Near-infrared-II compound, preparation method thereof and application of near-infrared-II compound in near-infrared-II photoacoustic imaging contrast agent

Abstract

The invention relates to the technical field of nano biomedical imaging, in particular to a near-infrared-II compound, a preparation method of the near-infrared-II compound and application of the near-infrared-II compound in a near-infrared-II photoacoustic imaging contrast agent. The electron-rich phenothiazine group is used as a hypochlorous acid recognition response part and an electron acceptor precursor. The near-infrared-II compound disclosed by the invention has near-infrared-II absorption and intramolecular charge transfer characteristics after being activated by hypochlorous acid, is a typical D-A-D type organic small molecule, can realize a better photoacoustic imaging effect, and provides a high-sensitivity imaging means for disease diagnosis.

Description

Technical Field

[0001] The present invention relates to the field of nano-biomedical imaging technology, in particular to a near-infrared-II compound and a preparation method thereof and application in a near-infrared-II photoacoustic imaging contrast agent. Background Art

[0002] Photoacoustic imaging is an emerging imaging modality that combines the advantages of optics and acoustics to enable real-time, non-invasive, and radiation-free measurement of optical tissue properties. In biological tissue, because acoustic signals scatter very little, the acoustic signals received by photoacoustic imaging penetrate deeper into biological tissue than the fluorescent signals of conventional fluorescence imaging. Furthermore, optical excitation provides higher tissue contrast than ultrasound imaging, enabling photoacoustic imaging to achieve high tissue contrast, deeper tissue penetration, and higher resolution in biological imaging.

[0003] Previous studies have shown that photoacoustic imaging in the near-infrared (NIR) II region offers significant advantages over NIR-I, such as deeper tissue penetration and higher imaging resolution. These advantages have led to widespread application in medical diagnostics, including early diagnosis of various cancers, tracking of tumor metastases, gastrointestinal endoscopic imaging, and monitoring the effectiveness of treatments.

[0004] Currently, a variety of inorganic and organic contrast agents have been developed for near-infrared-II photoacoustic imaging. Among them, organic molecules without heavy metal toxicity, including conjugated polymers and some small molecules, have greater potential for clinical translation. However, conjugated polymers suffer from poor biodegradability and low synthetic reproducibility, while traditional small molecules, such as polymethine cyanine dyes, are hampered by poor photostability, limiting their further application.

[0005] Although donor-acceptor-donor (DAD) conjugated small molecules have great potential in constructing near-infrared-II photoacoustic contrast agents due to their well-defined chemical structure, reliable biodegradability / biocompatibility, and flexible optical properties, and multiple strategies have been developed to shift the absorption wavelength to the near-infrared-II window, most current near-infrared-II photoacoustic imaging contrast agents have a signal that is always on, easily affected by background signals, and have poor sensitivity, resulting in photoacoustic imaging effects that cannot meet practical needs. Therefore, the development of near-infrared-II organic dyes with excellent optical properties and near-infrared-II absorption is urgent. Summary of the Invention

[0006] The purpose of the present invention is to provide a near infrared-II compound and a preparation method thereof and application in near infrared-II photoacoustic imaging contrast agents to overcome the deficiencies and defects in the prior art.

[0007] To achieve the above objectives, the present invention provides a near-infrared-II compound, wherein the near-infrared-II compound uses a triphenylamine group and a piperazine group as electron acceptors, and an electron-rich phenothiazine group as a hypochlorous acid recognition response site and an electron acceptor precursor, and has the following structural formula:

[0008]

[0009] The present invention also provides a method for preparing the above-mentioned near infrared-II compound, comprising the following steps:

[0010] S1. Adding a phenothiazine derivative, a triphenylamine derivative, and a catalyst to an organic solvent in the absence of light, and conducting a Suzuki coupling reaction under a protective atmosphere to obtain a compound of formula I;

[0011] The structural formula of the compound of formula I is as follows:

[0012]

[0013] S2. Under light-shielding conditions, add the compound of formula I, 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine and a catalyst to an organic solvent, and carry out a Suzuki coupling reaction under a protective atmosphere to prepare a compound of formula II, i.e., a near-infrared-II compound.

[0014] Preferably, the molar ratio of the phenothiazine derivative to the triphenylamine derivative in S1 is 0.8-1.2:0.8-1.2.

[0015] Preferably, the molar ratio of the compound of formula I in S2 to 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine is 0.8-1.2:0.8-1.2.

[0016] Preferably, the Suzuki coupling reaction temperature in S1 and S2 is 90-110°C, and the reaction time is 12-24h;

[0017] The catalysts were all palladium catalysts, and the organic solvents were all anhydrous toluene.

[0018] The present invention also provides the use of the above-mentioned near-infrared-II compound in a near-infrared-II photoacoustic imaging contrast agent. The organic solution of the near-infrared-II compound and the aqueous solution of the amphiphilic block copolymer are mixed under ultrasonic conditions, and after nano-coprecipitation of the near-infrared-II compound and the amphiphilic block copolymer, the organic solvent from the organic solution is removed to prepare a water-soluble and activatable near-infrared-II photoacoustic imaging contrast agent.

[0019] Preferably, the concentration of the near infrared-II compound represented by the near infrared-II compound in the organic solution is 0.1 to 1 mg / mL, and the concentration of the amphiphilic block polymer aqueous solution is 1 to 20 mg / mL.

[0020] Preferably, the volume ratio of the organic solution to the aqueous solution of the amphiphilic front-stage polymer is less than or equal to 1:5.

[0021] Preferably, the mass ratio of the near infrared-II compound to the amphiphilic block copolymer is 1:5-100.

[0022] Preferably, the organic solvent of the organic solution is tetrahydrofuran, and the amphiphilic block copolymer is a polyoxyethylene-polyoxypropylene-polyoxyethylene triblock copolymer.

[0023] Beneficial effects of the present invention:

[0024] (1) The near-infrared-II compound of the present invention has near-infrared-II absorption and intramolecular charge transfer characteristics after activation with hypochlorous acid, and is a typical DAD-type organic small molecule, which can achieve better photoacoustic imaging effects and provide a highly sensitive imaging method for disease diagnosis;

[0025] (2) The preparation method of the near infrared-II compound of the present invention is simple, the reaction conditions are mild, and it is easy to operate and control, which is conducive to improving the repeatability and yield of the reaction;

[0026] (3) The preparation method of the near-infrared-II photoacoustic imaging contrast agent of the present invention combines a near-infrared-II compound (photoacoustic imaging small molecule) with an amphiphilic polymer through self-assembly. The prepared contrast agent has activatable near-infrared second-region absorption and can realize photoacoustic imaging in the near-infrared-II window, greatly improving the imaging quality of living tumors. The embodiments of the present invention prove that it can realize NIR-II photoacoustic imaging of living tumors in mice.

[0027] The technical solution of the present invention is further described in detail below through the accompanying drawings and embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 is the hydrogen nuclear magnetic resonance spectrum of the compound of formula I prepared in Example 1 of the present invention;

[0029] Figure 2 This is the hydrogen nuclear magnetic resonance spectrum of the near infrared-II compound prepared in Example 1 of the present invention;

[0030] Figure 3 is the mass spectrum of the near infrared-II compound prepared in Example 1 of the present invention;

[0031] Figure 4Schematic diagram of the hydrodynamic diameter of the near-infrared-II photoacoustic imaging contrast agent prepared in Example 4 of the present invention measured by dynamic light scattering;

[0032] Figure 5 This is an absorption spectrum of an aqueous solution of the near-infrared-II photoacoustic imaging contrast agent prepared in Example 4 of the present invention. DETAILED DESCRIPTION

[0033] The present invention is further described below with reference to the accompanying drawings and examples. Unless otherwise defined, technical or scientific terms used herein shall have the same meanings as those commonly understood by persons of ordinary skill in the art to which the present invention pertains. The above-mentioned features or features described in the specific examples of the present invention may be combined in any manner. These specific examples are intended only to illustrate the present invention and are not intended to limit the scope of the present invention.

[0034] The present invention provides a near-infrared-II compound. The near-infrared-II compound uses a triphenylamine group and a piperazine group as electron acceptors, and an electron-rich phenothiazine group as a hypochlorous acid recognition response site and an electron acceptor precursor. The structural formula is as follows:

[0035]

[0036] The above-mentioned near-infrared-II compound has intramolecular charge transfer characteristics (ICT) after activation by hypochlorous acid. It is a typical DAD-type organic small molecule and has near-infrared-II absorption, achieving better photoacoustic imaging effects.

[0037] The present invention also provides a method for preparing the above-mentioned near infrared-II compound, comprising the following steps:

[0038] S1. Adding a phenothiazine derivative, a triphenylamine derivative, and a catalyst to an organic solvent in the absence of light, and conducting a Suzuki coupling reaction under a protective atmosphere to obtain a compound of formula I;

[0039] The structural formula of the compound of formula I is as follows:

[0040]

[0041] S2. Under light-shielding conditions, add the compound of formula I, 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine and a catalyst to an organic solvent, and carry out a Suzuki coupling reaction under a protective atmosphere to prepare a compound of formula II, i.e., a near-infrared-II compound.

[0042] Preferably, the molar ratio of the phenothiazine derivative to the triphenylamine derivative is 0.8-1.2:0.8-1.2.

[0043] In some embodiments of the present invention, the molar ratio of the phenothiazine derivative to the triphenylamine derivative is 1: 1. Controlling the molar ratio within the above range is beneficial to reducing the generation of by-products, lowering reaction costs and improving product yield.

[0044] In some embodiments of the present invention, the phenothiazine derivative is 3,7-dibromo-10H-phenothiazine, and the triphenylamine derivative is 4-boronate-4',4'-dimethoxytriphenylamine.

[0045] In some embodiments of the present invention, the synthetic route of step S1 is as follows:

[0046]

[0047] In some embodiments of the present invention, the synthesis route of step S2 is as follows:

[0048]

[0049] Preferably, the molar ratio of the compound of formula I in S2 to 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine is 0.8-1.2:0.8-1.2.

[0050] In some embodiments of the present invention, the molar ratio of the compound of Formula I to 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine is 1:1. Controlling the molar ratio within the above range is beneficial for reducing the production of by-products, lowering reaction costs, and improving product yield.

[0051] Preferably, the Suzuki coupling reaction temperature in S1 and S2 is 90-110°C, and the reaction time is 12-24h;

[0052] The catalysts were all palladium catalysts, and the organic solvents were all anhydrous toluene.

[0053] In some embodiments of the present invention, the palladium catalysts in S1 and S2 each independently include tetrakis(triphenylphosphine)palladium. The role of tetrakis(triphenylphosphine)palladium is only to catalyze the reaction and not as a reactant. Therefore, its amount is not further limited and can be used in an amount familiar to those skilled in the art.

[0054] In some embodiments of the present invention, the Suzuki coupling reaction temperature in S1 and S2 is both 100° C., and the reaction time is both 24 h.

[0055] In some embodiments of the present invention, the protective atmospheres in S1 and S2 each independently include nitrogen.

[0056] In some embodiments of the present invention, the organic solvent is treated to remove water and / or oxygen before use.

[0057] In some embodiments of the present invention, anhydrous toluene is bubbled with nitrogen or argon before use to remove oxygen.

[0058] In some embodiments of the present invention, after the Suzuki coupling reaction of S1 and S2 is completed, organic solvents are independently added to the system to dissolve the reaction products, and the solid-liquid separation is performed. After silica gel powder is added to the obtained liquid to adsorb the reaction products, the silica gel powder is loaded into a column and eluted using a silica gel column chromatography method with an eluent, the reaction product solution is collected, and the solvent is removed.

[0059] In some embodiments of the present invention, the organic solvent for dissolving the reaction product is dichloromethane. Dichloromethane serves only as a solvent and does not act as a reactant, so its amount is not further limited and can be used in an amount familiar to those skilled in the art.

[0060] In some embodiments of the present invention, the silica gel powder has a particle size of 200 mesh, the organic solvent added to the system is dichloromethane, and the eluent is a mixture of dichloromethane and methanol. The present invention does not specifically limit the ratio of dichloromethane to methanol in the eluent; amounts known to those skilled in the art can be used.

[0061] The present invention also provides the use of the above-mentioned near-infrared-II compound in a near-infrared-II photoacoustic imaging contrast agent. The organic solution of the near-infrared-II compound and the aqueous solution of the amphiphilic block copolymer are mixed under ultrasonic conditions, and after nano-coprecipitation of the near-infrared-II compound and the amphiphilic block copolymer, the organic solvent from the organic solution is removed to prepare a water-soluble and activatable near-infrared-II photoacoustic imaging contrast agent.

[0062] In some embodiments of the present invention, near-infrared-II photoacoustic imaging contrast agents are used for high-sensitivity near-infrared-II photoacoustic imaging for disease diagnosis purposes.

[0063] In some embodiments of the present invention, the NIR-II compound and the amphiphilic block copolymer are self-assembled in a solution, which can achieve water solubility of the NIR-II compound, and the formed nanostructure has good biocompatibility.

[0064] Preferably, the concentration of the near infrared-II compound represented by the near infrared-II compound in the organic solution is 0.1 to 1 mg / mL, and the concentration of the amphiphilic block polymer aqueous solution is 1 to 20 mg / mL.

[0065] In some embodiments of the present invention, the concentration of the near infrared-II compound shown as the near infrared-II compound in the organic solution is 0.1 to 0.5 mg / mL, and the concentration of the amphiphilic block polymer aqueous solution is 1 to 2 mg / mL.

[0066] Preferably, the volume ratio of the organic solution to the aqueous solution of the amphiphilic front-stage polymer is less than or equal to 1:5.

[0067] Preferably, the mass ratio of the near infrared-II compound to the amphiphilic block copolymer is 1:5-100.

[0068] In some embodiments of the present invention, the mass ratio of the near-infrared-II compound to the amphiphilic block copolymer is 1:20. Controlling the mass ratio within this range facilitates the encapsulation of the near-infrared-II compound within the amphiphilic block copolymer shell to form uniformly sized, spherical nanoparticles with good water solubility, while also preventing leakage of the near-infrared-II compound and providing enhanced biosafety.

[0069] Preferably, the organic solvent of the organic solution is tetrahydrofuran, and the amphiphilic block copolymer is a polyoxyethylene-polyoxypropylene-polyoxyethylene triblock copolymer (F-127).

[0070] In some embodiments of the present invention, the organic solvent may be removed from the organic solution by a blowing volatilization method.

[0071] Example 1

[0072] A method for preparing a near infrared-II compound comprises the following steps:

[0073] S1. In a 50 mL flask, 0.1 mmol of 3,7-dibromo-10H-phenothiazine, 0.1 mmol of 4-boronate-4',4'-dimethoxytriphenylamine, and 0.0006 mmol of tetrakis(triphenylphosphine)palladium catalyst were added to the flask in the dark. A reflux line was connected and the entire system was evacuated and filled with nitrogen. Anhydrous toluene, which had been bubbled with nitrogen, was then added to the flask and stirred at 100°C for a Suzuki coupling reaction for 24 hours. After the reaction, dichloromethane was added to dissolve the reaction product. The insoluble matter was filtered to obtain a crude product solution. 50 g of silica gel powder (200 mesh) was added and all solvents were removed by rotary evaporation to allow the silica gel powder to fully adsorb the crude product. The silica gel powder adsorbed with the crude product was loaded onto a column and separated by silica gel column chromatography, eluting with a dichloromethane / methanol mixture to obtain a pure product solution. After rotary evaporation to remove the solvent, the solution was dried under vacuum to obtain the compound of formula I.

[0074] S2. Under light-proof conditions, 0.1mmol of the compound of formula I, 0.1mmol of 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine and 0.0006mmol of tetrakis(triphenylphosphine)palladium catalyst were added to a 50mL flask, a reflux tube was connected, the entire system was evacuated and filled with nitrogen, and then anhydrous toluene that had been bubbled (the gas introduced was nitrogen) was added to the flask and stirred at 100°C for Suzuki coupling reaction for 24h. After the reaction, dichloromethane was added to dissolve the reaction product, the insoluble matter was removed by filtration to obtain a crude product solution, 50g of silica gel powder (200 mesh) was added, and all solvents were removed by rotary evaporation to allow the silica gel powder to fully adsorb the crude product. The silica gel powder that adsorbed the crude product was loaded onto a column and then subjected to silica gel column chromatography, eluted with a dichloromethane / methanol mixed solution to obtain a pure product solution. After removing the solvent by rotary evaporation and vacuum drying, the compound of formula II, namely the near infrared-II compound, is prepared.

[0075] Example 2

[0076] A method for preparing a near infrared-II compound comprises the following steps:

[0077] S1. In a 50 mL flask, 0.08 mmol of 3,7-dibromo-10H-phenothiazine, 0.1 mmol of 4-boronate-4',4'-dimethoxytriphenylamine, and 0.0006 mmol of tetrakis(triphenylphosphine)palladium catalyst were added to the flask in the dark. A reflux line was connected and the entire system was evacuated and filled with nitrogen. Anhydrous toluene, which had been bubbled with nitrogen, was then added to the flask and stirred at 100°C for a Suzuki coupling reaction for 24 hours. After the reaction, dichloromethane was added to dissolve the reaction product. The insoluble matter was filtered to obtain a crude product solution. 50 g of silica gel powder (200 mesh) was added and all solvent was removed by rotary evaporation to allow the silica gel powder to fully adsorb the crude product. The silica gel powder adsorbed with the crude product was loaded onto a column and separated by silica gel column chromatography, eluting with a dichloromethane / methanol mixture to obtain a pure product solution. After rotary evaporation to remove the solvent, the solution was dried under vacuum to obtain the compound of formula I.

[0078] S2. Under light-proof conditions, 0.08 mmol of the compound of formula I, 0.1 mmol of 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine and 0.0006 mmol of tetrakis(triphenylphosphine)palladium catalyst were added to a 50 mL flask, a reflux tube was connected, the entire system was evacuated and filled with nitrogen, and then anhydrous toluene that had been bubbled (the gas introduced was nitrogen) was added to the flask and stirred at 100 ° C for Suzuki coupling reaction for 24 hours. After the reaction, dichloromethane was added to dissolve the reaction product, and the insoluble matter was removed by filtration to obtain a crude product solution. 50 g of silica gel powder (200 mesh) was added, and all solvents were removed by rotary evaporation to allow the silica gel powder to fully adsorb the crude product. The silica gel powder that adsorbed the crude product was loaded onto a column and then subjected to silica gel column chromatography, eluted with a dichloromethane / methanol mixed solution to obtain a pure product solution. After removing the solvent by rotary evaporation and vacuum drying, the compound of formula II, namely the near infrared-II compound, is prepared.

[0079] Example 3

[0080] A method for preparing a near infrared-II compound comprises the following steps:

[0081] S1. In a 50 mL flask, 0.1 mmol of 3,7-dibromo-10H-phenothiazine, 0.12 mmol of 4-boronate-4',4'-dimethoxytriphenylamine, and 0.0006 mmol of tetrakis(triphenylphosphine)palladium catalyst were added to the flask in the dark. A reflux line was connected and the entire system was evacuated and filled with nitrogen. Anhydrous toluene, which had been bubbled with nitrogen, was then added to the flask and stirred at 100°C for a Suzuki coupling reaction for 24 hours. After the reaction, dichloromethane was added to dissolve the reaction product. The insoluble matter was filtered to obtain a crude product solution. 50 g of silica gel powder (200 mesh) was added and all solvent was removed by rotary evaporation to allow the silica gel powder to fully adsorb the crude product. The silica gel powder adsorbed with the crude product was loaded onto a column and separated by silica gel column chromatography, eluting with a dichloromethane / methanol mixture to obtain a pure product solution. After rotary evaporation to remove the solvent, the solution was dried under vacuum to obtain the compound of Formula I.

[0082] S2. Under light-proof conditions, 0.1mmol of the compound of formula I, 0.12mmol of 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine and 0.0006mmol of tetrakis(triphenylphosphine)palladium catalyst were added to a 50mL flask, a reflux tube was connected, the entire system was evacuated and filled with nitrogen, and then anhydrous toluene that had been bubbled (the gas introduced was nitrogen) was added to the flask and stirred at 100°C for Suzuki coupling reaction for 24h. After the reaction, dichloromethane was added to dissolve the reaction product, the insoluble matter was removed by filtration to obtain a crude product solution, 50g of silica gel powder (200 mesh) was added, and all solvents were removed by rotary evaporation to allow the silica gel powder to fully adsorb the crude product. The silica gel powder that adsorbed the crude product was loaded onto a column and then subjected to silica gel column chromatography, eluted with a dichloromethane / methanol mixed solution to obtain a pure product solution. After removing the solvent by rotary evaporation and vacuum drying, the compound of formula II, namely the near infrared-II compound, is prepared.

[0083] Example 4

[0084] The near-infrared-II compound prepared in Example 1 was prepared into a tetrahydrofuran solution with a near-infrared-II compound concentration of 1 mg / mL (denoted as solution A). Under intense ultrasonic conditions, the specific parameters were set to continuous ultrasonic time of 2 minutes, ultrasonic power ratio of 50%, and ultrasonic time interval of 8 seconds and 2 seconds. The solution was directly added to an aqueous solution of amphiphilic triblock polymer F-127 with a concentration of 2 mg / mL (denoted as solution B) and mixed. After self-assembly was completed under ultrasonic conditions, the excess tetrahydrofuran organic solvent was removed by blowing and volatilization to obtain a near-infrared-II photoacoustic imaging contrast agent. The volume ratio of solution A to solution B was 1:10.

[0085] Example 5

[0086] The near-infrared-II compound prepared in Example 1 was prepared into a tetrahydrofuran solution with a near-infrared-II compound concentration of 1 mg / mL (denoted as solution A). Under intense ultrasonic conditions, the specific parameters were set to continuous ultrasonic time of 2 minutes, ultrasonic power ratio of 50%, and ultrasonic time interval of 8 seconds and 2 seconds. The solution was directly added to an aqueous solution of amphiphilic triblock polymer F-127 with a concentration of 0.5 mg / mL (denoted as solution B) and mixed. After self-assembly was completed under ultrasonic conditions, the excess tetrahydrofuran organic solvent was removed by blowing and volatilization to obtain a near-infrared-II photoacoustic imaging contrast agent. The volume ratio of solution A to solution B was 1:5.

[0087] Example 6

[0088] The near-infrared-II compound prepared in Example 1 was prepared into a tetrahydrofuran solution with a near-infrared-II compound concentration of 1 mg / mL (denoted as solution A). Under intense ultrasonic conditions, the specific parameters were set to continuous ultrasonic time of 2 minutes, ultrasonic power ratio of 50%, and ultrasonic time interval of 8 seconds and 2 seconds. The solution was directly added to an aqueous solution of amphiphilic triblock polymer F-127 with a concentration of 10 mg / mL (denoted as solution B) and mixed. After self-assembly was completed under ultrasonic conditions, the excess tetrahydrofuran organic solvent was removed by blowing and volatilization to obtain a near-infrared-II photoacoustic imaging contrast agent. The volume ratio of solution A to solution B was 1:10.

[0089] Characterization testing

[0090] The compound of formula I obtained in step S1 of Example 1 was subjected to nuclear magnetic resonance detection, and the results were as follows: Figure 1 As shown, from Figure 1 The H NMR spectrum of can show characteristic proton signals with the same structure as the compound of formula I, which shows that the compound of formula I was successfully prepared in Example 1.

[0091] The near infrared-II compound prepared in step S2 of Example 1 was subjected to nuclear magnetic resonance detection and mass spectrometry analysis. The results are as follows: Figure 2 and Figure 3 As shown, from Figure 2 The H NMR spectrum shows the characteristic proton signal with the same structure as the near infrared-II compound. Figure 3 The mass spectrum shows that the molecular weight is 661.990, which is consistent with the theoretical molecular weight of the near-infrared-II compound of 662.27. Therefore, it can be seen that the near-infrared-II compound was successfully prepared in Example 1. The near-infrared-II photoacoustic imaging contrast agent prepared in Example 4 was prepared into a contrast agent aqueous solution with a near-infrared-II compound concentration of 0.01 mg / mL. The hydrodynamic radius of the contrast agent aqueous solution was measured by dynamic light scattering, and the absorption spectrum of the contrast agent aqueous solution was measured. The results are as follows: Figure 4 and Figure 5 shown.

[0092] Depend on Figure 4 The hydrodynamic diameter diagram shows that the hydrodynamic radius of the near-infrared-II photoacoustic imaging contrast agent prepared in Example 4 is 85 nm. Nanoparticles of this size have a good effect of long blood circulation and accumulation in in vivo applications. Figure 5 From the absorption spectrum, it can be seen that the near-infrared maximum absorption peak of the near-infrared-II photoacoustic imaging contrast agent prepared in Example 4 is around 860nm, and there is still good absorption at 1064nm, which is obviously a near-infrared-II absorption material.

[0093] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit the same. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that they can still modify or replace the technical solutions of the present invention with equivalents, and these modifications or equivalent replacements cannot cause the modified technical solutions to deviate from the spirit and scope of the technical solutions of the present invention.

Claims

1. A near infrared-II compound, characterized in that: The near-infrared-II compound uses triphenylamine and piperazine groups as electron acceptors, and the electron-rich phenothiazine group as the hypochlorous acid recognition response site and electron acceptor precursor. The structural formula is as follows:

2. A method for preparing the near infrared-II compound according to claim 1, characterized in that: The following steps are included: S1. Adding a phenothiazine derivative, a triphenylamine derivative, and a catalyst to an organic solvent in the absence of light, and conducting a Suzuki coupling reaction under a protective atmosphere to obtain a compound of formula I; The structural formula of the compound of formula I is as follows: S2. Under light-shielding conditions, add the compound of formula I, 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine and a catalyst to an organic solvent, and carry out a Suzuki coupling reaction under a protective atmosphere to prepare a compound of formula II, i.e., a near-infrared-II compound.

3. The method for preparing a near infrared-II compound according to claim 2, wherein: The molar ratio of the phenothiazine derivative to the triphenylamine derivative in S1 is 0.8-1.2:0.8-1.

2.

4. The method for preparing a near infrared-II compound according to claim 2, wherein: The molar ratio of the compound of formula I in S2 to 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine is 0.8-1.2:0.8-1.

2.

5. The method for preparing a near infrared-II compound according to claim 2, wherein: The Suzuki coupling reaction temperature in S1 and S2 was 90-110°C, and the reaction time was 12-24 h; The catalysts were all palladium catalysts, and the organic solvents were all anhydrous toluene.

6. Use of the near-infrared-II compound according to claim 1 in a near-infrared-II photoacoustic imaging contrast agent, characterized in that: An organic solution of a near-infrared-II compound and an aqueous solution of an amphiphilic block copolymer are mixed under ultrasonic conditions, and after nano-coprecipitation of the near-infrared-II compound and the amphiphilic block copolymer, the organic solvent from the organic solution is removed to prepare a water-soluble, activatable near-infrared-II photoacoustic imaging contrast agent.

7. Use of a near infrared-II compound as a near infrared-II photoacoustic imaging contrast agent according to claim 6, characterized in that: The concentration of the near infrared-II compound shown in the near infrared-II compound in the organic solution is 0.1 to 1 mg / mL, and the concentration of the amphiphilic block polymer aqueous solution is 1 to 20 mg / mL.

8. Use of a near-infrared-II compound in a near-infrared-II photoacoustic imaging contrast agent according to claim 6, characterized in that: The volume ratio of the organic solution to the amphiphilic front-stage polymer aqueous solution is less than or equal to 1:

5.

9. Use of a near-infrared-II compound in a near-infrared-II photoacoustic imaging contrast agent according to claim 6, characterized in that: The mass ratio of the near infrared-II compound to the amphiphilic block copolymer is 1:5-100.

10. Use of a near infrared-II compound in a near infrared-II photoacoustic imaging contrast agent according to claim 6, characterized in that: The organic solvent of the organic solution is tetrahydrofuran, and the amphiphilic block copolymer is a polyoxyethylene-polyoxypropylene-polyoxyethylene triblock copolymer.

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