Mesoporous silicon nano-composite for photo-thermal immunotherapy as well as preparation method and application of meso-porous silicon nano-composite

Abstract

The invention relates to a meso-porous silicon nano-composite for photo-thermal immunotherapy and a preparation method and application thereof. The meso-porous silicon nano-composite comprises meso-porous silicon nano-particles and bismuth nano-particles loaded on the surfaces of the meso-porous silicon nano-particles through electrostatic interaction. According to the invention, a self-enhanced immunotherapy storage cavern is constructed on the basis of loading bismuth nano-particles on mesoporous silicon nano-particles. Under the irradiation of near-infrared laser, the MSN (at) Bi platform shows excellent photothermal conversion efficiency, can locally generate high temperature in vivo and in vitro, and remarkably inhibits the proliferation of tumor cells; mild photothermal therapy of MSN (at) Bi not only directly destroys tumor cells, but also can induce death of immunogenic cells and promote the tumor cells to release damage-related molecular patterns, so that an immune system is activated. According to the invention, a strategy of combining photo-thermal therapy and immunoregulation is adopted, so that the anti-tumor effect is remarkably enhanced, the systematic toxicity is effectively reduced, and an efficient and low-toxicity multifunctional nano medical solution is provided for tumor treatment.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical technologies, and relates to a mesoporous silica nanocomposite for photothermal immunotherapy, a preparation method thereof, and an application thereof. Background Art

[0002] Cancer treatment faces multiple challenges, including tumor heterogeneity, drug resistance, and immunosuppressive tumor microenvironment (TME). These factors significantly limit the efficacy of traditional treatment strategies (such as chemotherapy and radiotherapy). For example, tumor heterogeneity results in significant differences in the responses of different cell populations to the same treatment method, and the problem of drug resistance further reduces the treatment effect. In addition, the immunosuppressive characteristics of TME weaken the body's immune system's ability to recognize and eliminate tumors, making it more difficult to cure cancer.

[0003] In recent years, photothermal therapy (PTT) has become an important research direction in tumor treatment due to its non-invasive, highly selective, and locally efficient tumor cell killing characteristics. PTT uses a photothermal conversion material to generate local high temperature under near-infrared light irradiation, inducing apoptosis or necrosis of tumor cells and having low systemic toxicity. However, single PTT often has difficulty effectively overcoming the immunosuppressive effect of TME, resulting in a relatively high risk of survival and recurrence of residual tumor cells after treatment. Therefore, relying solely on PTT is still difficult to achieve long-term and effective anti-tumor effects.

[0004] In order to overcome the immunosuppressive effect of TME and enhance the treatment effect of PTT, in recent years, researchers have been committed to constructing a nano-therapy system with both photothermal effect and immune regulation ability. By rationally designing nanomaterials, the tumor microenvironment can be regulated on the basis of PTT, the body's immune system can be activated, and the anti-tumor immune response can be promoted. For example, some nanomaterials can induce immunogenic cell death (ICD) through thermal effects, release tumor-associated antigens, and thus enhance the tumor vaccine effect. In addition, nanomaterials can be used to deliver immune adjuvants or regulate immune checkpoint signals to further improve anti-tumor immune activity. Therefore, developing a nano-therapy system with a photothermal-immune synergistic effect may provide a new strategy for improving the cancer treatment effect. Summary of the Invention

[0005] Aiming at the deficiencies of the prior art, the purpose of the present invention is to provide a mesoporous silica nanocomposite for photothermal immunotherapy, a preparation method thereof, and an application thereof. The present invention aims to solve the core problems such as tumor heterogeneity, drug resistance, and immunosuppressive microenvironment existing in traditional cancer treatment. By constructing a novel mesoporous silica-loaded bismuth composite system (MSN@Bi), multi-dimensional treatment goals are achieved: synergistic function integration, mild photothermal-triggered ICD, reversal of immunosuppressive TME, low systemic toxicity, and precise energy regulation.

[0006] To achieve the object of the present invention, the present invention adopts the following technical solutions:

[0007] In a first aspect, the present invention provides a mesoporous silica nanocomposite for photothermal immunotherapy, and the mesoporous silica nanocomposite includes mesoporous silica nanoparticles and bismuth nanoparticles loaded on the surface of the mesoporous silica nanoparticles by electrostatic interaction.

[0008] The composite system involved in the present invention is based on mesoporous silica nanoparticles loaded with bismuth nanoparticles (MSN@Bi) to construct a self-enhanced immunotherapy reservoir. Under near-infrared laser irradiation, the MSN@Bi platform exhibits excellent photothermal conversion efficiency, can locally generate high temperature in vivo and in vitro, and significantly inhibits the proliferation of tumor cells; the mild photothermal therapy of MSN@Bi not only directly destroys tumor cells, but also induces immunogenic cell death (ICD), promotes tumor cells to release damage-associated molecular patterns (DAMPs), thereby activating the immune system. The present invention adopts a strategy of combining photothermal therapy and immunomodulation, significantly enhances the anti-tumor effect, and effectively reduces systemic toxicity, providing a highly efficient and low-toxic multifunctional nanomedicine solution for tumor treatment.

[0009] Preferably, the mass ratio of the mesoporous silica nanoparticles to the bismuth nanoparticles is (1-5):1, such as 1:1, 2:1, 3:1, 4:1, 5:1, etc.

[0010] Preferably, the particle size of the bismuth nanoparticles is 1-5 nm, such as 1 nm, 1.5 nm, 2 nm, 2.5 nm, 3 nm, 3.5 nm, 4 nm, 5 nm, etc.

[0011] The particle size of the mesoporous silica nanoparticles is 130-180 nm, such as 130 nm, 140 nm, 150 nm, 155 nm, 160 nm, 170 nm, 180 nm, etc.

[0012] In a second aspect, the present invention provides a preparation method of the mesoporous silica nanocomposite for photothermal immunotherapy according to the first aspect, and the preparation method includes the following steps:

[0013] Mix and incubate the bismuth nanoparticles and the mesoporous silica nanoparticles in a solution to obtain a mesoporous silica nanocomposite for photothermal immunotherapy.

[0014] Preferably, the incubation is carried out at 15-40 °C (such as 15 °C, 20 °C, 25 °C, 30 °C, 35 °C, 40 °C, etc.) for 8-15 h (such as 8 h, 9 h, 10 h, 12 h, 13 h, 15 h, etc.).

[0015] Preferably, stirring treatment and / or ultrasonic treatment are also carried out during the incubation process.

[0016] The bismuth nanoparticles in the mesoporous silica nanocomposite involved in the present invention can be prepared by conventional methods in the art, for example, bismuth nanoparticles are synthesized by a biomineralization method.

[0017] Preferably, the preparation method of the bismuth nanoparticles comprises the following steps:

[0018] Under stirring conditions, a biomolecule solution is added dropwise to an aqueous bismuth salt solution as a template, and then incubated in an alkaline environment to obtain bismuth nanoparticles.

[0019] Preferably, the bismuth salt includes bismuth nitrate.

[0020] Preferably, the biomolecule includes BSA.

[0021] Preferably, the incubation is carried out at 20 - 30 °C (such as 20 °C, 23 °C, 25 °C, 27 °C, 30 °C, etc.) for 10 - 15 h (such as 10 h, 11 h, 12 h, 13 h, 15 h, etc.).

[0022] The mesoporous silica nanoparticles in the mesoporous silica nanocomposite loaded with gold nanoparticles involved in the present invention can be prepared by conventional methods in the art. For example, using raw materials such as cetyl bromide glycol (CPB), urea, ultrapure water, cyclohexane, n-butanol, and tetraethyl orthosilicate (TEOS), through a multi-stage temperature-controlled reaction, MSN with uniform pore size and high specific surface area is synthesized. This MSN has good drug-loading capacity and stability, providing an excellent platform for the subsequent loading of gold nanoparticles.

[0023] Preferably, the preparation method of the mesoporous silica nanoparticles comprises the following steps:

[0024] Using cetyl bromide glycol, urea, water, organic solvent, and tetraethyl orthosilicate as reaction raw materials; after mixing them, the reaction is first carried out at 60 - 80 °C (such as 60 °C, 65 °C, 70 °C, 75 °C, 80 °C, etc.) for 40 - 80 min (such as 40 min, 50 min, 60 min, 70 min, 80 min, etc.), then at 0 - 10 °C (such as 0 °C, 2 °C, 4 °C, 8 °C, 10 °C, etc.) for 90 - 150 min (such as 90 min, 100 min, 120 min, 130 min, 150 min, etc.), and finally at 60 - 80 °C (such as 60 °C, 65 °C, 70 °C, 75 °C, 80 °C, etc.) for 8 - 15 h (such as 8 h, 10 h, 12 h, 13 h, 14 h, 15 h, etc.) to obtain mesoporous silica nanoparticles.

[0025] Preferably, the organic solvent includes cyclohexane and n-butanol.

[0026] Preferably, solid-liquid separation is also carried out after the reaction.

[0027] Preferably, after the solid-liquid separation, the solid product is further washed with ethanol to remove impurities.

[0028] Thirdly, the present invention provides an application of the mesoporous silica nanocomposite for photothermal immunotherapy according to the first aspect in the preparation of anti-tumor drugs.

[0029] All specific point values not listed within the numerical ranges involved in the present invention are within the protection scope of the present invention. Considering the space and brief description, they will not be elaborated one by one here.

[0030] Compared with the prior art, the present invention has the following beneficial effects:

[0031] The composite system involved in the present invention is based on mesoporous silica nanoparticles loaded with bismuth nanoparticles (MSN@Bi), and constructs a self-enhanced immunotherapy reservoir. Under near-infrared laser irradiation, the MSN@Bi platform exhibits excellent photothermal conversion efficiency, can locally generate high temperature in vitro and in vivo, and significantly inhibits the proliferation of tumor cells; the mild photothermal therapy of MSN@Bi not only directly destroys tumor cells, but also induces immunogenic cell death (ICD), promotes tumor cells to release damage-associated molecular patterns (DAMPs), thereby activating the immune system, forming a positive feedback loop of "photothermal ablation-immune activation-microenvironment remodeling", significantly amplifying the anti-tumor effect, and effectively reducing systemic toxicity. Single-dose administration can simultaneously achieve physical tumor killing, immune system activation and long-term immune memory, providing an efficient and low-toxic nanomedicine solution for the treatment of solid tumors. Description of the Drawings

[0032] Figure 1 is the transmission electron microscope image of MSN prepared in Example 1;

[0033] Figure 2 is the transmission electron microscope image of bismuth nanoparticles prepared in Example 2;

[0034] Figure 3 is the transmission electron microscope image of MSN@Bi prepared in Example 3;

[0035] Figure 4 is the potential measurement result graph of bismuth nanoparticles, MSN and MSN@Bi;

[0036] Figure 5 is the dynamic light scattering (DLS) graph of MSN and MSN@Bi;

[0037] Figure 6 is the photothermal performance evaluation result graph of MSN@Bi;

[0038] Figure 7Fluorescence staining images of 4T1 cells incubated with MSN, Bi, and MSN@Bi under different irradiation conditions;

[0039] Figure 8 Thermal imaging diagrams of different treatment groups;

[0040] Figure 9 Is CD80 in tumor-draining lymph nodes + CD86 + Flow cytometry analysis diagrams of DC;

[0041] Figure 10 Is the flow cytometry analysis diagram of MHC I in DC + ;

[0042] Figure 11 Tumor anatomy diagrams of different treatment groups;

[0043] Figure 12 Statistical graphs of tumor growth curves of different treatment groups;

[0044] Figure 13 High-resolution confocal microscopy images of CRT expression levels in different treatment groups;

[0045] Figure 14 Statistical result diagrams of CRT expression levels in different treatment groups;

[0046] Figure 15 Statistical result diagrams of the body weights of mice in different groups during treatment;

[0047] Figure 16 Hematoxylin and eosin (H&E) staining images of major organs (heart, spleen, liver, lung, and kidney). Detailed implementation manners

[0048] The technical solution of the present invention will be further described below through specific implementation manners. Those skilled in the art should understand that the embodiments are only for helping to understand the present invention and should not be regarded as specific limitations to the present invention.

[0049] Example 1

[0050] Preparation of MSN:

[0051] Mix 2 g of cetylpyridinium bromide (CPB), 1.2 g of urea and 30 mL of ultrapure water. Add 40 mL of cyclohexane and 1.1 mL of n-butanol to the above mixture. Under continuous stirring, add dropwise 5 mL of tetraethoxysilane (TEOS). Stir at 25 °C for 30 minutes. Transfer the reaction mixture to an oil bath at 70 °C and react for 1 hour. Then place it in an ice bath at 10 °C and react for 2 hours. Finally, return it to the oil bath at 70 °C and react for 12 hours. After the reaction is completed, centrifuge the product and wash it three times with ethanol. The obtained product is MSN dispersed in ethanol.

[0052] Example 2

[0053] Preparation of bismuth nanoparticles:

[0054] Dropwise add an aqueous solution containing Bi(NO3)3 to a BSA solution (16 mL, concentration 25 mg / mL, temperature 25 °C) under vigorous stirring. After 2 minutes of dropping, quickly add NaOH solution (2 M) to gradually change the color of the solution from light yellow to light brown and further to dark black after 30 minutes. Subsequently, incubate the reaction mixture at 25 °C for 12 hours to ensure a complete reaction.

[0055] Example 3

[0056] Preparation of MSN@Bi composite:

[0057] Mix the Bi particle solution prepared in Example 2 with the MSN prepared in Example 1 at 30 °C for 15 h to load Bi on the surface of MSN, forming an MSN@Bi composite, and store it in PBS and keep it at 4 °C for later use.

[0058] Test Example 1

[0059] Morphology characterization:

[0060] Characterize the morphology of the products prepared in Examples 1 - 3 by transmission electron microscopy. The results are as follows Figures 1 - 3 shown. Transmission electron microscopy (TEM) analysis results show that the synthesized MSN has excellent monodispersity and structural uniformity, and the prepared bismuth nanoparticles have a particle size of about 3 nm. Subsequently, through electrostatic interaction, the positively charged bismuth nanoparticles are successfully loaded on the surface of MSN. The TEM image further reveals that a high-density and uniformly distributed bismuth coating is formed on the surface of MSN, showing a distinct contrast effect of close packing between particles.

[0061] Test Example 2

[0062] Particle size and potential characterization:

[0063] The products obtained in Example 1, Example 2 and Example 3 were subjected to dynamic light scattering (DLS) and zeta potential measurements, and the results are as Figures 4 - 5 shown, indicating the successful preparation of the products at each stage.

[0064] Test Example 3

[0065] Evaluation of photothermal performance:

[0066] To evaluate the photothermal effect of the MSN@Bi complex, aqueous solutions of MSN@Bi with different concentrations (0, 32, 128, and 512 μg / mL) were prepared and placed in 1.5 mL EP tubes. Under the irradiation of near-infrared light with a wavelength of 808 nm, continuous irradiation was carried out for 480 seconds, and the temperature was recorded every 30 seconds using a digital near-infrared photothermal imaging system (FLIR, Germany). The results are as Figure 6 shown. All MSN@Bi solutions showed a significant increase in temperature after NIR irradiation, and the temperature curve showed an obvious time dependence. It is worth noting that the photothermal response of MSN@Bi is concentration-dependent, and its temperature rise amplitude can be enhanced with the increase of nanoparticle concentration. This result verifies that the photothermal effect of MSN@Bi can be precisely regulated by the nano-dose, providing an efficient and adjustable treatment platform for photothermal therapy targeting tumor sites.

[0067] Test Example 4

[0068] In vitro anti-tumor evaluation:

[0069] (1) Cell culture:

[0070] The 4T1 mouse breast cancer cell line was purchased from the Cell Bank of the Chinese Academy of Sciences (Shanghai, China) and cultured in RPMI 1640 medium (Wisent Inc.). The medium was supplemented with 10% fetal bovine serum (FBS, Gibco) and 100 U / mL penicillin-streptomycin (Invitrogen). The cells were cultured at a constant temperature in a humidified environment of 37 °C and 5% CO2 to maintain cell proliferation and biological characteristics.

[0071] (2) Evaluation of in vitro anti-tumor effect:

[0072] The Calcein-AM and propidium iodide (PI) double fluorescence staining technique was used to evaluate the viability of cells under different treatment conditions, and an inverted fluorescence microscope (Leica) was used to observe the cell survival situation. Specifically, the 4T1 cells were seeded at 8×10 4Cells were inoculated at a density of [number] / well into 6-well plates and incubated overnight in an environment of 37 °C and 5% CO₂. Subsequently, cells were treated with Bi (50 μg / mL, corresponding to the Bi concentration in MSN@Bi), MSN (100 μg / mL, corresponding to the carrier concentration in MSN@Bi), and MSN@Bi nanoparticles, respectively. After incubation for 6 hours, a laser with a wavelength of 808 nm was applied and irradiated at a power of 1 W / cm 2 or 1.5 W / cm 2 for 5 minutes. After further incubation for 24 hours, the cells were subjected to live / dead fluorescence staining analysis.

[0073] The results are as Figure 7 shown. In the experimental groups without laser irradiation, the cells mainly showed green fluorescence, indicating that MSN and MSN@Bi alone did not cause obvious cell damage. After irradiation with an 808 nm laser in the MSN@Bi group, the cells showed obvious red fluorescence signals, and the red fluorescence signals increased with the increase in the irradiation power density, further confirming that its photothermal effect could effectively induce cell death.

[0074] Test Example 5

[0075] Evaluation of anti-tumor effect in vivo:

[0076] (1) Six-week-old female BALB / c mice were purchased, and a 4T1 tumor model was established by subcutaneous injection of 1×10 5 4T1 tumor cell suspension (100 μL PBS) on the right back of each mouse (recorded as day 0 of the experiment).

[0077] (2) The mice were randomly divided into four groups (5 mice in each group) and received different nanoparticle injections on day 10 of the experiment: 1) control group (only injected with PBS); 2) only injected with MSN@Bi (150 μg Bi per mouse); 3) injected with Bi and received 808 nm laser near-infrared (NIR) irradiation; 4) injected with MSN@Bi and received 808 nm laser NIR irradiation. All groups were injected only once. For the NIR irradiation group, they received 808 nm laser (1 W / cm 2 , for 5 minutes) irradiation 6 hours after injection. At different times after injection, an infrared thermal imaging system was used to record the temperature changes of the tumors, as Figure 8 shown.

[0078] (3) On the 17th day of the experiment, the lymph nodes adjacent to the tumor were excised. These excised lymph nodes were then digested with RPMI 1640 medium (supplemented with 0.5 mg / mL collagenase IV and 0.1 mg / mL DNase I) at 37 °C for 30 minutes. After digestion, a single-cell suspension was obtained through a 40-μm cell strainer. The isolated lymph node cells were washed with RPMI 1640 medium and then stained with specific antibodies: anti-CD11c (at a concentration of 0.25 μg / 100 μL), anti-CD80 (1.0 μg / 100 μL), anti-CD86 (0.25 μg / 100 μL), and incubated on ice for 1 hour while detecting the expression level of MHC-I molecules. Finally, the stained cell samples were analyzed by flow cytometry.

[0079] The results showed that the activation degree of dendritic cells (DCs) was significantly increased, among which the CD80 in the tumor-draining lymph nodes + CD86 + The proportion of mature DC subsets in the MSN@Bi plus laser group was approximately 25.1%, which was significantly higher than that in the Bi plus laser group and the MSN@Bi alone group ( Figure 9 ). The phenotypic maturation of DCs was accompanied by an increase in the expression level of major histocompatibility complex class I (MHC-I) molecules, suggesting that this treatment strategy could enhance the antigen cross-presentation ability and thus promote the activation of adaptive immune responses ( Figure 10 ).

[0080] (4) On the 28th day of the experiment, the tumors were collected as Figure 11 and Figure 12 shown, and the tumor volume was measured. The formula for calculating the tumor volume was: volume = length × width 2 / 2, which confirmed that MSN@Bi achieved the best therapeutic effect of photothermal-chemical synergistic regulation of ICD.

[0081] To explore the mechanism of enhancing the therapeutic effect, the tumors of different groups were fixed in 4% PFA for immunofluorescence staining to systematically study the biomarkers of immunogenic cell death (ICD). The results of high-resolution confocal microscopy imaging were as Figure 13 shown, indicating that in the tumor tissues treated with the combination of MSN@Bi and laser irradiation, the translocation of calreticulin (CRT) to the cell membrane was significantly enhanced. As a key "eat me" signal of antigen-presenting cells, the exposure level of CRT was increased by approximately 4.6 times compared with the MSN@Bi group without laser irradiation ( Figure 14 ), which confirmed that photothermal-induced cytoplasmic stress could synergistically act with nanodrug delivery to enhance the induction effect of ICD.

[0082] The above quantitative pathological indicators jointly verified that the treatment strategy could achieve the successful transformation of immunosuppressive ("cold") tumors into immunologically activated ("hot") tumors by photothermal-chemical synergistic regulation of the ICD pathway.

[0083] Test Example 6

[0084] Biological safety evaluation:

[0085] To verify the biological safety of the composite nanosystem and ensure its feasibility for in vivo applications, the body weight changes of experimental animals were evaluated. After intravenous injection, the body weights of mice in each group were monitored every three days. As Figure 15 shown, during the entire treatment process, the mice in each experimental group did not show abnormal behaviors, and there were no significant fluctuations in body weight.

[0086] Meanwhile, the histological characteristics of the main organs of experimental animals were systematically evaluated. After the animal experiment, the main organs (heart, liver, spleen, lung, and kidney) were collected, fixed with 4% paraformaldehyde (PFA) solution, and routinely processed into paraffin sections. The main organs of the sections were stained with H&E and observed through an inverted fluorescence microscope system (Nikon-Ti-S). The results were as Figure 16 shown. The morphological analysis results of the H&E-stained tissue sections indicated that there were no obvious pathological damages or abnormalities in the tissue structures, whether in the control group or the experimental group. This result demonstrated that Bi and MSN@Bi exhibited low acute toxicity in animals.

[0087] In summary, the preliminary biological safety evaluation results obtained through body weight monitoring and histopathological analysis both indicated that the composite nanosystem had high biological safety, laying a good foundation for its further applications in vivo and in vitro.

[0088] The applicant declares that the present invention uses the above embodiments to illustrate the technical solutions of the present invention, but the present invention is not limited to the above embodiments, that is, it does not mean that the present invention must rely on the above embodiments to be implemented. Those skilled in the art should understand that any improvement to the present invention, the equivalent replacement of each raw material of the products of the present invention, the addition of auxiliary components, and the selection of specific methods, etc., all fall within the protection scope and the disclosure scope of the present invention.

[0089] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solutions of the present invention, and these simple modifications all belong to the protection scope of the present invention.

[0090] In addition, it should be noted that, for each of the specific technical features described in the above specific embodiments, they can be combined in any appropriate manner without conflict. To avoid unnecessary repetition, the present invention will not separately describe various possible combination manners.

Claims

1. A mesoporous silicon nanocomposite for photothermal immunotherapy, characterized in that: The mesoporous silicon nanocomposite comprises mesoporous silicon nanoparticles and bismuth nanoparticles loaded on the surface of the mesoporous silicon nanoparticles through electrostatic action.

2. The mesoporous silicon nanocomposite for photothermal immunotherapy according to claim 1, characterized in that: The mass ratio of the mesoporous silicon nanoparticles to the bismuth nanoparticles is (1-5):

1.

3. The mesoporous silicon nanocomposite for photothermal immunotherapy according to claim 1, characterized in that: The particle size of the bismuth nanoparticles is 1-5 nm; The particle size of the mesoporous silicon nanoparticles is 130-180 nm.

4. The method for preparing a mesoporous silicon nanocomposite for photothermal immunotherapy according to any one of claims 1 to 3, characterized in that: The preparation method comprises the following steps: Bismuth nanoparticles and mesoporous silicon nanoparticles are mixed and incubated in a solution to obtain a mesoporous silicon nanocomposite for photothermal immunotherapy.

5. The preparation method according to claim 4, characterized in that: The incubation is carried out at 15-40° C. for 8-15 h; Preferably, stirring treatment and / or ultrasonic treatment are also performed during the incubation process.

6. The preparation method according to claim 4, characterized in that: The method for preparing the bismuth nanoparticles comprises the following steps: A biomolecule solution is added dropwise as a template to a bismuth salt aqueous solution under stirring conditions, and then the solution is incubated in an alkaline environment to obtain bismuth nanoparticles.

7. The preparation method according to claim 6, characterized in that: The bismuth salt includes bismuth nitrate; Preferably, the biomolecule comprises BSA; Preferably, the incubation is performed at 20-30°C for 10-15h.

8. The preparation method according to claim 4, characterized in that: The method for preparing the mesoporous silicon nanoparticles comprises the following steps: Bromohexadecanediol, urea, water, an organic solvent and tetraethoxysilane are used as reaction raw materials; after mixing, they are first reacted at 60-80°C for 40-80 minutes, then reacted at 0-10°C for 90-150 minutes, and finally reacted at 60-80°C for 8-15 hours to obtain mesoporous silicon nanoparticles.

9. The preparation method according to claim 8, characterized in that: The organic solvent includes cyclohexane and n-butanol; Preferably, solid-liquid separation is also performed after the reaction is completed; Preferably, after the solid-liquid separation, the solid product is washed with ethanol to remove impurities.

10. Use of the mesoporous silicon nanocomposite for photothermal immunotherapy according to any one of claims 1 to 3 in the preparation of anti-tumor drugs.

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