Diammonium salt reagent for deep specific photoacoustic imaging as well as preparation method and application of diammonium salt reagent
By developing macromolecular diammonium salt reagents with significant NIR-IIb window absorption characteristics, the problem of insufficient application of existing photoacoustic imaging technology in NIR-IIb windows is solved, deep-specific photoacoustic imaging is achieved, and the contrast and resolution of imaging are significantly improved.
Patent Information
- Application Number
- CN202510094285.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-21
- Publication Date
- 2025-05-02
AI Technical Summary
The existing photoacoustic imaging technology is less used in the NIR-IIb window, resulting in limited imaging depth, signal attenuation and background noise, limiting the resolution and contrast of imaging.
A macromolecular diammonium salt reagent with significant NIR-IIb window absorption characteristics was developed to achieve deep-specific photoacoustic imaging by optimizing its optical properties, improving targeting and biodegradability.
This diammonium salt reagent significantly improves the contrast and resolution of imaging, can penetrate several centimeters deep into the skin, reduce background noise, improve signal-to-noise ratio, and is suitable for imaging in deep tissues.
Smart Images
Figure CN119912361A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of photoacoustic imaging contrast agents, and specifically relates to a diammonium salt reagent for deep-layer specific photoacoustic imaging and its application in deep-layer specific photoacoustic imaging; the invention also provides a method for preparing the diammonium salt reagent. Background Art
[0002] Photoacoustic imaging (PAI) is an emerging biomedical imaging technology that combines the advantages of high contrast of optical imaging and high spatial resolution of ultrasound imaging. It can break through the limitations of traditional imaging technology and provide more comprehensive and accurate diagnostic information. PAI emits short pulses of laser to biological tissue, and uses the absorption characteristics of different components in the tissue to produce thermal expansion, thereby generating ultrasonic signals. These signals contain information about the light absorption characteristics of the tissue and can be used for high-resolution imaging. Since the absorption coefficient of light is closely related to the wavelength, the imaging contrast of PAI is mainly determined by the spectral characteristics of the laser source.
[0003] Optical excitation of PAI usually uses laser sources in the ultraviolet (UV) and near-infrared (NIR) bands. In the UV band (such as 200-400nm), the light absorption properties of nucleic acids and aromatic amino acids give them unique advantages in imaging the nucleus and cytoplasm. In the NIR band, the strong light absorption ability of hemoglobin (Hb) enables PAI to efficiently image vascular networks and monitor blood oxygen saturation and vascular morphology. In recent years, with the advancement of laser technology, the research on PAI has gradually expanded from the first near-infrared window (NIR-I, 780-900nm) to the second near-infrared window (NIR-II, 1000-1700nm). Compared with NIR-I, the penetration depth of NIR-II light in biological tissues is significantly increased, while the background absorption and scattering are significantly reduced, thereby greatly improving the signal-to-noise ratio (SNR) and spatial resolution of imaging.
[0004] Although PAI has shown great potential in preclinical studies, its practical application still faces some challenges. Traditional PAI contrast agents (such as indocyanine green ICG, methylene blue MB, etc.) mainly work in the NIR-I window, which has limited imaging depth and is easily interfered by biological media (such as water and hemoglobin), resulting in signal attenuation and increased background noise. In addition, the spectral domain signal reception capability of the NIR-I window is insufficient, which limits the resolution and contrast of imaging. In contrast, contrast agents in the NIR-II window have deeper tissue penetration, higher spatial resolution, and lower background noise, providing new possibilities for the clinical application of PAI. In particular, the NIR-IIb subwindow (1500-1700nm) is considered to be an ideal band for achieving deeper penetration and high-resolution imaging due to its longer wavelength and lower tissue absorption and scattering.
[0005] However, the research on PAI contrast agents for the NIR-IIb window is still in its infancy, and there are few related reports. The development of NIR-IIb window contrast agents with efficient light absorption characteristics, good biocompatibility and stability is the key to promoting the transformation of PAI technology to deeper clinical applications. By optimizing the optical properties of contrast agents and improving their targeting and biodegradability, PAI is expected to become an important tool for clinical diagnosis and treatment monitoring in the future, providing strong technical support for early disease diagnosis, precision treatment and efficacy evaluation. Summary of the invention
[0006] In view of this, the purpose of the present invention is to provide a diammonium salt reagent for deep-layer specific photoacoustic imaging, which exhibits strong NIR-II window absorption characteristics, with the farthest absorption wavelength reaching 1700nm, and can be applied to deep-layer specific photoacoustic imaging. The present invention also provides a method for preparing the reagent.
[0007] Specifically, the present invention provides a compound having the following structure:
[0008]
[0009] Among them, the formula X- is
[0010] The present invention also provides a method for preparing the compound of formula (I), which uses lithium bis(trifluoromethanesulfonyl)imide or lithium bis(oxalatoborate) or silver tetrafluoroborate and N,N,N',N'-tetrakis[4-(dibutylamino)phenyl]-1,4-phenylenediamine as raw materials.
[0011] In some specific embodiments of the present invention, the X - for The specific preparation steps are as follows: add dimethylformamide to a reaction container, then add N,N,N',N'-tetrakis[4-(dibutylamino)phenyl]-1,4-phenylenediamine, stir at room temperature to dissolve it, add silver tetrafluoroborate dissolved in dimethylformamide, stir at room temperature until reaction occurs, and after the reaction is completed, filter to obtain a mixed solution; then concentrate the mixed solution under vacuum, add ether to precipitate it to form a solid, collect the solid, wash and dry it with ether and petroleum ether respectively, and finally obtain the product.
[0012] In some specific embodiments of the present invention, the X - for The specific preparation steps are as follows: N,N,N',N'-tetrakis[4-(dibutylamino)phenyl]-1,4-phenylenediamine and lithium bis(trifluoromethanesulfonyl)imide are reacted in an acetone medium and sodium persulfate at 60°C in the dark with stirring; after the reaction is completed, the reaction mixture is cooled to room temperature, acetone is added for washing, and then the solvent is evaporated and dried; the dried substance is dissolved in dichloromethane, and then a large amount of water is added for extraction, and the organic phase containing the solution is retained and placed in a vacuum oven for evaporation and drying; thereafter, a small amount of dichloromethane is added to the dried substance to dissolve it, and then a large amount of n-hexane is added for recrystallization, and the recrystallization is performed three times; and finally the product is obtained.
[0013] In some specific embodiments of the present invention, the X - for The specific preparation steps are as follows: N,N,N',N'-tetrakis[4-(dibutylamino)phenyl]-1,4-phenylenediamine and lithium dioxalatoborate are reacted in dichloromethane and ethanol at room temperature for 2-4 hours; then Na 2 S 2 O 8 The water continues to react for 2-4 hours; then a large amount of water is added to terminate the reaction; after the reaction is terminated, dichloromethane is added for extraction, and then anhydrous magnesium sulfate is added to the organic phase for drying, and then the filtered solution is rotary evaporated to dry to obtain the earliest product.
[0014] The present invention also provides a diammonium salt reagent for deep-layer specific photoacoustic imaging, wherein the diammonium salt reagent is a nanoparticle prepared by a nanoprecipitation method based on the compound of formula (I) as a raw material.
[0015] In some specific embodiments of the present invention, the preparation of the diammonium salt nanoparticles comprises the following steps:
[0016] The compound of formula (I) is dissolved in tetrahydrofuran and then slowly added dropwise to an aqueous solution of 1,2-distearoyl-SN-glycero-3-phosphoethanolamine-N-carboxyl-polyethylene glycol 2000; subsequently, the mixture is exposed to air and stirred at room temperature overnight, and the tetrahydrofuran is naturally evaporated, and finally, a diammonium salt nanoparticle solution is obtained.
[0017] The present invention also provides a method for preparing a diammonium salt reagent for deep-layer specific photoacoustic imaging, comprising the following steps:
[0018] The compound of formula (I) is dissolved in tetrahydrofuran and then slowly added dropwise to an aqueous solution of 1,2-distearoyl-SN-glycero-3-phosphoethanolamine-N-carboxyl-polyethylene glycol 2000; subsequently, the mixture is exposed to air and stirred at room temperature overnight, and the tetrahydrofuran is naturally evaporated, and finally, a diammonium salt nanoparticle solution is obtained.
[0019] The present invention also provides a photoacoustic imaging contrast agent, comprising a compound of formula (I) or a compound prepared by the preparation method of the compound of formula (I) or the diammonium salt reagent for deep-layer specific photoacoustic imaging or the diammonium salt reagent for deep-layer specific photoacoustic imaging prepared by the preparation method and a dispersion medium.
[0020] The present invention also provides the use of the compound of formula (I) or the compound prepared by the preparation method of the compound of formula (I) or the diammonium salt reagent for deep-layer specific photoacoustic imaging or the diammonium salt reagent for deep-layer specific photoacoustic imaging prepared by the preparation method in photoacoustic imaging.
[0021] The present invention also provides the use of the compound of formula (I) or the compound prepared by the preparation method of the compound of formula (I) or the diammonium salt reagent for deep-layer specific photoacoustic imaging or the diammonium salt reagent for deep-layer specific photoacoustic imaging prepared by the preparation method in the preparation of photoacoustic imaging contrast agents or photothermal therapy materials.
[0022] Compared with the prior art, the present invention has the following significant advantages and effects:
[0023] (1) Excellent NIR-IIb absorption performance
[0024] The diammonium salt reagent prepared by a one-step synthesis method has significant absorption capacity in the NIR-IIb region, a longer wavelength range, and weaker interaction with biological tissues. It can effectively reduce the scattering and absorption of incident light by biological tissues, thereby significantly improving the contrast and resolution of imaging.
[0025] (2) Deep tissue imaging capability:
[0026] Compared with traditional fluorescence imaging, the photoacoustic imaging based on the diammonium salt reagent provided by the present invention can penetrate several centimeters into the subcutaneous tissue, is suitable for imaging deep tissues, can capture deeper biological information, and provide more comprehensive imaging support for disease diagnosis.
[0027] (3) High contrast and low background noise:
[0028] Since light in the NIR-IIb region is less scattered and absorbed in biological tissues, the diammonium salt reagent provided by the present invention can significantly reduce background noise and improve the signal-to-noise ratio during imaging, thereby obtaining clearer and more accurate images. This feature gives it a significant advantage in the precise positioning of tiny lesions and the accurate observation of vascular structures.
[0029] (4) High biosafety:
[0030] The diammonium salt reagent provided by the present invention is a class of organic small molecules, which has a relatively fast metabolism and excretion rate in the body, has a relatively small long-term effect on the organism, has good biocompatibility and safety, and is suitable for long-term or repeated use.
[0031] (5) Pioneering technological advantages:
[0032] The diammonium salt reagent provided by the present invention is the first type of contrast agent developed and applied to photoacoustic imaging in the NIR-IIb region. Compared with the photoacoustic contrast agents in the NIR-I region, it has significant advantages in imaging depth, contrast and resolution, and provides a new direction for the development of photoacoustic imaging technology.
[0033] (6) Wide application potential
[0034] The photoacoustic imaging technology based on the diammonium salt reagent provided by the present invention has broad application prospects in biomedical fields such as early disease diagnosis, vascular imaging, and tumor localization, and particularly exhibits unique advantages in scenarios requiring high resolution, high contrast, and deep imaging.
[0035] In summary, the diammonium salt reagent and the photoacoustic imaging technology provided by the present invention have significant advantages such as large imaging depth, high contrast, excellent resolution, and good biological safety, and provide an efficient and reliable new method for the field of biomedical imaging. BRIEF DESCRIPTION OF THE DRAWINGS
[0036] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.
[0037] Figure 1 Schematic diagram of the preparation process of DB-TFSI nanoparticles.
[0038] Figure 2 is the UV absorption spectrum of DB-TFSI in tetrahydrofuran.
[0039] Figure 3UV absorption spectrum of DB-TFSI nanoparticles in heavy water.
[0040] Figure 4 Schematic diagram of transmission electron microscopy of DB-TFSI nanoparticles.
[0041] Figure 5 Schematic diagram of dynamic light scattering of DB-TFSI nanoparticles.
[0042] Figure 6 Modeling intrauterine adhesions.
[0043] Figure 7 This is an image of the mouse abdomen sutured after surgery.
[0044] Figure 8 This is a photoacoustic imaging image of the uterus excited by a 1064-nanometer pulsed laser.
[0045] Fig. 9 This is a photoacoustic imaging image of the uterus excited by a 1700-nanometer pulsed laser.
[0046] Fig.10 The photoacoustic signal intensity of the blood vessels marked by pink circles (1064 nm: from Figure 8 ).
[0047] Fig.11 The photoacoustic signal intensity of the blood vessels marked by pink circles (1700 nm: from Fig. 9 ).
[0048] Fig.12 This is a photoacoustic imaging image of the kidney stimulated by 1064 nm pulsed laser.
[0049] Fig.13 This is a photoacoustic imaging image of the kidney excited by 1700 nm pulsed laser.
[0050] Fig.14 The photoacoustic signal intensity of the blood vessels marked by pink circles (1064 nm: from Fig.12 ).
[0051] Fig.15 The photoacoustic signal intensity of the blood vessels marked by pink circles (1700 nm: from Fig.13 ). DETAILED DESCRIPTION
[0052] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention and should not be used to limit the protection scope of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work belong to the protection scope of the present invention.
[0053] Example 1: Synthesis of compound of formula (I)—DB-TFSI
[0054] The synthetic route is as follows:
[0055]
[0056] The specific steps are as follows:
[0057] In a 50mL single-necked flask, N,N,N',N'-tetrakis[4-(dibutylamino)phenyl]-1,4-phenylenediamine (0.972mmoL), lithium bis(trifluoromethanesulfonyl)imide (5.72mmoL), sodium persulfate (1.26mmoL) and 20mL acetone were added, and the reaction mixture was stirred at 60°C for 1 hour in the dark. After the reaction mixture was cooled to room temperature, 20mL acetone was added for washing, and then the solvent was evaporated and dried. The dried substance was dissolved in 10mL dichloromethane, and then a large amount of water was added for extraction. The organic phase containing the solution was retained and placed in a vacuum oven at 40°C for evaporation and drying. After that, a small amount of dichloromethane was added to the dried substance to dissolve it. A large amount of n-hexane was added for recrystallization, and the recrystallization was performed three times to finally obtain the compound of formula (I) (DB-TFSI).
[0058] Example 2: Compound of formula (I)—TPD-B (C 2 O 4 ) 2 Synthesis
[0059] The synthetic route is as follows:
[0060]
[0061] The specific steps are as follows:
[0062] In a 50 mL single-necked flask, N,N,N',N'-tetrakis[4-(dibutylamino)phenyl]-1,4-phenylenediamine (TPD, 0.54 mmol), lithium dioxalatoborate (1.29 mmol), 5 mL of dichloromethane and 2 mL of ethanol were added and reacted at room temperature for 2 h to obtain a dark green solution. Then, Na 2 S 2 O 8(0.765mmol) and 4mL of water were added to continue the reaction for 2h. Then a large amount of water was added to terminate the reaction. A certain amount of dichloromethane was added to extract several times. Then a small amount of anhydrous magnesium sulfate was added to the organic phase for drying. The filtered solution was dried by rotary evaporation. Finally, one of the compounds of formula (I) was obtained, namely TPD-B (C 2 O 4 ) 2 .
[0063] Example 3: Compound of formula (I)—TPD-BF 4 Synthesis
[0064] The synthetic route is as follows:
[0065]
[0066] The specific steps are as follows:
[0067] Add 10 mL of dimethylformamide to a 50 mL single-necked flask, then add N,N,N',N'-tetrakis[4-(dibutylamino)phenyl]-1,4-phenylenediamine (TPD, 2.00 mmol), stir at room temperature for 10 minutes to dissolve it, add silver tetrafluoroborate (AgBF4, 2.00 mmol) dissolved in 10 mL of dimethylformamide, stir at room temperature for 30 minutes, and filter to obtain a dark green solution. Then concentrate the mixed solution to about 5 mL under vacuum, add 50 mL of ether to precipitate in a refrigerator to form a solid, collect the solid, and wash and dry it with ether and petroleum ether respectively. Finally, one of the compounds of formula (Ⅰ) is obtained, namely TPD-BF 4 .
[0068] Example 4: Preparation of diammonium salt reagent for deep-layer specific photoacoustic imaging
[0069] The compound of formula (I) synthesized above was dissolved in tetrahydrofuran (2 mL) and then slowly added dropwise to the DSPE-PEG 2000 -COOH (1,2-distearoyl-SN-glycero-3-phosphoethanolamine-N-carboxyl-polyethylene glycol 2000) aqueous solution (5mL, concentration of 1mg / mL). Subsequently, the mixture was exposed to air and placed on a magnetic stirrer at room temperature, the stirring speed was adjusted to 700rpm / min, and stirred overnight. After that, tetrahydrofuran was naturally evaporated. Finally, a diammonium salt reagent (DB-TFSI NPs) solution with a concentration of 200μg / mL was obtained.
[0070] The schematic diagram of the preparation process of DB-TFSI NPs is shown in the attached figure. Figure 1As shown. Through the nanoprecipitation method, disordered molecules can be aggregated into orderly stacked NPs. In addition, there is a certain amount of free space between molecules for molecular movement, which effectively suppresses the radiation transition. The nanoparticles modified with polyethylene glycol (PEG) can significantly enhance their dispersibility and stability in aqueous solution.
[0071] Example 5: Physical Characterization of DB-TFSI and DB-TFSI NPs
[0072] (1) UV-NIR absorption spectrum test of DB-TFSI
[0073] First, the ultraviolet-near infrared absorption spectrum of DB-TFSI was tested. The test results (see attached Figure 2 ) showed that DB-TFSI exhibited good near-infrared (NIR) absorption in the range of 750 to 1600 nanometers (nm). In particular, a very strong absorption peak appeared at 1100nm, while good absorption was also maintained at 1600nm. This result shows that DB-TFSI has the potential to be used as a near-infrared absorption material.
[0074] (2) UV-NIR absorption spectra of DB-TFSI NPs in deuterated water
[0075] Considering the strong absorption interference of water at about 1500nm, this embodiment uses deuterated water (D 2 O) as solvent to prepare DB-TFSI NPs and test their 2 O in the UV-NIR absorption spectrum. Test results (see attached Figure 3 ) showed that DB-TFSI NPs still exhibited strong NIR-II (near infrared region II) absorption in the band above 1000nm. Even more strikingly, good NIR-IIb (near infrared region IIb) absorption was observed above 1700nm. This discovery not only confirms the excellent absorption performance of DB-TFSI NPs in the near-infrared region, but also expands its absorption range to the NIR-IIb region, providing the possibility for deep in vivo and in vitro photoacoustic imaging (PAI) applications.
[0076] (3) Particle size measurement of DB-TFSI NPs
[0077] In order to further understand the physical properties of DB-TFSI NPs, this example uses transmission electron microscopy (TEM) and dynamic light scattering (DLS) technology to measure its particle size. Figure 4 ) and DLS test results (see attached Figure 5) showed that the particle size of DB-TFSI NPs was about 100 nm. This uniform particle size distribution contributes to the stability and biocompatibility of DB-TFSI NPs in vivo, and also lays the foundation for its excellent performance in biomedical applications such as PAI.
[0078] Example 6: In vivo photoacoustic imaging test using DB-TFSI NPs
[0079] Photoacoustic imaging (PAI) is a non-invasive imaging technique that relies on light absorption in biological tissues. Its imaging contrast and resolution are affected by the absorption of light energy. Figure 2 and Figure 3 As shown in the UV-visible spectrum, DB-TFSI dye molecules exhibit excellent NIR-II absorption characteristics in both monomeric and aggregated states, and can extend to the NIR-IIb region. Based on this spectral characteristic analysis, this embodiment selects 1064nm (NIR-II region) and 1700nm (NIR-IIb region) as the pulsed laser source for photoacoustic imaging.
[0080] Intrauterine adhesion is a gynecological disease that seriously affects female fertility. Its etiology is complex and prone to recurrence. Timely prevention and clinical diagnosis are essential. At the same time, in order to evaluate the application potential of DB-TFSI NPs in biomedical imaging, this example uses the intrauterine adhesion disease model as the research object. The experiment selected 8-10 week old female mice and successfully established an intrauterine adhesion model (such as Figure 6-7 After DB-TFSI NPs (1 mM, 200 μL) were administered vaginally, photoacoustic imaging was performed using 1064 nm and 1700 nm pulsed laser sources, respectively. The imaging results showed ( Figure 8-9 ), the images excited by the 1700nm laser source are significantly better than those excited by the 1064nm laser source in terms of resolution and contrast. This difference is mainly due to the light absorption characteristics of endogenous substances in biological tissues: the 1064nm wavelength is easily absorbed by water and hemoglobin, resulting in enhanced background interference signals and reduced image contrast; while the 1700nm wavelength is mainly absorbed specifically by DB-TFSI NPs, effectively reducing the self-interference signal. In order to quantitatively evaluate the imaging effect, in this embodiment, a blood vessel near the uterus was enlarged and marked using ImageJ software, and its signal intensity was measured. The results showed that the signal intensity excited by the 1700nm pulsed laser source was 99.43, which is about five times the intensity of the 1064nm excitation signal ( Fig.10 and Fig.11 ).
[0081] In order to further verify that DB-TFSI NPs excited by a 1700 nm pulsed laser source have lower self-signal interference, this example also observed the peripheral signal intensity of kidney images excited by two different pulsed laser sources. Fig.12 and Fig.13 As shown in the figure, the kidney image excited by 1700nm has higher contrast and clarity, and the kidney outline is clearer. The blood vessels in the kidney area were enlarged and marked and the PA signal intensity was measured. It was found that the signal intensity of 1700nm excitation (156.96) was significantly stronger than the signal intensity of 1064nm excitation (99.69) ( Fig.14 and Fig.15 ).
[0082] In summary, this example fully demonstrates the excellent photoacoustic imaging performance of DB-TFSI NPs in the NIR-IIb region by comparing the photoacoustic imaging effects of 1064 nm and 1700 nm pulsed laser sources in the intrauterine adhesion mouse model.
[0083] Although the present invention is described using the above embodiments, it should be understood that the present invention may be further modified and varied without departing from the spirit of the present invention, and these modifications and variations are all within the scope of protection of the present invention.
Claims
1. A compound having the following structure: in, Formula X - for 2. The method for preparing the compound according to claim 1, characterized in that: It is prepared using lithium bis(trifluoromethanesulfonyl)imide or lithium bis(oxalatoborate) or silver tetrafluoroborate and N,N,N',N'-tetrakis[4-(dibutylamino)phenyl]-1,4-phenylenediamine as raw materials.
3. A diammonium salt reagent for deep-layer specific photoacoustic imaging, characterized in that: The diammonium salt reagent is diammonium salt nanoparticles prepared by nanoprecipitation method based on the compound described in claim 1 as a raw material.
4. The diammonium salt reagent for deep-layer specific photoacoustic imaging according to claim 3, characterized in that: The preparation of the diammonium salt nanoparticles comprises the following steps: The compound described in claim 1 is dissolved in tetrahydrofuran and then slowly added dropwise to an aqueous solution of 1,2-distearoyl-SN-glycero-3-phosphoethanolamine-N-carboxyl-polyethylene glycol 2000; subsequently, the mixture is exposed to air and stirred at room temperature for 12-24 hours, and the tetrahydrofuran is naturally evaporated, and finally, a diammonium salt nanoparticle solution is obtained.
5. A method for preparing a diammonium salt reagent for deep-layer specific photoacoustic imaging, characterized in that: The steps include: The compound described in claim 1 is dissolved in tetrahydrofuran and then slowly added dropwise to an aqueous solution of 1,2-distearoyl-SN-glycero-3-phosphoethanolamine-N-carboxyl-polyethylene glycol 2000; subsequently, the mixture is exposed to air and stirred at room temperature overnight, and the tetrahydrofuran is naturally evaporated, and finally, a diammonium salt nanoparticle solution is obtained.
6. A photoacoustic imaging contrast agent, characterized in that: It comprises the compound according to claim 1 or the compound prepared by the preparation method according to claim 2 or the diammonium salt reagent for deep-layer specific photoacoustic imaging according to any one of claims 3 to 4 or the diammonium salt reagent for deep-layer specific photoacoustic imaging prepared by the preparation method according to claim 5 and a dispersion medium.
7. Use of the compound according to claim 1 or the compound prepared by the preparation method according to claim 2, or the diammonium salt reagent for deep-layer specific photoacoustic imaging according to any one of claims 3 to 4, or the diammonium salt reagent for deep-layer specific photoacoustic imaging prepared by the preparation method according to claim 5 in photoacoustic imaging.
8. Use of the compound according to claim 1 or the compound prepared by the preparation method according to claim 2, or the diammonium salt reagent for deep-layer specific photoacoustic imaging according to any one of claims 3 to 4, or the diammonium salt reagent for deep-layer specific photoacoustic imaging prepared by the preparation method according to claim 5 in the preparation of photoacoustic imaging contrast agents, disease diagnostic reagents or photothermal therapeutic materials.