Preparation method and application of red light activated hydrogen sulfide donor heavy-atom-free photosensitizer based on BODIPY dye
The red light-activated hydrogen sulfide donor nanoparticles prepared by fluoroboron dipyrrole dye have solved the problems of limited efficacy and phototoxicity of PDT in hypoxic environments, and achieved highly efficient combined treatment of deep tumors.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- TIANJIN POLYTECHNIC UNIV
- Filing Date
- 2024-11-12
- Publication Date
- 2026-05-12
AI Technical Summary
Existing photodynamic therapy (PDT) has limited efficacy in hypoxic tumor microenvironments, and the use of ultraviolet and short-wavelength light has insufficient tissue penetration and may produce phototoxicity, limiting its application in the treatment of deep tumors.
Develop a red-light-activated hydrogen sulfide donor photosensitizer based on fluoroboron dipyrrole dye, which releases hydrogen sulfide and singlet oxygen in the form of nanoparticles under red light, enabling combined treatment with gas therapy, photodynamic therapy and immunotherapy.
Under red light irradiation, the killing efficiency of tumor cells is significantly improved, oxygen dependence is reduced, and immune response is promoted, thus achieving precise treatment of deep tumors.
Smart Images
Figure CN122010990A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of nanomedicine technology for cancer treatment, specifically relating to a method for preparing a red light-activated hydrogen sulfide donor non-heavy atom photosensitizer of fluoroboron dipyrrole dye (BODIPY) and its application. Background Technology
[0002] Common cancer treatments include phototherapy, chemotherapy, radiotherapy, and microwave hyperthermia. Among these, photodynamic therapy (PDT) has become a promising cancer treatment method due to its advantages such as spatiotemporal controllability, low toxicity, significant immune activation effects, and non-invasiveness. PDT mainly works through two photochemical mechanisms: type I and type II reactions. In type I reactions, the photosensitizer generates free radicals and hydrogen peroxide through electron transfer; while in type II reactions, the photosensitizer interacts with molecular oxygen through a triplet-triplet mechanism to generate singlet oxygen (…). 1 Type II photosensitizers (PDT) can kill cancer cells by delivering oxygen (O2). However, a major drawback of PDT is its high dependence on oxygen, which is particularly pronounced in the hypoxic tumor microenvironment, greatly limiting its efficacy. To overcome this problem, researchers are developing new treatment strategies. For example, designing type I photosensitizers to generate free radicals to kill cancer cells. Although the generation of free radicals can alleviate the oxygen dependence problem to some extent, the extremely short half-life of free radicals and their susceptibility to reduction by intracellular reducing agents such as glutathione (GSH) limit the therapeutic potential of this strategy. Furthermore, some studies have attempted to deliver oxygen directly to the tumor site to alleviate hypoxia; however, this method may simultaneously promote tumor cell growth, leading to side effects. Another approach is to introduce heavy atoms into organic functional molecules, utilizing the heavy atom effect to increase the singlet oxygen quantum yield of photosensitizers, thereby enhancing their ability to kill cancer cells. However, photosensitizers containing heavy atoms may induce significant cytotoxicity, limiting their clinical application prospects. Therefore, how to improve the efficacy of PDT while avoiding oxygen dependence and reducing potential toxicity remains an important direction for current research.
[0003] In cancer treatment, the effects of single-therapy approaches are often limited; therefore, combining multiple treatment strategies is crucial for improving efficacy. Hydrogen sulfide (H2S), as an important bioactive gas, has demonstrated significant anti-tumor potential in regulating the tumor microenvironment (TME) and immune responses. H2S can inhibit tumor growth by improving tumor vascular permeability, inhibiting mitochondrial respiration, alleviating tumor hypoxia, suppressing the proliferation of myeloid-derived suppressor cells (MDSCs), enhancing the maturation of dendritic cells (DCs) in the immune system, and promoting immune response. Given the multiple roles of H2S in regulating the tumor microenvironment and immune activation, it is considered an "auxiliary gas" for photodynamic therapy (PDT), enhancing its anti-cancer effects. By combining H2S with PDT, treatment efficacy can be further improved on the basis of PDT, such as increasing tumor drug sensitivity, promoting immune system activation, and reducing PDT's oxygen dependence, thus forming a more effective anti-tumor strategy. This synergistic effect provides a promising research direction for future cancer treatment.
[0004] Currently, a wide variety of hydrogen sulfide (H2S) donors have been developed, among which photoactivated H2S donors have attracted widespread attention due to their unique advantages. Photoactivated H2S donors can achieve precise H2S release through external light control without interfering with normal biochemical processes. This control method effectively reduces off-target effects and achieves precise temporal and tertiary control, thereby minimizing damage to healthy tissues. However, most current photoactivated H2S donors require ultraviolet or short-wavelength visible light for triggering, which limits tissue penetration depth. Ultraviolet and short-wavelength light have weak penetrability and may cause phototoxicity or damage to normal tissues at higher doses, especially when treating deep tumors. Therefore, developing H2S donors that can be activated by long-wavelength light (such as red or near-infrared light) has become a current research focus. Long-wavelength light has stronger tissue penetration, enabling precise treatment of deep tumors without damaging normal tissues, which provides a broader prospect for the clinical application of photoactivated H2S donors.
[0005] Fluoroboron dipyrrole dyes, with their superior optical properties and chemical stability, have wide applications in life sciences, chemical sensing, and photonics. Therefore, in this invention, we have rationally designed and developed a heavy-atom-free photosensitizer that can be activated by red light and carries a hydrogen sulfide donor, aiming to effectively address the problems of insufficient penetration depth, high oxygen dependence, and low treatment efficiency currently faced in cancer treatment. This invention not only provides an innovative solution to overcome these challenges but also opens up new strategies for the integrated diagnosis and treatment of cancer. Summary of the Invention
[0006] The purpose of this invention is to develop a heavy-atom-free photosensitizer that can be activated by red light-activated hydrogen sulfide donors. When this photosensitizer is assembled into nanoparticles, it can achieve combined treatment of gas therapy, photodynamic therapy, and immunotherapy under irradiation with a single 660nm laser beam, providing an effective cancer treatment strategy.
[0007] A method for preparing a red light-activated hydrogen sulfide donor-free photosensitizer based on fluoroboron dipyrrole dye, characterized in that the structural formula of the photosensitizer is shown in Figure 1.
[0008] A method for preparing a red-light-activated hydrogen sulfide donor photosensitizer without heavy atoms based on fluoroboron dipyrrole dye according to claim 1, as shown in Figure 2, is characterized by comprising the following steps:
[0009] Step 1: Add 1b (1.69 g, 5.5 mmol) to a solution of 1a (2 g, 10 mmol) in anhydrous dichloromethane (50 mL) and stir under nitrogen for 12 h. Cool the reaction to room temperature, add triethylamine (1.75 mL, 12.5 mmol), and then add boron trifluoride diethyl ether (1.58 mL, 12.5 mmol) dropwise. Stir for another 0.5 h, evaporate the solvent under reduced pressure, and purify the crude mixture by column chromatography (1:2, petroleum ether / dichloromethane) to obtain B1 (0.8 g, 1.15 mmol, 23%).
[0010] Step 2: Dissolve B1 (300 mg, 0.4 mmol) in 10 mL of anhydrous dichloromethane and add methyl magnesium bromide (2.07 mL, 17.9 mmol) dropwise. Stir the reaction at 0 °C for 10 min and monitor the reaction using thin-layer chromatography (1:1, petroleum ether / dichloromethane). After the reaction is complete, add 50 mL of saturated ammonium chloride to quench the reaction, and collect the organic phase using a separating funnel. Wash the organic phase with saturated salt water and then filter with solid sodium sulfate. Concentrate the reaction mixture on a rotary evaporator and purify it by column chromatography (1:1, petroleum ether / dichloromethane) to obtain B2 (60 mg, 0.42 mmol, 20%).
[0011] Step 3: Dissolve B2 (60 mg, 0.087 mmol) in 50 mL of anhydrous dichloromethane, then add DDQ (39 mg, 0.17 mmol) and stir for 10 min. After the reaction is complete, the post-treatment is the same as in Step 2. The pure product B3 (50 mg, 0.07 mmol, 83%) is obtained as a black solid by column chromatography (1:1, petroleum ether / dichloromethane).
[0012] The method for preparing a red light-activated hydrogen sulfide donor photosensitizer without heavy atoms based on fluoroboron dipyrrole dye according to claim 2 is characterized in that: in step 1, the molar ratio of 1a to 1b is 1:0.6-0.8.
[0013] The method for preparing a red light-activated hydrogen sulfide donor photosensitizer without heavy atoms based on fluoroboron dipyrrole dye according to claim 2 is characterized in that: in step 2, the molar ratio of B1 to methyl magnesium bromide is 1:30.
[0014] The method for preparing a red light-activated hydrogen sulfide donor photosensitizer without heavy atoms based on fluoroboron dipyrrole dye according to claim 2 is characterized in that: in step 3, the molar ratio of B2 to 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) is 1:2 to 4.
[0015] The preparation method of red light-activated hydrogen sulfide donor photosensitizer nanoparticles based on fluoroboron dipyrrole dye according to claim 2 is characterized by the following:
[0016] A certain mass of fluoroboron dipyrrole dye molecules was weighed and dissolved in DMSO (1 mg / mL), and a certain mass of F127 polymer was weighed and dissolved in ultrapure water (1 mg / mL). The F127 polymer solution was placed under ultrasonic conditions, and then the solution of fluoroboron dipyrrole dye molecules was slowly added dropwise. After dialyzing with ultrapure water, the solution was filtered through a 0.22 μm aqueous filter membrane to obtain a solution of fluoroboron dipyrrole dye nanoparticles.
[0017] The nanoparticles prepared by the method for preparing red light-activated hydrogen sulfide donor photosensitizer nanoparticles based on fluoroboron dipyrrole dyes according to claims 1-6 have a hydrogen sulfide release efficiency of 78% and a singlet oxygen quantum yield of 0.21 within one hour of light irradiation.
[0018] The red light-activated hydrogen sulfide donor photosensitizer nanoparticles based on fluoroboron dipyrrole dye obtained by the preparation method according to claims 1-6 have a killing efficiency of up to 90% against 4T1 cells under the conditions of a concentration of 10 μM and light irradiation (LED, 660 nm, 0.5 W / cm2) for 15 minutes.
[0019] The red light-activated, heavy atom-free photosensitizer nanoparticles prepared according to the methods described in claims 1-6 can effectively induce pyroptosis in 4T1 cells.
[0020] In a 4T1 subcutaneous tumor model, red light-activated hydrogen sulfide donor nanoparticles based on fluoroboron dipyrrole dye, without heavy atom photosensitizers, exhibited remarkable antitumor effects. Following intravenous injection of 100 μM nanoparticles, 30 minutes of 660 nm LED irradiation resulted in the death of most tumor cells, significantly promoted dendritic cell maturation, activated immune responses, and achieved a tumor inhibition rate of 99%.
[0021] The beneficial effects of this invention are as follows:
[0022] 1. This invention connects a photocage of a thiocarbamate that releases hydrogen sulfide via photoactivation to the meso site of a BODIPY dye. On one hand, through reasonable structural adjustments, the release efficiency of hydrogen sulfide and the quantum yield of singlet oxygen are significantly improved; on the other hand, this molecule can simultaneously release hydrogen sulfide and singlet oxygen under red light irradiation. These two active substances work synergistically to more effectively kill tumor cells. This invention is the first to propose an organic photofunctional small molecule that simultaneously releases hydrogen sulfide and singlet oxygen under single-beam light irradiation. Its raw materials are inexpensive, the synthesis process is simple, and it has high application potential.
[0023] 2. The photosensitizer of this invention, when assembled into nanoparticles, can effectively kill tumor cells. This treatment strategy alleviates the hypoxic state of tumor cells by reducing oxygen consumption, thereby enhancing the uptake of nanoparticles by tumor cells. Simultaneously, this strategy successfully solves the oxygen dependence problem in type II photodynamic therapy (PDT), significantly increasing the generation of singlet oxygen within tumor cells, thus enhancing the efficacy of PDT. More importantly, the enhanced singlet oxygen can promote the maturation of dendritic cells, triggering a strong anti-tumor immune response. Therefore, this photosensitizer, through the combined action of gas therapy, photodynamic therapy, and immunotherapy, forms an effective synergistic treatment method that significantly inhibits tumor growth. This research provides a highly promising innovative strategy for cancer treatment. Attached Figure Description
[0024] Figure 1 It is the structural formula of photosensitizer B3 in Example 1.
[0025] Figure 2 This is the synthetic route for photosensitizer B3 in Example 1.
[0026] Figure 3 This is the 1H NMR spectrum of photosensitizer B3 in Example 1.
[0027] Figure 4 This is the mass spectrum of photosensitizer B3 in Example 1.
[0028] Figure 5 This is the absorption spectrum of photosensitizer B3 in Example 1.
[0029] Figure 6 This is the fluorescence spectrum of photosensitizer B3 in Example 1.
[0030] Figure 7 This is a particle size diagram of photosensitizer B3 after it is assembled into nanoparticles B3 NPs in Example 2.
[0031] Figure 8This is the ultraviolet absorption spectrum of the reactive oxygen species probe DPBF under 660nm laser irradiation in Example 2.
[0032] Figure 9 This is the absorption intensity spectrum of the hydrogen sulfide probe DTNB in Example 2 under 660nm laser irradiation.
[0033] Figure 10 This is a diagram of the cytotoxicity experiment of photosensitizer B3 NPs on 4T1 cells in Example 2.
[0034] Figure 11 This is a cell photograph showing pyroptosis induced in 4T1 cells by photosensitizer B3 NPs in Example 2.
[0035] Figure 12 This is a quantitative graph showing the tumor growth inhibition effect of photosensitizer B3 NPs on 4T1 tumor-bearing mice in Example 2.
[0036] Figure 13 This is a quantitative diagram showing the immune-promoting effect on dendritic cell maturation induced by the photosensitizer B3 NPs in 4T1 tumor-bearing mice after treatment in Example 2. Detailed Implementation
[0037] The present invention will now be described in detail with reference to the accompanying drawings and embodiments, but the scope of protection of the present invention is not limited to these embodiments.
[0038] Example 1
[0039] This embodiment takes the preparation of a heavy atom-free photosensitizer B3 with a red light-activated hydrogen sulfide donor as an example. The molecular structure formula is attached. Figure 1 The synthetic route is attached. Figure 2 :
[0040] Step 1: 1b (1.69 g, 5.5 mmol) was added to a solution of 1a (2 g, 10 mmol) in 50 mL of anhydrous dichloromethane, and the mixture was stirred under nitrogen for 12 h. The reaction was cooled to room temperature, and triethylamine (1.75 mL, 12.5 mmol) was added, followed by dropwise addition of boron trifluoride diethyl ether (1.58 mL, 12.5 mmol). The mixture was stirred for another 0.5 h, the solvent was evaporated under reduced pressure, and the crude mixture was purified by column chromatography (1:2, petroleum ether / dichloromethane) to obtain B1 (0.8 g, 1.15 mmol, 23%).
[0041] Step 2: Dissolve B1 (300 mg, 0.4 mmol) in 10 mL of anhydrous dichloromethane and add methyl magnesium bromide (2.07 mL, 17.9 mmol) dropwise. Stir the reaction at 0 °C for 10 min and monitor the reaction using thin-layer chromatography (1:1, petroleum ether / dichloromethane). After the reaction is complete, quench the reaction with 50 mL of saturated ammonium chloride and collect the organic phase using a separating funnel. Wash the organic phase with saturated brine solution and filter with solid sodium sulfate. Concentrate the reaction mixture on a rotary evaporator and purify it by column chromatography (1:1, petroleum ether / dichloromethane) to obtain B2 (60 mg, 0.42 mmol, 20%).
[0042] Step 3: Dissolve B2 (60 mg, 0.087 mmol) in 50 mL of anhydrous dichloromethane, then add DDQ (39 mg, 0.17 mmol) and stir for 10 min. After the reaction is complete, the post-treatment is the same as in Step 2. The pure product B3 (50 mg, 0.07 mmol, 83%) is obtained as a black solid by column chromatography (1:1, petroleum ether / dichloromethane).
[0043] The photosensitizer B3 was subjected to 1H NMR and mass spectrometry tests, and the results are as follows:
[0044] As attached Figure 3 As shown, the 1H NMR data of photosensitizer B3 are as follows: 1H NMR (400MHz, Chloroform-d) δ 9.04 (d, J = 8Hz, 2H), 7.54 (s, 2H), 7.40-7.26 (m, 4H), 7.21-7.27 (m, 10H), 7.22 (d, J = 8.9Hz, 2H), 7.14 (d, J = 2.7Hz, 2H), 5.48 (s, 2H), 3.98 (s, 6H), 2.12 (s, 3H).
[0045] As attached Figure 4 As shown, the mass spectrometry data of photosensitizer B3 are: MALDI-MS: C43H36BN3O3S[M+22.9892]+ Theoretical value 708.2462, measured value 708.2474.
[0046] The absorption and emission spectra of photosensitizer B3 are shown in the attached figure. Figure 5 , 6 As shown, the maximum absorption peak of photosensitizer B3 is located at 676 nm, and the maximum emission peak is located at 706 nm.
[0047] Example 2
[0048] Preparation and biological applications of B3 NPs, a nanoparticle with a red light-activated hydrogen sulfide donor and no heavy atom photosensitizer.
[0049] A certain mass of fluoroboron dipyrrole dye B3 molecules was weighed and dissolved in DMSO to prepare a 1 mg / mL solution. A certain mass of F127 polymer was weighed and dissolved in ultrapure water to similarly prepare a 1 mg / mL solution. The F127 polymer solution was placed in an ultrasonic environment, and under ultrasonic conditions, the fluoroboron dipyrrole dye B3 molecule solution was slowly added dropwise. Subsequently, the resulting mixture was dialyzed with ultrapure water, and finally filtered through a 0.22 μm aqueous filter membrane to obtain a solution of fluoroboron dipyrrole dye B3 nanoparticles.
[0050] As attached Figure 7 As shown, the photosensitizer nanoparticles B3 NPs have a particle size of 131 nm.
[0051] Various performance tests were conducted on the above B3 NPs, and the specific tests are as follows:
[0052] 1. Photodynamic performance test
[0053] As attached Figure 8 As shown, the photodynamic properties of B3 NPs were tested using the reactive oxygen species probe 1,3-diphenylisobenzofuran (DPBF). The UV absorption spectrum of the solution was recorded after irradiation with a 660 nm (0.5 W / cm2) laser, proving that it has the ability to generate ROS.
[0054] 2. Hydrogen sulfide release performance test
[0055] As attached Figure 9 As shown, B3 NPs solution (3 ml, c = 15 μM) was added to PBS buffer (pH 7.4, 10 mM) and placed in a 1.0 cm quartz tube fitted with a PTFE screw cap and a stir bar. Carbonic anhydrase (50 μM) and DTNB (50 μM) solutions were added to the sample solution. The mixture was then degassed by purging with nitrogen (N2). After stirring, the solution was irradiated with an LED (λmax = 660 nm). After irradiation (~60 min), the absorbance of the sample at 412 nm was recorded.
[0056] 3. External phototherapy effect test
[0057] As attached Figure 10 As shown, 4T1 cells were seeded at a density of 8000 cells per well in 96-well plates. Cells were treated with different concentrations of B3NPs for 12 h, washed three times with PBS, irradiated with LED light for 15 min, and then incubated overnight. To determine cell viability, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT, 1 mg / mL, 100 μL) was added to each well, and the cells were incubated at 37°C for 6 h. The culture medium was then removed, and 100 μL of DMSO was added to each well. The absorbance (OD) at 490 nm was measured using a microplate reader.
[0058] As attached Figure 10 As shown, in the absence of light, the survival rate of 4T1 cells incubated with B3 NPs was over 90%, indicating that B3 NPs have good biocompatibility. Under light irradiation, when the concentration of B3 NPs was 10 μM, the cell viability decreased to 10%, indicating that B3 NPs can effectively kill tumor cells.
[0059] As attached Figure 11 As shown, significant cell swelling and plasma membrane vesicles were observed in the dead cells of the B3 NPs+L group, consistent with the typical characteristics of pyroptosis.
[0060] 4. In vivo diagnostic and treatment effect test
[0061] In vivo anti-tumor assay: A 4T1 subcutaneous tumor-bearing mouse model was established using female BALB / c mice. The 4T1 tumor-bearing mice were divided into 5 groups, and the tumor volume changes were monitored every two days after light exposure to evaluate the treatment outcome during treatment.
[0062] As attached Figure 12 As shown, the tumors in the unexposed experimental group and the PBS group exposed to light grew rapidly and had almost no anti-tumor effect, while the B3 NPs group exposed to light achieved an anti-tumor inhibition rate of 93.15% after 14 days, indicating that B3 NPs have excellent anti-tumor ability under light irradiation.
[0063] As attached Figure 13 As shown, flow cytometry was used to detect the maturation of dendritic cells in lymph node cells.
[0064] As attached Figure 13 As shown, dendritic cells were effectively activated, proving that the photosensitizer successfully activated the immune response.
Claims
1. A method for preparing a red-light-activated hydrogen sulfide donor-free photosensitizer based on fluoroboron dipyrrole dye, characterized in that, The photosensitizer has the following structural formula.
2. A method for preparing a red-light-activated hydrogen sulfide donor photosensitizer without heavy atoms based on fluoroboron dipyrrole dye according to claim 1, characterized in that, Includes the following steps: Step 1: Add 1b (1.69 g, 5.5 mmol) to a solution of 1a (2 g, 10 mmol) in anhydrous dichloromethane (50 mL) and stir under nitrogen for 12 h. Cool the reaction to room temperature, add triethylamine (1.75 mL, 12.5 mmol), and then add boron trifluoride diethyl ether (1.58 mL, 12.5 mmol) dropwise. Stir for another 0.5 h, evaporate the solvent under reduced pressure, and purify the mixture by column chromatography (1:2, petroleum ether / dichloromethane) to obtain B1 (0.8 g, 1.15 mmol, 23%). Step 2: Dissolve B1 (300 mg, 0.4 mmol) in 10 mL of anhydrous dichloromethane and add methyl magnesium bromide (2.07 mL, 17.9 mmol) dropwise. Stir the reaction at 0 °C for 10 min and monitor the reaction using thin-layer chromatography (1:1, petroleum ether / dichloromethane). After the reaction is complete, add 50 mL of saturated ammonium chloride to quench the reaction, and collect the organic phase using a separating funnel. Wash the organic phase with saturated salt water and then filter with solid sodium sulfate. Concentrate the reaction mixture on a rotary evaporator and purify it by column chromatography (1:1, petroleum ether / dichloromethane) to obtain B2 (60 mg, 0.42 mmol, 20%). Step 3: Dissolve B2 (60 mg, 0.087 mmol) in 50 mL of anhydrous dichloromethane, then add DDQ (39 mg, 0.17 mmol) and stir for 10 min. After the reaction is complete, the post-treatment is the same as in Step 2. The pure product B3 (50 mg, 0.07 mmol, 83%) is obtained as a black solid by column chromatography (1:1, petroleum ether / dichloromethane).
3. The method for preparing a red-light-activated hydrogen sulfide donor photosensitizer based on fluoroboron dipyrrole dye according to claim 2, characterized in that: In step 1, the molar ratio of 1a to 1b is 1:0.6 to 0.
8.
4. The method for preparing a red-light-activated hydrogen sulfide donor photosensitizer based on fluoroboron dipyrrole dye according to claim 2, characterized in that: In step 2, the molar ratio of B1 to methyl magnesium bromide is 1:
30.
5. The method for preparing a red-light-activated hydrogen sulfide donor photosensitizer based on fluoroboron dipyrrole dye according to claim 2, characterized in that: In step 3, the molar ratio of B2 to 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) is 1:2 to 4.
6. The preparation of red-light-activated hydrogen sulfide donor photosensitizer nanoparticles based on fluoroboron dipyrrole dye according to claim 2, characterized in that, The preparation method is as follows: A certain mass of fluoroboron dipyrrole dye molecules was weighed and dissolved in DMSO (1 mg / mL), and a certain mass of F127 polymer was weighed and dissolved in ultrapure water (1 mg / mL). The F127 polymer solution was placed under ultrasonic conditions, and then the solution of fluoroboron dipyrrole dye molecules was slowly added dropwise. After dialyzing with ultrapure water, the solution was filtered through a 0.22 μm aqueous filter membrane to obtain a solution of fluoroboron dipyrrole dye nanoparticles.
7. The nanoparticles prepared by the method of preparing red light-activated hydrogen sulfide donor photosensitizer nanoparticles based on fluoroboron dipyrrole dye according to claims 1-6 have a hydrogen sulfide release efficiency of 78% and a singlet oxygen quantum yield of 0.21 within one hour of light irradiation.
8. The red-light-activated hydrogen sulfide donor photosensitizer nanoparticles based on fluoroboron dipyrrole dye obtained by the preparation method according to claims 1-6, at a concentration of 10 μM and under illumination (LED, 660 nm, 0.5 W / cm²), 2 Under 15 minutes of conditions, the killing efficiency against 4T1 cells is as high as 90%.
9. The red light-activated, heavy atom-free photosensitizer nanoparticles prepared according to the methods described in claims 1-6 can effectively induce pyroptosis in 4T1 cells.
10. In the 4T1 subcutaneous tumor model, red light-activated hydrogen sulfide donor nanoparticles based on fluoroboron dipyrrole dye, without heavy atom photosensitizers, exhibited excellent anti-tumor effects. After intravenous injection of 100 μM nanoparticles, most tumor cells died after 30 minutes of irradiation, while dendritic cell maturation was significantly promoted, activating the immune response, and the tumor inhibition rate reached 99%.