A near-infrared emitting dye molecule and its preparation method and application

Abstract

The present invention relates to the technical field of fluorescent dyes, and provides a near-infrared emitting dye molecule and a preparation method and application thereof. The dye molecule provided by the present invention is a D-A-D configuration, has near-infrared emission performance, has a strong ability to produce reactive oxygen species (ROS), can be used to kill Gram-positive bacteria, and can be effectively sterilized under both illumination and no illumination conditions, and has a better sterilization effect under illumination conditions, and can be used for synergistic antibacterial of photodynamic therapy and chemotherapy; at the same time, the dye molecule provided by the present invention also has good photothermal performance, and can be used to construct a photothermal therapy drug guided by near-infrared fluorescence imaging.

Description

Technical Field

[0001] The invention relates to the technical field of fluorescent dyes, and in particular to a near-infrared emitting dye molecule and a preparation method and application thereof. Background Art

[0002] Photothermal therapy has been a hot topic in cancer treatment in recent years. Unlike conventional chemotherapy drugs, photothermal therapy converts near-infrared light into heat through fluorescent dyes. When the heat accumulates to a certain level, it will kill cancer cells.

[0003] Since Professor Tang Benzhong proposed the concept of aggregation-induced emission (AIE), fluorescent dyes with AIE properties have attracted much attention. AIE fluorescent dye materials can overcome the aggregation-induced fluorescence quenching phenomenon of traditional fluorescent molecules and have been widely used in photodynamic therapy. At present, commonly used AIE fluorescent dyes include tetraphenylethylene, triphenylamine, silole, etc., but these traditional fluorescent dyes are all visible region luminescent dye molecules. In practical applications, they are very susceptible to interference from background signals in the body, resulting in a decrease in the imaging signal-to-noise ratio. The shorter emission wavelength also reflects poor deep tissue penetration ability.

[0004] Compared with traditional AIE fluorescent dyes that emit light in the visible region, AIE fluorescent dyes with near-infrared light have higher signal-to-background ratio (SBR), good tissue penetration and high photothermal conversion efficiency, and can be used to kill tumor cells or ablate bacteria. Therefore, the design and synthesis of near-infrared AIE luminescent molecules with high photothermal conversion efficiency have very broad application prospects in medical treatment and diagnosis. Summary of the invention

[0005] In view of this, the present invention provides a near-infrared emitting dye molecule and a preparation method and application thereof. The near-infrared emitting dye molecule provided by the present invention has AIE characteristics, high photothermal conversion efficiency, good bactericidal activity, and has broad application prospects in photothermal therapy or antibacterial guided by near-infrared fluorescence imaging.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] A near-infrared emitting dye molecule having a structure shown in formula I:

[0008]

[0009] The present invention also provides a method for preparing the near-infrared emitting dye molecule described in the above scheme, comprising the following steps:

[0010] A compound having a structure shown in Formula II, 7,7,8,8-tetracyanoquinodimethane and an organic solvent are mixed and subjected to a condensation reaction to obtain the near-infrared emitting dye molecule;

[0011]

[0012] Preferably, the molar ratio of the compound having the structure shown in Formula II to 7,7,8,8-tetracyanoquinodimethane is 1:(1-1.5).

[0013] Preferably, the temperature of the condensation reaction is 50-60°C.

[0014] Preferably, the method for preparing the compound having the structure shown in Formula II comprises the following steps:

[0015] 4-bromotriphenylamine, trimethylsilyl acetylene, a palladium catalyst, cuprous iodide, 1,8-diazacyclo[5,4,0]undecene-7 and a benzene solvent are mixed to carry out a Sonogashira coupling reaction to obtain the compound having the structure shown in formula II.

[0016] Preferably, the molar ratio of 4-bromotriphenylamine to trimethylsilyl acetylene is 1:0.8-1.0;

[0017] The molar ratio of the 4-bromotriphenylamine to the palladium catalyst is 1:0.15-0.25;

[0018] The molar ratio of 4-bromotriphenylamine to cuprous iodide is 1:0.08-0.12;

[0019] The molar ratio of the 4-bromotriphenylamine to 1,8-diazacyclo[5,4,0]undecene-7 is 1:5-8.

[0020] Preferably, the temperature of the Sonogashira coupling reaction is 75-85° C., and the time is 18-24 hours; the Sonogashira coupling reaction is carried out under a protective atmosphere and in the dark.

[0021] The present invention also provides the use of the near-infrared emitting dye molecule described in the above scheme or the near-infrared emitting dye molecule prepared by the preparation method described in the above scheme in the preparation of antibacterial drugs or photothermal therapy drugs.

[0022] The present invention also provides a method for preparing near-infrared emitting dye molecule water-dispersible nanoparticles, comprising the following steps:

[0023] Dissolving near-infrared emitting dye molecules and polyethylene glycol-distearoyl phosphatidylethanolamine in an organic solvent to obtain a mixed solution; adding the mixed solution into water for ultrasonic coprecipitation, and dialyzing the obtained coprecipitation liquid to obtain water-dispersible nanoparticles of near-infrared emitting dye molecules; the near-infrared emitting dye molecules are the near-infrared emitting dye molecules described in the above scheme or the near-infrared emitting dye molecules prepared by the preparation method described in the above scheme.

[0024] The present invention also provides water-dispersible nanoparticles of near-infrared emitting dye molecules prepared by the preparation method described in the above scheme.

[0025] The present invention provides a near-infrared emitting dye molecule having a structure shown in formula I. The dye molecule structure provided by the present invention has a strong electron-donating unit (triphenylamine part) and a strong electron-withdrawing unit (cyanobenzoquinone part), so the molecule has a strong DA interaction, and its molecular structure belongs to a DAD configuration. Due to the DA interaction, an effective intramolecular charge transfer (ICT) effect can be generated, and the absorption wavelength and the emission wavelength are red-shifted, so that its fluorescence emission reaches the near-infrared region; at the same time, the dye molecule having the structure shown in formula I provided by the present invention has a high reactive oxygen species (ROS) generation ability, can be used for killing Gram-positive bacteria, and can be effectively sterilized under both illumination and no illumination conditions, and the sterilization effect is better under illumination conditions, and can be used for synergistic antibacterial of photodynamic therapy and chemotherapy; in addition, the dye molecule provided by the present invention also has good photothermal performance, and the photothermal conversion efficiency can reach 53%, which can be used to construct a photothermal therapy drug guided by near-infrared fluorescence imaging; and the dye molecule having the structure shown in formula I provided by the present invention also has an obvious aggregation-induced luminescence effect, and can emit stronger fluorescence in an aggregated state, and has a high ROS generation efficiency.

[0026] The present invention also provides a method for preparing the near-infrared emitting dye molecule described in the above technical solution. The preparation method provided by the present invention has simple steps, is easy to operate, and is suitable for industrial production.

[0027] The present invention also provides a near-infrared emitting dye molecule water-dispersible nanoparticle. The present invention prepares the near-infrared emitting dye molecule into water-dispersible nanoparticle for use. After the nanoparticle is prepared, the biocompatibility of the molecule can be improved. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 The fluorescence intensity test results of TP-TCNQ in DMSO / n-hexane mixed solutions with different n-hexane volume fractions;

[0029] Figure 2 The fluorescence emission spectrum of the mixed solution of TP-TCNQ and DCFH changes with the illumination time;

[0030] Figure 3 The photodynamic killing of Staphylococcus aureus by TP-TCNQ at different concentrations;

[0031] Figure 4 The temperature change of TP-TCNQ NPs with a concentration of 100 μM under different laser powers;

[0032] Figure 5 The laser power is 0.3W / cm 2 Temperature changes of TP-TCNQ NPs with different concentrations when .

[0033] Figure 6 The calculation results of the photothermal conversion efficiency of TP-TCNQ NPs;

[0034] Figure 7 Thermal stability test results of TP-TCNQ NPs. DETAILED DESCRIPTION

[0035] The present invention provides a near-infrared emitting dye molecule having a structure shown in Formula I:

[0036]

[0037] The near-infrared dye molecules provided by the present invention have a near-infrared emission wavelength (>650nm), and have the ability to generate active oxygen, efficient photothermal conversion ability and obvious aggregation-induced emission effect (AIE), and have broad application prospects in photothermal therapy or photodynamic antibacterial guided by near-infrared fluorescence imaging.

[0038] The present invention also provides a method for preparing the near-infrared emitting dye molecule described in the above scheme, comprising the following steps:

[0039] A compound having a structure shown in Formula II, 7,7,8,8-tetracyanoquinodimethane and an organic solvent are mixed and subjected to a condensation reaction to obtain the near-infrared emitting dye molecule;

[0040]

[0041] In the present invention, the method for preparing the compound having the structure shown in Formula II preferably comprises the following steps:

[0042] 4-bromotriphenylamine, trimethylsilyl acetylene, a palladium catalyst, cuprous iodide, 1,8-diazacyclo[5,4,0]undecene-7 and a benzene solvent are mixed to carry out a Sonogashira coupling reaction to obtain the compound having the structure shown in formula II.

[0043] In the present invention, the molar ratio of the 4-bromotriphenylamine to trimethylsilylacetylene is preferably 1:0.8-1.0; the molar ratio of the 4-bromotriphenylamine to the palladium catalyst is preferably 1:0.15-0.25, more preferably 1:0.2; the molar ratio of the 4-bromotriphenylamine to cuprous iodide is preferably 1:0.08-0.12, more preferably 1:0.1; the molar ratio of the 4-bromotriphenylamine to 1,8-diazacyclo[5,4,0]undecene-7 is preferably 1:5-8, more preferably 1:6; the palladium catalyst is preferably bis(triphenylphosphine)palladium(II) chloride; the benzene solvent is preferably anhydrous toluene. The present invention has no special requirements on the amount of the benzene solvent, as long as it can ensure the smooth progress of the Sonogashira coupling reaction.

[0044] In the present invention, the temperature of the Sonogashira coupling reaction is preferably 75-85°C, more preferably 80°C, and the time is preferably 18-24h, more preferably 20h; the Sonogashira coupling reaction is preferably carried out under a protective atmosphere and light-proof conditions; the protective atmosphere is preferably nitrogen.

[0045] In the present invention, the reaction formula of the Sonogashira coupling reaction is as follows:

[0046]

[0047] After the Sonogashira coupling reaction is completed, the present invention preferably performs post-treatment on the obtained product liquid; the post-treatment preferably comprises the following steps: cooling the obtained product liquid of the Sonogashira coupling reaction to room temperature, extracting with dichloromethane, hydrochloric acid solution and saturated saline, combining the obtained organic layers, drying, filtering and concentrating in sequence to obtain a crude product; purifying the crude product by column chromatography to obtain a compound having a structure shown in Formula II, which is a yellow solid; the mass fraction of the hydrochloric acid solution is preferably 8-12%, more preferably 10%; the drying desiccant is preferably anhydrous sodium sulfate; the column chromatography purification eluent is preferably a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the mixed solvent is preferably 100:1.

[0048] After obtaining the compound having the structure shown in Formula II, the present invention mixes the compound having the structure shown in Formula II, 7,7,8,8-tetracyanoquinodimethane (TCNQ) and an organic solvent for condensation reaction to obtain a near-infrared emitting dye molecule having the structure shown in Formula I. In the present invention, the molar ratio of the compound having the structure shown in Formula II and 7,7,8,8-tetracyanoquinodimethane is preferably 1:(1-1.5), more preferably 1:(1-1.2); the organic solvent is preferably 1,2-dichloroethane; the temperature of the condensation reaction is preferably 50-60°C; in a specific embodiment of the present invention, the condensation reaction is preferably carried out under reflux and light-proof conditions; the condensation reaction is preferably carried out under stirring conditions, and the present invention has no special requirements for the stirring rate, and it is sufficient to stir evenly; the present invention has no special requirements for the time of the condensation reaction, and it is preferred to use a thin layer chromatography spot plate (TLC plate) to monitor the reaction until the compound having the structure shown in Formula II completely disappears; in a specific embodiment of the present invention, the time of the condensation reaction is 10-15h.

[0049] In the present invention, the reaction formula of the condensation reaction is as follows:

[0050]

[0051] After the condensation reaction is completed, the present invention preferably performs post-treatment on the obtained product liquid; the post-treatment preferably comprises the following steps: cooling the obtained product liquid to room temperature, extracting with dichloromethane and saturated brine, combining the obtained organic layers, filtering, drying and concentrating in sequence to obtain a crude product; purifying the crude product by column chromatography to obtain a compound having a structure shown in Formula I, which is a dark green solid; the drying desiccant is preferably anhydrous sodium sulfate; the eluent for column chromatography purification is preferably a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the mixed solvent is preferably 20:1.

[0052] The present invention provides the use of the near-infrared emitting dye molecules described in the above scheme or the near-infrared emitting dye molecules prepared by the preparation method described in the above scheme in the preparation of bactericidal drugs or photothermal therapeutic drugs. In the present invention, the bactericidal drug is preferably a photodynamic bactericidal drug. The near-infrared dye molecules provided by the present invention have certain bactericidal activity under conditions of illumination or no illumination, can effectively kill Gram-positive bacteria, and can produce active oxygen under white light, with higher bactericidal efficiency; the near-infrared dye molecules provided by the present invention also have a high photothermal conversion efficiency, and can be used to construct photothermal therapeutic drugs guided by near-infrared fluorescence imaging.

[0053] The present invention also provides a method for preparing near-infrared emitting dye molecule water-dispersible nanoparticles, comprising the following steps:

[0054] Dissolving near-infrared emitting dye molecules and polyethylene glycol-distearoyl phosphatidylethanolamine (DSPE-mPEG) in an organic solvent to obtain a mixed solution; adding the mixed solution into water for ultrasonic coprecipitation, and dialyzing the obtained coprecipitation liquid to obtain water-dispersible nanoparticles of near-infrared emitting dye molecules; the near-infrared emitting dye molecules are the near-infrared emitting dye molecules described in the above scheme or the near-infrared emitting dye molecules prepared by the preparation method described in the above scheme.

[0055] In the present invention, the polyethylene glycol-distearoyl phosphatidylethanolamine is preferably DSPE-mPEG2000, and the mass ratio of the near-infrared emitting dye molecule and the polyethylene glycol-distearoyl phosphatidylethanolamine is preferably 1:5-8; the organic solvent is preferably tetrahydrofuran; the dosage ratio of the near-infrared dye molecule and the organic solvent is preferably 1 mg:2-3 mL; the present invention preferably first dissolves the near-infrared emitting dye molecule and DSPE-mPEG in an organic solvent respectively to obtain a dye molecule solution and a DSPE-mPEG solution, and then mixes the dye molecule solution and the DSPE-mPEG solution under ultrasonic conditions; the volume ratio of the mixed solution and water is preferably 1:8-12, and the present invention preferably adds the mixed solution dropwise into water; the ultrasonic power of the ultrasonic coprecipitation is preferably 100-200 W, and the ultrasonic time is preferably 3-10 min; the ultrasonic coprecipitation is preferably carried out in a cell disruptor; after the ultrasonic coprecipitation is completed, the present invention preferably dialyzes the obtained coprecipitation liquid in ultrapure water; the dialysis time is preferably 12-24 h. The present invention utilizes DSPE-mPEG to cover near-infrared emitting dye molecules, thereby improving the water solubility of the dye molecules.

[0056] The present invention also provides water-dispersible nanoparticles of near-infrared emitting dye molecules prepared by the preparation method described in the above scheme. The present invention prepares the near-infrared dye molecules into water-dispersible nanoparticles, which can further improve their biocompatibility.

[0057] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0058] Example 1

[0059] (1) Preparation of the compound having the structure shown in Formula II

[0060] 4-Bromotriphenylamine (1mmol, 324.21mg), trimethylsilyl acetylene (0.8mmol, 78.6mg), bis(triphenylphosphine)palladium chloride (II) (0.2mmol, 140.4mg), cuprous iodide (0.1mmol, 19.0mg) and 1,8-diazacyclo[5,4,0]undecene-7 (6mmol, 913.4mg) were added to a two-necked round-bottom flask and dissolved in anhydrous toluene (10mL), and reacted in a nitrogen atmosphere at 80°C in the dark for 20h. After the reaction was completed and cooled to room temperature, it was extracted with dichloromethane, 10% HCl and saturated brine, and then the combined organic layer was dried with anhydrous sodium sulfate, filtered, and concentrated under vacuum. The concentrate was subjected to column chromatography using petroleum ether / ethyl acetate (100:1, v / v) as the eluent to obtain a yellow solid, which is the compound having the structure shown in formula II, with a yield of 70%.

[0061] The obtained solid was characterized, and the specific data are as follows:

[0062] 1 H NMR (500MHz, CDCl3) δ7.37(d,J=8.6Hz,4H),7.32–7.27(m,8H),7.13(d,J=7.7Hz,8H),7.07(t,J=7.3Hz,4H),7.02(d,J=8.6Hz,4H).

[0063] (2) Preparation of near-infrared emitting dye molecules having the structure shown in Formula I

[0064] Add the compound having the structure shown in Formula II (1mmol, 512.64mg) and 7,7,8,8-tetracyano-p-benzoquinone dimethane (1mmol, 204.19mg) to an eggplant-shaped bottle and dissolve in 1,2-dichloroethane (10mL), react at 60°C in the dark, and reflux overnight. After the reaction is completed and cooled to room temperature, extract with dichloromethane and saturated brine, and then dry the combined organic layer with anhydrous sodium sulfate, filter, and concentrate under vacuum. The mixture is chromatographed with petroleum ether / ethyl acetate (20:1, v / v) as the eluent to obtain a dark green solid, which is a near-infrared emitting dye molecule having the structure shown in Formula I (denoted as TP-TCNQ), with a yield of 80%.

[0065] The obtained solid was characterized, and the specific data are as follows:

[0066] 1H NMR(500MHz,DMSO-d6)δ7.61-7.55(m,3H),7.45-7.38(m,11H),7.35(d,J=9.4Hz,1H),7 .28-7.19(m,13H),7.11(d,J=9.8Hz,1H),6.78(d,J=9.0Hz,2H),6.72(d,J=9.2Hz,2H). 13 C NMR (600MHz, CDCl3) δ168.92,154.30,153.09,152.15,151.49,150.77,145.46,144.81,135.23,134.60,133.36,132.02,131.98,131.23,1 30.02,129.89,127.23,126.87,126.55,126.40,125.80,125.49,125. 19,124.39,119.34,118.03,114.39,114.30,114.28,113.60,111.54.

[0067] Performance Test:

[0068] (1) AIE property test of TP-TCNQ: n-Hexane is a poor solvent for TP-TCNQ. DMSO solution (1 mM) of TP-TCNQ was added to DMSO / n-hexane mixed solutions with different n-hexane volume fractions to obtain TP-TCNQ solutions with a concentration of 10 μM. The fluorescence intensity of TP-TCNQ in the mixed solutions with different n-hexane volume fractions was measured.

[0069] Figure 1 The fluorescence intensity test results of TP-TCNQ in DMSO / n-hexane mixed solutions with different n-hexane volume fractions (the volume fractions of n-hexane from low to high are 0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 99% and the excitation light wavelength is 650nm). Figure 1 It can be seen that with the increase of n-hexane volume fraction, the fluorescence intensity of TP-TCNQ gradually increases, indicating that TP-TCNQ has AIE characteristics.

[0070] (2) Test of TP-TCNQ's ability to produce active oxygen: prepare the DMSO stock solution of the sample to be tested, take 20 μL of the sample to be tested and 50 μL of the active oxygen scavenger DCFH, add them to a cuvette containing 2 mL of PBS buffer solution, so that the final test concentration of TP-TCNQ is 10 μM and the final concentration of DCFH is 40 μM. Use FL-4700 fluorescence spectrometer for testing, set the excitation wavelength to 489 nm, first measure the fluorescence spectrum in the absence of light (0 min), and then measure the sample spectrum at the same interval to obtain the ratio of real-time luminescence intensity to initial luminescence intensity; at the same time, use a single DCFH solution (concentration of 40 μM) and a single TP-TCNQ solution (concentration of 10 μM) as controls. The results are as follows: Figure 1 shown.

[0071] Figure 2 The fluorescence emission spectrum of the mixed solution of TP-TCNQ and DCFH changes with the illumination time, where the interval between each two tests is 2 minutes, and the test is carried out under white light (10W). Figure 2 It can be seen that with the increase of illumination time, the fluorescence intensity of the mixed solution gradually increased and reached saturation at 24 min, indicating that TP-TCNQ has the ability to produce reactive oxygen species.

[0072] (3) Test of the photodynamic killing ability of TP-TCNQ on Staphylococcus aureus. The specific steps are as follows:

[0073] The Staphylococcus aureus strain was revived and inoculated into LB liquid medium and cultured in a shaker at 37°C and 220 r / min for 16 h. At this time, the concentration of Staphylococcus aureus in the bacterial suspension was about 2×10 9 CFU / mL; 1 mL of cultured Staphylococcus aureus was taken, the culture medium was removed, and it was washed with PBS; different volumes of DMSO solution of TP-TCNQ were added to make the final concentration of TP-TCNQ 0 μM, 2 μM, 4 μM, and 6 μM, respectively. After the bacterial suspension was incubated in a shaker at 37°C and 220 r / min for 10 min, the bacterial suspension was illuminated for 20 min using a solar simulator equipped with a 400 nm filter; after the illumination, the bacterial suspension was gradiently diluted to 1×10 7 The cells were plated on LB agar solid medium and cultured in a 37°C incubator for 16 h before colony counting and survival rate calculation, which was used as the phototoxicity group. The cells were cultured and counted without light treatment, which was used as the dark toxicity group.

[0074] Figure 3 The photodynamic killing of Staphylococcus aureus by TP-TCNQ at different concentrations. Figure 3It can be seen that with the increase of TP-TCNQ concentration, the survival rates of Staphylococcus aureus in both the phototoxicity group and the dark toxicity group decreased significantly, among which the survival rate of the phototoxicity group decreased more, indicating that TP-TCNQ has antibacterial activity under both light and dark conditions, and can be used for synergistic antibacterial research of photodynamic therapy and chemotherapy.

[0075] (4) Photothermal performance test of TP-TCNQ

[0076] First, in order to increase the water solubility of TP-TCNQ, TP-TCNQ nanoparticles (TP-TCNQ NPs) were obtained by encapsulating DSPE-mPEG2000. The preparation method of TP-TCNQ NPs is as follows: TP-TCNQ and DSPE-mPEG2000 were weighed and dissolved in 1.5 mL of tetrahydrofuran (THF) respectively, and the two were mixed evenly under ultrasonic conditions. In a cell disruptor, the mixed solution was added dropwise to 15 mL of water, and a clear solution was formed after ultrasonic treatment for 5 minutes. The obtained solution was transferred into a dialysis bag and dialyzed in ultrapure water for 12 hours, then taken out and evenly covered with polyethylene glycol to precipitate excess water to obtain a TP-TCNQ NPs aqueous dispersion. By changing the amount of TP-TCNQ and DSPE-mPEG2000, TP-TCNQ NPs aqueous dispersions with concentrations of 25 μM, 50 μM and 100 μM were obtained, respectively.

[0077] TP-TCNQ NPs aqueous dispersions with different concentrations were packaged and tested for photothermal properties. During the test, a 660nm laser source was used for irradiation, and a FLIR thermal imager was used to record temperature changes. The data was then processed using FLIRTools software.

[0078] Figure 4 The temperature change of TP-TCNQ NPs with a concentration of 100 μM under different laser powers; Figure 4 It can be seen that with the increase of laser power, the temperature of the test solution gradually increases. When the power is 0.5W / cm 2 When the irradiation time was 300s, the temperature of the test solution reached 70°C, which was nearly 45°C higher than that at room temperature. Therefore, TP-TCNQ NPs have good photothermal generation ability.

[0079] Figure 5 The laser power is 0.3W / cm 2 Temperature changes of TP-TCNQ NPs with different concentrations. Figure 5It can be seen that as the concentration increases, the heat generated by the nanoparticles becomes higher. When the concentration is 100 μM and the irradiation time is 300 s, the temperature of the test solution reaches 50 °C, so TP-TCNQ NPs have good photothermal properties.

[0080] At a laser power of 0.3 W / cm 2 Under the condition of , 100μM TP-TCNQ NPs were irradiated with a 660nm laser source for 300s and then cooled for 600s. During this period, the temperature change of the test solution was recorded and the photothermal conversion efficiency of TP-TCNQ NPs was calculated. The results are shown in Figure 6 As shown. Figure 6 It can be seen that the photothermal conversion efficiency of 100μM TP-TCNQ NPs under 660nm laser irradiation is as high as 53%.

[0081] The thermal stability of TP-TCNQ NPs was tested under 660 nm laser irradiation. Specifically, when the laser power was 0.3 W / cm 2 Under the condition of TP-TCNQ NPs concentration of 100 μM, the laser was irradiated for 10 min and cooled for 10 min as one cycle. The temperature change of the test solution during the cycle was recorded. A total of five cycles were tested. The results are as follows: Figure 7 As shown. Figure 7 It can be seen that TP-TCNQ NPs have good stability, and the photothermal conversion ability has not changed much before and after five cycles.

[0082] It can be seen from the above embodiments that the near-infrared emitting dye molecules provided by the present invention have high photothermal conversion efficiency and can be used to construct photothermal therapy drugs guided by near-infrared fluorescence imaging; and have the ability to produce active oxygen and strong bactericidal ability, especially under light conditions, the bactericidal efficiency is higher, and can be used to construct photodynamic bactericidal drugs.

[0083] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A near-infrared emitting dye molecule, characterized in that: It has the structure shown in formula I:

2. The method for preparing the near-infrared emitting dye molecule according to claim 1, characterized in that: The following steps are involved: A compound having a structure shown in Formula II, 7,7,8,8-tetracyanoquinodimethane and an organic solvent are mixed and subjected to a condensation reaction to obtain the near-infrared emitting dye molecule; 3. The preparation method according to claim 2, characterized in that: The molar ratio of the compound having the structure shown in Formula II to 7,7,8,8-tetracyanoquinodimethane is 1:(1-1.5).

4. The preparation method according to claim 2, characterized in that: The temperature of the condensation reaction is 50-60°C.

5. The preparation method according to claim 2, characterized in that: The method for preparing the compound having the structure shown in Formula II comprises the following steps: 4-bromotriphenylamine, trimethylsilyl acetylene, a palladium catalyst, cuprous iodide, 1,8-diazacyclo[5,4,0]undecene-7 and a benzene solvent are mixed to carry out a Sonogashira coupling reaction to obtain the compound having the structure shown in formula II.

6. The preparation method according to claim 5, characterized in that: The molar ratio of 4-bromotriphenylamine to trimethylsilyl acetylene is 1:0.8-1.0; The molar ratio of the 4-bromotriphenylamine to the palladium catalyst is 1:0.15-0.25; The molar ratio of 4-bromotriphenylamine to cuprous iodide is 1:0.08-0.12; The molar ratio of the 4-bromotriphenylamine to 1,8-diazacyclo[5,4,0]undecene-7 is 1:5-8.

7. The preparation method according to claim 5, characterized in that: The temperature of the Sonogashira coupling reaction is 75-85° C., and the time is 18-24 hours; the Sonogashira coupling reaction is carried out under a protective atmosphere and light-proof conditions.

8. Use of the near-infrared emitting dye molecule according to claim 1 or the near-infrared emitting dye molecule prepared by the preparation method according to any one of claims 2 to 7 in the preparation of antibacterial drugs or photothermal therapeutic drugs.

9. A method for preparing water-dispersible nanoparticles of near-infrared emitting dye molecules, characterized in that: The following steps are involved: Dissolving near-infrared emitting dye molecules and polyethylene glycol-distearoyl phosphatidylethanolamine in an organic solvent to obtain a mixed solution; adding the mixed solution into water for ultrasonic coprecipitation, and dialyzing the obtained coprecipitation liquid to obtain water-dispersible nanoparticles of near-infrared emitting dye molecules; the near-infrared emitting dye molecules are the near-infrared emitting dye molecules described in claim 1 or the near-infrared emitting dye molecules prepared by the preparation method described in any one of claims 2 to 7.

10. Water-dispersible nanoparticles of near-infrared emitting dye molecules prepared by the preparation method of claim 9.

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