Preparation and application of a type I near-infrared second-window photosensitizer

Abstract

The present invention belongs to the field of biochemical materials and organic optoelectronic information materials, and specifically relates to the preparation and application of a type I near-infrared two-window photosensitizer. The present invention connects an (iso)quinoline structure with an alkylaniline to an azapyrrolidine parent structure to construct a type I near-infrared two-window photosensitizer, which can be used for near-infrared two-window fluorescence imaging-guided tumor photothermal therapy and type I photodynamic therapy synergistic therapy, achieving an inhibitory effect on tumor growth. The photosensitizer of the present invention exhibits significantly enhanced fluorescence signals, photoacoustic signals, and photothermal signals, and can effectively inhibit the growth of tumor cells.

Description

Technical Field

[0001] The invention belongs to the field of biochemical materials and organic optoelectronic information materials, and specifically relates to the preparation and application of a type I near-infrared two-window photosensitizer. Background Art

[0002] Light-regulated tumor treatment mainly includes photothermal therapy, chemotherapy, photodynamic therapy, etc. In recent years, many light-regulated near-infrared agents have been reported, and have shown good application prospects in the field of tumor treatment. At present, there are many studies on photodynamic therapy that rely on oxygen to produce singlet oxygen. However, the abnormal metabolism of tumor cells leads to hypoxia in the tumor site, which seriously weakens the effect of photodynamic therapy. In addition, the abnormal metabolism of tumor cells causes blood vessels in the tumor site to rupture and block, which is not conducive to the uniform distribution of agents in the tumor site, further reducing the photodynamic therapy effect of the tumor. Thermal therapy can effectively promote blood circulation and promote the distribution of agents in the tumor site, thereby effectively improving the treatment of tumors.

[0003] In type I photodynamic therapy, the production of ·OH does not rely on oxygen and has a good therapeutic effect on hypoxic tumors. However, due to the need for energy level matching, photosensitizers used in type I photodynamic therapy for hypoxic tumors are usually excited by visible light. Compared with short wavelengths, long wavelengths have a deeper penetration depth and cause less damage to the body. Therefore, it is very necessary to design and synthesize photosensitizers that are easy to obtain and have near-infrared second-window emission for tumor photothermal therapy and type I photodynamic therapy. Summary of the invention

[0004] In order to solve the problems in the prior art, the present invention connects the (iso)quinoline structure with alkylaniline to the azapyrrolidine parent structure to construct a type I near-infrared two-window photosensitizer, which can be used for near-infrared two-window fluorescence imaging-guided tumor photothermal therapy and type I photodynamic therapy synergistic treatment, achieving an inhibitory effect on tumor growth. The present invention provides a photosensitizer that can be excited by near-infrared light to achieve photothermal therapy and type I photodynamic tumor therapy under the guidance of near-infrared two-window fluorescence imaging. The photosensitizer exhibits significantly enhanced fluorescence signals, photoacoustic signals, and photothermal signals, and can effectively inhibit the growth of tumor cells.

[0005] The purpose of the present invention is achieved through the following technical solutions:

[0006] In the first aspect, the present invention provides a type I near-infrared second-window photosensitizer having a structure shown in any one of formulas Ⅰ to Ⅳ:

[0007] ;

[0008] Wherein, Z1 and Z2 are either C or N, and Z1 and Z2 are different;

[0009] Z3 and Z4 are either C or N, and Z3 and Z4 are different;

[0010] X is H or a halogen atom;

[0011] R1 and R2 are none or each independently any one of a halogen atom, a methyl group, a trifluoromethyl group, a methoxy group, an alkyl group, an aryl group, an alkoxy group, an amino group and an N-substituted amino group, and R1 and R2 are the same or different;

[0012] R3 and R4 are each independently a straight chain or branched chain alkyl group or an aromatic ring group having 2 to 16 carbon atoms, and R3 and R4 are the same or different.

[0013] The halogen atom is selected from fluorine, chlorine, bromine and iodine.

[0014] In a preferred embodiment, X is H.

[0015] In some embodiments, R1 and R2 are none or are independently any one of a halogen atom, a methyl group, a trifluoromethyl group, and a methoxy group, and R1 and R2 are the same or different.

[0016] In some embodiments, R1 and R2 are none or any one of a halogen atom, a methyl group, a trifluoromethyl group, and a methoxy group, and R1 and R2 are the same.

[0017] In a preferred embodiment, R1 and R2 are none.

[0018] In some embodiments, R3 and R4 are each independently a straight chain or branched alkyl group having 2 to 5 carbon atoms, and the straight chain or branched alkyl group having 2 to 5 carbon atoms is selected from ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, and n-pentyl.

[0019] In a preferred embodiment, R3 and R4 are ethyl groups.

[0020] Furthermore, the type I near-infrared second window photosensitizer is selected from one of the following structures:

[0021] .

[0022] In a second aspect, the present invention provides a method for preparing the type I near-infrared second window photosensitizer described in the first aspect, wherein the synthesis of formula I comprises the following steps:

[0023] S1, compound 1' and compound 2' react in a mixed solution of water and alcohol of sodium hydroxide to obtain compound 3';

[0024] S2, compound 3' reacts with nitromethane to obtain compound 4';

[0025] S3, compound 4' reacts in a mixed solution of alcohol or acetic acid and ammonium acetate to obtain compound 5';

[0026] S4, compound 5' undergoes coordination reaction with boron trifluoride ether to obtain the structure shown in formula I;

[0027] Among them, compound 1' is or ; Compound 2' is ; Compound 3' is or ; Compound 4' is or ; Compound 5' is ;

[0028] R1, R2, R3, R4, Z1, Z2, Z3, Z4, X are as defined in the first aspect.

[0029] Further, in step S1, in a mixed solution of water and alcohol (H2O: ROH = 1: 10) of sodium hydroxide, equimolar amounts of compound 1' and compound 2' undergo addition elimination reaction (3-24 h) at room temperature to obtain compound 3';

[0030] In step S2, in a weakly alkaline (diethylamine) solution of alcohol (methanol or ethanol, ROH), compound 3' and nitromethane undergo addition reaction under reflux (65-85° C.) to obtain compound 4';

[0031] In step S3, compound 4' is reacted in alcohol (ethanol or n-butanol) or a mixed solution of acetic acid and ammonium acetate under reflux (85-100° C.) to obtain compound 5';

[0032] In step S4, compound 5' undergoes coordination reaction with boron trifluoride etherate in a DCM or THF solution under weak base (triethylamine, diisopropylamine) conditions to obtain the compound of formula I.

[0033] The synthesis of formula II comprises the following steps:

[0034] S1, compound 1' and compound 2-1' react in a mixed solution of water and alcohol of sodium hydroxide to obtain compound 3-1';

[0035] S2, compound 3-1' reacts with nitromethane to obtain compound 4-1';

[0036] S3, compound 4-1' reacts in a mixed solution of alcohol or acetic acid and ammonium acetate to obtain compound 5-1';

[0037] S4, compound 5-1' undergoes coordination reaction with boron trifluoride ether to obtain the structure shown in formula II;

[0038] Among them, compound 1' is or ; Compound 2-1' is ; Compound 3-1' is or ; Compound 4-1' is or ; Compound 5-1' is ;

[0039] R1, R2, R3, R4, Z1, Z2, Z3, Z4, X are as defined in the first aspect.

[0040] Further, in step S1, in a mixed solution of water and alcohol (H2O: ROH = 1: 10) of sodium hydroxide, equimolar amounts of compound 1' and compound 2-1' undergo addition elimination reaction (3-24 h) at room temperature to obtain compound 3-1';

[0041] In step S2, in a weakly alkaline (diethylamine) solution of alcohol (methanol or ethanol, ROH), compound 3-1' and nitromethane undergo addition reaction under reflux (65-85° C.) to obtain compound 4-1';

[0042] In step S3, compound 4-1' is reacted in alcohol (ethanol or n-butanol) or a mixed solution of acetic acid and ammonium acetate under reflux (85-100° C.) to obtain compound 5-1';

[0043] In step S4, compound 5-1' undergoes coordination reaction with boron trifluoride etherate in a DCM or THF solution under weak base (triethylamine, diisopropylamine) conditions to obtain the compound of formula II.

[0044] In a third aspect, the present invention provides use of the type I near-infrared second-window photosensitizer described in the first aspect in the preparation of a drug for treating tumors.

[0045] Furthermore, the type I near-infrared second-window photosensitizer is used for photothermal therapy of hypoxic tumors and type I photodynamic therapy.

[0046] Specifically, under near-infrared light excitation conditions, the photosensitizer generates heat and ·OH, which are used for tumor photothermal therapy and type I photodynamic therapy guided by near-infrared two-window fluorescence imaging.

[0047] Furthermore, the photosensitizer achieves tumor immunotherapy by stimulating the body's immune system.

[0048] The beneficial effects of the technical solution of the present invention are mainly reflected in:

[0049] The photosensitizer of the present invention is a near-infrared light-excitable (iso)quinoline structure combined with alkylaniline connected to an azapyrrolidine skeleton. Under the irradiation condition of near-infrared light, the photosensitizer can produce toxic substances such as reactive oxygen through a photoinduced electron transfer mechanism to kill tumor cells, including type I photodynamic therapy for tumors. Under the irradiation of a long-wavelength light source, the phototherapy agent exhibits significantly enhanced photothermal effects and photothermal, photoacoustic, and fluorescent signals. The increase in temperature can also promote the circulation of blood in the tumor site, further promote the uniform distribution of the photosensitizer in the tumor site, and improve the effects of photodynamic and photothermal therapy of the tumor. This has important guiding significance for the design and synthesis of efficient photosensitizers.

[0050] The design and synthesis of the photosensitizer of the present invention are supported by theoretical basis, and the preparation method is simple, the synthesis conditions are mild, and the raw materials are abundant, which has important guiding significance for the design of multifunctional near-infrared biological phototherapy agents in the future. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] The accompanying drawings in the specification, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0052] Figure 1 A in Example 1 of the present invention 1 H-NMR spectrum;

[0053] Figure 2 A-1 in Example 2 of the present invention 1 H-NMR spectrum;

[0054] Figure 3 A-2 in Example 3 of the present invention 1 H-NMR spectrum;

[0055] Figure 4 is the absorption spectra of A, A-1 and A-2 in Examples 1, 2 and 3 of the present invention;

[0056] Figure 5 The fluorescence spectra of A, A-1 and A-2 in Examples 1, 2 and 3 of the present invention are shown;

[0057] Figure 6 A in Example 1 of the present invention is released under near-infrared light 1 Proof of O2;

[0058] Figure 7 A-1 in Example 2 of the present invention releases under near-infrared light 1 Proof of O2;

[0059] Figure 8 A-2 in Example 3 of the present invention releases under near-infrared light 1Proof of O2;

[0060] Fig. 9 This is a proof that A in Example 1 of the present invention releases ·OH under near-infrared light;

[0061] Fig.10 This is a proof that A-1 in Example 2 of the present invention releases ·OH under near-infrared light;

[0062] Fig.11 This is a proof that A-2 in Example 3 of the present invention releases ·OH under near-infrared light;

[0063] Fig.12 The photothermal effects of A, A-1 and A-2 in Examples 1, 2 and 3 of the present invention are compared. DETAILED DESCRIPTION

[0064] It should be noted that the following detailed descriptions are illustrative and are intended to provide further explanation of the present application. Unless otherwise specified, all technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art to which the present application belongs.

[0065] If no specific experimental steps or conditions are specified in the examples, the conventional experimental steps or conditions described in the literature in the art can be used. The raw materials or instruments used are all conventional products that can be obtained commercially, including but not limited to the raw materials or instruments used in the examples of this application.

[0066] The yield calculation method of the present invention is "product (mol) / reaction substrate (mol)*100%". In the present invention, a nuclear magnetic resonance spectrometer (NMR) is used to characterize the chemical structure of the target compound. An ultraviolet spectrophotometer (UV-3600UV-vis-NIR spectrophotometer) and a steady-state / transient fluorescence spectrometer (FLS-920spectrometer) are used to test the absorption and emission spectra of the compound, respectively. A near-infrared thermal imager (E40) is used to test the temperature change of the material.

[0067] Embodiment 1:

[0068] The chemical structure and synthesis route of photosensitizer A are as follows:

[0069]

[0070] Synthesis of compound 3:

[0071] 10 mL of sodium hydride solution (containing 2.00 g of sodium hydroxide) was slowly added to a mixture of 3.82 g of p-diethylaminoacetophenone (about 20 mmol), 3.14 g (about 20 mmol) of 4-quinolinecarboxaldehyde and 30 mL of ethanol solution. After reacting at room temperature for 12 h, 4.09 g of compound 3 (yield of about 62%) was obtained by column chromatography.

[0072] Compound 3: 1 H NMR (400 MHz, CDCl3) δ 8.96 (d, J = 4.5 Hz, 1H), 8.48 (d, J =15.5 Hz, 1H), 8.26 (d, J = 8.5 Hz, 1H), 8.17 –8.15(m, 1H), 8.05 – 8.00 (m, 2H),7.79 – 7.74 (m, 2H), 7.66 – 7.61 (m, 2H), 6.79 – 6.65 (m, 2H), 3.46 (q, J = 7.1Hz, 4H), 1.24 (t, J = 7.1 Hz, 6H).

[0073] Synthesis of compound 4:

[0074] A mixture of 3.31 g of compound 3 (about 10 mmol), 15 mL of nitromethane, 8 mL of diethylamine and 20 mL of ethanol was reacted at 65 - 85 °C under reflux conditions overnight, and 3.44 g of compound 4 was obtained by column chromatography (yield of about 88%).

[0075] Compound 4: 1 H NMR (400 MHz, CDCl3) δ 8.89 (s, 1H), 8.30 –8.22 (m, 2H),7.83 – 7.76 (m, 3H), 7.70 (t, J = 8.2 Hz, 1H), 7.41 (s, 1H), 6.59 (d, J = 9.0 Hz,2H), 5.22 – 5.15 (m, 1H), 5.03 (dd, J = 13.0, 6.1 Hz, 1H), 4.92 (dd, J = 13.1,7.9 Hz, 1H), 3.48 – 3.37 (m, 6H), 1.19 (t, J= 7.1 Hz, 6H).

[0076] Synthesis of compound 5:

[0077] A mixture of compound 4, 50 g of ammonium acetate solid and 20 mL of ethanol was heated to 85-100 °C and refluxed for 24 h. The reaction solution was filtered under reduced pressure and washed with cold ethanol, and the obtained compound 5 was directly used in the next step reaction.

[0078] Synthesis of compound A:

[0079] In a mixture of 0.139 g (0.2 mmol) of compound 5, 15 mL of dry dichloromethane, and 2 mL of diisopropylethylamine, 3 mL of boron trifluoride etherate was slowly added and reacted at room temperature for 4 hours. After the reaction was completed, the excess boron trifluoride etherate was quenched with ethanol, the low-boiling point solvent was removed under low pressure, and the solid was filtered under reduced pressure and washed with cold ethanol. The target compound A was finally obtained by separation on a silica gel plate with a yield of about 25%.

[0080] Compound A: 1 H NMR (400 MHz, DMSO) δ 8.75 (d, J = 4.5 Hz, 2H), 8.26 (t, J =9.4 Hz, 6H), 8.03 (d, J = 10.1 Hz, 2H), 7.81 (t, J = 7.0 Hz, 2H), 7.70 – 7.62 (m,6H), 6.89 (d, J = 9.4 Hz, 4H), 3.54 (q, J = 7.0 Hz, 8H), 1.20 (t, J = 7.0 Hz, 12H).

[0081] Embodiment 2:

[0082] The chemical structure and synthesis route of photosensitizer A-1 are as follows: .

[0083] 10 mL of sodium hydride solution (containing 2.00 g of sodium hydroxide) was slowly added to a mixture of 3.82 g of p-diethylaminoacetophenone (about 20 mmol), 3.14 g (about 20 mmol) of 4-isoquinolinecarboxaldehyde and 30 mL of ethanol solution. After reacting at room temperature for 12 h, 4.09 g of compound 3-1 (yield of about 62%) was obtained by column chromatography.

[0084] Compound 3-1: 1 H NMR (400 MHz, CDCl3) δ 9.19 (s, 1H), 8.72 (s, 1H), 8.30 –8.26 (m, 1H), 8.18 (d, J = 8.6Hz, 1H), 8.01 (d, J = 7.3 Hz, 1H), 7.90 – 7.86 (m,2H), 7.81 – 7.77 (m, 1H), 7.65 – 7.60 (m, 2H), 6.59 – 6.53 (m, 2H), 3.31 (q, J = 7.1 Hz, 4H), 1.08 (t, J = 7.1 Hz, 6H).

[0085] Synthesis of compound 4-1:

[0086] A mixture of 3.31 g of compound 3-1 (about 10 mmol), 15 mL of nitromethane, 8 mL of diethylamine and 20 mL of ethanol was reacted under reflux conditions at 65 - 85 °C overnight, and 3.44 g of compound 4-1 (yield of about 88%) was obtained by column chromatography.

[0087] Compound 4-1: 1 H NMR (400 MHz, CDCl3) δ 9.37 (s, 1H), 8.69 (s, 1H), 8.53(d, J = 8.6 Hz, 1H), 8.27 (d, J = 8.1 Hz, 1H), 8.14 (t, J = 7.2 Hz, 1H), 7.92 (t, J =7.8 Hz, 1H), 7.79 (d, J = 9.0 Hz, 2H), 6.61 (d, J = 8.9 Hz, 2H), 5.25 – 5.19 (m,1H), 5.02 – 4.93 (m, 2H), 3.64 – 3.55 (m, 2H), 3.42 (q, J = 7.0 Hz, 4H), 1.20(t, J = 7.1 Hz, 6H). Synthesis of compound 5-1:

[0088] A mixture of compound 4-1, 50 g of ammonium acetate solid and 20 mL of ethanol was heated to 85-100 °C and refluxed for 24 h. The reaction solution was filtered under reduced pressure and washed with cold ethanol. The obtained compound 5-1 was directly used for the next step reaction.

[0089] Synthesis of compound A-1:

[0090] In a mixture of 0.139 g (0.2 mmol) of compound 5-1, 15 mL of dry dichloromethane, and 2 mL of diisopropylethylamine, 3 mL of boron trifluoride etherate was slowly added and reacted at room temperature for 4 hours. After the reaction was completed, the excess boron trifluoride etherate was quenched with ethanol, the low-boiling point solvent was removed under low pressure, and the solid was filtered under reduced pressure and washed with cold ethanol. The target compound A-1 was finally obtained by separation on a silica gel plate with a yield of about 25%.

[0091] Compound A-1: 1 H NMR (400 MHz, CDCl3) δ 9.05 (s, 2H), 8.55 (s, 2H), 8.17 –8.11 (m, 6H), 7.88 – 7.85 (m, 2H), 7.62 – 7.57 (m, 2H), 7.55 – 7.51 (m, 2H),7.11 (s, 2H), 6.75 – 6.70 (m, 4H), 3.41 (q, J = 7.1 Hz, 8H), 1.18 (d, J = 7.1 Hz,12H).

[0092] Example 3

[0093] The chemical structure and synthesis route of photosensitizer A-2 are as follows:

[0094] 10 mL of sodium hydride solution (containing 2.00 g of sodium hydroxide) was slowly added to a mixture of 3.82 g of p-diethylaminoacetophenone (about 20 mmol), 3.14 g (about 20 mmol) of 3-quinolinecarboxaldehyde and 30 mL of ethanol solution. After reacting at room temperature for 12 h, 4.09 g of compound 3-2 (yield of about 62%) was obtained by column chromatography.

[0095] Compound 3-2: 1 H NMR (400 MHz, CDCl3) δ 9.22 (d, J = 2.2 Hz, 1H), 8.31 (s,1H), 8.13 (d, J= 8.5 Hz, 1H), 8.05 – 8.02 (m, 2H), 7.93 (d, J = 15.8 Hz, 1H),7.87 (d, J = 8.2 Hz, 1H), 7.81 (d, J = 15.8 Hz, 1H), 7.77 – 7.73 (m, 1H), 7.61 –7.57 (m, 1H), 6.73– 6.68 (m, 2H), 3.46 (q, J = 7.1 Hz, 4H), 1.24 (t, J = 7.2 Hz,6H).

[0096] Synthesis of compound 4-2:

[0097] A mixture of 3.31 g of compound 3-2 (about 10 mmol), 15 mL of nitromethane, 8 mL of diethylamine and 20 mL of ethanol was reacted under reflux conditions at 65 - 85 °C overnight, and 3.44 g of compound 4-2 (yield of about 88%) was obtained by column chromatography.

[0098] Compound 4-2: 1 H NMR (400 MHz, CDCl3) δ 8.91 (d, J = 2.4 Hz, 1H), 8.11 –8.06 (m, 2H), 7.82 – 7.77 (m, 3H), 7.73 – 7.68 (m, 1H), 7.55(t, J = 8.0 Hz,1H), 6.62 – 6.57 (m, 2H), 4.98 (dd, J = 12.9, 6.0 Hz, 1H), 4.83 (dd, J = 12.9,8.6 Hz, 1H), 4.48 – 4.41 (m, 1H), 3.46 – 3.38 (m, 6H), 1.19 (t, J = 7.1 Hz,6H).

[0099] Synthesis of compound 5-2:

[0100] A mixture of compound 4-2, 50 g of ammonium acetate solid and 20 mL of ethanol was heated to 85-100°C and refluxed for 24 h. The reaction solution was filtered under reduced pressure and washed with cold ethanol, and the obtained compound 5-2 was directly used for the next step reaction.

[0101] Synthesis of compound A-2:

[0102] In a mixture of 0.139 g (0.2 mmol) 5-2, 15 mL dry dichloromethane, and 2 mL diisopropylethylamine, 3 mL of boron trifluoride etherate was slowly added and reacted at room temperature for 4 hours. After the reaction was completed, the excess boron trifluoride etherate was quenched with ethanol, the low boiling point solvent was removed under low pressure, and the solid was filtered under reduced pressure and washed with cold ethanol. The target compound A-2 was finally obtained by separation on a silica gel plate with a yield of about 25%.

[0103] Compound A-2: 1 H NMR (400 MHz, CDCl3) δ 9.45 (d, J = 2.2 Hz, 2H), 8.99 –8.96 (m, 2H), 8.21 – 8.13 (m, 6H), 7.77 – 7.70 (m, 4H), 7.53 – 7.49 (m, 2H),7.32 (s, 2H), 6.79 – 6.73 (m, 4H), 3.45 (q, J = 7.1 Hz, 8H), 1.23 (t, J = 7.1 Hz,12H).

[0104] The performance of the compounds obtained in Examples 1-3 was verified, and the results were as follows Figures 1 to 12 shown.

[0105] By nuclear magnetic resonance spectroscopy ( Figures 1 to 3 ) proved the correctness of compounds A, A-1 and A-2.

[0106] By absorption spectroscopy ( Figure 4 ), proving that compounds A, A-1 and A-2 have near-infrared second window absorption.

[0107] By fluorescence spectroscopy ( Figure 5 ), proving that compounds A, A-1 and A-2 have near-infrared second window emission.

[0108] By absorption spectroscopy ( Figure 6 , Figure 7 and Figure 8 ), using commercial 1 O2 probe (DPBF) demonstrated that near-infrared light-stimulated materials can release 1 O2.

[0109] By absorption spectroscopy ( Fig. 9 , Fig.10 and Fig.11), using a commercial ·OH probe (MB), demonstrated that near-infrared light-stimulated materials can release ·OH.

[0110] Through the photothermal effect ( Fig.12 ), proving that compounds A, A-1 and A-2 have photothermal conversion capabilities.

[0111] Under the irradiation of longer wavelength near-infrared light, the target material can not only produce 1 O2 and ·OH are used for photodynamic therapy of tumors, including type I photodynamic therapy. It also shows obvious photothermal conversion ability and photoacoustic, photothermal, and fluorescence signals, and can dilate blood vessels to improve the uniform distribution of materials in the tumor site. It can be used for tumor photothermal therapy and type I photodynamic therapy under the guidance of near-infrared two-window multimodal imaging (photothermal imaging, fluorescence imaging).

[0112] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A type I near-infrared second window photosensitizer, characterized in that: Having a structure shown in any one of formulas Ⅰ to Ⅱ: ； Wherein, Z1 and Z2 are either C or N, and Z1 and Z2 are different; Z3 and Z4 are either C or N, and Z3 and Z4 are different; X is H or a halogen atom; R1 and R2 are none or are independently any one of a halogen atom, a methyl group, a trifluoromethyl group, and a methoxy group, and R1 and R2 are the same or different; R3 and R4 are each independently a straight chain or branched chain alkyl group having 2 to 16 carbon atoms, and R3 and R4 are the same or different.

2. The type I near-infrared second window photosensitizer according to claim 1, characterized in that: R1 and R2 are none or any one of a halogen atom, a methyl group, a trifluoromethyl group, and a methoxy group, and R1 and R2 are the same.

3. The type I near-infrared second window photosensitizer according to claim 1, characterized in that: R3 and R4 are each independently a linear or branched alkyl group having 2 to 5 carbon atoms.

4. The type I near-infrared second window photosensitizer according to claim 1, characterized in that: R3 and R4 are ethyl groups.

5. The type I near-infrared second window photosensitizer according to claim 1, characterized in that: Select from the following 。 6. The method for preparing the type I near-infrared second window photosensitizer according to claim 1, characterized in that: The following steps are involved: S1, compound 1' and compound 2' react in a mixed solution of water and alcohol of sodium hydroxide to obtain compound 3'; S2, compound 3' reacts with nitromethane to obtain compound 4'; S3, compound 4' reacts in a mixed solution of alcohol or acetic acid and ammonium acetate to obtain compound 5'; S4, compound 5' undergoes coordination reaction with boron trifluoride ether to obtain the structure shown in formula I; Among them, compound 1' is or ; Compound 2' is or ; Compound 3' is or ; Compound 4' is or ; Compound 5' is ; R1, R2, R3, R4, Z1, Z2, Z3, Z4, and X are as defined in any one of claims 1 to 4.

7. The method for preparing the type I near-infrared second window photosensitizer according to claim 1, characterized in that: The following steps are involved: S1, compound 1' and compound 2-1' react in a mixed solution of water and alcohol of sodium hydroxide to obtain compound 3-1'; S2, compound 3-1' reacts with nitromethane to obtain compound 4-1'; S3, compound 4-1' reacts in a mixed solution of alcohol or acetic acid and ammonium acetate to obtain compound 5-1'; S4, compound 5-1' undergoes coordination reaction with boron trifluoride ether to obtain the structure shown in formula II; Among them, compound 1' is or ; Compound 2-1' is; or ; Compound 3-1' is or ; Compound 4-1' is or ; Compound 5-1' is ; R1, R2, R3, R4, Z1, Z2, Z3, Z4, and X are as defined in any one of claims 1 to 4.

8. Use of the type I near-infrared second window photosensitizer according to any one of claims 1 to 5 in the preparation of a drug for treating tumors; the specific application is: using the type I near-infrared second window photosensitizer for photothermal therapy of hypoxic tumors and type I photodynamic therapy.

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