Preparation method and application of squaraine dye and J-aggregated nanoparticles thereof

Abstract

The present invention belongs to the field of optical diagnosis and treatment, specifically relating to a NIR-II organic small molecule cyanine dye with J-aggregate properties, and discloses methods for preparing and applying the dye and its J-aggregate nanoparticles. The cyanine dye of the present invention has an optimal absorption wavelength of 980nm in the monomeric state (in THF solution). Based on its excellent J-aggregation properties, J-aggregate nanoparticles (JSQ-1065) uniformly dispersed in an aqueous system are prepared by a nano-coprecipitation method. JSQ-1065 extends absorption into the NIR-II region while addressing the widespread problem of low fluorescence emission efficiency in the NIR-II window. JSQ-1065 has optimal optical absorption at 1065nm, precisely matching a 1064nm laser light source and maximizing the total amount of photon absorption. Its application in high-efficiency phototherapy guided by NIR-II imaging has achieved excellent results and has great prospects for clinical translation.

Description

Technical Field

[0001] The present invention belongs to the field of optical diagnosis and treatment, and in particular relates to a preparation method and application of a squaraine dye and J-aggregated nanoparticles thereof. Background Art

[0002] Phototheranostics is a precision medicine technology that combines diagnosis and treatment into a single system. It boasts low toxicity, is noninvasive, precise, and rapid. Phototherapy involves converting absorbed photons into either imaging (PAI / FLI) or therapeutic effects (PTT). Their clever combination can overcome the limitations of each. Phototheranostics (PTAs), particularly those absorbing in the near-infrared (NIR-II) window (1000–1700 nm), have long been a core focus of phototherapy research due to the deeper tissue penetration, weaker photon scattering, and higher maximum permissible exposure (MPE) offered by NIR-II excitation sources. However, due to the inherently low band gap of NIR-II fluorophores, most of the absorbed photon energy is dissipated through non-radiative pathways, resulting in poor emission efficiency.

[0003] Currently, effective strategies for enhancing fluorescence include molecular engineering (such as inserting shielding units and steric hindrance), J aggregation, and utilizing AIE properties. Among them, J aggregation is often used to develop high-efficiency NIR-II emitters due to its unique advantages of simple structural modification and strong red-shifted absorption. However, the limited J-type molecular skeleton and the fact that most reported fluorophores exhibit H aggregation or disordered aggregation in poor solvents make it a challenge to achieve ideal J aggregates for phototherapy.

[0004] Functional squaraine dyes possess a unique DAD conjugated structure and typical cyanine-like photophysical properties, exhibiting strong absorption and fluorescence emission in the visible and near-infrared regions. These excellent optical properties have led to their widespread application in the detection of biomolecules, proteins, amino acids, environmental pollutants, and metal ions. Furthermore, strong van der Waals and π-π interactions between squaraine dyes contribute to their strong aggregation properties, leading to their tendency to form J-aggregates and H-aggregates under the influence of external environments. However, despite these excellent aggregation properties and broad application range, research on squaraine J-aggregates remains limited, and their applications are even rarer.

[0005] In view of this, it is extremely urgent to develop a cyanine dye with J-aggregate characteristics and apply it to efficient phototherapy guided by NIR-II imaging. Summary of the Invention

[0006] In response to the above-mentioned defects or improvement needs of the prior art, the present invention provides an organic small molecule cyanine dye with J-aggregate characteristics, and a method for preparing J-aggregate nanoparticles based on the dye, and applies it to high-efficiency phototherapy guided by NIR-II imaging, which has broad clinical application prospects.

[0007] In order to achieve the above object, the present invention provides the following technical solutions:

[0008] The first object of the present invention is to provide an organic small molecule cyanine dye having J-aggregate characteristics, the molecular structure of which is shown below:

[0009] .

[0010] Furthermore, in the above technical solution, the optimal absorption wavelength of the squaraine cyanine dye is 980 nm, and the maximum emission wavelength is 1044 nm.

[0011] A second object of the present invention is to provide a method for preparing the above-mentioned organic small molecule cyanine dye, comprising the following steps:

[0012] S1, dissolving 1,8-naphtholactimide (Compound 1) in chloroform, slowly adding liquid bromine in an ice-water bath, and then stirring at room temperature for 2-3 days. After the reaction is complete, quenching with a saturated aqueous sodium thiosulfate solution; filtering the obtained residue and rinsing with water to obtain Compound 2;

[0013] S2, compound 2 was dissolved in N, N-dimethylformamide (DMF) solvent, stirred in an ice-water bath at 0°C for 5-10 min, sodium hydride (NaH) was slowly added in batches, and 1-bromo-2-octyldodecane (BrC) was added dropwise after 30 min. 20 H 41 ), react for 2 h, add water dropwise to quench the reaction, extract with ethyl acetate and sodium chloride aqueous solution, dry the organic layer with anhydrous sodium sulfate and filter, and remove the solvent by rotary evaporation of the filtrate under reduced pressure to obtain a crude product, which was purified by silica gel column to obtain compound 3;

[0014] S3, compound 3, phenylboronic acid pinacol ester, cesium carbonate (Cs2CO3) and tetrakistriphenylphosphine palladium (Pb(PPh3)4) were added to a mixed solvent of 1,4-dioxane / water, and the mixture was stirred at 100°C under nitrogen (N2) for 12 hours. After the reaction was completed, the mixture was cooled to room temperature and the solvent was evaporated under reduced pressure. The obtained mixture was extracted with ethyl acetate and water; the organic layer was dried over anhydrous sodium sulfate and filtered; the solvent was evaporated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography to obtain compound 4;

[0015] S4, a solution of methylmagnesium chloride (CH3MgCl) in tetrahydrofuran (THF) was added dropwise to a solution of compound 4 in anhydrous tetrahydrofuran in a 0°C ice-water bath. After the addition was complete, the reaction system was heated to 50°C and stirred for 2 hours. After the reaction was completed, the system was cooled to 0°C and quenched with water. Then, 1-3 mL of a 70% mass concentration perchloric acid (HClO4) solution was added to the reaction mixture. The dark blue solution was then extracted with dichloromethane and water. The organic layer was dried over sodium sulfate and filtered, and the solvent was evaporated under reduced pressure to obtain a crude product, thereby obtaining compound 5, which was directly processed to the next step without purification.

[0016] S5. A toluene / n-butanol (n-BuOH) solution of compound 5 and malondicyanine-squaric acid was heated to reflux for 2 h in a Dean-Stark apparatus. After the reaction was complete, the solvent was evaporated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography to obtain the final product 6, designated as SQ-980.

[0017] The reaction formula is as follows:

[0018]

[0019] Furthermore, in the above technical solution S1, the molar ratio of the 1,8-naphtholactimide and liquid bromine is 1:5, and the liquid bromine needs to be dripped completely within 5 minutes; in S2, the molar ratio of the compound 1, 1-bromo-2-octyldodecane, and sodium hydride is 1:3:5, and the eluent for column chromatography is a mixture of analytical grade petroleum ether and ethyl acetate in a volume ratio of 50:1; in S3, the molar ratio of the compound 3, phenylboronic acid pinacol ester, cesium carbonate and tetrakistriphenylphosphine palladium is 1:1:3:0.01, the mixed solvent is a mixed solvent of 1,4-dioxane and water in a volume ratio of 6:1, and the eluent for column chromatography is a mixture of analytical grade petroleum ether and ethyl acetate in a volume ratio of 30:1.

[0020] Furthermore, in the above technical solution S4, the concentration of the tetrahydrofuran solution of methylmagnesium chloride is 3 mol / L, and the molar ratio of the compound 4 to methylmagnesium chloride is 1:5; in S5, the molar ratio of the compound 5 to malondicyanine-squaric acid is 2:1, the reaction solvent is a mixed solvent of toluene and n-butanol in a volume ratio of 1:1, and the eluent for column chromatography is a mixture of analytical grade petroleum ether and ethyl acetate in a volume ratio of 5:1.

[0021] The third object of the present invention is to provide J-aggregate nanoparticles prepared using the above-mentioned squaraine dye as a raw material.

[0022] Furthermore, in the above technical solution, the optimal absorption wavelength of the J-aggregate nanoparticles is 1065 nm, and the maximum emission wavelength is 1131 nm.

[0023] A fourth object of the present invention is to provide a method for preparing J-aggregate nanoparticles, comprising the following steps: dissolving a squaraine dye SQ-980 in a tetrahydrofuran solution, dissolving liposomes (DSPE-PEG2000) in an ultrapure aqueous solution, ultrasonically dispersing the mixture for 10 to 15 minutes, uniformly injecting the tetrahydrofuran solution of SQ-980 into the ultrapure aqueous solution of the liposomes, and further ultrasonically dispersing the resulting dispersion for 15 to 30 minutes to obtain a colloidal dispersion; adding the colloidal dispersion to a round-bottom flask of a rotary evaporator, performing reduced pressure rotary evaporation in a water bath at 50° C. for 3 to 5 minutes to remove the tetrahydrofuran solution, filtering the resulting colloidal dispersion with a disposable syringe filter, and dialyzing the mixture for 2 to 4 days, replacing the ultrapure water every 4 to 6 hours during the dialysis process; then dialyzing the dispersion with physiological saline, and collecting the solution in the dialysis bag to obtain J-aggregate nanoparticles, designated as JSQ-1065.

[0024] Furthermore, in the above technical solution, the molar ratio of SQ-980 to liposomes is 1:5; the volume ratio of the tetrahydrofuran solution to ultrapure water is 1:5; the pore size of the disposable syringe filter is 0.22 μm; and the dialysis bag is a regenerated cellulose dialysis bag 3500.

[0025] The fifth object of the present invention is to provide an application of the above-mentioned J-aggregate nanoparticles in the preparation of tumor photothermal therapy drugs under the guidance of vascular imaging and fluorescence imaging.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] The organic small molecule squaraine dye SQ-980 described in this invention has a unique structure, a high molar absorptivity, and strong fluorescence emission. The optimal absorption wavelength of the monomer (in THF solution) reaches 980 nm. Leveraging its J-aggregate properties, J-aggregate nanoparticles JSQ-1065, uniformly dispersed in water, were prepared using a nano-coprecipitation method. These J-aggregate nanoparticles extend both the optimal optical absorption and fluorescence emission wavelengths into the NIR-II region. JSQ-1065 has an optimal optical absorption at 1065 nm, precisely matching a 1064 nm laser source, maximizing total photon absorption, amplifying fluorescence, and optimizing non-radiative decay processes. It demonstrates excellent results for high-resolution in vivo vascular imaging and image-guided phototherapy. In summary, JSQ-1065 is a highly effective phototherapy material urgently needed in the biomedical field. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments recorded in this application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0029] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of the SQ-980 organic small molecule cyanine dye in Example 1 of the present invention.

[0030] Figure 2 This is the carbon nuclear magnetic resonance spectrum of the SQ-980 organic small molecule cyanine dye in Example 1 of the present invention.

[0031] Figure 3 This is the high-resolution mass spectrum of the SQ-980 organic small molecule squaraine dye in Example 1 of the present invention.

[0032] Figure 4 These are the absorption and emission spectra of the SQ-980 organic small molecule squaraine dye in tetrahydrofuran (THF) in Example 1 of the present invention, and the absorption and emission spectra of the J-aggregate nanoparticles JSQ-1065 in ultrapure water in Example 2 of the present invention.

[0033] Figure 5 2. Transmission electron microscope photograph and particle size analysis diagram of J-aggregate nanoparticles JSQ-1065 in Example 2 of the present invention.

[0034] Figure 6 1 is the photothermal temperature rise curve of J-aggregate nanoparticles JSQ-1065 at different concentrations in Example 3 of the present invention.

[0035] Figure 7 This is the NIR-II fluorescence / photoacoustic imaging of mouse tumors in Application Example 1 of the present invention.

[0036] Figure 8 This is the tumor treatment status of mice after 14 days of different treatments in Application Example 2 of the present invention.

[0037] Figure 9 This is the NIR-II whole-body vascular fluorescence imaging of mice after JSQ-1065 was injected via the tail vein in Application Example 3 of the present invention. DETAILED DESCRIPTION

[0038] The experimental methods in the following examples are conventional methods unless otherwise specified. The raw materials involved in the following examples are common commercial products and can be purchased from the market unless otherwise specified.

[0039] The above-mentioned technical features of the present invention and the technical features specifically described below (such as implementation cases) can be combined with each other to form new or preferred technical solutions.

[0040] The raw materials involved in the embodiments of the present invention are either existing commercially available products or can be prepared according to existing methods.

[0041] Example 1: Preparation of organic small molecule cyanine dyes with J-aggregate properties

[0042] The organic small molecule cyanine dye with J-aggregate characteristics of this embodiment is denoted as cyanine dye SQ-980, and its molecular structure is as follows:

[0043] .

[0044] The specific synthetic route is as follows:

[0045]

[0046] The preparation method of this embodiment comprises the following steps:

[0047] S1, 1,8-naphtholactimide (Compound 1) (100 mmol, 16.9 g) was dissolved in chloroform, and liquid bromine (500 mmol, 79.9 g) was slowly added in an ice-water bath, followed by stirring at room temperature for 2-3 days. After the reaction was complete, the mixture was quenched with saturated aqueous sodium thiosulfate solution. The residue was filtered and rinsed with water to obtain Compound 2 as a yellow solid (21.1 g, 85.1%).

[0048] S2, compound 2 (15 mmol, 2.54 g) was dissolved in N,N-dimethylformamide solvent, stirred in an ice-water bath at 0°C for 5-10 min, and sodium hydride (75 mmol, 1.80 g) was slowly added in batches. After 30 min, 1-bromo-2-octyldodecane (30 mmol, 10.83 g) was added dropwise. The reaction was allowed to react for 2 h, and water was added dropwise to quench the reaction. The reaction was extracted with ethyl acetate and sodium chloride aqueous solution. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was rotary evaporated under reduced pressure to remove the solvent to obtain a crude product, which was purified by silica gel column to obtain compound 3 (4.94 g, 62.3%).

[0049] S3, compound 3 (2.53 mmol, 1.34 g), phenylboronic acid pinacol ester (2.53 mmol, 0.52 g), cesium carbonate (7.60 mmol, 2.47 g), and tetrakistriphenylphosphine palladium (0.25 mmol, 0.28 g) were added to a 1,4-dioxane / water mixed solvent, and the mixture was stirred at 100°C under nitrogen for 12 h. After the reaction was completed, the mixture was cooled to room temperature and the solvent was evaporated under reduced pressure. The resulting mixture was extracted with ethyl acetate and water; the organic layer was dried over anhydrous sodium sulfate and filtered; the solvent was evaporated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography to obtain compound 4 (1.21 g, 91.0%);

[0050] S4, a tetrahydrofuran solution of methylmagnesium chloride (about 5 mL) was added dropwise to a solution of compound 4 (2.28 mmol, 1.20 g) in anhydrous tetrahydrofuran in an ice-water bath at 0°C. After the addition was complete, the reaction system was heated to 50°C and stirred for 2 h. After the reaction was completed, the system was cooled to 0°C and quenched with water. Then, 1-3 mL of a 70% perchloric acid solution was added to the reaction mixture. The dark blue solution was then extracted with dichloromethane and water. The organic layer was dried over sodium sulfate and filtered, and the solvent was evaporated under reduced pressure to obtain a crude product, namely compound 5 (1.41 g), which was directly used in the next step without purification and drying.

[0051] S5, a toluene / n-butanol solution of compound 5 (2.30 mmol, 1.41 g) and malondicyanine-squaric acid (1.15 mmol, 0.27 g) was heated under reflux for 2 h in a Dean-Stark apparatus. After completion of the reaction, the solvent was evaporated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography to obtain the final product 6 (0.34 g, 29.0%), designated as SQ-980;

[0052] The SQ-980 organic small molecule cyanine dye was characterized by H / C NMR and high resolution mass spectrometry. The results were as follows: Figure 1 、 Figure 2 and Figure 3 In tetrahydrofuran, the obtained organic small molecule cyanine dye SQ-980 with J-aggregate characteristics was tested for absorption spectrum using UV-visible-near infrared absorption spectroscopy and fluorescence spectrum using steady-state fluorescence spectrometer. It was found that its optimal absorption wavelength was 980nm and the maximum emission wavelength was 1044nm, as shown in Figure 2. Figure 4 shown.

[0053] Example 2: Preparation of J-aggregate nanoparticles

[0054] The J-aggregate nanoparticles were prepared using the organic small molecule squaraine dye having J-aggregate characteristics obtained in Example 1 as a raw material. The preparation method is as follows:

[0055] SQ-980 was dissolved in a tetrahydrofuran solution, and liposome DSPE-PEG2000 was dissolved in an ultrapure water solution. The mixture was ultrasonically dispersed for 10-15 minutes. The tetrahydrofuran solution of SQ-980 was evenly injected into the ultrapure water solution of the liposomes, and the resulting dispersion was ultrasonically dispersed for another 15-30 minutes to obtain a colloidal dispersion. The colloidal dispersion was added to a round-bottom flask of a rotary evaporator, and the tetrahydrofuran solution was removed by rotary evaporation under reduced pressure in a water bath at 50°C for 3-5 minutes. The resulting colloidal dispersion was filtered using a disposable syringe filter and dialyzed for 2-4 days. The ultrapure water was replaced every 4-6 hours during the dialysis process. The dispersion was then dialyzed with physiological saline, and the solution in the dialysis bag was collected to obtain J-aggregate nanoparticles, which were designated as JSQ-1065.

[0056] In ultrapure water, the J-aggregate nanoparticles JSQ-1065 were tested for absorption spectrum using UV-visible-near infrared absorption spectroscopy and fluorescence spectrum using steady-state fluorescence spectrometer. The results are as follows: Figure 4 As shown, the optimal absorption wavelength is exactly 1065 nm and the maximum emission wavelength is 1131 nm.

[0057] The size and morphology of the J-aggregate nanoparticles were characterized by transmission electron microscopy and particle size analyzer, respectively. Figure 5 As shown, the particle size analysis data of the nanoparticles showed that the hydrated particle size was 120 nm, and the TEM image showed that the nanoparticles were spherical with a diameter of 90 nm.

[0058] Example 3: Photothermal performance test of J-aggregate nanoparticles

[0059] The photothermal performance of the J-aggregate nanoparticles was tested using an infrared thermal imager. The experiment used a 1064 nm laser (0.8 W / cm 2 ) as the excitation light source, the nanoparticle aqueous solution with concentrations of 0, 5, 10, 20, 40, and 80 μM was irradiated with laser for 360 seconds, and the temperature change was recorded with an infrared thermal imager. The results are shown in the figure. Figure 6 As shown, the photothermal temperature of the nanoparticles increases with the increase of material concentration.

[0060] Application Example 1: Using JSQ-1065 for NIR-II Fluorescence / Photoacoustic Imaging of Mouse Tumors

[0061] JSQ-1065 (200 μL, 80 μM) was injected into the tail vein of a 4T1 subcutaneous breast cancer nude mouse model. The NIR-II tumor fluorescence / photoacoustic signals were collected and recorded at different time points (0.1, 4, 8, 12, 24, 36, and 72 h) after injection, achieving excellent tumor imaging results. Figure 7As shown, the fluorescence / photoacoustic signal was strongest 24 hours after tail vein injection, proving that JSQ-1065 was most enriched in the tumor at this time.

[0062] Application Example 2: Using JSQ-1065 for Photothermal Therapy of Tumors in Mice

[0063] JSQ-1065 (200 μL, 80 μM) was injected into the tail vein of 4T1 subcutaneous breast cancer nude mice for 24 h. The tumor site was treated with 1064 nm laser (0.8 W / cm 2 ) irradiation for 6 minutes. After 14 days, the treatment effect is as follows Figure 8 As shown, only the JSQ-1065 nanoparticles combined with laser irradiation group (JSQ-1065 NPs+L) can effectively inhibit tumor growth and complete photothermal ablation of the tumor.

[0064] Application Example 3: Using JSQ-1065 for NIR-II Whole-Body Vascular Fluorescence Imaging in Mice

[0065] After JSQ-1065 (200 μL, 80 μM) was injected into the tail vein of a 4T1 subcutaneous breast cancer nude mouse model, the whole-body vascular imaging of the mouse was performed using a NIR-Ⅱ small animal fluorescence imager with an excitation wavelength of 1064 nm. Figure 9 It can be found that the blood vessels throughout the mouse are clearly visible, indicating that the J-aggregate nanoparticle preparation has excellent NIR-Ⅱ fluorescence imaging performance.

[0066] Finally, it should be emphasized that the above 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 changes and modifications. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A cyanine dye, characterized in that The structural formula of the cyanine dye is shown below: 。 2. A cyanine dye according to claim 1, characterized in that, The optimal absorption wavelength of the squaraine cyanine dye is 980 nm, and the maximum emission wavelength is 1044 nm.

3. A method for preparing a cyanine dye according to claim 1 or 2, characterized in that: The steps include: S1, 1,8-naphtholactimide was dissolved in chloroform, and liquid bromine was slowly added in an ice-water bath, followed by stirring at room temperature for 2-3 days. After the reaction was completed, the mixture was quenched with a saturated aqueous sodium thiosulfate solution. The residue was filtered and rinsed with water to obtain compound 2, the structure of which is shown below: ; S2, compound 2 was dissolved in N,N-dimethylformamide solvent, stirred in an ice-water bath at 0°C for 5-10 min, sodium hydride was slowly added in batches, 1-bromo-2-octyldodecane was added dropwise after 30 min, the reaction was allowed to react for 2 h, water was added dropwise to quench the reaction, and the mixture was extracted with ethyl acetate and sodium chloride aqueous solution. The organic layer was dried over anhydrous sodium sulfate and filtered, and the filtrate was rotary evaporated under reduced pressure to remove the solvent to obtain a crude product, which was purified by silica gel column to obtain compound 3, whose structure is shown below: ; S3, compound 3, phenylboronic acid pinacol ester, cesium carbonate and tetrakistriphenylphosphine palladium were added to a mixed solvent of 1,4-dioxane / water, and the mixture was stirred at 100°C for 12 hours under nitrogen. After the reaction was completed, the mixture was cooled to room temperature and the solvent was evaporated under reduced pressure to remove the solvent. The obtained mixture was extracted with ethyl acetate and water; the organic layer was dried over anhydrous sodium sulfate and filtered; the solvent was evaporated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography to obtain compound 4, whose structure is shown below: ; S4, a tetrahydrofuran solution of methylmagnesium chloride was added dropwise to a tetrahydrofuran solution of compound 4 in an anhydrous tetrahydrofuran solution under a 0°C ice-water bath. After the addition was complete, the reaction system was heated to 50°C and stirred for 2 hours. After the reaction was completed, the system was cooled to 0°C and quenched with water. Then, 1-3 mL of a 70% mass concentration perchloric acid solution was added to the reaction mixture; the dark blue solution was then extracted with dichloromethane and water; the organic layer was dried over sodium sulfate and filtered, and the solvent was evaporated under reduced pressure to obtain a crude product to obtain a crude product of compound 5, which was directly carried out to the next step without purification. The structure of compound 5 is shown below: ; S5, a toluene / n-butanol solution of compound 5 and malondicyanine-squaric acid was heated to reflux for 2 h in a Dean-Stark apparatus. After the reaction was completed, the solvent was evaporated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography to obtain the final product, a squaric acid cyanine dye, which was designated as SQ-980. The structure of the malondicyanine-squaric acid is shown below: .

4. The preparation method of squaraine dye according to claim 3, wherein In S1, the molar ratio of the 1,8-naphtholactimide and liquid bromine is 1:5, and the liquid bromine needs to be dripped completely within 5 minutes; in S2, the molar ratio of the compound 1, 1-bromo-2-octyldodecane, and sodium hydride is 1:3:5, and the eluent for column chromatography is a mixture of analytical grade petroleum ether and ethyl acetate in a volume ratio of 50:1; in S3, the molar ratio of the compound 3, phenylboronic acid pinacol ester, cesium carbonate, and tetrakistriphenylphosphine palladium is 1:1:3:0.01, the mixed solvent is a mixed solvent of 1,4-dioxane and water in a volume ratio of 6:1, and the eluent for column chromatography is a mixture of analytical grade petroleum ether and ethyl acetate in a volume ratio of 30:

1.

5. The preparation method of squaraine dye according to claim 3, wherein In S4, the concentration of the tetrahydrofuran solution of methylmagnesium chloride is 3 mol / L, and the molar ratio of the compound 4 to methylmagnesium chloride is 1:5; in S5, the molar ratio of the compound 5 to malondicyanine-squaric acid is 2:1, the reaction solvent is a mixed solvent of toluene and n-butanol in a volume ratio of 1:1, and the eluent for column chromatography is a mixture of analytical grade petroleum ether and ethyl acetate in a volume ratio of 5:

1.

6. A J-aggregate nanoparticle, characterized in that The J-aggregate nanoparticles contain the squaraine dye according to claim 1 or 2 or the squaraine dye prepared by the preparation method according to any one of claims 3 to 5.

7. The J-aggregate nanoparticle according to claim 6, characterized in that: The optimal absorption wavelength of the J-aggregate nanoparticles is 1065 nm, and the maximum emission wavelength is 1131 nm.

8. The method for preparing J-aggregate nanoparticles according to claim 6 or 7, wherein: The following steps are involved: The squaraine dye SQ-980 was dissolved in a tetrahydrofuran solution, and the liposomes were dissolved in an ultrapure water solution. The mixture was ultrasonically dispersed for 10-15 minutes. The tetrahydrofuran solution of SQ-980 was evenly injected into the ultrapure water solution of the liposomes, and the resulting dispersion was ultrasonically dispersed for 15-30 minutes to obtain a colloidal dispersion. The colloidal dispersion was added to a round-bottom flask of a rotary evaporator, and the tetrahydrofuran solution was removed by reduced pressure rotary evaporation in a water bath at 50°C for 3-5 minutes. The resulting colloidal dispersion was filtered with a disposable syringe filter and dialyzed for 2-4 days. The ultrapure water was replaced every 4-6 hours during the dialysis process. The dispersion was then dialyzed with physiological saline, and the solution in the dialysis bag was collected to obtain J-aggregate nanoparticles, which were designated as JSQ-1065.

9. The method for preparing J-aggregate nanoparticles according to claim 8, wherein: The molar ratio of SQ-980 to liposomes is 1:5; the volume ratio of tetrahydrofuran solution to ultrapure water is 1:5; the pore size of the disposable syringe filter is 0.22 μm; and the dialysis bag is a regenerated cellulose dialysis bag 3500.

10. Use of the J-aggregate nanoparticles according to claim 6 or 7 in preparing drugs for photothermal therapy of tumors under the guidance of vascular imaging and fluorescence imaging.

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