Near-infrared two-region aggregation-induced emission material, preparation method and application

Abstract

The invention discloses a near-infrared two-region aggregation-induced emission material as well as a preparation method and application thereof, and belongs to the technical field of aggregation-induced emission materials. The invention provides a fluorescent material with aggregation-induced emission (AIE) property, which can have high luminous efficiency in an NIR-II (1000 nm to 1500 nm) region. The invention aims to carry out rational structure design through the multilevel space confinement effect of molecule and aggregate levels. Through modification of a methyl group and a side chain substituent group, free rotation of an aromatic ring is effectively inhibited, and a rigid mortise and tenon interlocking structure is formed in the crystal. The water-soluble nanoparticles prepared from the synthesized aggregation-induced emission material can achieve a fluorescence quantum yield of 28.2%. By utilizing the nanoparticles with high fluorescence efficiency, the application of real-time dynamic monitoring and the like on intestinal vessels of a living body can be realized, and a new method is provided for early diagnosis and surgical intervention of acute intestinal ischemia.

Description

Technical Field

[0001] The present invention relates to the technical field of aggregation-induced luminescence materials, and in particular to a near-infrared second-region aggregation-induced luminescence material, a preparation method and an application thereof. Background Art

[0002] At a time when integrated biomedical imaging and diagnosis and treatment technologies are developing rapidly, luminescent materials in the second near-infrared window (NIR-II, wavelength range 1000-1700nm) have attracted much attention due to their unique advantages of real-time, in situ and high spatiotemporal resolution. These outstanding characteristics make NIR-II fluorescence imaging an ideal tool for guiding complex treatment processes in vivo, especially for disease scenarios that are highly dependent on surgery, such as tumor boundary definition, tissue necrosis judgment and organ transplant monitoring. In addition to imaging equipment, imaging quality is also heavily dependent on the photophysical properties of contrast agents. Among them, quantum yield has a decisive influence on imaging sensitivity and tissue penetration depth. Contrast agents with high quantum yield can produce strong fluorescence signals at lower excitation light intensities, thereby improving the signal-to-noise ratio of imaging and enhancing the ability to detect weak biological signals. However, due to the interference of various photophysical processes such as excited state structural relaxation, ground state-excited state coupling and concentration quenching, the luminescence efficiency of NIR-II materials is generally low (less than 1%). Although numerous molecular systems with red-shifted emission wavelengths have been developed, there has been limited progress in effective strategies to improve quantum yield, making it a major challenge to achieve NIR-II imaging with high signal-to-noise ratio and deep tissue penetration.

[0003] Reducing the energy gap by constructing an extended planar conjugated skeleton or strong intramolecular donor-acceptor interactions is a common strategy for developing long-wavelength luminophores. However, the unavoidable intermolecular π-π stacking and molecular motion between the donor and acceptor accelerate the non-radiative decay process, resulting in a significant decrease in the luminescence efficiency of NIR-II materials in aqueous physiological environments. Therefore, while strengthening the rigid structure at the molecular level, establishing a rigid environment that limits molecular deformation at the aggregate level is expected to be an effective way to develop high quantum yield NIR-II materials. However, due to weak intermolecular non-covalent interactions, current strategies make it difficult to achieve directional assembly of molecules to form a rigid aggregation environment. Summary of the Invention

[0004] The purpose of the present invention is to provide a near-infrared second-region aggregation-induced luminescence nanomaterial, a preparation method and an application thereof, so as to solve the above-mentioned problems in the background technology.

[0005] To achieve the above object, the present invention provides the following technical solutions:

[0006] One of the technical solutions of the present invention is to provide a near-infrared second region aggregation-induced luminescence material, wherein the near-infrared second region aggregation-induced luminescence material comprises a material having one of the following structural formulas:

[0007]

[0008] A second technical solution of the present invention provides a method for preparing the aforementioned near-infrared second-region aggregation-induced emission material, wherein, when preparing B-DpMeT, the preparation method is as shown in Method 1; Method 1 comprises the following steps: under a protective atmosphere, mixing Compound 1, DpMeT-DB, potassium carbonate, and tetrakis(triphenylphosphine)palladium in a mixed solvent of tetrahydrofuran and water, and heating the mixture for reaction to obtain the B-DpMeT;

[0009] When preparing B-ToMeT, the preparation method is as shown in Method 2; Method 2 comprises the following steps: under a protective atmosphere, mixing compound 1, ToMeT-DB, potassium carbonate and tetrakis(triphenylphosphine)palladium in a mixed solvent of tetrahydrofuran and water, heating and reacting to obtain the B-ToMeT;

[0010] When preparing TPE-cT-BBT, the preparation method is as shown in Method 3; Method 3 comprises the following steps: under a protective atmosphere, mixing compound 2, TPE-cT, tris(dibenzylideneacetone)dipalladium and tri(o-tolyl)phosphine in toluene, and reacting under reflux conditions to obtain the TPE-cT-BBT;

[0011] When preparing TPE-pT-BBT, the preparation method is as shown in Method 4; Method 4 comprises the following steps: under a protective atmosphere, mixing compound 2, TPE-pT, tris(dibenzylideneacetone)dipalladium and tri(o-tolyl)phosphine in toluene, and reacting under reflux conditions to obtain the TPE-pT-BBT;

[0012] The chemical formula of compound 1 is The chemical formula of compound 2 is The chemical formula of the TPE-cT is The chemical formula of the TPE-pT is The chemical formula of the DpMeT-DB is The chemical formula of the ToMeT-DB is

[0013] The synthesis route of the near-infrared second-region aggregation-induced emission material is as follows:

[0014]

[0015] Preferably, in method 1: the molar ratio of compound 1, DpMeT-DB, potassium carbonate and tetrakis(triphenylphosphine)palladium is 1:3:3:0.1-0.3; and / or, the heating reaction temperature is 70° C. and the time is 5 h.

[0016] Preferably, in method 2: the molar ratio of compound 1, ToMeT-DB, potassium carbonate and tetrakis(triphenylphosphine)palladium is 1:3:3:0.2; and / or the heating reaction temperature is 70° C. and the time is 5 h.

[0017] Preferably, in method 3: the molar ratio of compound 2, TPE-cT, tris(dibenzylideneacetone)dipalladium and tri(o-tolyl)phosphine is 1:2:0.05-0.15:1; and / or the reaction time under reflux conditions is 12 h.

[0018] Preferably, in method 4: the molar ratio of compound 2, TPE-pT, tris(dibenzylideneacetone)dipalladium and tri(o-tolyl)phosphine is 1:2:0.05-0.15:1; and / or the reaction time under reflux conditions is 12 hours.

[0019] The third technical solution of the present invention is to provide a composition comprising the aforementioned near-infrared second region aggregation-induced emission material and a matrix for encapsulating the near-infrared second region aggregation-induced emission material.

[0020] Preferably, the composition is in the form of nanoparticles.

[0021] Preferably, the composition is capable of emitting fluorescence in the near-infrared region of 1000-1500 nm.

[0022] The fourth technical solution of the present invention: provides an application of the above-mentioned near-infrared second-region aggregation-induced emission material or the above-mentioned composition in the preparation of a fluorescent contrast agent.

[0023] The fifth technical solution of the present invention: provides an application of the above-mentioned near-infrared second-region aggregation-induced luminescence material or the above-mentioned composition in intestinal ischemia detection and surgical navigation for non-diagnostic or therapeutic purposes.

[0024] The technical principles of the present invention are as follows:

[0025] The present invention aims to achieve rational structural design through multi-level spatial confinement effects at the molecular and aggregate levels. Modification with methyl groups and side chain substituents not only effectively inhibits the free rotation of the aromatic ring, but also promotes the formation of a rigid mortise and tenon interlocking structure within the crystal. Water-soluble nanoparticles prepared using synthesized aggregation-induced luminescence materials can achieve a fluorescence quantum yield of 28.2%. The use of such high-fluorescence-efficiency nanoparticles can realize applications such as real-time dynamic monitoring of intestinal blood vessels in living beings, providing a new method for early diagnosis and surgical intervention of acute intestinal ischemia.

[0026] The target molecule described in this invention uses benzobisthiadiazole, a strong electron-withdrawing molecule, as an electron acceptor, and a triphenylamine derivative or tetraphenylethylene group as an electron donor. These two are coupled to create an organic fluorescent material with intramolecular charge transfer characteristics. By introducing a methyl steric group into the electron donor and modifying the structure with various side chain groups, both intramolecular and intermolecular interactions are enhanced, suppressing rapid excited-state molecular motion and effectively improving the material's luminous efficiency.

[0027] The beneficial technical effects of the present invention are as follows:

[0028] The present invention provides a fluorescent material capable of high luminescence efficiency in the NIR-II (1000nm to 1500nm) region. By introducing a methyl steric group into the electron donor group, the intramolecular steric interaction is enhanced, and excited-state molecular motion is suppressed, thereby effectively improving the luminescence efficiency of the molecule. Nanoparticles prepared using the aggregation-induced emission material of the present invention have the advantages of high luminescence efficiency, good dimensional stability, and deep penetration, and can be used in fields such as early diagnosis of acute intestinal ischemia in mice and surgical navigation treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments. 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 any creative work.

[0030] Figure 1 Figure 2 shows the fluorescence spectra of B-DpMeT and B-ToMeT under different water content conditions. (a) is B-DpMeT, and (b) is B-ToMeT.

[0031] Figure 2 The crystal structures and stacking patterns of B-DpMeT and B-ToMeT are shown in Figure 1. (a) The crystal structure of B-DpMeT, (b) The crystal structure of B-ToMeT, (c) A schematic diagram of the intermolecular interactions in the B-DpMeT crystal structure, (d) A schematic diagram of the intermolecular interactions in the B-ToMeT crystal structure, (e) A simulated diagram of the stacking pattern of B-DpMeT, and (f) A simulated diagram of the stacking pattern of B-ToMeT.

[0032] Figure 3 Schematic diagram of the preparation process of B-ToMeT nanoparticles.

[0033] Figure 4Transmission electron microscopy (TEM) images and dynamic light scattering (DLS) particle size distribution of B-ToMeT nanoparticles. a is TEM and b is DLS.

[0034] Figure 5 Figure 2 shows the photophysical properties of B-ToMeT nanoparticles and B-DpMeT nanoparticles. Where a is the emission spectrum and b is the fluorescence quantum yield.

[0035] Figure 6 Biocompatibility evaluation of B-ToMeT nanoparticles at the cellular level (a) and animal level (b).

[0036] Figure 7 The penetration depth of B-DpMeT nanoparticles and B-ToMeT nanoparticles is evaluated. (a) is the penetration depth imaging image, and (b) is the curve of the signal-to-noise ratio as a function of penetration depth.

[0037] Figure 8 Evaluation of the blood circulation time of B-ToMeT nanoparticles.

[0038] Figure 9 Figure 1 shows images of intestinal arteries and veins captured using B-ToMeT nanoparticles and the corresponding signal-to-noise ratio analysis. (a) shows a white light image of the intestine, (b) and (c) show fluorescence images of the intestinal arteries and veins, and (d) shows the signal-to-noise ratio analysis.

[0039] Figure 10 Figure 2 shows the early diagnosis of acute intestinal ischemia using B-ToMeT nanoparticles and the corresponding signal-to-noise ratio analysis. (a) Intestinal obstruction and (b) Intestinal volvulus.

[0040] Figure 11 This image shows surgical navigation for acute intestinal ischemia using B-ToMeT nanoparticles. Figures a and b are white-light and fluorescence images related to surgical navigation for intestinal obstruction, and c and d are white-light and fluorescence images related to surgical navigation for intestinal volvulus. DETAILED DESCRIPTION

[0041] Various exemplary embodiments of the present invention are now described in detail. This detailed description should not be considered as a limitation of the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention. It should be understood that the terms used in the present invention are only for describing specific embodiments and are not intended to limit the present invention.

[0042] In addition, for numerical ranges in the present invention, it is understood that each intervening value between the upper and lower limits of the range is also specifically disclosed. Each smaller range between any stated value or stated range, and any other stated value or intervening value in the stated range, is also included in the present invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range.

[0043] Unless otherwise specified, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which the present invention pertains. Although preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention. It should be noted that any details not described herein are conventional procedures in the art and are not the focus of the present invention.

[0044] The terms “include,” “including,” “have,” “contain,” etc. used in the present invention are open-ended terms, meaning including but not limited to.

[0045] Unless otherwise specified, the "room temperature" in the present invention is 10-30°C.

[0046] The raw materials used in the following examples and comparative examples of the present invention are all commercially available products.

[0047] Example 1

[0048] The synthetic route of compound B-DpMeT is as follows:

[0049]

[0050] Its specific preparation method is:

[0051] Under a nitrogen atmosphere, compound 1 (68 mg, 0.1 mmol), DpMeT-DB (120 mg, 0.3 mmol), potassium carbonate (41 mg, 0.3 mmol), and tetrakis(triphenylphosphine)palladium (23 mg, 0.02 mmol, Pd(PPh3)4) were dissolved in a mixture of tetrahydrofuran (12 mL, THF) and deionized water (3 mL) and reacted at 70°C for 5 h. After completion of the reaction, the reaction solution was cooled to room temperature and extracted three times with dichloromethane, and the organic phase was dried over sodium sulfate. The solvent in the reaction system was removed under reduced pressure, and the resulting crude product was purified by column chromatography to obtain B-DpMeT as a blue solid (yield 64%).

[0052] 1H NMR (500MHz, CDCl3) δ7.52(d,J=8.7,2H),7.34(s,1H),7.10(d,J=8.3,4H),7.04(dd,J=8.3,6.4,6H ),2.65–2.53(m,2H),2.33(s,6H),1.67–1.56(m,2H),1.19–1.04(m,6H),0.74–0.72(t,J=7.0,3H). 13 C NMR (126MHz, CDCl3) δ153.25,148.02,147.24,145.65,144.99,132.93,129.99,127.96,127.27,126.67,124 .93,124.59,122.14,116.09,31.54,30.52,30.31,29.13,22.49,20.88,14.02.MS(MALDI-TOF)[m / z]:calcd forC 66 H 64 N6S4,1068.4075; found,1068.3427.

[0053] Example 2

[0054] The synthetic route of compound B-ToMeT is as follows:

[0055]

[0056] Its specific preparation method is:

[0057] Under a nitrogen atmosphere, compound 1 (68 mg, 0.1 mmol), ToMeT-DB (124 mg, 0.3 mmol), potassium carbonate (41 mg, 0.3 mmol), and tetrakis(triphenylphosphine)palladium (23 mg, 0.02 mmol, Pd(PPh3)4) were dissolved in a mixed solution of tetrahydrofuran (12 mL, THF) and deionized water (3 mL) and reacted at 70°C for 5 h. After the reaction, the reaction solution was cooled to room temperature and extracted three times with dichloromethane, and the organic phase was dried over sodium sulfate. The solvent in the reaction system was removed under reduced pressure, and the crude product was purified by column chromatography to obtain a blue solid B-ToMeT (yield 53%).

[0058] 1H NMR (500MHz, CDCl3) δ7.44(s,1H),7.37–7.28(m,2H),7.14–7.07(m,2H),7.03(dd,J=16.9,8.0,2H),6.96(d,J=6.8,2H),6.76 (d,J=7.9,1H),6.69(t,J=7.5,2H),2.50(s,2H),1.92–1.79(m,9H),1.60–1.51(m,2H),1.12–0.97(m,6H),0.66(t,J=7.0,3H). 13 C NMR (126MHz, CDCl3) δ153.25,147.29,147.05,145.65,133.34,131.69,129.39,129.20,128.21,126.70,125 .30,124.84,124.14,123.89,31.53,30.49,30.29,29.11,22.48,18.74,14.01.MS(MALDI-TOF)[m / z]:calcd for C 68 H 68 N6S4,1096.4388; found,1096.5420.

[0059] Example 3

[0060] The synthetic route of the compound TPE-cT-BBT is as follows:

[0061]

[0062] Its specific preparation method is:

[0063] Under a nitrogen atmosphere, compound 2 (176 mg, 0.5 mmol), TPE-cT (786 mg, 1 mmol), tris(dibenzylideneacetone)dipalladium (46 mg, 0.05 mmol, Pd2(dba)3), and tri(o-tolyl)phosphine (152 mg, 0.5 mmol, P(o-lol)3) were dissolved in toluene (12 mL, toluene) and reacted at reflux (120°C) for 12 h. After completion of the reaction, the reaction solution was cooled to room temperature and extracted three times with dichloromethane, and the organic phase was dried over sodium sulfate. The solvent in the reaction system was removed under reduced pressure, and the resulting crude product was purified by column chromatography to obtain the product TPE-cT-BBT (yield 55%).

[0064] 1H NMR (500MHz, CDCl3) δ7.49-7.48(m,6H),7.17-7.16(m,12H),7.15(d,J=1.5Hz, 2H),7.14(d,J=1.5Hz,4H),7.12(d,J=3.0Hz,4H),7.10(m,3H),7.09(m,3H),7. 07(m,4H),2.47-2.43(m,2H),2.08(d,J=11.5Hz,4H),1.77(d,J=13.5Hz,4H),1 .67(d,J=12.5Hz,2H),1.59-1.51(m,7H),1.29-1.25(m,2H),1.10-1.02(m,4H).

[0065] Example 4

[0066] The synthetic route of compound TPE-pT-BBT is as follows:

[0067]

[0068] Its specific preparation method is:

[0069] Under a nitrogen atmosphere, compound 2 (176 mg, 0.5 mmol), TPE-pT (780 mg, 1 mmol), tris(dibenzylideneacetone)dipalladium (46 mg, 0.05 mmol, Pd2(dba)3), and tri(o-tolyl)phosphine (152 mg, 0.5 mmol, P(o-lol)3) were dissolved in toluene (12 mL, toluene) and reacted at reflux (120°C) for 12 h. After completion of the reaction, the reaction solution was cooled to room temperature and extracted three times with dichloromethane, and the organic phase was dried over sodium sulfate. The solvent in the reaction system was removed under reduced pressure, and the resulting crude product was purified by column chromatography to obtain the product TPE-pT-BBT (yield 63%).

[0070] 1H NMR (500MHz, CDCl3) δ7.58 (s, 2H), 7.49 (d, J = 8.5Hz), 7.13-7.03 (m, 44H).13CNMR (126MHz, CDCl3) δ152.78,147.13,145.00,143.83,143.64,143.47,141.54,140. 37,137.12,132.00,131.81,131.47,131.39,129.11,128.19,128.08,127.87,127.80,127.70,126.79,126.70,126.63,126.56,126.49,125.80,125.13,115.90.

[0071] Example 5

[0072] A fluorescent composite nanoparticle, the preparation method is as follows:

[0073] The B-ToMeT and F127 (polyoxyethylene-polyoxypropylene-polyoxyethylene triblock copolymer) in Example 2 were dissolved in tetrahydrofuran and uniformly mixed to obtain concentrations of 1 mg / mL and 4 mg / mL, respectively. The mixed solution was injected from the middle inlet of the microfluidic chip at a flow rate of 3 mL / h using a syringe pump, and ultrapure water was injected from the inlets on both sides at a flow rate of 100 mL / h using another syringe pump. After starting the microfluidic device, the product was collected from the outlet and recorded as B-ToMeT nanoparticles;

[0074] The product obtained by replacing the B-ToMeT of Example 2 with an equal mass of B-DpMeT of Example 1 during the preparation of B-ToMeT nanoparticles was recorded as B-DpMeT nanoparticles.

[0075] Figure 3 Schematic diagram of the preparation process of B-ToMeT nanoparticles.

[0076] Effect verification

[0077] 1. Characterization of AIE properties

[0078] The AIE properties were tested by adjusting the volume ratio of the good solvent tetrahydrofuran and the poor solvent water.

[0079] Figure 1 Figure 2 shows the fluorescence spectra of B-DpMeT and B-ToMeT under different water content conditions. (a) is B-DpMeT, and (b) is B-ToMeT.

[0080] from Figure 1As can be seen from the figure, the B-DpMeT and B-ToMeT prepared in Examples 1-2 emit weak light in tetrahydrofuran, a good solvent. As the poor solvent water is added, aggregates are formed and the fluorescence gradually increases. This indicates that these materials all have AIE properties.

[0081] 2. Characterization of Crystal Structure and Packing Pattern

[0082] B-DpMeT and B-ToMeT crystals were obtained by slow solvent evaporation in toluene / methanol and tetrahydrofuran / methanol, respectively, and then characterized accordingly.

[0083] Figure 2 The crystal structures and stacking patterns of B-DpMeT and B-ToMeT are shown in Figure 1. (a) The crystal structure of B-DpMeT, (b) The crystal structure of B-ToMeT, (c) A schematic diagram of the intermolecular interactions in the B-DpMeT crystal structure, (d) A schematic diagram of the intermolecular interactions in the B-ToMeT crystal structure, (e) A simulated diagram of the stacking pattern of B-DpMeT, and (f) A simulated diagram of the stacking pattern of B-ToMeT.

[0084] from Figure 2 It can be seen that in the crystal, B-DpMeT molecules adopt a layer-by-layer stacking pattern, while B-ToMeT molecules adopt a mortise and tenon interlocking structure, indicating that B-ToMeT crystals have stronger intermolecular interactions and structural rigidity.

[0085] 3. Structural Characterization of B-ToMeT Nanoparticles

[0086] Figure 4 Transmission electron microscopy (TEM) images and dynamic light scattering (DLS) particle size distribution of B-ToMeT nanoparticles. a is TEM and b is DLS.

[0087] Figure 4 The two small figures on the left and right of a represent TEM images at different magnifications. Figure 4 TEM images of the B-ToMeT nanoparticles show lattice fringes and diffraction signals, indicating good crystallinity. DLS images show that the B-ToMeT nanoparticles have a particle size of approximately 60 nm and good stability.

[0088] 4. Characterization of Photophysical Properties of B-ToMeT Nanoparticles and B-DpMeT Nanoparticles

[0089] Figure 5 Figure 2 shows the photophysical properties of B-ToMeT nanoparticles and B-DpMeT nanoparticles. Where a is the emission spectrum and b is the fluorescence quantum yield.

[0090] Figure 5a shows that the emission peaks of B-ToMeT nanoparticles and B-DpMeT nanoparticles are located in the second near-infrared region. Figure 5 Figure b shows that the fluorescence quantum yields of B-DpMeT nanoparticles and B-ToMeT nanoparticles are 10.2% and 28.2%, respectively, indicating that the fluorescence performance of both has reached a very high level, and B-ToMeT nanoparticles have better luminescence properties, which is conducive to obtaining better imaging effects.

[0091] 5. Biocompatibility evaluation of B-ToMeT nanoparticles at the cellular and animal levels

[0092] NIH 3T3 and HUVEC cells were used to evaluate the cytotoxicity of B-ToMeT nanoparticles. NIH 3T3 and HUVEC cells were plated in 96-well plates and cultured for 24 hours, then co-cultured with different concentrations of B-ToMeT nanoparticles for 24 hours. The cytotoxicity of the cells was detected by MTT. The test results are shown in Figure 6 a.

[0093] Healthy BALB / c nude mice were used to evaluate the toxicity of B-ToMeT nanoparticles at the animal level. B-ToMeT nanoparticles were injected into the Balb / c nude mice via the tail vein. Two weeks later, the main organs (heart, liver, spleen, lung, and kidney) of the nude mice were taken for pathological analysis. The test results are shown in Figure 6 b.

[0094] Figure 6 Biocompatibility evaluation of B-ToMeT nanoparticles at the cellular level (a) and animal level (b).

[0095] like Figure 6 As shown in a, B-ToMeT nanoparticles have no obvious cytotoxicity. Figure 6 As shown in b, there were no obvious lesions in the main organs of the mice, indicating that B-ToMeT nanoparticles have excellent biocompatibility.

[0096] 6. Evaluation of the Penetration Depth of B-ToMeT Nanoparticles

[0097] B-ToMeT nanoparticles were loaded into capillaries and covered with tissue phantoms of different thicknesses to evaluate the penetration depth.

[0098] Figure 7 The penetration depth of B-DpMeT nanoparticles and B-ToMeT nanoparticles is evaluated. (a) is the penetration depth imaging image, and (b) is the curve of the signal-to-noise ratio as a function of penetration depth.

[0099] like Figure 7As shown in the figure, the penetration depths of B-DpMeT nanoparticles and B-ToMeT nanoparticles reached a high level, and the penetration depth of B-ToMeT nanoparticles could reach 1.5 cm, indicating that they are suitable for deep tissue imaging.

[0100] 7. Evaluation of Blood Circulation Time of B-ToMeT Nanoparticles

[0101] B-ToMeT nanoparticles were injected into Balb / c nude mice via the tail vein, and blood was collected from the mice at different time points to measure the fluorescence intensity and evaluate the blood circulation time.

[0102] Figure 8 Evaluation of the blood circulation time of B-ToMeT nanoparticles.

[0103] like Figure 8 As shown, the blood circulation time of B-ToMeT nanoparticles is as long as 18.45 hours, which is conducive to long-term fluorescence imaging.

[0104] 8. Mouse Intestinal Vascular Imaging

[0105] B-ToMeT nanoparticles were injected into healthy mice through the tail vein, and the fluorescence signals of the intestinal blood vessels of the mice were collected using a fluorescence imager (long pass 1300 nm).

[0106] Figure 9 Figure 1 shows images of intestinal arteries and veins captured using B-ToMeT nanoparticles and the corresponding signal-to-noise ratio analysis. (a) shows a white light image of the intestine, (b) and (c) show fluorescence images of the intestinal arteries and veins, and (d) shows the signal-to-noise ratio analysis.

[0107] like Figure 9 As shown in a, b, and c, after the injection of nanoparticles, the arteries and veins in the intestines of mice were clearly visible, and the signal-to-noise ratios reached 5.02 and 4.28, respectively. Figure 9 d).

[0108] 9. Early Monitoring and Recovery Assessment of Acute Intestinal Ischemia in Mice

[0109] First, two models of mesenteric thrombosis (intestinal obstruction) and intestinal volvulus were established, and the relevant data were tested respectively.

[0110] Figure 10 Figure 2 shows the early diagnosis of acute intestinal ischemia using B-ToMeT nanoparticles and the corresponding signal-to-noise ratio analysis. (a) Intestinal obstruction and (b) Intestinal volvulus.

[0111] like Figure 10As shown in Figure a, after tail vein injection of B-ToMeT nanoparticles, obvious fluorescent signals were observed in the healthy part of the intestine, while no fluorescent signals could be detected in the ischemic part due to the obstruction of the intestinal artery. After the obstruction was cleared, the fluorescence was restored, indicating that blood flow was restored to the ischemic part. Similarly, B-ToMeT nanoparticles were also used to evaluate ischemia caused by intestinal volvulus; as shown in Figure 4, the fluorescence signal was not detected in the ischemic part. Figure 10 As shown in (b), after tail vein injection of B-ToMeT nanoparticles, the healthy part of the intestine showed a clear fluorescent signal, while the torsion part showed almost no fluorescent signal due to blood flow obstruction. As the torsion recovered, fluorescence appeared, indicating that blood supply had been successfully restored.

[0112] 10. Fluorescence Imaging Surgical Navigation for Acute Intestinal Ischemia in Mice

[0113] Surgery was performed on mice with acute intestinal ischemia (ileus and volvulus), and relevant data before and after the surgery were collected.

[0114] Figure 11 This image shows surgical navigation for acute intestinal ischemia using B-ToMeT nanoparticles. Figures a and b are white-light and fluorescence images related to surgical navigation for intestinal obstruction, and c and d are white-light and fluorescence images related to surgical navigation for intestinal volvulus.

[0115] like Figure 11 As shown in a and b, after the tail vein injection of B-ToMeT nanoparticles, there is almost no fluorescence signal in the ischemic part. After the obstruction is removed, the fluorescence cannot be restored, indicating that the ischemic part has been necrotic. To ensure the health of the remaining intestine, the necrotic part is removed and the intestinal anastomosis is performed under fluorescence guidance. Similarly, B-ToMeT nanoparticles can also be used for surgical navigation of ischemic necrosis caused by torsion of the intestine, such as Figure 11 As shown in c and d, under fluorescence guidance, the necrotic intestinal part was precisely resected and then intestinal anastomosis was performed.

[0116] The embodiments described above are merely descriptions of preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Without departing from the spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by persons skilled in the art should fall within the scope of protection defined by the claims of the present invention.

Claims

1. A near-infrared second-region aggregation-induced emission material, characterized in that: The near-infrared second-region aggregation-induced emission material includes a material having one of the following structural formulas:

2. A method for preparing the near-infrared second-region aggregation-induced emission material according to claim 1, characterized in that: When preparing B-DpMeT, the preparation method is as shown in Method 1; Method 1 comprises the following steps: under a protective atmosphere, mixing Compound 1, DpMeT-DB, potassium carbonate and tetrakis(triphenylphosphine)palladium in a mixed solvent of tetrahydrofuran and water, heating and reacting to obtain the B-DpMeT; When preparing B-ToMeT, the preparation method is as shown in Method 2; Method 2 comprises the following steps: under a protective atmosphere, mixing compound 1, ToMeT-DB, potassium carbonate and tetrakis(triphenylphosphine)palladium in a mixed solvent of tetrahydrofuran and water, heating and reacting to obtain the B-ToMeT; When preparing TPE-cT-BBT, the preparation method is as shown in Method 3; Method 3 comprises the following steps: under a protective atmosphere, mixing compound 2, TPE-cT, tris(dibenzylideneacetone)dipalladium and tri(o-tolyl)phosphine in toluene, and reacting under reflux conditions to obtain the TPE-cT-BBT; When preparing TPE-pT-BBT, the preparation method is as shown in Method 4; Method 4 comprises the following steps: under a protective atmosphere, mixing compound 2, TPE-pT, tris(dibenzylideneacetone)dipalladium and tri(o-tolyl)phosphine in toluene, and reacting under reflux conditions to obtain the TPE-pT-BBT; The chemical formula of compound 1 is The chemical formula of compound 2 is The chemical formula of the TPE-cT is The chemical formula of the TPE-pT is The chemical formula of the DpMeT-DB is The chemical formula of the ToMeT-DB is 3. The preparation method according to claim 2, characterized in that In method 1, the molar ratio of compound 1, DpMeT-DB, potassium carbonate and tetrakis(triphenylphosphine)palladium is 1:3:3:0.1-0.3; and / or the heating reaction temperature is 70° C. and the time is 5 hours.

4. The preparation method according to claim 2, characterized in that In method 2: the molar ratio of compound 1, ToMeT-DB, potassium carbonate and tetrakis(triphenylphosphine)palladium is 1:3:3:0.2; and / or the heating reaction temperature is 70° C. and the time is 5 hours.

5. The preparation method according to claim 2, characterized in that In method 3: the molar ratio of compound 2, TPE-cT, tris(dibenzylideneacetone)dipalladium and tri(o-tolyl)phosphine is 1:2:0.05-0.15:1; and / or the reaction time under reflux conditions is 12 hours.

6. The preparation method according to claim 2, characterized in that In method 4: the molar ratio of compound 2, TPE-pT, tris(dibenzylideneacetone)dipalladium and tri(o-tolyl)phosphine is 1:2:0.05-0.15:1; and / or the reaction time under reflux conditions is 12 hours.

7. A composition, characterized in that The invention comprises the near-infrared second-region aggregation-induced emission material according to claim 1, and a matrix for encapsulating the near-infrared second-region aggregation-induced emission material.

8. Use of the near-infrared second-region aggregation-induced emission material according to claim 1 or the composition according to claim 7 in the preparation of a fluorescent contrast agent.

9. Use of the near-infrared second-region aggregation-induced emission material according to claim 1 or the composition according to claim 7 in intestinal ischemia detection and surgical navigation for non-diagnostic or therapeutic purposes.

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