A ruthenium-based aggregation-induced emission material, a preparation method thereof and application thereof in photocatalytic hydrogen production and antitumor

Abstract

The application discloses a ruthenium-based aggregation-induced emission material, a preparation method thereof and application of the material in photocatalytic hydrogen production and anti-tumor, and belongs to the technical field of biological medicines and aggregation-induced emission materials. The material has photocatalytic glutathione oxidation coupling hydrogen production activity, can catalyze glutathione to be oxidized into oxidized glutathione under an oxygen-free condition, and synchronously releases hydrogen. The material is applied to the preparation of anti-tumor drugs and tumor cell fluorescent imaging reagents. The material can destroy the oxidation-reduction balance in tumor cells under the condition of not depending on oxygen, overcomes the treatment resistance caused by hypoxia, simultaneously produces hydrogen, cooperatively activates the anti-tumor immune response, and can induce tumor cell ferroptosis, and reduces the risk of drug resistance. The application provides a brand-new solution for overcoming the problems of hypoxia dependence and drug resistance of traditional photodynamic therapy.

Description

Technical Field

[0001] This invention belongs to the field of biomedicine and aggregation-induced emission materials technology, specifically relating to a ruthenium-based aggregation-induced emission material, its preparation method, and its application in photocatalytic hydrogen production for anti-tumor purposes. Background Technology

[0002] Cancer is a major disease posing a serious threat to human health worldwide, and its occurrence and development are closely related to the imbalance of intracellular redox homeostasis. The redox pair formed by glutathione and its oxidized form is a core hub for maintaining intracellular redox balance and is crucial for regulating signal transduction and cellular metabolism. In cancer cells, due to abnormally active metabolism and elevated levels of oxidative stress, glutathione is usually highly expressed, providing a protective barrier for abnormal proliferation, drug resistance, and immune evasion of cancer cells.

[0003] Photodynamic therapy (PDT), a non-invasive cancer treatment, utilizes photosensitizers to generate reactive oxygen species (ROS) under light irradiation to kill cancer cells. It has gained widespread attention due to its minimal side effects and ease of operation. However, traditional PDT has several significant drawbacks: First, the generation of ROS in traditional PDT is highly dependent on local oxygen concentration. PDT typically relies on a type II photochemical process, where the photosensitizer transfers energy to triplet oxygen to generate cytotoxic singlet oxygen. However, the hypoxic microenvironment prevalent in solid tumors severely weakens the efficiency of ROS generation, significantly limiting treatment efficacy. Second, prolonged ROS stimulation may induce adaptive antioxidant responses in cancer cells. Continuous oxidative stress activates antioxidant signaling pathways in cancer cells, upregulating antioxidant systems such as glutathione synthase and peroxide reductase, enhancing the cancer cells' tolerance to oxidative damage, thus leading to decreased treatment sensitivity. Third, traditional photosensitizers often experience fluorescence quenching due to intermolecular π-π stacking interactions in their aggregated state. This aggregation-induced quenching effect severely weakens the fluorescence imaging capability of photosensitizers, affects the precision of image-guided therapy, and limits their application in integrated diagnosis and treatment.

[0004] In summary, current photodynamic therapy suffers from technical limitations such as oxygen dependence, susceptibility to oxidative defense, and limited imaging guidance capabilities, resulting in poor efficacy in tumor treatment. Therefore, developing a novel photosensitizer that can effectively exert anti-tumor effects under hypoxic conditions, weaken tumor cell oxidative defense, and possess excellent imaging performance is of significant clinical importance and application value. Summary of the Invention

[0005] To address the technical problems of existing photodynamic therapy, such as high dependence on oxygen, potential activation of tumor cell antioxidant defenses due to long-term oxidative stress, and fluorescence quenching caused by the aggregation of traditional photosensitizers, resulting in poor tumor treatment efficacy, strong drug resistance, and limited imaging guidance capabilities, the present invention aims to provide a ruthenium-based aggregation-induced emission material, its preparation method, and its application in photocatalytic hydrogen production for anti-tumor therapy.

[0006] To achieve the above objectives, the present invention employs the following technical solution: In a first aspect, the present invention provides a ruthenium-based aggregation-induced emission material with the following structural formula: .

[0007] The aggregation-induced emission material exhibits photocatalytic activity for glutathione oxidation-coupling hydrogen production, and under anaerobic conditions, it can catalyze the oxidation of glutathione to oxidized glutathione while simultaneously releasing hydrogen gas. This achieves oxygen-independent redox regulation: by consuming the highly expressed GSH in tumor cells, its redox balance is disrupted; simultaneously, the generated hydrogen gas can act as a therapeutic gas to synergistically activate the anti-tumor immune response, thereby effectively overcoming treatment resistance caused by hypoxia in solid tumors.

[0008] Secondly, the present invention provides a method for preparing a ruthenium-based aggregation-induced emission material, comprising: activating compound a with a silver salt and then reacting it with compound b to obtain the aggregation-induced emission material; wherein, the structural formula of compound a is as follows: The structural formula of compound b is: .

[0009] The silver salt is silver trifluoromethanesulfonate; the reaction is carried out in methanol solvent at room temperature for 40 h to 52 h.

[0010] Preferably, the reaction time is 48 h.

[0011] The molar ratio of compound a to compound b is 1:1.

[0012] Thirdly, the present invention provides the application of the ruthenium-based aggregation-induced emission material in the preparation of antitumor drugs.

[0013] The antitumor drug is a photocatalytic antitumor drug; the photocatalytic antitumor drug is activated under 450 nm light irradiation. Under this wavelength of light irradiation, the material can efficiently initiate the photocatalytic reaction, producing a therapeutic effect, while avoiding non-specific damage to normal tissues.

[0014] The antitumor drug exerts its antitumor effect through one or more of the following mechanisms: (a) Disrupting the redox balance in tumor cells under oxygen-free conditions to overcome treatment resistance caused by hypoxia; (b) Catalyzes the oxidative coupling of glutathione in tumor cells, while generating hydrogen gas, which synergistically activates the anti-tumor immune response; (c) Induces tumor cell ferroptosis, reducing the risk of drug resistance.

[0015] This material differs from existing technologies in its multi-level mechanism of action: it not only overcomes the hypoxia problem, but also bypasses the traditional apoptosis and drug resistance pathway through hydrogen-assisted immunity and ferroptosis, achieving a comprehensive anti-tumor effect with high efficiency and low drug resistance.

[0016] Fourthly, the present invention provides the application of the ruthenium-based aggregation-induced emission material in the preparation of tumor cell fluorescence imaging reagents.

[0017] The aggregation-induced luminescent material can be taken up by tumor cells and label the cell membrane within 30 minutes, and its fluorescence emission wavelength range is 600-700 nm.

[0018] Fifthly, the present invention provides a photocatalytic antitumor system comprising the aforementioned ruthenium-based aggregation-induced luminescence material and a pharmaceutically acceptable carrier.

[0019] The photocatalytic antitumor system is activated under 450 nm light irradiation. It exerts an oxygen-independent antitumor effect through photocatalytic glutathione oxidation coupling to produce hydrogen, and simultaneously achieves fluorescence imaging of tumor cells.

[0020] Compared with the prior art, the present invention has the following beneficial effects: The ruthenium-based aggregation-induced emission material provided by this invention is a metal complex with aggregation-induced emission properties, laying the material foundation for its subsequent multifunctional applications in photocatalysis, anti-tumor, and imaging. By introducing a triphenylamine rotational group, its fluorescence is enhanced in the aggregated state, overcoming the aggregation-induced quenching defect of traditional photosensitizers. Through coordination with ruthenium, intramolecular charge transfer is enhanced, spin-orbit coupling is strengthened, and the lifetime of the charge-separated state is extended, thus exhibiting both excellent luminescent performance and photocatalytic activity.

[0021] The preparation method provided by this invention involves activating compound a with silver salt and then reacting it with compound b to obtain the target product. This method is a simple, efficient, and reproducible synthetic route. It utilizes silver salt to promote ligand exchange reactions, obtaining high-purity ruthenium-based AIE complexes under mild conditions. Compared with complex multi-step synthetic routes, the method of this invention has advantages such as readily available raw materials, controllable process, and simple post-processing, which is beneficial for the stable preparation of the target material and subsequent biomedical application research.

[0022] The application provided by this invention transforms the unique mechanism of photocatalytic GSH oxidative coupling to hydrogen production into practical anti-tumor uses. Under light irradiation, this material can induce intramolecular charge transfer and form a relatively long-lived charge-separated state, thereby promoting the oxidative coupling of intracellular GSH to generate GSSG, and simultaneously achieving in-situ H2 generation. This process differs from traditional photodynamic therapy, which mainly relies on oxygen to generate ROS. It can disrupt the GSH / GSSG redox balance of tumor cells in the hypoxic tumor microenvironment through an oxygen-independent photocatalytic redox process, reducing the cell's antioxidant defense capacity and inducing ferroptosis and other cell damage processes. This provides a novel direction for drug development to address the problems of oxygen dependence and decreased therapeutic sensitivity in existing photodynamic therapy. Simultaneously, the material of this invention possesses aggregation-induced emission (AIE) properties, avoiding the fluorescence quenching problem of traditional photosensitizers in the aggregated state, and enabling rapid, high-resolution fluorescence imaging at the cellular level. Utilizing its AIE properties, rapid (within 30 minutes) high-resolution fluorescence imaging is achieved on the cell membrane. The imaging signal is strong and photostable, clearly labeling tumor cells, providing a powerful imaging tool for achieving "therapeutic integration" (real-time monitoring during treatment).

[0023] This invention develops a novel photocatalytic antitumor system based on ruthenium-based aggregation-induced emission, which has the following advantages: 1. It can disrupt the redox balance in tumor cells without relying on oxygen, overcoming treatment resistance caused by hypoxia; 2. It can simultaneously generate hydrogen gas, synergistically activating the antitumor immune response; 3. It can induce ferroptosis in tumor cells, reducing the risk of drug resistance. Attached Figure Description

[0024] Figure 1 This is a graph showing the performance results of RuL-TBPy in vitro photocatalytic oxidative coupling of glutathione (GSH) to produce hydrogen, prepared in Example 1 of this invention. Figure 2 This is a fluorescence colocalization imaging image of RuL-TBPy in 4T1 cells in Example 3 of the present invention; wherein, green fluorescence is staining with the commercial cell membrane probe Dio, red fluorescence is staining with RuL-TBPy, and the yellow area after the superposition of the two indicates the colocalization location, and the scale bar length is 10μm; Figure 3 The graph shows the results of the dark toxicity and phototoxicity tests of RuL-TBPy on 4T1 cells in Example 4 of this invention; where the vertical axis represents cell viability (%) and the horizontal axis represents RuL-TBPy concentration (μM). Figure 4 This is a graph showing the change in tumor volume over time in mice of each treatment group in Example 4 of the present invention; where the vertical axis represents tumor volume (mm). 3The horizontal axis represents the number of days of treatment, and the curves represent the PBS control group, the PBS + light irradiation group, the RuL-TBPy alone group, and the RuL-TBPy + light irradiation group, respectively.

[0025] Figure 5 This is a comparison chart of tumor weight in mice after treatment in Example 4 of the present invention; where the vertical axis represents tumor weight (g), and the bar charts represent the mean ± standard deviation of tumor weight in the PBS control group, PBS + light irradiation group, RuL-TBPy alone group, and RuL-TBPy + light irradiation group, respectively. This indicates that the difference between the control group and the control group is P<0.01. Detailed Implementation

[0026] The following will describe the concept and technical effects of the present invention clearly and completely with reference to the embodiments, so as to fully understand the purpose, features and effects of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are all within the scope of protection of the present invention. Unless otherwise specified, the experimental methods used in the embodiments are conventional methods; the materials and reagents used, unless otherwise specified, are commercially available.

[0027] Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. In this invention, the following terms or abbreviations have the following meanings: Aggregation-induced emission (AIE) refers to a photophysical phenomenon in which fluorescent molecules emit weak or no light in dilute solutions, but their fluorescence is significantly enhanced in aggregated states (such as solids, thin films, or nano-aggregates in unsuitable solvents).

[0028] Glutathione (GSH) is a tripeptide composed of glutamic acid, cysteine, and glycine. It is the most abundant non-protein thiol compound in cells and plays a central role in maintaining intracellular redox balance. Its oxidized form is called oxidized glutathione (GSSG).

[0029] Ferroptosis: an iron-dependent, regulated form of cell death distinct from apoptosis, necrosis, and autophagy, characterized by the lethal accumulation of lipid peroxides and glutathione depletion.

[0030] Hypoxic microenvironment: refers to the pathological state in solid tumors where the local oxygen partial pressure is significantly lower than that of normal tissues due to abnormal vascular structure and restricted oxygen diffusion. It is usually defined as an oxygen concentration of less than 1% O2.

[0031] Photocatalysis: In this invention, it specifically refers to the process by which a photosensitizer, under light excitation, directly catalyzes the redox reaction of a substrate (such as GSH) without relying on oxygen, which is different from the traditional photodynamic process that relies on oxygen to generate reactive oxygen species.

[0032] Gas chromatography (GC) for hydrogen detection: Quantitative analysis of hydrogen was performed using a gas chromatograph equipped with a thermal conductivity detector (TCD). The chromatographic column was a 5 Å molecular sieve packed column (3 m × 2 mm), the carrier gas was high-purity nitrogen (purity ≥ 99.999%), the column temperature was 50 °C, the injection port temperature was 100 °C, and the detector temperature was 150 °C. The gas injection volume was 50 μL, and the hydrogen content was calculated using the standard curve method. Hydrogen yield was expressed as millimoles of hydrogen produced per gram of photosensitizer (mmol·g). -1 ).

[0033] Ellman assay for glutathione concentration: Take 20 μL of reaction solution, add 0.5 mL of Tris-HCl buffer (0.1 M, pH 8.0) and 50 μL of DTNB solution (5,5′-dithiobis(2-nitrobenzoic acid), 4 mg / mL dissolved in buffer), mix well, and incubate at room temperature in the dark for 5 minutes. Measure the absorbance at 412 nm using a UV-Vis spectrophotometer. Plot a standard curve using GSH standard solutions of known concentrations, and calculate the remaining GSH concentration in the sample using a regression equation.

[0034] Cell viability was assessed using the CCK-8 assay: Cell viability was detected using the Cell Counting Kit-8 (CCK-8). The principle is that dehydrogenases in the mitochondria of live cells reduce WST-8 in CCK-8 to an orange-yellow formazan product, the amount of which is directly proportional to the number of live cells. For the assay, 10 μL of CCK-8 reagent and 100 μL of culture medium were added to each well, and the cells were incubated at 37°C for 2 hours. The absorbance at 450 nm (reference wavelength 630 nm) was then measured using a microplate reader. Cell viability (%) = (Experimental group absorbance) / (Absorbance of experimental group) (Absorbance of blank group) / (Absorbance of control group) (Absorbance of blank group) × 100%.

[0035] Compound a used in this invention was purchased from Zhengzhou Alpha Pharmaceutical Co., Ltd., model number 52462-29-0; compound b was purchased from Zhengzhou Alpha Pharmaceutical Co., Ltd., model number 2757954-49-5. Silver trifluoromethanesulfonate (AgOTf) was purchased from Bide Pharmaceutical Co., Ltd., model number BD151178; glutathione (GSH) was purchased from Bide Pharmaceutical Co., Ltd., model number BD132398; 5,5′-dithiobis(2-nitrobenzoic acid) was purchased from Bide Pharmaceutical Co., Ltd., model number BD15685; and 4T1 mouse breast cancer cells were purchased from the Shanghai Institute of Cell Biology, Chinese Academy of Sciences.

[0036] This invention develops a novel photocatalytic system based on ruthenium-based aggregation-induced emission, and utilizes the photocatalytic glutathione oxidation-coupling hydrogen production performance of this material to achieve oxygen-independent anti-tumor immunotherapy.

[0037] The above-mentioned new aggregation-induced emission compounds have the following molecular structural characteristics:

[0038] It has the following synthetic route:

[0039] This invention utilizes confocal fluorescence microscopy to image and evaluate the material.

[0040] Example 1: Preparation of Ruthenium-based aggregation-induced emission material RuL-TBPy This embodiment provides a ruthenium-based aggregation-induced emission material RuL-TBPy, with the following reaction formula:

[0041] Compound a (60 mg, 0.09 mmol) and silver trifluoromethanesulfonate (46 mg, 0.18 mmol) were dissolved in methanol (20 mL) at room temperature, and the mixture was stirred at room temperature for 2 h. After the reaction was completed, the mixture was filtered, and the red filtrate was collected. Compound b (49.2 mg, 0.06 mmol) was added to the red filtrate, and the mixture was stirred at room temperature for 48 h. After the reaction was completed, the solvent was evaporated under reduced pressure, the residue was dissolved in dichloromethane and filtered, the filtrate was concentrated, and recrystallized from diethyl ether to obtain a dark red solid powder, which was the target product RuL-TBPy (88 mg, yield 50%).

[0042] The obtained product is a solid powder, and its nuclear magnetic resonance hydrogen spectrum (NMR spectrum) is as follows: 1 HNMR and carbon spectroscopy (HNMR) 13 The CNMR data is as follows: 1H NMR(400 MHz, DMSO-d6): δ 9.40 (s, 4H), 9.06 (d, 4H, J = 6 Hz), 8.79 (d, 4H, J =8.4 Hz), 8.25-8.21 (m, 4H), 8.15 (s, 4H), 8.09-8.08 (m, 2H), 7.68-7.66 (m,4H), 7.44-7.40 (m, 8H), 7.21-7.17 (m, 12H), 7.10-7.08 (m, 4H), 5.51 (d, 8H, J= 6 Hz), 5.24 (d, 8H, J = 6 Hz), 2.78-2.73 (m, 4H), 2.16 (s, 6H), 2.13 (s,6H), 1.26-1.18 (m, 24H). 13 C NMR (100 MHz, DMSO-d6): δ 174.5, 164.9, 164.6,152.4, 146.6, 145.9, 145.7, 144.9, 130.9, 130.4, 130.3, 129.2, 126.5, 126.1,126.0, 122.7, 119.4, 107.3, 106.8, 105.2, 101.1, 100.5, 95.8, 89.8, 87.0,86.8, 86.0, 85.9, 83.1, 80.4, 30.9, 30.8, 30.6, 30.4, 22.5, 21.9, 18.3, 17.7.

[0043] Example 2: In vitro photocatalytic glutathione oxidative coupling hydrogen production performance test Based on Example 1, this embodiment tests the in vitro photocatalytic glutathione oxidative coupling hydrogen production performance of the aggregation-induced emission material RuL-TBPy of the present invention. The specific steps are as follows: The hydrogen production performance of RuL-TBPy in the in vitro photocatalytic oxidative coupling reaction of glutathione (GSH) was determined by gas chromatography. A mixed solution of RuL-TBPy (0.3 mg / mL) and GSH (10 mM) was placed in a sealed glass bottle, and an oxygen-free atmosphere was established by purging with argon gas. The reaction was carried out under 450 nm illumination. Samples were taken from the top space of the vial using a microsyringe at different time points (0, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours), and the amount of hydrogen generated was detected by gas chromatography. Simultaneously, the Ellman method was used to quantitatively detect the consumption of glutathione in the reaction system using 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) as a probe. 20 μL of the reaction solution was taken, and 0.5 mL of Tris-HCl buffer (0.1 M, pH 8.0) and 50 μL of DTNB solution (4 mg / mL) were added. After mixing and incubation at room temperature for 5 minutes, the absorbance at 412 nm was measured using a UV-Vis spectrophotometer. The GSH concentration was calculated based on the standard curve. The results are as follows: Figure 1 As shown, with prolonged illumination, hydrogen production in the system gradually increased, while GSH concentration decreased accordingly. After 12 hours of illumination, the cumulative hydrogen production reached approximately 40 mmol / g, and GSH consumption was approximately 80 mM. The molar ratio of hydrogen production to GSH consumption was close to 1:2, and the hydrogen production rate reached 3.4 mmol / g. -1 h -1 The above results indicate that RuL-TBPy can efficiently catalyze the oxidative coupling of glutathione to oxidized glutathione (GSSG) under anaerobic conditions, and release hydrogen gas simultaneously.

[0044] Example 3: Application of Cell Fluorescence Imaging This embodiment, based on Example 1, examines the imaging effect of the aggregation-induced emission material RuL-TBPy of the present invention in living cells. The imaging effect of RuL-TBPy in living cells is observed using a confocal microscope. The specific steps are as follows: 4T1 mouse breast cancer cells (purchased from Shanghai Institute of Cell Biology, Chinese Academy of Sciences) were seeded into 6-well plates, approximately 2 × 10⁶ cells per plate. 5Cells were cultured in RPMI 1640 medium containing 10% fetal bovine serum and 1% penicillin-streptomycin at 37°C in a 5% CO2 incubator for 24 h. After cell adhesion, the original medium was discarded, and fresh medium containing RuL-TBPy (10 μM) prepared in Example 1 was added. The cells were incubated for another 30 min, followed by staining with the commercial cell membrane probe Dio (Beyotime C1993S) for 30 min. After staining, the cells were washed three times with phosphate-buffered saline (PBS, pH 7.4) for 2 minutes each time, and then fresh phenol red-free medium was added. Images were taken under a super-resolution confocal microscope (Leica, model TCS SP8 STED3X, excitation wavelength: RuL-TBPy 405 nm, Dio 488 nm; emission wavelength collection range: RuL-TBPy 600-700 nm, Dio 500-550 nm). The results are shown below. Figure 2 As shown, RuL-TBPy exhibits strong red fluorescence in a DMSO / toluene mixed solvent, and its red fluorescence signal highly overlaps with the green fluorescence of Dio (Pearson correlation coefficient > 0.85), indicating that RuL-TBPy can be rapidly taken up by 4T1 cells within 30 minutes and clearly label the cell membrane, demonstrating good cell membrane targeting imaging capability and high imaging resolution.

[0045] Example 4: Photocatalytic antitumor application (1) Cell dark toxicity and phototoxicity test The dark toxicity and phototoxicity of RuL-TBPy on 4T1 cells were determined using the CCK-8 assay. 4T1 cells in logarithmic growth phase were inoculated at 5 × 10⁻⁶ cells / cells. 4 Cells / mL were seeded in 96-well plates at a density of 100 μL per well and incubated at 37°C in a 5% CO2 incubator for 24 h. The original culture medium was discarded, and culture medium containing different concentrations of RuL-TBPy (0, 0.5, 1, 2, 5, 10, 20, 50 μM) was added to each well at 100 μL, with 5 replicates for each concentration. The plates were then incubated for another 24 h.

[0046] Dark toxicity test: Discard the drug-containing culture medium, add 100 μL of RPMI 1640 medium containing CCK-8 (10 μL), and continue incubation in an incubator for 2 hours. Then, measure the absorbance at 450 nm using a microplate reader. With the cell viability of the untreated control wells as 100%, calculate the cell viability at each concentration.

[0047] Phototoxicity test: After cell administration, the cells were irradiated with a 450nm laser, and the remaining steps were the same as the dark toxicity test.

[0048] The results are as follows Figure 3As shown, under dark conditions, even at a RuL-TBPy concentration as high as 50 μM, the survival rate of 4T1 cells remained greater than 85%, indicating that this material has good biocompatibility (low dark toxicity). Under 450 nm illumination, RuL-TBPy exhibited a concentration-dependent killing effect on 4T1 cells; at 20 μM, the cell survival rate decreased to approximately 20%, with an IC50 concentration of [missing value]. 50 The value is approximately 8 μM, indicating that the material has good photocatalytic antitumor activity.

[0049] (2) Evaluation of in vivo antitumor efficacy The in vivo antitumor efficacy of RuL-TBPy was evaluated using a 4T1 tumor-bearing mouse model. 4T1 cells (2 × 10⁻⁶) were used. 6 Each tumor sample (suspended in 100 μL of serum-free RPMI 1640 medium) was inoculated under the right second mammary fat pad of 6-8 week old, approximately 20 g female BALB / c mice until the tumor volume reached approximately 100 mm. 3 At that time, the mice were randomly divided into four groups (6 mice in each group): PBS control group (PBS group); PBS combined with light exposure group (PBS + light exposure group); RuL-TBPy monotherapy group (RuL-TBPy group). RuL-TBPy combined illumination group (RuL-TBPy+ illumination group).

[0050] Dosage regimen: The PBS and RuL-TBPy groups received a 200 μL tail vein injection every two days, with RuL-TBPy at a dose of 5 mg / kg (based on mouse body weight). The light irradiation groups received 450 nm laser irradiation on the tumor site 24 hours after each injection. Tumor volume was monitored and recorded every two days, with treatment continuing for 14 days. After the experiment, mice that had just died were examined; tumors were collected, weighed, and photographed. Results are as follows: Figure 4 and Figure 5 As shown, tumors grew rapidly in both the PBS group and the PBS+light irradiation group, with an average tumor volume exceeding 1500 mm² on day 14. 3 RuL-TBPy alone showed some inhibition of tumor growth, but the effect was limited. In the RuL-TBPy + light-induced group, tumor volume was significantly reduced, with an average tumor volume of approximately 300 mm² on day 14. 3 The tumor weight of the mice in the group was significantly lower than that in the other groups, and the body weight of the mice in each group did not decrease significantly during the treatment period, indicating that RuL-TBPy combined with phototherapy has good biocompatibility.

[0051] The above results indicate that RuL-TBPy combined with 450nm light irradiation can effectively inhibit tumor growth in 4T1 tumor-bearing mice.

[0052] The above content is only for illustrating the technical concept of the present invention and should not be construed as limiting the scope of protection of the present invention. Any modifications made to the technical solution based on the technical concept proposed in this invention shall fall within the scope of protection of the claims of this invention.

Claims

1. A ruthenium-based aggregation-induced light-emitting material, characterized in that, The structural formula is as follows: 。 2. The ruthenium-based aggregation-induced light-emitting material according to claim 1, characterized in that, The aggregation-induced light-emitting material has photocatalytic activity for glutathione oxidation coupling to produce hydrogen, and can catalyze the oxidation of glutathione to oxidized glutathione under anaerobic conditions and release hydrogen gas simultaneously.

3. The method for preparing a ruthenium-based aggregation-induced emission material according to claim 1 or 2, characterized in that, include: The aggregation-induced emission material was prepared by activating compound a with silver salt and then reacting it with compound b; wherein, the structural formula of compound a is as follows: The structural formula of compound b is: .

4. The method for preparing a ruthenium-based aggregation-induced emission material according to claim 3, characterized in that, The silver salt is silver trifluoromethanesulfonate; the reaction is carried out in methanol solvent at room temperature for 40 h to 52 h.

5. The method for preparing a ruthenium-based aggregation-induced emission material according to claim 3, characterized in that, The molar ratio of compound a to compound b is 1:

1.

6. The use of the ruthenium-based aggregation-induced emission material according to claim 1 or 2 in the preparation of antitumor drugs.

7. The application according to claim 6, characterized in that, The antitumor drug is a photocatalytic antitumor drug; the photocatalytic antitumor drug is activated under 450 nm light irradiation.

8. The application according to claim 6, characterized in that, The antitumor drug exerts its antitumor effect through one or more of the following mechanisms: (a) Disrupting the redox balance in tumor cells under oxygen-independent conditions to overcome treatment resistance caused by hypoxia; (b) Catalyzes the oxidative coupling of glutathione in tumor cells, while generating hydrogen gas, which synergistically activates the anti-tumor immune response; (c) Induces tumor cell ferroptosis, reducing the risk of drug resistance.

9. The application of the aggregation-induced emission material according to claim 1 or 2 in the preparation of tumor cell fluorescence imaging reagents.

10. A photocatalytic antitumor system, characterized in that, It comprises the ruthenium-based aggregation-induced emission material as described in claim 1 or 2, and a pharmaceutically acceptable carrier.

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