Tumor immune microenvironment-regulating light-activated ferroptosis nanoparticles and their preparation method and application

Abstract

The present invention discloses a tumor immune microenvironment-regulated light-activated ferroptosis nanoparticle, a preparation method, and an application thereof, relating to the field of biomedicine technology. The preparation method comprises the following steps: dissolving albumin and ferritin in water, adjusting the pH to alkaline, adding a photosensitizer and lipoic acid, mixing, then adding a solvent, performing a mixing reaction, then adding a cross-linking agent, continuing the reaction, and then centrifuging and drying to obtain the tumor immune microenvironment-regulated light-activated ferroptosis nanoparticle. The tumor immune microenvironment-regulated light-activated ferroptosis nanoparticle reverses the tumor immunosuppressive microenvironment by inducing ferroptosis of tumor cells, activating dendritic cells, and regulating the M1 polarization of M2 tumor-associated macrophages, thereby enhancing the effect of tumor immunotherapy.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and in particular to a tumor immune microenvironment-regulating light-activated ferroptosis nanoparticle, a preparation method thereof, and an application thereof. Background Art

[0002] Tumor immunotherapy is an effective anti-tumor strategy developed in recent years that activates the body's own immune system to recognize and kill tumors. However, due to the low immunogenicity of solid tumors and the presence of an immunosuppressive tumor microenvironment, tumor immunotherapy has a low response rate and poor efficacy in some patients. Dendritic cells (DCs) and macrophages, as the main effector cells of the innate immune response, play a key role in triggering anti-tumor immune responses. They are also an important link in connecting the body's innate and adaptive immune responses and are considered to be one of the key targets for enhancing the effectiveness of tumor immunotherapy.

[0003] Ferroptosis-inducing drugs utilize iron-dependent excess accumulation of lipid peroxides to induce immunogenic death of tumor cells, release damage-associated molecular patterns as "immune stimulatory signals", promote DCs maturation, and activate cytotoxic CD8 + T lymphocyte response, initiating anti-tumor immune response. In addition, the ferroptosis of tumor cells also plays an important role in regulating the polarization of tumor-associated macrophages (TAMs) from M2 to M1 phenotype. The above studies indicate that ferroptosis-assisted tumor immunotherapy will become a new strategy for tumor immunotherapy. With the development of nanotechnology, various iron-based nanomaterials, including iron oxide nanoparticles, amorphous iron nanoparticles and iron-organic framework materials, have been widely used in tumor ferroptosis treatment research. However, excessive use of iron-based nanomaterials may increase the risk of adverse health caused by liver damage and chronic kidney disease. Therefore, it is necessary to develop a new tumor immune microenvironment-regulating light-activated ferroptosis nanoparticle to reshape the tumor immune microenvironment and enhance the effect of tumor immunotherapy. Summary of the Invention

[0004] The present invention aims to provide a tumor immune microenvironment-modulating light-activated ferroptosis nanoparticle, its preparation method, and application, to address the above-mentioned problems in the prior art. The tumor immune microenvironment-modulating light-activated ferroptosis nanoparticle reverses the tumor immunosuppressive microenvironment by inducing ferroptosis in tumor cells, activating DCs, and regulating the M1 polarization of M2 TAMs, thereby enhancing the efficacy of tumor immunotherapy.

[0005] Ferritin is a common iron storage protein in organisms. The iron in it can be converted into Fe 2+. Using ferritin as a drug that induces ferroptosis provides a possibility for avoiding the toxicity problem caused by excessive exogenous metallic iron. Studies have shown that under appropriate laser irradiation, the reactive oxygen species (ROS) produced by photosensitizers can destroy the ferritin structure, accelerate the release of iron from ferritin, cause an increase in intracellular iron content, and activate ferroptosis in tumor cells. Other studies have shown that the ROS produced by photosensitizers under laser irradiation can not only induce DCs maturation, but also regulate the M1 polarization of M2-TAMs.

[0006] Tumor cells, DCs, and TAMs interact closely with each other, and drug delivery strategies that simultaneously target and regulate "tumor cells, DCs, and TAMs" may become a new entry point for enhancing anti-tumor immune efficacy. However, ferroptosis-inducing drugs may indiscriminately induce the death of tumor cells, DCs, and TAMs in the tumor microenvironment. Therefore, how to achieve ferroptosis drugs killing tumor cells while activating DCs and TAMs, synergistically regulating "DCs, TAMs, and tumor cells," and reshaping the tumor immune microenvironment may become the key to enhancing the efficacy of immunotherapy for solid tumors.

[0007] The present invention uses ferritin and albumin as nano drug carriers, and prepares a tumor immune microenvironment-regulating light-activated ferroptosis nanoparticle by co-loading lipoic acid and photosensitizer. The light-activated nanoparticle can generate ROS under near-infrared laser irradiation, accelerating the degradation of ferritin in the nanoparticle to release Fe 3+ , induces ferroptosis of tumor cells; Fe 3+ Under the action of high concentrations of reduced glutathione (GSH) in tumor cells, it can be converted into Fe 2+ , induce immunogenic death of tumor cells; use lipoic acid to promote Fe 3+ -Fe 2+ Circulating in tumor cells can enhance the cumulative effect of iron ions and synergistically enhance ferroptosis. The immunogenic death of tumor cells due to ferroptosis can indirectly promote the maturation of DCs and regulate the M1 polarization of M2 TAMs. At the same time, the ROS generated by the light-activated nanoparticles can directly activate DCs and regulate the M1 polarization of M2 TAMs. This light-activated ferroptosis nanoparticle achieves a "killing three birds with one stone" strategy of synergistically regulating "tumor cells, DCs, and TAMs," reversing the tumor's immunosuppressive microenvironment and demonstrating significant anti-tumor immunotherapy efficacy.

[0008] Based on this, the present invention provides the following solutions:

[0009] The present invention provides a method for preparing tumor immune microenvironment-regulated light-activated ferroptosis nanoparticles, comprising the following steps:

[0010] Albumin and ferritin are dissolved in water, and after adjusting the pH to alkaline, a photosensitizer and lipoic acid are added, and then a solvent is added after mixing to carry out a mixing reaction. Then, a cross-linking agent is added, and the reaction is continued. After centrifugation and drying, the tumor immune microenvironment-regulated light-activated ferroptosis nanoparticles are obtained.

[0011] Furthermore, the photosensitizer is indocyanine green or neoindocyanine green; and / or

[0012] The cross-linking agent is glutaraldehyde.

[0013] The CAS number of indocyanine green is 3599-32-4, and the CAS number of neoindocyanine green is 172616-80-7.

[0014] Furthermore, the mass ratio of the albumin, the ferritin, the lipoic acid and the photosensitizer is 15:5:2.5:0.5.

[0015] Furthermore, the solvent is anhydrous ethanol.

[0016] Furthermore, adjusting the pH to alkaline means adjusting the pH to 9.0.

[0017] The present invention also provides tumor immune microenvironment-regulated light-activated ferroptosis nanoparticles prepared according to the above preparation method.

[0018] The present invention also provides the use of the above-mentioned tumor immune microenvironment regulating light-activated ferroptosis nanoparticles in the preparation of tumor immunotherapy drugs.

[0019] Furthermore, the drug reverses the tumor immunosuppressive microenvironment by inducing ferroptosis of tumor cells, activating DCs, and regulating the M1 polarization of M2 TAMs.

[0020] The present invention also provides a tumor immunotherapy drug, the active ingredient of which includes the above-mentioned tumor immune microenvironment regulating light-activated ferroptosis nanoparticles.

[0021] Furthermore, the tumor immunotherapy drug also includes pharmaceutically acceptable excipients.

[0022] The present invention discloses the following technical effects:

[0023] The present invention uses albumin and ferritin as nanodrug carriers, and by co-loading lipoic acid and a photosensitizer, prepares a tumor immune microenvironment-regulated light-activated ferroptosis nanoparticle. This nanodrug can avoid the toxicity problem caused by excessive exogenous metals, enhance the cumulative effect of iron ions in tumor cells, and synergistically enhance the ferroptosis-inducing effect.

[0024] The photosensitizer in the nanoparticles of the present invention can generate light-activated ROS under near-infrared laser irradiation, accelerate the degradation of ferritin in the nanoparticles to release iron ions, and induce the immunogenic death of tumor cells based on ferroptosis, thereby indirectly promoting the maturation of DCs and regulating the M1 polarization of M2 TAMs; in addition, the ROS generated by the light-activated nanoparticles can directly activate DCs and regulate the M1 polarization of M2 TAMs, realizing a synergistic mechanism of dual regulation of DCs and TAMs, initiating anti-tumor immune responses, and reversing the tumor immunosuppressive microenvironment.

[0025] The nanoparticles of the present invention can selectively kill tumor cells in the tumor microenvironment and activate DCs and TAMs, thereby realizing a "killing three birds with one stone" tumor immunotherapy strategy of synergistically regulating "DCs, TAMs and tumor cells". BRIEF DESCRIPTION OF THE DRAWINGS

[0026] 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.

[0027] Figure 1 The particle size and Zeta potential stability of the nanoparticles prepared in the present invention are investigated.

[0028] Figure 2 The toxicity test results of the nanoparticles of the present invention on 4T1 mouse breast tumor cells, DC2.4 cells and RAW264.7 cells under near-infrared laser irradiation are shown;

[0029] Figure 3 The effect of the ferroptosis-based immunogenic death of tumor cells induced by the nanoparticles of the present invention on the maturation of BMDCs;

[0030] Figure 4 The results of the polarization experiment on M2-BMDMs cells by the nanoparticles of the present invention are as follows;

[0031] Figure 5 To compare the results of tumor tissue re-tumor in different treatment groups;

[0032] Figure 6 The results of the analysis of the proportion of DCs in mouse tumors after the nanoparticles of the present invention were injected into mice bearing breast cancer 4T1 tumors;

[0033] Figure 7 These are the analysis results of the proportion of M2 TAMs in mouse tumors after the nanoparticles of the present invention were injected into mice bearing breast cancer 4T1 tumors. DETAILED DESCRIPTION

[0034] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0035] It should be understood that the terms described herein are intended only to describe particular embodiments and are not intended to limit the present invention. In addition, for numerical ranges herein, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. The intermediate value within any stated value or stated range, and each smaller range between any other stated value or intermediate value within the stated range, is also encompassed within the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded within the scope.

[0036] Unless otherwise indicated, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of any conflict with any incorporated document, the contents of this specification shall prevail.

[0037] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments described herein without departing from the scope or spirit of the invention. Other embodiments will be apparent to those skilled in the art from the description of the invention. The description and examples are intended to be exemplary only.

[0038] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0039] The albumin used in the following examples was purchased from Beijing Solebow Technology Co., Ltd., and the ferritin was purchased from Sigma.

[0040] Example 1

[0041] A method for preparing tumor immune microenvironment-regulating photoactivated ferroptosis nanoparticles comprises the following steps:

[0042] (a) Weigh 15 mg of albumin and 5 mg of ferritin into 1 mL of pure water. Add NaOH solution to adjust the pH to 9.0. Then, add 100 μL of a 25 mg / mL lipoic acid solution in dimethyl sulfoxide and 100 μL of a 5 mg / mL indocyanine green (or neoindocyanine green) solution in dimethyl sulfoxide. Stir and react for 15 min.

[0043] (b) After the stirring reaction was completed, 4 mL of anhydrous ethanol was added and reacted for 3 h. Then, 20 μL of an 80 mg / mL glutaraldehyde aqueous solution was added and the stirring reaction was continued for 12 h. The mixture was centrifuged at 2500 rpm for 20 min using an ultrafiltration tube and freeze-dried to obtain tumor immune microenvironment-modulating photoactivated ferroptosis nanoparticles (also named indocyanine green & lipoic acid@ferritin & albumin nanoparticles).

[0044] The stability of tumor immune microenvironment-regulated photoactivated ferroptosis nanoparticles in 10% serum PBS (pH = 7.4) buffer solution was investigated using a Malvern particle size analyzer. Figure 1 As shown. Figure 1 It can be seen that the prepared tumor immune microenvironment-regulated light-activated ferroptosis nanoparticles have good stability in the medium and can maintain stable particle size distribution and potential distribution within 72 hours.

[0045] Comparative Example 1

[0046] (a) 15 mg of albumin and 5 mg of ferritin were weighed and added to 1 mL of pure water. NaOH solution was added to adjust the pH to 9.0. 100 μL of a 5 mg / mL indocyanine green dimethyl sulfoxide solution was then added and stirred for 15 min.

[0047] (b) After the stirring reaction was completed, 4 mL of anhydrous ethanol was added and the reaction was continued for 3 h. Then, 20 μL of an 80 mg / mL glutaraldehyde aqueous solution was added and the reaction was continued with stirring for 12 h. The mixture was centrifuged at 2500 rpm for 20 min using an ultrafiltration tube and freeze-dried to obtain indocyanine green@ferritin & albumin nanoparticles.

[0048] Comparative Example 2

[0049] (a) Weigh 20 mg of albumin and add it to 1 mL of pure water. Add NaOH solution to adjust the pH to 9.0. Then add 100 μL of 5 mg / mL indocyanine green dimethyl sulfoxide solution and stir for 15 min.

[0050] (b) After adding 4 mL of anhydrous ethanol and reacting for 3 h, 20 μL of an 80 mg / mL glutaraldehyde aqueous solution was added, and the reaction was continued with stirring for 12 h. The mixture was centrifuged at 2500 rpm for 20 min using an ultrafiltration tube, and freeze-dried to obtain indocyanine green nanoparticles.

[0051] Example 2

[0052] Toxicity experiments on 4T1 mouse mammary tumor cells, DC2.4 cells, and RAW264.7 cells were conducted under near-infrared laser irradiation, as detailed below:

[0053] Experimental methods:

[0054] 4T1 tumor cells were cultured at a rate of 5×103 The cells were evenly plated in a 96-well plate at a density of 100 μg / well. After 24 hours of culture, the original culture medium was removed and the cells were divided into free indocyanine green group, indocyanine green nanoparticle group, indocyanine green@ferritin & albumin nanoparticle group and indocyanine green & lipoic acid@ferritin & albumin nanoparticle group. The drugs of each experimental group were added at an indocyanine green concentration of 20 μg / mL. After incubation for 4 hours, the culture medium was discarded. The cells in each experimental group were treated with 1 w / cm 2 After laser irradiation (808 nm, 1 min), the cells were cultured for 24 h and the cell survival rate was detected by CCK8 method.

[0055] The toxicity experimental study methods for DC2.4 cells and RAW264.7 cells were the same as above.

[0056] The experimental results are as follows Figure 2 As shown by Figure 2 As we know, at 1w / cm 2 Under the action of laser (808nm, 1min), the cytotoxicity of each drug group on 4T1 cells showed that the cell survival rate of both the free indocyanine green group and the nanoparticle group containing indocyanine green decreased, among which the cell survival rate of the indocyanine green & lipoic acid @ ferritin & albumin nanoparticle group decreased significantly (about 30%). This shows that indocyanine green & lipoic acid @ ferritin & albumin nanoparticles can effectively induce ferroptosis of tumor cells under the action of laser. 2 Under laser irradiation (808 nm, 1 min), treatment with the indocyanine green, lipoic acid@ferritin, and albumin nanoparticles resulted in cell survival rates exceeding 80% for both DC2.4 and RAW264.7 cells. These results demonstrate that indocyanine green, lipoic acid@ferritin, and albumin nanoparticles can selectively kill tumor cells, potentially enabling the coordinated regulation of DCs, TAMs, and tumor cells in tumor immunotherapy.

[0057] Example 3

[0058] Experimental study on the effect of ferroptosis-based immunogenic death of tumor cells induced by the nanoparticles of the present invention on the maturation of BMDCs:

[0059] Experimental methods:

[0060] (1) 4T1 tumor cells were cultured at a rate of 2×10 5 The cells were evenly plated in a 12-well plate at a density of 100 μg / well. After 24 hours of culture, the original culture medium was removed and the cells were divided into PBS group, free indocyanine green group, indocyanine green nanoparticle group, indocyanine green@ferritin & albumin nanoparticle group and indocyanine green & lipoic acid@ferritin & albumin nanoparticle group. The drug of each experimental group was added at a concentration of 20 μg / mL of indocyanine green. After incubation for 4 hours, the culture medium was discarded. The cells in each experimental group were treated with 1 w / cm2 After laser irradiation (808 nm, 1 min), the cells were cultured for 24 h.

[0061] (2) BMDCs were cultured at a rate of 1×10 6 The cells were evenly plated in a 12-well plate at a density of 5 × 10 cells / well. After incubation for 2 hours, the supernatant of the 4T1 cells after laser irradiation in step (1) and continued to be cultured for 24 hours was collected and added to BMDCs. At the same time, the tumor cells after laser irradiation in step (1) and continued to be cultured for 24 hours were collected and added to the plate at a density of 5 × 10 cells / well. 4 The cells were re-plated into the wells containing BMDCs at a density of 100 cells / well. After 24 h of co-culture, BMDCs were collected and stained with different fluorescent-labeled antibodies and detected by flow cytometry. The results were as follows: Figure 3 shown.

[0062] Depend on Figure 3 It can be seen that compared with the PBS group, after BMDCs were co-incubated with 4T1 cells irradiated by each nanoparticle group, CD11c + CD80 + CD86 + The proportion of BMDCs increased significantly, among which the CD11c + CD80 + CD86 + The proportion of BMDCs increased the most (about 66%), indicating that ICG & LA@Ferritin & Albumin NPs can mediate the maturation of BMDCs through ferroptosis-based immunogenic death of tumor cells.

[0063] Example 4

[0064] Experimental study on the polarization of BMDMs cells by the nanoparticles of the present invention:

[0065] Experimental methods:

[0066] BMDMs cells were cultured at a rate of 1×10 6 Cells were evenly plated in a 12-well plate at a density of 100 μg / well and cultured overnight. After adding 40 ng / mL of IL-4 and culturing for 24 hours, the original culture medium was removed and the cells were divided into PBS group, free indocyanine green group, indocyanine green nanoparticle group, indocyanine green@ferritin & albumin nanoparticle group and indocyanine green & lipoic acid@ferritin & albumin nanoparticle group. Drugs were added to each experimental group at an indocyanine green concentration of 20 μg / mL. After incubation for 4 hours, the culture medium was discarded. Cells in each experimental group were subjected to 1 w / cm (808 nm, 1 min) 1 w / cm 2 After laser irradiation, the culture was continued for 24 h, and BMDMs were collected for staining with different fluorescent-labeled antibodies and detected by flow cytometry. Figure 4 shown.

[0067] Depend on Figure 4 As we know, compared with the PBS group, the F4 / 80 + CD206 + The proportion of BMDMs was significantly reduced in the indocyanine green@ferritin & albumin nanoparticles group and the indocyanine green & lipoic acid@ferritin & albumin nanoparticles group F4 / 80 + CD206 + The proportion of BMDMs was the lowest (about 25%), indicating that indocyanine green & lipoic acid@ferritin & albumin nanoparticles can effectively promote the polarization of M2-BMDMs to M1 type.

[0068] Example 5

[0069] In vivo tumor inhibition effect study:

[0070] Experimental method: According to 1×10 6 Mouse mammary tumor cells 4T1 were subcutaneously inoculated into the right side of the back of female Balb / c mice at a seeding density of 10 cells / mouse. When the tumor reached 50 mm 3 Mice were randomly divided into 4 groups (n=5), namely normal saline group, free indocyanine green group, indocyanine green nanoparticle group, indocyanine green@ferritin & albumin nanoparticle group and indocyanine green & lipoic acid@ferritin & albumin nanoparticle group (indocyanine green: 5 mg / kg, administered by tail vein injection). The drugs were administered once a day for three days. Twelve hours after administration, the tumor sites of mice in the laser group were irradiated with 0.5W / cm 2 , 1.5 min of laser irradiation, and the tumor volume of each group of experimental mice was measured every two days; when the tumor volume of the mice in the normal saline group reached ~2000mm 3 The experiment was terminated at 1 pm. The excised tumor tissue was weighed. Another tumor tissue was ground, sieved, and lysed with red blood cell lysis buffer to remove red blood cells. It was then stained with different fluorescent-labeled antibodies and analyzed by flow cytometry. The measurement results were as follows: Figure 5-Figure 7 shown.

[0071] Depend on Figure 5 As shown, compared with the saline group, the free indocyanine green group, the indocyanine green nanoparticle group, the indocyanine green@ferritin & albumin nanoparticle group, and the indocyanine green & lipoic acid@ferritin & albumin nanoparticle group all inhibited tumor growth; the indocyanine green & lipoic acid@ferritin & albumin nanoparticle group had the lowest average tumor weight. This indicates that the indocyanine green & lipoic acid@ferritin & albumin nanoparticles of the present invention exhibit a stronger synergistic effect under laser treatment, effectively inhibiting tumor growth.

[0072] Depend on Figure 6It can be seen that compared with the normal saline group, the free indocyanine green group, the indocyanine green nanoparticles group, the indocyanine green@ferritin & albumin nanoparticles group and the indocyanine green & lipoic acid@ferritin & albumin nanoparticles group, the CD11C + CD86 + The proportion of DCs increased significantly; among them, the CD11C in tumor tissue of the indocyanine green & lipoic acid @ ferritin & albumin nanoparticles group increased significantly. + CD86 + The proportion of DCs was the highest. This indicates that the indocyanine green & lipoic acid@ferritin & albumin nanoparticles of the present invention have a better synergistic effect under laser treatment, significantly promoting the maturation and activation of DCs in tumor tissue, initiating anti-tumor immune responses, and producing the best therapeutic effect.

[0073] Depend on Figure 7 It can be seen that compared with the normal saline group, the free indocyanine green group, the indocyanine green nanoparticles group, the indocyanine green@ferritin & albumin nanoparticles and the indocyanine green & lipoic acid@ferritin & albumin nanoparticles groups, the F4 / 80 + CD206 + The proportion of TAMs was significantly reduced in the indocyanine green & lipoic acid@ferritin & albumin nanoparticles group. + CD206 + The proportion of TAMs was the lowest. This indicates that the indocyanine green & lipoic acid@ferritin & albumin nanoparticles of the present invention have a better synergistic effect under laser treatment, significantly reducing the proportion of M2-TAMs in tumor tissue, regulating the tumor immunosuppressive microenvironment, and inhibiting tumor growth.

[0074] 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 method for preparing tumor immune microenvironment-regulating photoactivated ferroptosis nanoparticles, characterized in that: The following steps are involved: Albumin and ferritin are dissolved in water, and after adjusting the pH to alkaline, a photosensitizer and lipoic acid are added, and then a solvent is added after mixing to carry out a mixing reaction. Then, a cross-linking agent is added, and the reaction is continued. After centrifugation and drying, the tumor immune microenvironment-regulated light-activated ferroptosis nanoparticles are obtained.

2. The preparation method according to claim 1, characterized in that The photosensitizer is indocyanine green or neoindocyanine green; and / or The cross-linking agent is glutaraldehyde.

3. The preparation method according to claim 1, characterized in that The mass ratio of the albumin, the ferritin, the lipoic acid and the photosensitizer is 15:5:2.5:0.

5.

4. The preparation method according to claim 1, characterized in that The solvent is anhydrous ethanol.

5. The preparation method according to claim 1, characterized in that The adjusting the pH to be alkaline refers to adjusting the pH to 9.

0.

6. A tumor immune microenvironment-regulating photoactivated ferroptosis nanoparticle prepared according to the preparation method according to any one of claims 1 to 5.

7. Use of the tumor immune microenvironment-regulating light-activated ferroptosis nanoparticles according to claim 6 in the preparation of tumor immunotherapy drugs.

8. The use according to claim 7, characterized in that The drug reverses the tumor immunosuppressive microenvironment by inducing ferroptosis of tumor cells, activating dendritic cells, and regulating the M1 polarization of M2 tumor-associated macrophages.

9. A tumor immunotherapy drug, characterized in that: The active ingredient includes the tumor immune microenvironment regulating light-activated ferroptosis nanoparticles according to claim 6.

10. The tumor immunotherapy drug according to claim 9, characterized in that The tumor immunotherapy drug also includes pharmaceutically acceptable excipients.

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