 1.45 - 1.35 (m, 9H), 1.35(t, J = 1.5 Hz, 2H), 1.37 - 1.31 (m, 4H), 1.35 - 1.22 (m, 48H), 0.89 (tdd, J =7.3, 3.5, 2.0 Hz, 20H).

[0027] (4) Dissolve 182 mg I-1-5 and 142 mg I-1-6 in 15 mL toluene, add 100 μL of boron trifluoride ether and 500 μL of acetic anhydride, react at 60 °C for 10 min, separate by column chromatography (eluents were dichloromethane and methanol) to obtain 120 mg I-1-7. The 1H NMR data are as follows: 1 H NMR (400 MHz, Chloroform- d ) δ 8.74 (dd, J= 4.1,2.0 Hz, 2H), 8.09 - 8.02 (m, 4H), 7.65 - 7.54 (m, 6H), 5.39 - 5.27 (m, 2H), 4.27 (dd, J = 5.5, 2.8 Hz, 4H), 3.02 - 2.83 (m, 4H), 1.84 (pt, J = 6.8, 5.5 Hz,2H), 1.65 - 1.50 (m, 4H), 1.45 - 1.34 (m, 6H), 1.39 - 1.33 (m, 4H), 1.38 -1.26 (m, 27H), 1.31 - 1.22 (m, 26H), 0.89 (tdd, J = 7.3, 3.5, 2.0 Hz, 19H).

[0028] Equation (MN1)

[0029] (5) 30 mg of Ⅰ-1-7 and 20 mg of the compound with the structure shown in formula (MN1) were dissolved in a mixed solution of dichloromethane and methanol (volume ratio 3:1) and reacted at 40 °C for 12 h. The mixture was then separated by column chromatography (eluents were dichloromethane and methanol) to obtain 25 mg of the metal-based photosensitizer with the structure shown in formula (1). The 1H NMR data are as follows: 1 H NMR (400 MHz, CH3CN- d ) δ8.28 (dd, J = 7.8, 1.4 Hz, 2H), 8.20 - 8.08 (m, 4H), 8.04 (d, J = 1.7 Hz, 2H),8.02 - 7.90 (m, 6H), 7.80 (td, J = 7.7, 1.2 Hz, 2H), 7.68 - 7.59 (m, 3H), 7.62(s, 3H), 7.42 (s, 2H), 7.21 (td, J = 7.6, 1.4 Hz, 2H), 7.11 (td, J = 7.3, 1.4 Hz, 2H), 6.97 (ddd, J= 9.8, 7.1, 1.3 Hz, 2H), 6.62 (s, 2H), 5.39 - 5.27 (m, 2H), 4.34 - 4.20 (m, 4H), 3.02 - 2.83 (m, 4H), 1.84 (pt, J = 6.8, 5.5 Hz, 2H), 1.65- 1.50 (m, 4H), 1.45 - 1.22 (m, 60H), 0.89 (tdd, J = 7.2, 3.4, 2.0 Hz, 18H).

[0030] Example 2: In the small molecule structure of the metal-based photosensitizer shown in formula (I), for R1 is R2 is R3 is X represents selenium. 1 + , For Cl - Its structure is shown in equation (2):

[0031] Its synthetic route is as follows: .

[0032] Specific preparation methods include: (1) Dissolve 500 mg of Ⅰ-2-1 in THF, add 13 mL of 1 mM LiAlH4 THF solution under ice bath conditions, react at 80 °C for 12 h, quench with ice water, extract with dichloromethane, dry with anhydrous magnesium sulfate and then add 280 mg of Ⅰ-2 directly to the next step of the reaction.

[0033] (2) 280 mg of I-2-2 and I-2-3 were dissolved in 20 mL of a mixed solution of chloroform and glacial acetic acid (volume ratio 3:1), and reacted at 110 °C for 24 h. The solutions were then separated by column chromatography (eluents were dichloromethane and methanol) to obtain 200 mg of I-2-4. The 1H NMR data are as follows: 1 H NMR (400 MHz, Chloroform- d ) δ 8.74 (dd, J = 4.1, 2.0 Hz, 2H), 8.06 (dd, J = 7.1, 2.0 Hz, 2H), 7.95 - 7.88 (m, 1H), 7.59 (dd, J= 7.1, 4.1 Hz,2H), 5.39 - 5.27 (m, 2H), 4.29 - 4.12 (m, 4H), 2.73 (tt, J = 6.9, 1.0 Hz, 4H), 1.84 (pt, J = 6.8, 5.5 Hz, 2H), 1.52 - 1.21 (m, 68H), 0.89 (tdd, J = 7.3, 3.4, 2.0 Hz, 18H).

[0034] (3) 200 mg of I-2-4 was dissolved in 20 mL of 1,2-dichloroethane and 5 mL of DMF, and 2 mL of phosphorus oxychloride was added. The mixture was reacted at 70 °C for 12 h. The reaction was separated by column chromatography (eluents were dichloromethane and methanol) to obtain 165 mg of I-2-5. The 1H NMR data are as follows: 1 H NMR (400 MHz, Chloroform- d ) δ 9.61 (s, 2H), 8.74 (dd, J = 4.1, 2.0Hz, 2H), 8.06 (dd, J = 7.1, 2.0 Hz, 2H), 7.59 (dd, J = 7.1, 4.1 Hz, 2H), 5.39 -5.27 (m, 2H), 4.29 - 4.12 (m, 4H), 2.60 (td, J = 7.0, 2.3 Hz, 4H), 1.84 (pt, J =6.8, 5.5 Hz, 2H), 1.53 - 1.40 (m, 4H), 1.46 - 1.33 (m, 8H), 1.38 - 1.28 (m,19H), 1.33 - 1.21 (m, 37H), 0.89 (tdd, J = 7.2, 3.4, 2.0 Hz, 19H).

[0035] (4) Dissolve 165 mg I-2-5 and 81 mg I-2-6 in 12 mL of toluene, add 100 μL of etherified boron trifluoride and 500 μL of acetic anhydride, and react at 60 °C for 10 min to obtain 120 mg I-7. The 1H NMR data are as follows: 1 H NMR (400MHz, Chloroform- d ) δ 8.74 (dd, J= 4.1, 2.0 Hz, 2H), 8.10 - 8.01 (m, 4H), 7.66- 7.54 (m, 4H), 7.36 (s, 2H), 5.39 - 5.27 (m, 2H), 4.29 - 4.12 (m, 4H), 2.67- 2.50 (m, 4H), 1.84 (pt, J = 6.8, 5.5 Hz, 2H), 1.53 - 1.39 (m, 4H), 1.45 -1.33 (m, 10H), 1.38 - 1.29 (m, 10H), 1.33 - 1.21 (m, 44H), 0.89 (tdd, J = 7.2, 3.4, 2.0 Hz, 19H).

[0036] (5) 30 mg of I-2-7 and 20 mg of the compound with the structure shown in formula (MN1) were dissolved in a mixed solution of dichloromethane and methanol (volume ratio 3:1) and reacted at 40 °C for 12 h. The mixture was separated by column chromatography (eluents were dichloromethane and methanol) to obtain 25 mg of the metal-based photosensitizer with the structure shown in formula (2). The 1H NMR data are as follows: 1 H NMR (400 MHz, CH3CN- d ) δ8.28 (dd, J = 8.3, 1.4 Hz, 2H), 8.19 - 8.09 (m, 4H), 8.05 (d, J = 1.6 Hz, 2H),8.02 - 7.90 (m, 6H), 7.80 (td, J = 7.7, 1.3 Hz, 2H), 7.68 - 7.61 (m, 4H), 7.42(s, 1H), 7.36 (s, 1H), 7.21 (td, J = 7.7, 1.5 Hz, 2H), 7.11 (td, J = 7.5, 1.4 Hz, 2H), 6.97 (ddd, J = 9.7, 7.1, 1.2 Hz, 2H), 6.62 (s, 1H), 5.38 - 5.28 (m, 2H), 4.28 - 4.13 (m, 4H), 2.66 - 2.51 (m, 4H), 1.84 (tt, J= 6.8, 5.4 Hz, 2H), 1.51- 1.42 (m, 3H), 1.47 - 1.37 (m, 3H), 1.41 - 1.34 (m, 6H), 1.37 - 1.28 (m,19H), 1.33 - 1.22 (m, 36H), 0.95 - 0.83 (m, 18H).

[0037] Example 3: In the small molecule structure of the metal-based photosensitizer shown in formula (I), for R1 is R2 is R3 is X is sulfur. 2 + , 2Cl - Its structure is shown in equation (3):

[0038] Specific preparation methods include: The synthesis was carried out according to the synthesis steps in Example 1, wherein steps 1 to 4 were the same as in Example 1, and in step 5, MN was replaced with 10 mg of cis-bis(2,2-dipyridine)ruthenium(II) dichloride hydrate, finally yielding 26 mg of a metal-based photosensitizer with the structure shown in formula (3). The 1H NMR data are as follows: 1 H NMR (400 MHz, CH3CN- d ) δ 8.46 (dd, J = 8.6, 1.5Hz, 2H), 8.29 (dd, J = 8.6, 1.1 Hz, 4H), 8.16 (ddd, J = 9.8, 7.4, 1.4 Hz, 2H),8.04 (d, J = 1.7 Hz, 2H), 7.92 (dd, J = 8.7, 7.3 Hz, 2H), 7.77 (dd, J = 8.3, 1.4Hz, 4H), 7.67 - 7.59 (m, 5H), 7.47 (ddd, J = 8.5, 7.6, 1.2 Hz, 4H), 7.24 - 7.12(m, 7H), 5.39 - 5.27 (m, 2H), 4.34 - 4.20 (m, 4H), 3.02 - 2.83 (m, J= 7.7 Hz, 4H), 1.84 (pt, J = 6.8, 5.5 Hz, 2H), 1.65 - 1.50 (m, 4H), 1.45 - 1.22 (m, 59H), 0.89 (tdd, J = 7.3, 3.4, 2.0 Hz, 18H).

[0039] Example 4: In the small molecule structure of the metal-based photosensitizer shown in formula (I), for R1 is R2 is R3 is X represents selenium. 2 + , 2Cl - Its structure is shown in equation (4):

[0040] Specific preparation methods include: The synthesis was carried out according to the steps in Example 2, wherein steps 1 to 4 were the same as in Example 2, and in step 5, MN was replaced with 10 mg of cis-bis(2,2-dipyridine)ruthenium(II) dichloride hydrate, finally yielding 34 mg of a metal-based photosensitizer with the structure shown in formula (4). The 1H NMR data are as follows: 1 H NMR (400 MHz, CH3CN- d ) δ 8.46 (dd, J = 8.6, 1.5Hz, 2H), 8.29 (dd, J = 8.6, 1.2 Hz, 4H), 8.16 (ddd, J = 9.8, 7.4, 1.4 Hz, 2H),8.05 (d, J = 1.7 Hz, 2H), 7.92 (dd, J = 8.7, 7.3 Hz, 2H), 7.77 (dd, J = 8.3, 1.4Hz, 4H), 7.67 - 7.60 (m, 4H), 7.47 (ddd, J = 8.5, 7.6, 1.2 Hz, 4H), 7.36 (s,2H), 7.24 - 7.12 (m, 7H), 5.33 (q, J= 7.1 Hz, 2H), 4.29 - 4.12 (m, 4H), 2.67 -2.50 (m, 4H), 1.84 (pt, J = 6.8, 5.5 Hz, 2H), 1.53 - 1.21 (m, 64H), 0.89 (tdd, J = 7.3, 3.4, 2.0 Hz, 18H).

[0041] Example 5: In the small molecule structure of the metal-based photosensitizer shown in formula (I), for R1 is R2 is R3 is X is sulfur. 2 + , 2Cl - Its structure is shown in equation (5):

[0042] Specific preparation methods include: The synthesis was carried out according to the steps in Example 1, wherein steps 1-4 were the same as in Example 1, and in step 5, MN was replaced with 9 mg of bis(2,2-bipyridine)osmium(II) dichloride, yielding 24 mg of a metal-based photosensitizer with the structure shown in formula (5). The 1H NMR data are as follows: 1 H NMR (400 MHz, CH3CN- d ) δ 8.46 (dd, J = 8.4, 1.6 Hz, 2H), 8.28(dd, J = 8.6, 1.2 Hz, 4H), 8.15 (dt, J = 7.4, 1.7 Hz, 2H), 8.10 (dd, J = 8.4, 7.3Hz, 2H), 8.04 (d, J = 1.7 Hz, 2H), 7.91 (s, 2H), 7.75 (dd, J = 8.3, 1.4 Hz, 4H), 7.62 (d, J = 1.5 Hz, 4H), 7.48 (ddd, J = 8.5, 7.6, 1.2 Hz, 4H), 7.28 - 7.16 (m,8H), 5.39 - 5.27 (m, 2H), 4.27 (dd, J= 5.5, 2.8 Hz, 4H), 3.02 - 2.83 (m, J = 7.7Hz, 4H), 1.84 (pt, J = 6.8, 5.5 Hz, 2H), 1.65 - 1.50 (m, 4H), 1.45 - 1.36 (m,3H), 1.41 - 1.32 (m, 8H), 1.31 (ddt, J = 9.8, 5.2, 1.8 Hz, 18H), 1.31 - 1.22(m, 31H), 0.89 (tdd, J = 7.3, 3.4, 2.0 Hz, 18H).

[0043] Example 6: In the small molecule structure of the metal-based photosensitizer shown in formula (I), for R1 is R2 is R3 is X represents selenium. 2 + , 2Cl - Its structure is shown in equation (6):

[0044] Specific preparation methods include: The synthesis was carried out according to the steps in Example 2, wherein steps 1-4 were the same as in Example 2, and in step 5, MN was replaced with 9 mg of bis(2,2-bipyridine)osmium(II) dichloride, yielding 36 mg of a metal-based photosensitizer with the structure shown in formula (6). The 1H NMR data are as follows: 1 H NMR (400 MHz, CH3CN- d ) δ 8.46 (dd, J = 8.4, 1.6 Hz, 2H), 8.28(dd, J = 8.6, 1.2 Hz, 4H), 8.20 - 8.02 (m, 6H), 7.91 (s, 2H), 7.75 (dd, J = 8.3, 1.4 Hz, 4H), 7.63 (d, J = 1.7 Hz, 2H), 7.48 (ddd, J = 8.5, 7.5, 1.2 Hz, 4H), 7.36(s, 2H), 7.28 - 7.16 (m, 7H), 5.33 (q,J = 7.1 Hz, 2H), 4.29 - 4.12 (m, 4H), 2.67 - 2.50 (m, 4H), 1.84 (pt, J = 6.8, 5.5 Hz, 2H), 1.53 - 1.39 (m, 4H), 1.45- 1.33 (m, 6H), 1.39 - 1.26 (m, 25H), 1.32 - 1.24 (m, 20H), 1.27 (d, J = 2.0Hz, 11H), 0.89 (tdd, J = 7.2, 3.4, 2.0 Hz, 18H).

[0045] Example 7: In the small molecule structure of the metal-based photosensitizer shown in formula (I), for R1 is R2 is R3 is X is sulfur. 1 + , For Cl - Its structure is shown in equation (7):

[0046] Specific preparation methods include:

[0047] The synthesis was carried out according to the synthesis steps in Example 1, wherein steps 1 to 4 are the same as in Example 1, and in step 5, MN is replaced with 15 mg yielded 23 mg of a metal-based photosensitizer with the structure shown in formula (7). The 1H NMR spectroscopy data are as follows: 1 H NMR (400 MHz, CH3CN- d ) δ 8.74 (dd, J = 6.4, 1.5 Hz, 2H), 8.28 (dt, J =7.3, 1.6 Hz, 2H), 8.04 (d, J = 1.7 Hz, 2H), 7.96 (dd, J = 7.4, 6.3 Hz, 2H), 7.62(d, J = 1.6 Hz, 4H), 7.06 (s, 2H), 6.91 (dq, J = 5.0, 1.0 Hz, 2H), 6.77 (dd, J=5.0, 1.0 Hz, 2H), 5.39 - 5.27 (m, 2H), 4.36 - 4.18 (m, 4H), 3.02 - 2.83 (m,7H), 2.82 (ddt, J = 13.3, 6.6, 1.0 Hz, 1H), 2.24 - 2.19 (m, 2H), 1.84 (pt, J =6.8, 5.5 Hz, 2H), 1.65 - 1.50 (m, 4H), 1.48 - 1.22 (m, 62H), 0.96 - 0.85 (m, 25H).

[0048] Example 8: In the small molecule structure of the metal-based photosensitizer shown in formula (I), for R1 is R2 is R3 is X is sulfur. 1 + , For Cl - Its structure is shown in equation (8):

[0049] The synthesis was carried out according to the synthesis steps in Example 1, wherein steps 1 to 4 are the same as in Example 1, and in step 5, MN is replaced with 17 mg yielded 28 mg of a metal-based photosensitizer with the structure shown in formula (8). The 1H NMR data are as follows: 1 H NMR (400 MHz, CH3CN- d ) δ 8.74 (dd, J = 6.4, 1.5 Hz, 2H), 8.27 (ddd, J = 6.9, 5.3, 1.4 Hz, 2H), 8.04 (d, J = 1.7 Hz, 2H), 7.62 (d, J = 1.6 Hz, 4H), 7.52(dd, J = 7.4, 6.3 Hz, 2H), 7.51 (s, 2H), 6.91 (dq, J = 5.0, 1.0 Hz, 2H), 6.77(dd, J= 5.0, 1.0 Hz, 2H), 5.39 - 5.27 (m, 2H), 4.36 - 4.18 (m, 4H), 3.02 -2.77 (m, 8H), 2.24 - 2.19 (m, 2H), 1.84 (pt, J = 6.8, 5.5 Hz, 2H), 1.65 - 1.50 (m, 4H), 1.48 - 1.22 (m, 62H), 0.96 - 0.85 (m, 25H).

[0050] Example 9: In the small molecule structure of the metal-based photosensitizer shown in formula (I), for R1 is R2 is R3 is X is sulfur. 1 + , For Cl - Its structure is shown in equation (9):

[0051] Specific preparation methods include:

[0052] The synthesis was carried out according to the synthesis steps in Example 1, wherein steps 1 to 4 are the same as in Example 1, and in step 5, MN is replaced with 17 mg yielded 29 mg of a metal-based photosensitizer with the structure shown in formula (9). The 1H NMR data are as follows: 1 H NMR (400 MHz, CH3CN- d ) δ 8.74 (dd, J = 6.4, 1.5 Hz, 2H), 8.26 (ddd, J = 10.9, 7.4, 1.4 Hz, 2H), 8.04 (d, J = 1.7 Hz, 2H), 7.98 (dd, J = 7.4, 6.3 Hz, 2H), 7.62 (d, J = 1.6 Hz, 4H), 6.94 - 6.84 (m, 4H), 6.77 (dd, J= 5.0, 1.0 Hz,2H), 5.39 - 5.27 (m, 2H), 4.36 - 4.18 (m, 4H), 2.93 (s, 4H), 3.02 - 2.77 (m,4H), 2.24 - 2.19 (m, 2H), 1.84 (pt, J = 6.8, 5.5 Hz, 2H), 1.65 - 1.50 (m, 4H), 1.48 - 1.35 (m, 7H), 1.39 - 1.30 (m, 10H), 1.35 - 1.25 (m, 31H), 1.30 - 1.22(m, 15H), 0.96 - 0.85 (m, 24H).

[0053] Example 10: In the small molecule structure of the metal-based photosensitizer shown in formula (I), for R1 is R2 is R3 is X represents selenium. 1 + , For Cl - Its structure is shown in equation (10):

[0054] Specific preparation methods include:

[0055] The synthesis was carried out according to the synthesis steps in Example 2, wherein steps 1 to 4 are the same as in Example 2, and in step 5, MN is replaced with 15 mg yielded 35 mg of a metal-based photosensitizer with the structure shown in formula (10). The 1H NMR data are as follows: 1 H NMR (400 MHz, CH3CN- d ) δ 8.74 (dd, J = 6.4, 1.5 Hz, 2H), 8.28 (dt, J = 7.3, 1.6 Hz, 2H), 8.05 (d, J = 1.7 Hz, 2H), 7.96 (dd, J = 7.4, 6.3 Hz, 2H), 7.63 (d, J = 1.7 Hz, 2H), 7.36 (s, 2H), 7.06 (s, 2H), 6.91 (dq, J= 5.0, 1.0 Hz,2H), 6.81 - 6.73 (m, 2H), 5.33 (q, J = 7.1 Hz, 2H), 4.27 (dd, J = 13.4, 5.5 Hz, 2H), 4.13 (dd, J = 13.4, 5.5 Hz, 2H), 2.92 (s, 3H), 2.89 - 2.76 (m, 1H), 2.67 -2.50 (m, 4H), 2.25 - 2.18 (m, 2H), 1.84 (pt, J = 6.9, 5.5 Hz, 2H), 1.53 - 1.21(m, 66H), 0.89 (td, J = 6.8, 3.0 Hz, 25H).

[0056] Example 11: In the small molecule structure of the metal-based photosensitizer shown in formula (I), for R1 is R2 is R3 is X represents selenium. 1 + , For Cl - Its structure is shown in equation (11):

[0057] Specific preparation methods include: The synthesis was carried out according to the synthesis steps in Example 2, wherein steps 1 to 4 are the same as in Example 2, and in step 5, MN is replaced with 17 mg yielded 40 mg of a metal-based photosensitizer with the structure shown in formula (11). The 1H NMR data are as follows: 1 H NMR (400 MHz, CH3CN- d ) δ 8.74 (dd, J = 6.4, 1.5 Hz, 2H), 8.27 (ddd, J = 6.9, 5.3, 1.4 Hz, 2H), 8.05 (d, J = 1.7 Hz, 2H), 7.63 (d, J = 1.7 Hz, 2H), 7.52(dd, J= 7.4, 6.3 Hz, 2H), 7.51 (s, 2H), 7.36 (s, 2H), 6.91 (dq, J = 5.0, 1.0 Hz,2H), 6.81 - 6.73 (m, 2H), 5.33 (q, J = 7.1 Hz, 2H), 4.27 (dd, J = 13.4, 5.5 Hz, 2H), 4.13 (dd, J = 13.4, 5.5 Hz, 2H), 2.92 - 2.76 (m, 4H), 2.67 - 2.50 (m, 4H), 2.25 - 2.18 (m, 2H), 1.84 (pt, J = 6.9, 5.5 Hz, 2H), 1.53 - 1.21 (m, 66H), 0.89(td, J = 6.8, 3.0 Hz, 26H).

[0058] Example 12: In the small molecule structure of the metal-based photosensitizer shown in formula (I), for R1 is R2 is R3 is X represents selenium. 1 + , For Cl - Its structure is shown in equation (12):

[0059] Specific preparation methods include:

[0060] The synthesis was carried out according to the synthesis steps in Example 2, wherein steps 1 to 4 are the same as in Example 2, and in step 5, MN is replaced with 17 mg yielded 39 mg of a metal-based photosensitizer with the structure shown in formula (12). The 1H NMR data are as follows: 1 H NMR (400 MHz, CH3CN- d ) δ 8.74 (dd, J = 6.4, 1.5 Hz, 2H), 8.26 (ddd, J = 10.9, 7.4, 1.4 Hz, 2H), 8.05 (d, J = 1.7 Hz, 2H), 7.98 (dd, J= 7.4, 6.3 Hz, 2H), 7.63 (d, J = 1.7 Hz, 2H), 7.36 (s, 2H), 6.95 - 6.83 (m, 4H), 6.77 (dd, J =5.0, 1.0 Hz, 2H), 5.33 (q, J = 7.1 Hz, 2H), 4.27 (dd, J = 13.4, 5.5 Hz, 2H), 4.13(dd, J = 13.4, 5.5 Hz, 2H), 2.93 (s, 3H), 2.89 - 2.76 (m, 1H), 2.67 - 2.50 (m,4H), 2.25 - 2.18 (m, 2H), 1.84 (pt, J = 6.9, 5.5 Hz, 2H), 1.53 - 1.41 (m, 4H),1.43 (tt, J = 2.9, 1.5 Hz, 1H), 1.44 - 1.35 (m, 6H), 1.39 - 1.30 (m, 9H), 1.35- 1.27 (m, 12H), 1.33 - 1.21 (m, 35H), 0.89 (td, J = 6.8, 3.0 Hz, 26H).

[0061] Example 13: In the small molecule structure of the metal-based photosensitizer shown in formula (I), for R1 is R2 is R3 is X is sulfur. and All are empty, and their structure is shown in equation (13):

[0062] Specific preparation methods include: The synthesis was carried out according to the steps in Example 1, wherein steps 1-4 were the same as in Example 1, and in step 5, MN was replaced with 7 mg of manganese pentacarbonyl bromide, to obtain 23 mg of a metal-based photosensitizer with the structure shown in formula (13). The 1H NMR spectroscopy data are as follows: 1 H NMR (400 MHz, CH3CN- d ) δ 9.58 (dd, J = 7.2, 1.4 Hz, 2H), 8.14 (ddd,J = 7.4,4.3, 1.4 Hz, 2H), 8.04 (d, J = 1.6 Hz, 2H), 7.62 (d, J = 1.5 Hz, 4H), 7.41 (t, J =7.3 Hz, 2H), 6.82 (s, 2H), 5.39 - 5.27 (m, 2H), 4.27 (dd, J = 5.5, 2.7 Hz, 4H),2.91 (hept, J = 7.7 Hz, 4H), 1.84 (pt, J = 6.8, 5.5 Hz, 2H), 1.59 (pd, J = 7.3, 1.3Hz, 4H), 1.45 - 1.22 (m, 64H), 0.97 - 0.83 (m, 20H).

[0063] Example 14: In the small molecule structure of the metal-based photosensitizer shown in formula (I), for R1 is R2 is R3 is X is sulfur. and All are empty, and their structure is shown in equation (14):

[0064] Specific preparation methods include: The synthesis was carried out according to the steps in Example 1, wherein steps 1-4 were the same as in Example 1, and in step 5, MN was replaced with 10 mg of rhenium pentacarbonyl bromide to obtain 25 mg of a metal-based photosensitizer with the structure shown in formula (14). The 1H NMR spectroscopy data are as follows: 1 H NMR (400 MHz, CH3CN- d ) δ 9.58 (dd, J = 7.2, 1.4 Hz, 2H), 8.15 (ddd, J = 7.2,5.6, 1.4 Hz, 2H), 8.04 (d, J = 1.6 Hz, 2H), 8.00 (t, J = 7.3 Hz, 2H), 7.62 (d, J=1.5 Hz, 4H), 6.47 (s, 2H), 5.39 - 5.27 (m, 2H), 4.27 (dd, J = 5.5, 2.7 Hz, 4H),2.91 (hept, J = 7.7 Hz, 4H), 1.84 (pt, J = 6.8, 5.5 Hz, 2H), 1.59 (pd, J = 7.3, 1.3Hz, 4H), 1.45 - 1.22 (m, 64H), 0.97 - 0.83 (m, 20H).

[0065] Example 15: In the small molecule structure of the metal-based photosensitizer shown in formula (I), for R1 is R2 is R3 is X represents selenium. and All are empty, and their structure is shown in equation (15):

[0066] Specific preparation methods include: The synthesis was carried out according to the steps in Example 2, wherein steps 1-4 were the same as in Example 2, and in step 5, MN was replaced with 7 mg of manganese pentacarbonyl bromide to obtain 20 mg of a metal-based photosensitizer with the structure shown in formula (15). The 1H NMR spectroscopy data are as follows: 1 H NMR (400 MHz, CH3CN- d ) δ 9.58 (dd, J = 7.2, 1.4 Hz, 2H), 8.14 (ddd, J = 7.4,4.3, 1.4 Hz, 2H), 8.05 (d, J = 1.7 Hz, 2H), 7.63 (d, J = 1.7 Hz, 2H), 7.46 - 7.33(m, 4H), 6.82 (s, 2H), 5.33 (q, J= 7.1 Hz, 2H), 4.29 - 4.12 (m, 4H), 2.67 -2.50 (m, 4H), 1.92 - 1.76 (m, 2H), 1.53 - 1.40 (m, 4H), 1.45 - 1.34 (m, 6H),1.40 - 1.30 (m, 13H), 1.34 - 1.25 (m, 28H), 1.27 (s, 8H), 1.27 (d, J = 2.0 Hz, 11H), 0.89 (tdd, J = 7.2, 3.4, 2.0 Hz, 18H).

[0067] Example 16: In the small molecule structure of the metal-based photosensitizer shown in formula (I), for R1 is R2 is R3 is X represents selenium. and All are empty, and their structure is shown in equation (16):

[0068] Specific preparation methods include: The synthesis was carried out according to the steps in Example 2, wherein steps 1-4 were the same as in Example 2, and in step 5, MN was replaced with 10 mg of rhenium pentacarbonyl bromide to obtain 33 mg of a metal-based photosensitizer with the structure shown in formula (16). The 1H NMR data are as follows: 1 H NMR (400 MHz, CH3CN- d ) δ 9.58 (dd, J = 7.2, 1.4 Hz, 2H), 8.15 (ddd, J = 7.2,5.6, 1.4 Hz, 2H), 8.05 (d, J = 1.7 Hz, 2H), 8.00 (t, J = 7.3 Hz, 2H), 7.63 (d, J =1.7 Hz, 2H), 7.36 (s, 2H), 6.47 (s, 2H), 5.33 (q, J0.89 (tdd, J = 7.2, 3.4, 2.0 Hz, 18H).

[0069] Example 17: In the small molecule structure of the metal-based photosensitizer shown in formula (I), for R1 is R2 is R3 is X is sulfur. 2 + , 2ClO4 - Its structure is shown in equation (17):

[0070] Specific preparation methods include: The synthesis was carried out according to the steps in Example 1, wherein steps 1-4 were the same as in Example 1, and in step 5, MN was replaced with 6 mg of dimethylpyridinium chloride and 8 mg of copper perchlorate hexahydrate, to obtain 27 mg of a metal-based photosensitizer with the structure shown in formula (17). The 1H NMR data are as follows: 1 H NMR (400 MHz, CH3CN- d ) δ 8.74 (dd, J = 4.1, 2.0 Hz, 2H), 8.50 (dd, J = 4.1, 1.7 Hz, 2H), 8.09 - 8.02 (m, 4H), 7.69 (td, J = 7.5, 1.7 Hz,2H), 7.64 - 7.55 (m, 6H), 7.51 (ddd, J = 7.3, 4.1, 1.4 Hz, 2H), 7.31 (dd, J =7.7, 1.4 Hz, 2H), 5.39 - 5.27 (m, 2H), 4.27 (dd, J = 5.5, 2.8 Hz, 4H), 4.01 (d, J = 5.9 Hz, 4H), 3.50 (p, J= 5.9 Hz, 1H), 3.02 - 2.83 (m, 4H), 1.84 (pt, J = 6.8,5.5 Hz, 2H), 1.65 - 1.50 (m, 4H), 1.45 - 1.36 (m, 5H), 1.40 - 1.32 (m, 6H),1.36 - 1.28 (m, 15H), 1.28 (tdd, J = 5.1, 3.8, 2.4 Hz, 36H), 0.89 (tdd, J = 7.2, 3.4, 2.0 Hz, 20H).

[0071] Example 18: In the small molecule structure of the metal-based photosensitizer shown in formula (I), for R1 is R2 is R3 is X is sulfur. 2 + , 2ClO4 - Its structure is shown in equation (18):

[0072] Specific preparation methods include: The synthesis was carried out according to the steps in Example 1, wherein steps 1-4 were the same as in Example 1, and in step 5, MN was replaced with 7 mg of methylbis(2-pyridylmethyl)amine and 8 mg of copper perchlorate hexahydrate, to obtain 28 mg of a metal-based photosensitizer with the structure shown in formula (18). The 1H NMR data are as follows: 1 H NMR (400 MHz, CH3CN- d ) δ 8.74 (dd, J = 4.1, 2.0 Hz, 2H), 8.51 (dd, J = 4.1, 1.7 Hz, 2H), 8.09 - 8.02 (m, 4H), 7.71 (td, J =7.5, 1.7 Hz, 2H), 7.65 - 7.55 (m, 6H), 7.51 (ddd, J = 7.3, 4.2, 1.4 Hz, 2H),7.38 (dd, J = 7.8, 1.4 Hz, 2H), 5.39 - 5.27 (m, 2H), 4.27 (dd, J= 5.5, 2.8 Hz,4H), 3.89 (s, 4H), 3.02 - 2.83 (m, J = 7.7 Hz, 4H), 2.34 (s, 3H), 1.84 (pt, J =6.8, 5.5 Hz, 2H), 1.65 - 1.50 (m, 4H), 1.45 - 1.22 (m, 61H), 0.97 - 0.83 (m, 20H).

[0073] Example 19: In the small molecule structure of the metal-based photosensitizer shown in formula (I), for R1 is R2 is R3 is X is sulfur. 2 + , 2ClO4 - Its structure is shown in equation (19):

[0074] Specific preparation methods include: The synthesis was carried out according to the steps in Example 1, wherein steps 1 to 4 were the same as in Example 1, and in step 5, MN was replaced with 7 mg of N,N-bis(pyridin-2-ylmethyl)prop-2-yn-1-amine and 8 mg of copper perchlorate hexahydrate, to obtain 28 mg of a metal-based photosensitizer with the structure shown in formula (19). The 1H NMR data are as follows: 1 H NMR (400 MHz, CH3CN- d ) δ 8.74(dd, J = 4.1, 2.0 Hz, 2H), 8.51 (dd, J = 4.1, 1.7 Hz, 2H), 8.09 - 8.02 (m, 4H), 7.71 (td, J = 7.6, 1.7 Hz, 2H), 7.65 - 7.55 (m, 6H), 7.51 (ddd, J = 7.3, 4.2, 1.4Hz, 2H), 7.40 (dd, J = 7.8, 1.4 Hz, 2H), 5.39 - 5.27 (m, 2H), 4.27 (dd, J = 5.5,2.8 Hz, 4H), 3.98 (s, 3H), 3.74 (d, J= 3.0 Hz, 2H), 3.02 - 2.83 (m, J = 7.7 Hz, 4H), 2.58 (t, J = 3.0 Hz, 1H), 1.84 (pt, J = 6.8, 5.5 Hz, 2H), 1.65 - 1.50 (m,4H), 1.45 - 1.22 (m, 64H), 0.97 - 0.82 (m, 19H).

[0075] Example 20: In the small molecule structure of the metal-based photosensitizer shown in formula (I), for R1 is R2 is R3 is X represents selenium. 2 + , 2ClO4 - Its structure is shown in equation (20):

[0076] Specific preparation methods include: The synthesis was carried out according to the steps in Example 2, wherein steps 1-4 were the same as in Example 2, and in step 5, MN was replaced with 6 mg of dimethylpyridinium chloride and 8 mg of copper perchlorate hexahydrate, to obtain 37 mg of a metal-based photosensitizer with the structure shown in formula (20). The 1H NMR data are as follows: 1 H NMR (400 MHz, CH3CN- d ) δ 8.74 (dd, J = 4.1, 2.0 Hz, 2H), 8.50 (dd, J = 4.1, 1.7 Hz, 2H), 8.10 - 8.01 (m, 4H), 7.69 (td, J = 7.5, 1.7 Hz,2H), 7.65 - 7.55 (m, 4H), 7.51 (ddd, J = 7.3, 4.1, 1.4 Hz, 2H), 7.36 (s, 2H), 7.31 (dd, J = 7.6, 1.4 Hz, 2H), 5.39 - 5.27 (m, 2H), 4.29 - 4.12 (m, 4H), 4.01(d, J = 5.9 Hz, 4H), 3.50 (p, J= 5.9 Hz, 1H), 2.67 - 2.50 (m, 4H), 1.84 (pt, J =6.8, 5.5 Hz, 2H), 1.53 - 1.21 (m, 67H), 0.89 (tdd, J = 7.2, 3.4, 2.0 Hz, 19H).

[0077] Example 21: In the small molecule structure of the metal-based photosensitizer shown in formula (I), for R1 is R2 is R3 is X represents selenium. 2 + , 2ClO4 - Its structure is shown in equation (21):

[0078] Specific preparation methods include: The synthesis was carried out according to the steps in Example 2, wherein steps 1-4 were the same as in Example 2, and in step 5, MN was replaced with 7 mg of methylbis(2-pyridylmethyl)amine and 8 mg of copper perchlorate hexahydrate, to obtain 38 mg of a metal-based photosensitizer with the structure shown in formula (21). The 1H NMR data are as follows: 1 H NMR (400 MHz, CH3CN- d ) δ 8.74 (dd, J = 4.1, 2.0 Hz, 2H), 8.51 (dd, J = 4.1, 1.7 Hz, 2H), 8.10 - 8.01 (m, 4H), 7.71 (td, J =7.6, 1.7 Hz, 2H), 7.66 - 7.55 (m, 4H), 7.51 (ddd, J = 7.3, 4.2, 1.4 Hz, 2H),7.38 (dd, J = 7.7, 1.4 Hz, 2H), 7.36 (s, 2H), 5.39 - 5.27 (m, 2H), 4.29 - 4.12(m, 4H), 3.89 (s, 3H), 2.67 - 2.50 (m, 4H), 2.34 (s, 3H), 1.84 (pt, J= 6.8,5.5 Hz, 2H), 1.53 - 1.21 (m, 69H), 0.97 - 0.83 (m, 19H).

[0079] Example 22: In the small molecule structure of the metal-based photosensitizer shown in formula (I), for R1 is R2 is R3 is X represents selenium. 2 + , 2ClO4 - Its structure is shown in equation (22):

[0080] Specific preparation methods include: The synthesis was carried out according to the synthesis steps in Example 2, wherein steps 1 to 4 were the same as in Example 2, and in step 5, MN was replaced with 7 mg of N,N-bis(pyridin-2-ylmethyl)prop-2-yn-1-amine and 8 mg of copper perchlorate hexahydrate, to obtain 38 mg of a metal-based photosensitizer with the structure shown in formula (22). The 1H NMR data are as follows: 1 H NMR (400 MHz, CH3CN- d ) δ 8.74(dd, J = 4.1, 2.0 Hz, 2H), 8.51 (dd, J = 4.1, 1.7 Hz, 2H), 8.10 - 8.01 (m, 4H), 7.71 (td, J = 7.6, 1.7 Hz, 2H), 7.66 - 7.55 (m, 4H), 7.51 (ddd, J = 7.3, 4.2, 1.4Hz, 2H), 7.44 - 7.33 (m, 4H), 5.39 - 5.27 (m, 2H), 4.29 - 4.12 (m, 4H), 3.98(s, 3H), 3.74 (d, J = 3.0 Hz, 2H), 2.67 - 2.50 (m, 5H), 1.84 (pt, J= 6.8, 5.5Hz, 2H), 1.53 - 1.41 (m, 4H), 1.46 - 1.36 (m, 3H), 1.41 - 1.28 (m, 20H), 1.34- 1.21 (m, 40H), 0.97 - 0.83 (m, 20H).

[0081] Experimental Example 1: Photophysical Properties Characterization of Metal-Based Photosensitizers 1. Preparation of PEG-coated nanoparticles with metal-based photosensitizers 1 mg of a metal-based photosensitizer with the structure shown in formula (1) was dissolved in 2 mL of tetrahydrofuran (THF) to prepare a 0.5 mg / mL stock solution. 0.5 mL of the stock solution was then mixed with an equal volume of a 0.5 mg / mL DSPE-PEG2000 THF solution to form a homogeneous solution. This solution was then rapidly introduced into 9 mL of deionized water while vigorous stirring for 48 h to completely remove THF at room temperature. Millipore Amicon with a molecular weight cutoff of 100 kDa was then used. ® The ultrafiltration centrifuge tubes were washed and concentrated to obtain a PEG-encapsulated nanoparticle solution of metal-based photosensitizer with the structure shown in formula (1), which was stored in a light-protected environment at 4°C.

[0082] 2. Measurement of maximum absorption wavelength The tests were conducted using an ultraviolet-visible-near-infrared spectrometer, with a scanning wavelength of 300~1100 nm, to obtain the corresponding absorption spectra.

[0083] The results are as follows Figure 1 As shown, the maximum absorption peak wavelength of the metal-based photosensitizer with the structure shown in formula (1) can reach 680 nm, and the maximum absorption peak wavelength of its PEG-encapsulated nanoparticles (1-NP) can reach 747 nm.

[0084] 2. Determination of the photothermal properties of metal photosensitizers Nanoparticles were encapsulated with PEG, a metal-based photosensitizer with the structure shown in formula (1), at a concentration of 30 μM and a volume of 0.5 mL. An 808 nm laser was used as the light source, with an irradiance of 1 W / cm². 2 Excitation was performed, and temperature changes were recorded every 30 seconds.

[0085] The results are as follows Figure 2 As shown, the PEG-encapsulated nanoparticles of the metal-based photosensitizer with the structure shown in formula (1) can reach nearly 70°C after irradiation for 10 min, exhibiting good photothermal properties.

[0086] 3. Determination of the photodynamic reactivity of metal photosensitizers A stock solution of 1 mg / mL was prepared using DMSO with indocyanine green (ICG), a commercial photosensitizer, as a control.

[0087] In a DCFH-DA solution with a final concentration of 40 μM, PEG-coated nanoparticles or ICG stock solutions containing metal-based photosensitizers with structures as shown in formula (1) were added, with a final concentration of 20 μg / mL for both. An 808 nm laser was used as the light source, with an irradiance of 0.33 W / cm². 2 Excitation was performed, and the changes in fluorescence intensity from 0 to 5 minutes were recorded. The ratio of fluorescence intensity to the initial fluorescence intensity, I / I0, was calculated.

[0088] The results are as follows Figure 3 As shown, the PEG-encapsulated nanoparticles of the metal-based photosensitizer with the structure shown in formula (1) can effectively generate reactive oxygen species under excitation, and the generation performance is significantly better than that of the commercial photosensitizer ICG.

[0089] Experimental Example 2: Determination of the Cancer Cell Killing Performance of Metal-Based Photosensitizers The cytotoxicity of the metal-based photosensitizer with the structure shown in formula (1) to mouse colon cancer cells MC38 was evaluated by the MTT assay.

[0090] S1, MC38 cells were loaded at 4×10 3 The cells were seeded at a density of 1 cell per well into 96-well plates and cultured overnight at 37°C and 5% CO2 to achieve a confluence of 65±5%. S2. For the non-light-illuminated group, replace the original culture medium with fresh culture medium containing PEG-encapsulated nanoparticles with a metal-based photosensitizer of the structure shown in formula (1) at a concentration of 0, 5, 10, 15, 20 or 25 μM, and continue to culture in an environment of 37 ℃ and 5% CO2 for 24 h. For the laser irradiation group, the original culture medium was replaced with fresh culture medium containing PEG-coated nanoparticles with a metal-based photosensitizer of the structure shown in formula (1) at concentrations of 0, 5, 10, 15, 20, or 25 μM. After culturing at 37°C and 5% CO2 for 4 h, the nanoparticles were irradiated with an irradiance of 0.33 W / cm². 2 Cells were irradiated with an 808 nm laser for 8 min and then cultured for 24 h at 37°C and 5% CO2. S3. Discard the original culture medium, add 100 μL of serum-free DMEM containing 0.5 mg / mL MTT to each well, and continue to incubate at 37℃ and 5% CO2 for 4 h. S4. Add 100 μL DMSO, shake for 1 min to completely dissolve the formazan, and measure the absorbance of each well at 490 nm using a microplate reader. Calculate the cell viability using the following formula: Cell viability (%) = A / A0 × 100 Where A is the absorbance of the experimental group and A0 is the absorbance of the control group (0 μg / mL).

[0091] The statistical results of cell survival rate in the non-light-illuminated group are as follows: Figure 4 As shown in Figure a, without laser irradiation, cells treated with PEG-encapsulated nanoparticles of the metal-based photosensitizer (structure shown in formula (1)) showed almost no cell death, indicating that the metal-based nanomedicine has good biocompatibility; while after low-power 808 nm laser irradiation, the results were as follows: Figure 4 As shown in b, at a drug concentration of 25 μM, the cell death rate was greater than 50%, indicating that the metal photosensitizer has a good photodynamic killing effect on cells.

Claims

1. A metal-based photosensitizer having a structure as shown in formula (I): ###0001### (I) wherein: R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26, R27, R28, R29, R30, R31, R32, R33, R34, R35, R36, R37, R38, R39, R40, R41, R42, R43, R44, R45, R46, R47, R48, R49, R50, R51, R52, R53, R54, R55, R56, R57, R58, R59, R60, R61, R62, R63, R64, R65, R66, R67, R68, R69, R70, R71, R72, R73, R74, R75, R76, R77, R78, R79, R80, R81, R82, R83, R84, R85, R86, R87, R88, R89, R90, R91, R92, R93, R94, R95, R96, R97, R98, R99, R100, R101, R102, R103, R104, R105, R106, R107, R108, R109, R110, R111, R112, R113, R114, R115, R116, R117, R118, R119, R120, R121, R122, R123, R124, R125, R126, R127, R128, R129, R130, R131, R132, R133, R134, R135, R136, R137, R138, R139, R140, R141, R142, R143, R144, R145, R146, R147, R148, R149, R150, R151, R152, R153, R154, R155, R156, R157, R158 Formula (I), wherein X is selected from any one of sulfur, selenium, R1is selected from , , R2is selected from , , , , , R3is selected from , , , , , , , , , is selected from , , , , , is 0 or 1 + or 2 + , consists of 0 or 1 or 2 halogen or triflate or CIO4 - or PF6 - ; The selected from the group consisting of , , , , , R is selected from the group consisting of H, halogen, alkyl, alkoxy; the is selected from the group consisting of , , , , , M 1 is selected from the group consisting of iridium or osmium; the is selected from the group consisting of , , , M 2 is selected from the group consisting of ruthenium or osmium or iridium; the M 3 is selected from the group consisting of manganese or rhenium; the is selected from the group consisting of , , .

2. The metal-based photosensitizer according to claim 1, wherein ​ formula (II-1), wherein X, R1, R2, R3, , R are the same as defined above, and A is selected from any one of halide, triflate, PF6 - .

3. The metal-based photosensitizer according to claim 1, wherein ​ Equation (II-2), wherein X, R1, R2, R3, , M 1 A is selected from any one of the group consisting of halide, triflate, PF6 - as defined previously.

4. The metal-based photosensitizer of claim 1, wherein ​ Equation (II-3), wherein X, R1, R2, R3, , M 2 A is selected from any one of the group consisting of halide, triflate, PF6 - as defined previously.

5. The metal-based photosensitizer of claim 1, wherein ​ Equation (II-4), wherein X, R1, R2, R3, M 3 The same as the foregoing definitions.

6. The metal-based photosensitizer of claim 1, wherein ​ Equation (II-5), wherein X, R1, R2, R3, The same as the foregoing definitions.

7. The metal-based photosensitizer according to any one of claims 1 to 6, wherein ​ 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 。 8. A pharmaceutical composition, characterized by, ​ ​ 10. Use according to claim 9, characterized in that, ​

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