Near-infrared two-region aggregation-induced emission material, preparation method thereof and application of near-infrared two-region aggregation-induced emission material in preparation of I-type photodynamic drugs

Abstract

The invention provides a near-infrared two-region aggregation-induced emission material, a preparation method thereof and application of the near-infrared two-region aggregation-induced emission material in preparation of I-type photodynamic drugs, and belongs to the technical field of biomedical engineering. The NDA / BA nano-particles are constructed by taking the obtained near-infrared two-region aggregation-induced emission material as a donor and thiaphthalimide as a receptor and integrating the donor and the receptor through poloxamer F127, and the NDA / BA nano-particles are further used for preparing I-type photodynamic drugs. The NDA / BA nano-particles show remarkably enhanced I-type photodynamic performance, the total active oxygen,. OH and O2 <.-> generation amount of the NDA / BA nano-particles are remarkably increased, the NDA / BA nano-particles are proved to have accurate near-infrared two-region imaging and photodynamic therapy effects, and a new scheme with a wide prospect is provided for near-infrared two-region image guided photodynamic diagnosis and treatment integration.

Description

Technical Field

[0001] This invention belongs to the field of biomedical engineering technology, and particularly relates to a near-infrared II region aggregation-induced emission material, its preparation method, and its application in the preparation of type I photodynamic drugs. Background Technology

[0002] Photodynamic therapy (PDT), as a well-tolerated and non-invasive treatment modality, has gained widespread attention in the clinical setting due to its spatiotemporal controllability under light irradiation and negligible systemic toxicity. Traditional type II PDT relies on converting molecular oxygen into highly toxic reactive oxygen species (ROS) and currently dominates therapeutic photosensitization methods. However, the efficacy of type II PDT is significantly limited by its oxygen dependence, particularly in the hypoxic tumor microenvironment caused by the high metabolic demands of rapidly proliferating tumor cells. To overcome these inherent limitations, an increasing number of strategies aimed at alleviating tumor hypoxia and breaking through the oxygen dependence bottleneck of PDT have been developed. Over the past few decades, mainstream approaches have focused on increasing oxygen concentration within solid tumors, with researchers investing considerable effort in constructing nanoplatforms capable of in-situ oxygen production or direct oxygen delivery to tumors. While these strategies have improved the efficacy of PDT, significant challenges remain hindering further preclinical and clinical translation, including complex material composition, spatiotemporal limitations, and the potential to promote tumor metastasis and proliferation. This highlights the urgent need to develop oxygen-independent photosensitizers through rationally controllable design methods to advance the clinical translation of PDT.

[0003] In recent years, the development of oxygen-independent type I photosensitizers has become an important approach to overcome the limitations associated with photodynamic hypoxia. Unlike type II photosensitizers, type I photosensitizers function through an oxygen-independent mechanism: excited photosensitizers promote the transfer of electrons or hydrogen atoms to the surrounding substrate, generating highly cytotoxic free radicals, such as superoxide anion radicals (O2). ·- Type I photosensitizers, along with hydroxyl radicals (·OH) and hydrogen peroxide (H2O2), exhibit significant advantages over traditional type II photosensitizers due to their oxygen dependence. However, despite these advantages, the development of type I photosensitizers remains in its early stages due to the lack of universal molecular design strategies and the challenge of finely controlling the balance of electron and energy transfer processes. To address this, Yan's research group proposed an innovative strategy to introduce strong electron acceptors into the classical type II photosensitizer system through supramolecular assembly to design highly efficient type I photosensitizers; Liu's research group developed a method to enhance type I O2 by coupling the natural ¹O2-sensitive substrate carvacrol with a classical type II photosensitizer, thereby promoting electron transfer between the photosensitizer and singlet oxygen. ·- The strategies for generation. These studies still have limitations such as incomplete understanding of the mechanisms and short emission wavelengths, which hinder wider biomedical applications.

[0004] Therefore, the development of long-wavelength type I photosensitizers and a comprehensive understanding of their photodynamic mechanisms are of great significance for promoting the development of type I photodynamic therapy and accelerating its clinical translation. To achieve the best results of cancer diagnosis and treatment integration, type I photosensitizers with imaging function can realize safe self-efficacy evaluation, precise diagnosis, and in vivo distribution monitoring. The emerging near-infrared second region imaging technology (wavelength > 950 nm) provides a new way for histopathology and physiology analysis, and shows significant advantages in high-resolution biological imaging of deep tissues. Therefore, the development of innovative near-infrared second region type I photosensitizers deserves more attention, and such materials provide a promising anticancer strategy for complex tumor identification. By introducing electron acceptors and other simple methods, the type I reactive oxygen species generation process of near-infrared second region photosensitizers is enhanced, which is crucial for the development of photodynamic diagnosis and treatment integration. SUMMARY

[0005] To solve the above technical problems, the present application provides a near-infrared second region aggregation-induced emission material, a preparation method thereof and an application thereof in preparing type I photodynamic drugs. The present application uses a light-induced intermolecular electron transfer strategy to accelerate type I reactive oxygen species generation by promoting electron-hole separation, which is used for hypoxic tumor treatment. Unlike previous researches focusing on enhancing commercial photosensitizers in the visible light region, the present application focuses on fine regulation of the electron-hole separation state of near-infrared second region molecules.

[0006] To achieve the above purpose, the present application provides the following technical solutions:

[0007] The present application provides a near-infrared second region aggregation-induced emission material (compound BBP-TPA), the structural formula of which is as follows:

[0008] .

[0009] The present application also provides a preparation method of the above near-infrared second region aggregation-induced emission material, which comprises the following steps:

[0010] The compound BBP, (4-(diphenylamino)phenyl)boronic acid, K2CO3 and Pd(PPh3)4 are mixed in an organic solution to obtain a mixture, the mixture is refluxed under a protective atmosphere, and then cooled to room temperature (25±2℃), and then extracted, purified, and recrystallized to obtain the near-infrared second region aggregation-induced emission material;

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

[0012] Further, the compound BBP, (4-(diphenylamino)phenyl)boronic acid, K2CO3 (potassium carbonate), Pd(PPh3)4 (tetrakis(triphenylphosphine)palladium) and the organic solution are used in a ratio of 1 mmol: 2.5 mmol: 0.01 mmol: 0.02 mmol: 20 mL.

[0013] Further, the organic solution is composed of 1,4-dioxane and water (H2O) in a volume ratio of 5:1.

[0014] Further, the mixture is refluxed at 110 DEG C for 12 hours under a nitrogen (N2) atmosphere.

[0015] Further, the preparation method of the compound BBP comprises the following steps:

[0016] 4,7-dibromobenzo[c][1,2,5]thiadiazole-5,6-diamine (1 mmol) and 1,2-bis(pyridin-2-yl)ethane-1,2-dione (1.5 mmol) are refluxed in 10 mL acetic acid at 80 DEG C for 8 hours, after the obtained mixture is cooled to room temperature, a yellowish brown precipitate is extracted and filtered under pressure using methanol to obtain the compound BBP.

[0017] The application further provides an NDA / BA nanoparticle (NDA / BA NPs) which is prepared by integrating a donor and an acceptor through poloxamer F127, wherein the donor is the above near-infrared two-region aggregation-induced emission material, and the acceptor is naphthacenediimide (NDA).

[0018] The application further provides a preparation method of the NDA / BA nanoparticle, comprising the following steps:

[0019] The naphthacenediimide and the above near-infrared two-region aggregation-induced emission material are dissolved in tetrahydrofuran, mixed with an aqueous solution of poloxamer F127, and ultrasonically treated to obtain the NDA / BA nanoparticle.

[0020] Further, the naphthacenediimide, the near-infrared two-region aggregation-induced emission material, the poloxamer F127 and the tetrahydrofuran are used in a ratio of 1.1 mg: 0.83 mg: 12 mg: 1 mL.

[0021] Further, the ultrasonic treatment is performed for 5 minutes.

[0022] The application further provides application of the above near-infrared two-region aggregation-induced emission material or the NDA / BA nanoparticle in preparation of a type I photodynamic drug.

[0023] Compared with the prior art, the application has the following advantages and technical effects:

[0024] (1) The present application designs and synthesizes an aggregation-induced emission material BBP-TPA with aggregation-induced emission characteristics but weak active oxygen generation capacity, and integrates the donor BBP-TPA and the acceptor NDA through the polymer F127 to construct the NDA / BA nanoparticles, and the NDA / BA nanoparticles exhibit significantly enhanced type I photodynamic performance, and the total active oxygen, ·OH and O2 ·- The generation amount reaches 7.1 times, 13.8 times and 5.8 times of the BBP-TPA nanoparticle (BA NPs) respectively, which proves that intermolecular electron transfer occurs between the donor BBP-TPA and the acceptor NDA under light.

[0025] (2) The present application designs and synthesizes a near-infrared two-zone nanoparticle NDA / BA with aggregation-induced emission characteristics and strong type I active oxygen generation capacity, and confirms that it has precise near-infrared two-zone imaging and photodynamic therapy effect, which provides a promising new scheme for near-infrared two-zone image-guided photodynamic diagnosis and treatment integration. BRIEF DESCRIPTION OF DRAWINGS

[0026] The accompanying drawings, which form a part of the present application, are used to provide further understanding of the present application, and the illustrative embodiments of the present application and their description are used to explain the present application, and do not constitute improper limitations on the present application. In the drawings:

[0027] Figure 1 It is the synthesis path diagram of the near-infrared two-zone aggregation-induced emission material of the embodiment of the present application;

[0028] Figure 2 It is the ultraviolet absorption and fluorescence emission spectrum test results of the nanoparticles prepared in Example 2 and Comparative Examples 1-2, wherein a is the ultraviolet absorption spectrum test result, and b is the fluorescence emission spectrum test result;

[0029] Figure 3 It is the active oxygen test results of the nanoparticles prepared in Example 2 and Comparative Examples 1-2, wherein a is the ROS generation test result, b is the ¹O2 generation test result, c is the O2 ·- generation test result, and d is the ·OH generation test result;

[0030] Figure 4 It is the intracellular active oxygen test results of the NDA / BA NPs prepared in Example 2 under normoxic or anoxic conditions;

[0031] Figure 5 It is the in vitro cytotoxicity test results of the NDA / BA NPs prepared in Example 2 under normoxic / anoxic+light / avoiding light conditions. DETAILED DESCRIPTION

[0032] Various exemplary embodiments of the present application will now be described in detail, which should be considered to be illustrative of certain aspects, features and embodiments of the present application and are not intended to limit the present application in any manner.

[0033] It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the present application. Additionally, for a range of values of a parameter, unless otherwise stated, each intervening value of the parameter is also specifically included within the scope of the present application. The intervening values of the parameter are combined with a stated value of the parameter in range form. These are only exemplary of the various preferred embodiments and are not intended to be limiting on the scope of the application.

[0034] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application, the preferred methods and materials are described. All patents, patent applications, publications, and descriptions mentioned herein are incorporated by reference in their entirety for the disclosure and

[0035] Many modifications and variations of this application can be made in the light of the above teachings without departing from the spirit and scope thereof, and it is to be understood that all such modifications and variations warrant the patentable subject matter under the patent laws. Other embodiments of the application will be apparent to those skilled in the art from consideration of the specification and practice of the application disclosed herein. The specification and examples given are exemplary only and are not intended to be limiting.

[0036] As used herein, the terms "comprise", "comprising", "include", "including", "have", "having" and the like are open-ended and do not exclude additional elements or steps.

[0037] The embodiment of the present application provides a near-infrared two-region aggregation-induced emission material (compound BBP-TPA), and a structural formula is as follows:

[0038] .

[0039] The molecular structure of the material (BBP-TPA) is the basis for realizing the core function. The structure design meets two key characteristics: one is the near-infrared two-region emission capability, which provides a premise for deep tissue imaging; the other is the aggregation-induced emission characteristic, which avoids the fluorescence quenching problem caused by the aggregation of traditional photosensitizers, and at the same time reserves a molecular structure site for subsequent electron transfer with an acceptor, which is a core donor substance for constructing an efficient I-type photodynamic system.

[0040] The embodiment of the present application further provides a preparation method of the near-infrared two-region aggregation-induced emission material.Figure 1 ), comprising the following steps:

[0041] (1) refluxing 4,7-dibromobenzo[c][1,2,5]thiadiazole-5,6-diamine (1 mmol, structural formula as ) and 1,2-bis(pyridin-2-yl)ethane-1,2-dione (1.5 mmol, structural formula as ) in 10 mL acetic acid at 80°C for 8 hours, after the obtained mixture is cooled to room temperature, a yellowish brown precipitate is extracted and filtered under pressure using methanol to obtain compound BBP (structural formula as );

[0042] (2) mixing compound BBP, (4-(diphenylamino)phenyl)boronic acid (structural formula as ), K2CO3, Pd(PPh3)4 in an organic solution to obtain a mixture, refluxing the mixture under a protective atmosphere, and then cooling the mixture to room temperature (25±2°C), extracting, purifying, and recrystallizing to obtain a near-infrared two-region aggregation-induced emission material.

[0043] In a preferred embodiment of the present application, the use amount ratio of compound BBP, (4-(diphenylamino)phenyl)boronic acid, K2CO3 (potassium carbonate), Pd(PPh3)4 (tetrakis(triphenylphosphine)palladium), and the organic solution is 1 mmol:2.5 mmol:0.01 mmol:0.02 mmol:20 mL.

[0044] In a preferred embodiment of the present application, the organic solution is composed of 1,4-dioxane and water (H2O) in a volume ratio of 5:1.

[0045] In a preferred embodiment of the present application, the mixture is refluxed at 110°C for 12 hours under a nitrogen (N2) atmosphere.

[0046] The present application also provides an NDA / BA nanoparticle (NDA / BA NP), which is constructed by integrating a donor and an acceptor through poloxamer F127, wherein the donor is the above-mentioned near-infrared two-region aggregation-induced emission material, and the acceptor is thianaphthene diimide (NDA).

[0047] The present application constructs a donor-acceptor supramolecular system by integrating BBP-TPA as a donor and NDA as an acceptor through poloxamer F127. The donor (BBP-TPA) provides near-infrared two-region light emission and electron donor capability, and the acceptor (NDA) has strong electron accepting capability. The combination of the two can form an intermolecular electron transfer channel to promote electron-hole separation. Poloxamer F127 serves as a biocompatible carrier to realize stable integration and dispersion of the donor and the acceptor, avoid agglomeration, and at the same time guarantee the safety of the nanoparticles for biological applications, thereby providing structural support for type I reactive oxygen species generation and in vivo diagnosis and treatment.

[0048] The application further provides a preparation method of the NDA / BA nanoparticle.

[0049] The thianaphthene dicyrimide, the near-infrared two-region aggregation-induced emission material, the poloxamer F127 and the tetrahydrofuran are mixed, and ultrasonic treatment is performed to obtain the NDA / BA nanoparticle.

[0050] In the preferred embodiment of the application, the thianaphthene dicyrimide, the near-infrared two-region aggregation-induced emission material, the poloxamer F127 and the tetrahydrofuran are mixed, and ultrasonic treatment is performed to obtain the NDA / BA nanoparticle.

[0051] In the preferred embodiment of the application, the thianaphthene dicyrimide, the near-infrared two-region aggregation-induced emission material, the poloxamer F127 and the tetrahydrofuran are mixed, and ultrasonic treatment is performed to obtain the NDA / BA nanoparticle.

[0052] The application further provides application of the near-infrared two-region aggregation-induced emission material or the NDA / BA nanoparticle in preparation of a type I photodynamic drug.

[0053] The raw materials used in the embodiments of the application are commercially available.

[0054] The technical solutions of the application are further described below through embodiments.

[0055] Embodiment 1

[0056] A preparation method of a near-infrared two-region aggregation-induced emission material (BBP-TPA) comprises the following steps:

[0057] (1) 4,7-dibromobenzo[c][1,2,5]thiazole-5,6-diamine (1 mmol) and 1,2-di(pyridin-2-yl)ethane-1,2-dione (1.5 mmol) are refluxed in 10 mL acetic acid at 80°C for 8 hours, the obtained mixture is cooled to room temperature, and then a yellowish-brown precipitate is extracted and filtered using methanol to obtain compound BBP (yield = 93.3%);

[0058] 1H NMR (500 MHz, CDCl3) δ (ppm) = 8.45 (d, J=10 Hz, 2H), 8.33 (d, J=5Hz, 2H), 8.01 (t, J=15 Hz, 2H), 7.36 (t, J=15 Hz, 2H). 13C10 NMR (125 MHz, CDCl3) δ (ppm) = 156.07, 155.03, 152.60, 148.05, 138.02, 137.31, 124.59, 123.99, 114.76. HRMS, m / z: ([M]+Na), calculated values ​​(C10) 18 H8Br2N6SNa): 522.8776, Measured value: 522.8767.

[0059] (2) The compound BBP (1 mmol), (4-(diphenylamino)phenyl)boronic acid (2.5 mmol), K2CO3 (0.01 mmol), and Pd(PPh3)4 (0.02 mmol) obtained in step (1) were mixed in 20 mL of organic solution (composed of 1,4-dioxane and H2O in a volume ratio of 5:1) to obtain a mixture. The mixture was refluxed at 110 °C for 12 hours under N2 atmosphere, and then cooled to room temperature (25 ± 2 °C). The mixture was extracted with water and dichloromethane to remove the catalyst and inorganic salts. The crude product was further purified by silica gel column chromatography using petroleum ether:dichloromethane (volume ratio = 1:1) as the eluent. The final product was recrystallized from dichloromethane (DCM) and methanol (MeOH) to obtain BBP-TPA (yield = 24.3%).

[0060] ¹H NMR (500 MHz, CDCl3) = 8.34 (t, J=15 Hz, 4H), 8.02 (d, J = 10 Hz,4H), 7.96 (s, 2H), 7.38 (t, J=15 Hz, 10H), 7.34 (m, 12H), 7.15 (t, J = 10 Hz, 4H). 13 C NMR (125 MHz, CD₂Cl₂) δ (ppm) = 157.26, 153.31, 152.61, 148.18, 148.02, 147.43, 136.76, 135.84, 134.06, 129.43, 128.89, 128.05, 125.31, 123.60, 123.27, 121.05. HRMS, m / z: ([M]+Na), calculated values ​​(C 54 H 36 N8SNa): 851.2681, Measured value: 851.2687.

[0061] Example 2

[0062] A method for preparing NDA / BA nanoparticles (NDA / BA NPs) using BBP-TPA obtained in Example 1 as a donor and NDA as an acceptor, is described. The donor and acceptor are integrated using poloxamer F127. The method includes the following steps: dissolving NDA (1.1 mg) and BBP-TPA (0.83 mg) in 1 mL of THF, mixing with poloxamer F127 (12 mg, referring to the mass of poloxamer F127) dissolved in 9 mL of water, sonicating for 5 minutes, and continuously stirring for 24 hours to remove residual THF. Subsequently, the obtained particles are concentrated in a centrifugal filter tube (molecular weight cutoff: 10 kDa) to remove free poloxamer F127. The obtained particle suspension is filtered through a 0.22 μm filter membrane to prepare NDA / BA NPs, which are then stored at 4 °C for later use.

[0063] Comparative Example 1

[0064] NDA (1.1 mg) was dissolved in 1 mL of THF and mixed with poloxamer F127 (12 mg) dissolved in water. The mixture was sonicated for 5 minutes and stirred continuously for 24 hours to remove residual THF. Subsequently, the resulting particles were concentrated in a centrifuge filter tube (molecular weight cutoff: 10 kDa) to remove free poloxamer F127. The resulting particle suspension was filtered through a 0.22 μm filter membrane to prepare NDA NPs, which were stored at 4 °C for later use.

[0065] Comparative Example 2

[0066] The BBP-TPA (0.83 mg) obtained in Example 1 was dissolved in 1 mL of THF and mixed with poloxamer F127 (12 mg) dissolved in water. The mixture was sonicated for 5 minutes and stirred continuously for 24 hours to remove residual THF. Subsequently, the resulting particles were concentrated in a centrifuge filter tube (molecular weight cutoff: 10 kDa) to remove free poloxamer F127. The resulting particle suspension was filtered through a 0.22 μm filter membrane to prepare BA NPs, which were stored at 4 °C for later use.

[0067] Performance testing

[0068] (1) Ultraviolet absorption and fluorescence emission spectroscopy test

[0069] The UV absorption and fluorescence emission spectra of the nanoparticles prepared in Example 2 and Comparative Examples 1-2 are shown in the figure. Figure 2 In the figure, a represents the UV absorption spectroscopy result, and b represents the fluorescence emission spectroscopy result. It can be seen that NDA NPs and NDA / BA NPs have similar maximum absorption and emission wavelengths.

[0070] (2) Reactive oxygen species test

[0071] ROS were detected using the fluorescent probe 2',7'-dichlorodihydrofluorescein (DCFH): 250 μL of DCFH (40 μM) was mixed with a 10 μM working concentration of NPs solution. For the control group, 250 μL of DCFH was mixed with 1.75 mL of PBS (phosphate-buffered saline). The mixture was then exposed to white light (30 mW / cm²). -2 The PL intensity was recorded at approximately 525 nm using a fluorescence spectrometer (excitation wavelength: 488 nm) for 20 seconds.

[0072] Detection of ·OH formation using HPF: Hydroxyphenylfluorescein (HPF) was used as an indicator to detect ·OH in solution. HPF is oxidized upon interaction with ·OH, emitting strong fluorescence centered at 525 nm. A 2 mL mixture of PBS containing 10 μM NPs and 5 μM HPF was exposed to white light (30 m·W / cm²). -2 The control group (HPF) was exposed to white light (30 mW / cm²) for 20 seconds. The control group was exposed to white light (30 mW / cm²) with 2 mL of PBS containing 5 μM HPF. -2 20 seconds later. The fluorescence change at 525 nm was measured using a fluorescence spectrometer (Eex=488nm).

[0073] O2 detection using the compound dihydrorhodamine 123 (DHR123) ·- Generation of O2: When O2 ·- Upon generation, DHR123 is oxidized and emits strong fluorescence centered at 525 nm. 10 μM NPs were dissolved in 2 mL of PBS containing 5 μM DHR123 and exposed to white light (30 m·W / cm²). -2 The control group (DHR123 NPs) was exposed to white light (30 m·W / cm²) for 20 seconds. The control group was exposed to white light (30 m·W / cm²) with 2 mL of PBS containing 5 μM DHR123. -2 20 seconds later, fluorescence changes at 525 nm were recorded using a fluorescence spectrometer (Eex=488nm).

[0074] ¹O₂ formation was detected using ABDA: Compound 9,10-anthratridiyl-bis(methylene)dimaleic acid (ABDA) was used as an indicator for ¹O₂ detection. A mixture of 10 μM NPs and 100 μM ABDA in 2 mL PBS was exposed to white light (30 m·W / cm²). -2 The control group (ABDA) was exposed to white light (30 m·W / cm²) for 20 seconds. The mixture of 100 μM ABDA in 2 mL PBS was then exposed to white light (30 m·W / cm²). -2 (20 seconds later) The absorbance change at 375 nm was monitored using UV-Vis spectroscopy.

[0075] The reactive oxygen species test results of the nanoparticles prepared in Example 2 and Comparative Examples 1-2 are as follows: Figure 3 As shown, a represents the ROS generation test result, b represents the O2 generation test result, and c represents the O2 generation test result. ·- The generation test results are shown in Figure 1, where d represents the generation test results for ·OH. It can be seen that the type I ROS generation ability of NDA / BA NPs is significantly enhanced.

[0076] (3) Intracellular ROS detection

[0077] Intracellular ROS production was measured using DCFH as a ROS indicator. 4T1 cells were cultured at 1×10⁻⁶. 5 Cells were seeded at a density of 1000 mcg / mL in 35 mm confocal culture dishes and cultured for 24 h under normoxic (21% O2) or hypoxic (2% O2) conditions. Cells were then incubated for 6 h in fresh medium containing 10 μM NDA / BA NPs, followed by treatment with 2 μM DCFH for 30 min. After washing with PBS, cells were entrained under white light (50 m·W / cm²). -2 Cells were irradiated for 15 minutes, and images were captured using a confocal laser scanning microscope (CLSM). Similarly, DHR123 / HPF was used as an indicator to assess intracellular O2. ·- The generation of ·OH was assessed using HPF as an indicator. The procedure was the same as for DCFH, except that 2 μM DHR123 or HPF was used instead of DCFH.

[0078] The intracellular reactive oxygen species (ROS) test results of the NDA / BA NPs prepared in Example 2 under normoxic or hypoxic conditions are as follows: Figure 4 It can be seen that NDA / BA NPs can also generate type I ROS within cells.

[0079] (4) In vitro cytotoxicity assessment

[0080] 4T1 cells were seeded in 96-well plates (5 × 10⁶ cells per well). 3 Cells were incubated for 24 hours under normoxic (21% O2) or hypoxic (2% O2) conditions. Cells were then treated with fresh medium containing different concentrations of NDA / BA NPs for 12 hours and exposed to white light (50 mW / cm²). -2 (30 minutes after exposure to light.) Cell viability was assessed using the MTT assay 8 hours later. Under the same conditions, dark toxicity was assessed without light exposure, and the results are as follows: Figure 5 As shown, NDA / BA NPs can effectively kill 4T1 cells under light conditions.

[0081] The above are merely preferred embodiments of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A near-infrared two-region aggregation-induced emission material, characterized in that, A structure is as follows: 。 2. A method for preparing the near-infrared two-region aggregation-induced emission material according to claim 1, characterized in that, The method comprises the following steps: The compound BBP, (4-(diphenylamino)phenyl)boronic acid, K2CO3 and Pd(PPh3)4 are mixed in an organic solution to obtain a mixture, the mixture is refluxed under a protective atmosphere, and then cooled to room temperature, extracted, purified, recrystallized, and the near-infrared two-region aggregation-induced emission material is obtained. The structural formula of the compound BBP is: .

3. The method for preparing the near-infrared II region aggregation-induced emission material according to claim 2, characterized in that, The compound BBP, (4-(diphenylamino)phenyl)boronic acid, K2CO3, Pd(PPh3)4 and the organic solution are used in a ratio of 1 mmol: 2.5 mmol: 0.01 mmol: 0.02 mmol: 20 mL.

4. The method for preparing the near-infrared II aggregation-induced emission material according to claim 2, characterized in that, The organic solution is composed of 1,4-dioxane and water in a volume ratio of 5:

1.

5. The method for preparing the near-infrared II aggregation-induced emission material according to claim 2, characterized in that, The mixture is refluxed at 110 DEG C under a nitrogen atmosphere for 12 hours.

6. An NDA / BA nanoparticle, characterized in that, The near-infrared two-region aggregation-induced emission material of claim 1 is used as a donor, a thianaphthalene diimide is used as an acceptor, and the donor and the acceptor are integrated by poloxamer F127 to construct.

7. A method of producing the NDA / BA nanoparticle of claim 6, wherein, The method comprises the following steps: The thianaphthalene diimide and the near-infrared two-region aggregation-induced emission material of claim 1 are dissolved in tetrahydrofuran, mixed with poloxamer F127 dissolved in water, and ultrasonically treated to obtain the NDA / BA nanoparticles.

8. The method of claim 7, wherein the NDA / BA nanoparticle is prepared by, The thianaphthalene diimide, the near-infrared two-region aggregation-induced emission material, poloxamer F127 and tetrahydrofuran are used in a ratio of 1.1 mg: 0.83 mg: 12 mg: 1 mL.

9. The method of claim 7, wherein the NDA / BA nanoparticle is prepared by, The ultrasonic treatment is performed for 5 minutes.

10. Use of the near-infrared two-region aggregation-induced emission material of claim 1 or the NDA / BA nanoparticles of claim 6 in preparation of a type I photodynamic drug.

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